Resiliency among Older Adults Receiving (Roar) Lung Cancer Treatment: A Feasibility Study

PURPOSE/HYPOTHESIS: Poor physical performance and negative mood are two risk factors for functional decline among older adults with lung cancer. Yet, targeted interventions to maintain independence prevent functional decline are not well studied. Our primary objective was to assess the feasibility of a novel virtual health physical therapy (PT) plus progressive muscle relaxation (PMR) intervention with longitudinal microbiome biospecimen collection delivered to older adults with advanced lung cancer. Secondary objectives were to characterize functional status and clinical factors pre and post-study intervention. NUMBER OF SUBJECTS: We accrued adults aged >=60 years with advanced non-small cell or extensive-stage small cell lung cancer receiving treatment at The Ohio State University James Comprehensive Cancer Center (OSU-JCCC) in the Thoracic Oncology department (N=22). There were no exclusion criteria pertaining to Eastern Cooperative Oncology Group (ECOG) performance status, laboratory values, prior cancer diagnoses, presence of comorbidities, or brain metastases. MATERIALS AND METHODS: Participants were asked about functional status, symptoms, mood through the PHQ-9, GAD-7, POMS, and acceptability questions about the program. PT evaluation and assessment included SPPB and 2- or 6-minute walk test outcomes. The study sought to collect gut microbiome samples for every in-person visit and activity monitoring data (Actigraph) on a subset. Feasibility was defined as successfully collecting specimens, wearing an Actigraph activity monitor, and adhering to the intervention. PT and psychologists evaluated participants in-person at the first and final visit. The rest of the 12-week intervention was conducted via virtual health. Physical therapy intervention consisted of endurance, strength, and flexibility exercises. RESULT(S): In total, 22 patients consented and 18 started the intervention (81.8%). Seven microbiome samples were collected from four participants. Six patients collected activity monitoring data. Among the 18 participants, 11 participants (61.1%) completed 70% or more of all the intervention visits. The SPPB data show a moderate effect size (Cohen's d=0.24) from pre- to post-data. On average patients improved by 1.8 total points on the SPPB. Patients demonstrated improvement on timed walk tests throughout intervention from an average of 108 feet pre-intervention to an average of 138.4 feet post intervention. CONCLUSION(S): Despite the challenges of the COVID-19 pandemic, longitudinal biospecimen and correlative data collection were feasible in the context of PT and PMR intervention among older adults with advanced lung cancer. Virtual physical therapy interventions can be safely delivered to improve physical performance as demonstrated by a moderate effect size for the SPPB in this patient population. CLINICAL RELEVANCE: Based on the feasibility study results, delivering a virtual PT intervention to older patients with lung cancer can improve SPPB score leading to decreased frailty and improve quality of life among patients.

Clinical Outcomes of Stage III Non-small Cell Lung Cancer Patients Treated With Radical Radiotherapy in a Institution in Brazil

Introduction: Lung cancer is the leading cause of cancer death. Most cases are diagnosed at advanced stages. Stage III cancers are treated in a curative manner, despite the low success rate. Our objective was to define the clinical and epidemiological profile of stage III non-small cell lung cancer (NSCLC) patients (pts) treated with radiotherapy (RT) and their response to therapy. Method(s): It is a retrospective and observational study of all non-surgical stage III NSCLC pts treated with RT with curative intent at a public cancer center in the south of Brazil between January/2016 and June/2022. Data collected: dates of biopsy, treatment initiation, image progression or relapse, death and last registration;ECOG-PS;sex;smoking status;histology;stage (TNM 7th Ed) and chemotherapy (CT) use. Survival analysis were performed using the Kaplan-Meier method and factors associated with the events were analyzed using Cox regression. Groups were compared with chi-square and Kruskal-Wallis tests. Result(s): Eighty-seven pts were identified;median age 63 years-old;46 (52%) male, 78 (90%) former or present smokers;51 (62%) ECOG-PS 0/1;49 (58%) squamous (sq) histology;48 (60%) stage IIIb;60 (68%) had abdomen, bone and brain scans;64 (73%) had concurrent CT, 11(13%) sequential and 12 (14%) exclusive RT;64 (74%) concluded RT;53 (60%) had disease progression or relapse and 47 (54%) died. It took a median of 77 days (d) from biopsy to treatment initiation, without difference between pre or during COVID-19 pandemic. The follow-up was of 305d, progression free survival 192d and overall survival 253d (median for all), using the treatment initiation as baseline date. Younger pts and ECOG-PS 0/1 pts were more commonly treated with concurrent CT (X2:8,87;p 0,0054 and X2:10,82;p 0,004 respectively). No factor influenced progression free survival on uni or multivariable analyses. Factors correlated with overall survival on univariable analysis were: ECOG-PS (hazard ratio (HR) 2,02;p 0,010);bone scan (HR 0,5;p 0,028);treatment conclusion (HR 3,53;p<0,0001). Multivariable analysis: ECOG-PS (HR 2,95;p 0,017), non-sq histology (HR 2,26;p 0,044);RT conclusion (HR 4,69;p<0,0001). Conclusion(s): Our study shows shorter overall and progression free survival than literature, with a large portion of patients being treated with ECOG-PS of 2 or greater and without adequate systemic staging. About one-quarter of patients did not conclude the treatment, and this was the most negative factor impacting survival next to ECOG-PS.Copyright © 2023

Neoadjuvant nivolumab (N) + platinum-doublet chemotherapy (C) for resectable NSCLC: 3-y update from CheckMate 816

Background The phase III CheckMate 816 study demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and pathologic complete response (pCR) with neoadjuvant N + C vs C in patients (pts) with resectable NSCLC. Here, we report 3-y efficacy, safety, and exploratory biomarker analyses from CheckMate 816. Methods Adults with stage IB (tumors >=4 cm)-IIIA (per AJCC 7th ed) resectable NSCLC, ECOG PS <= 1, and no known EGFR/ALK alterations were randomized to N 360 mg + C Q3W or C alone Q3W for 3 cycles followed by surgery. Primary endpoints were EFS and pCR, both per blinded independent review. Exploratory analyses included EFS by surgical approach and extent/completeness of resection, and EFS and pCR by a 4-gene (CD8A, CD274, STAT-1, LAG-3) inflammatory signature score derived from RNA sequencing of baseline (BL) tumor samples. Results At a median follow-up of 41.4 mo (database lock, Oct 14, 2022), continued EFS benefit was observed with N + C vs C (HR, 0.68;95% CI, 0.49-0.93);3-y EFS rates were 57% and 43%, respectively. N + C improved EFS vs C in pts who had surgery, regardless of surgical approach or extent of resection, and in pts with R0 resection (table). Recurrence occurred in 28% and 42% of pts who had surgery in the N + C (n = 149) and C arms (n = 135), respectively. In the N + C arm, BL 4-gene inflammatory signature scores were numerically higher in pts with pCR vs pts without, and EFS was improved in pts with high vs low scores (data to be presented). Grade 3-4 treatment-related and surgery-related adverse events occurred in 36% and 11% of pts in the N + C arm, respectively, vs 38% and 15% in the C arm. Conclusions Neoadjuvant N + C continues to provide long-term clinical benefit vs C in pts with resectable NSCLC, regardless of surgical approach or extent of resection. Exploratory analyses in pts treated with N + C suggested that high BL tumor inflammation may be associated with improved EFS and pCR. Clinical trial identification NCT02998528. Editorial acknowledgement Medical writing and editorial support for the development of this , under the direction of the authors, was provided by Adel Chowdhury, PharmD, Samantha Dwyer, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb. Legal entity responsible for the study Bristol Myers Squibb. Funding Bristol Myers Squibb. Disclosure P.M. Forde: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, F-Star, G1 Therapeutics, Genentech, Iteos, Janssen, Merck, Novartis, Sanofi, Surface;Financial Interests, Institutional, Research Grant: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus, Kyowa, Novartis, Regeneron;Financial Interests, Personal, Other, Trial steering committee member: AstraZeneca, BioNTech, Bristol Myers Squibb, Corvus;Non-Financial Interests, Personal, Member of the Board of Directors: Mesothelioma Applied Research Foundation;Non-Financial Interests, Personal, Advisory Role, Scientific advisory board member: LUNGevity Foundation. J. Spicer: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, CLS Therapeutics, Merck, Protalix Biotherapeutics, Roche;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Protalix Biotherapeutics, Regeneron, Roche, Xenetic Biosciences;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, PeerView;Non-Financial Interests, Personal, Other, Data safety monitoring board member: Deutsche Forschungsgemeinschaft;Non-Financial Interests, Personal, Leadership Role, Industry chair: Canadian Association of Thoracic Surgeons. [Formula presented] N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Tak da, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Personal, Other, Family member is an employee: AstraZeneca. M. Provencio: Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Janssen, Pfizer, Roche, Takeda;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Bristol Myers Squibb, MSD, Pfizer, Roche, Takeda. S. Lu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, GenomiCare, Hutchison MediPharma, Roche, Simcere, ZaiLab;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Hanosh, Roche. M. Awad: Financial Interests, Personal, Other, Consulting fees: ArcherDX, Ariad, AstraZeneca, Blueprint Medicine, Bristol Myers Squibb, EMD Serono, Genentech, Maverick, Merck, Mirati, Nektar, NextCure, Novartis, Syndax;Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Genentech, Eli Lilly. T. Mitsudomi: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, BridgeBio Pharma;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, MSD, Novartis, Ono, Pfizer;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant, Invitae, Merck, MSD, Novartis, Ono, Pfizer, Taiho;Financial Interests, Personal, Advisory Board: AstraZeneca;Non-Financial Interests, Personal, Leadership Role, Former president: IASLC. E. Felip: Financial Interests, Institutional, Research Grant: Fundacion Merck Salud, Merck KGAa;Financial Interests, Personal, Other, Consulting fees: Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, MSD, Novartis, Peptomyc, Pfizer, Sanofi, Takeda;Financial Interests, Personal, Speaker's Bureau: Amgen, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen, Medical Trends, Medscape, Merck, MSD, PeerVoice, Pfizer, Sanofi, Takeda, touchONCOLOGY;Non-Financial Interests, Personal, Member of the Board of Directors: Grifols. S.J. Swanson: Financial Interests, Personal, Speaker's Bureau: Ethicon. F. Tanaka: Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Chugai, Eli Lilly, Ono, Taiho;Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Chugai, Ono;Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Covidien, Eli Lilly, Intuitive, Johnson & Johnson, Kyowa Kirin, MSD, Olympus, Ono, Pfizer, Stryker, Taiho, Takeda. P. Tran: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Cai: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb;Financial Interests, Personal, Other, Travel support for attending meetings and travel: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J. Neely: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Other, patents planned, issued, or pending: Bristol Myers Squibb;Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. S.R. Broderick: Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by E sevier Inc.

Has the impact of the COVID-19 pandemic on uptake andusage of indwelling pleural catheters reduced its cost-effectiveness?

During the COVID pandemic, the British Thoracic Society recommended first-line indwelling pleural catheter (IPC)insertion or therapeutic aspiration for malignant pleural effusion (MPE) instead of admission for chest drain and talcpleurodesis to minimise hospital visits. This study aimed to review the uptake and usage of IPCs during and followingthe pandemic and its potential cost-effectiveness.Retrospective data analysis of IPCs between 2020-2021 was performed. Data collection included patient sex, age,WHO performance status (PS), indication and duration of IPC.187 IPCs were inserted;91% for MPE. 75% elected for IPC as first-line. 57% patients were PS 0-1 and 77% werePS 0-2. In 2020, 30% patients were self-draining compared to 12% in 2021. Mean duration IPC in-situ was 87 days(median 68 days). The pandemic saw increased use of first-line IPCs (75% 2020 vs 52% 2019) particularly in patients with good PS. This reduced initial hospitalisation (4.08 bed days) with an estimated cost saving of 1200 (300/day) per patient. Self-drainage rates also increased from 13% (2019) to 30% (2020) but have returned to pre-pandemic levels of selfdrainage at 12% in 2021 with need for district nurse visits for up to 3 months. Current practice of widespread first-line IPC use in the COVID endemic era may not be cost-effective and needs to be reviewed alongside the pre-existing evidence base.

Treatment of HER2-positive (HER2+) hormonereceptor positive (HR+) metastatic breast cancer (mBC) with the novel combination of zanidatamab, palbociclib, and fulvestrant

Background: HER2+ mBC remains incurable, with a need for new HER2-directed therapies and regimens, including chemotherapy-free options. Zanidatamab (zani) is a novel HER2-targeted bispecific antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of antitumor activity, including complement-dependent cytotoxicity. A CDK4/6 inhibitor combined with endocrine therapy is an approved treatment for HER2-negative/HR+ mBC and this combination has also demonstrated encouraging antitumor activity when paired with HER2-targeted therapy(ies) in HER2+/HR+ mBC. Here, we report results from ZWI-ZW25-202 (NCT04224272), an ongoing singlearm phase 2 study of zani combined with palbociclib (palbo) and fulvestrant (fulv) in pts with HER2+/HR+ mBC. Method(s): Eligibility requirements include: HER2+/HR+ unresectable, locally advanced BC or mBC;ECOG PS of 0 or 1;prior treatment with trastuzumab, pertuzumab and T DM1 (additional prior HER2-targeting agents are permitted);and no prior treatment with CDK4/6 inhibitors. Part 1 of the study evaluated the safety and tolerability of the zani/palbo/fulv combination and determined the recommended doses for use in Part 2, where the antitumor activity of the combination is being evaluated. Endpoints include safety outcomes, progression-free survival at 6 months (PFS6), confirmed objective response rate (cORR) per RECIST v1.1;disease control rate (DCR=complete response [CR] plus partial response [PR] plus stable disease [SD]);duration of response (DOR);PFS;and overall survival. Result(s): As of 24 Feb 2022, 34 pts (33 HER2+/HR+ per central analysis) with a median age of 52 (range 36-77) have been treated. In the metastatic setting, pts had received a median (range) of 4 (1-10) prior systemic regimens, including 3 (1-8) different prior HER2 targeted therapies, and 1 (0-4) endocrine therapy. Seven pts (20%) had prior T DXd treatment and 7 pts had prior fulv treatment. All pts received zani (20 mg/kg Q2W) and standard doses of palbo and fulv. Eighteen pts (53%) remained on treatment;median duration of zani treatment was 6.9 mo (range 0.5- 16.3). A dose-limiting toxicity (DLT) of neutropenia occurred in 1 of 7 DLT-evaluable pts in Part 1. Among all pts (n=34), the most common (>20%) treatment (zani, palbo and/or fulv)-related adverse events (TRAEs) were diarrhea (74%), neutrophil count decreased/neutropenia (62%), stomatitis (41%), asthenia (26%), nausea (24%), and anemia (21%). Grade (Gr) >=3 TRAEs in 2 or more pts included neutrophil count decreased/neutropenia (50%), anemia (6%), diarrhea (6%), and thrombocytopenia (6%). AEs of special interest were all Gr <=2 and included 4 pts with cardiac events (LVEF decrease of >=10% from baseline) and 1 pt with infusion-related reaction. There were no treatment-related serious AEs. Palbo was discontinued for 1 pt due to an AE (AST increase);no pt discontinued zani treatment as a result of AEs. Two deaths occurred: 1 due to disease progression and 1 due to an unrelated AE of pneumonia caused by COVID-19. In 29 pts with measurable disease, the cORR was 34.5% (95% CI: 17.9, 54.3), all responses were cPRs, of which 1 is pending CR confirmation. DOR ranged from 2.3 to 14.9+ mo, with 8 confirmed responses ongoing, and the DCR was 93.1% (95% CI: 77.2, 99.2). Interim median PFS was 11.3 mo (range 0.03-16.7;95% CI: 5.6, not estimable). PFS6 analysis is planned following the completion of enrollment. Conclusion(s): Zani in combination with palbo and fulv shows encouraging antitumor activity with durable responses in heavily pretreated pts and a manageable safety profile. This regimen has the potential to be a chemotherapy-free treatment option in pts with HER2+/HR+ mBC. Enrollment in the study is continuing.

Influence of COVID-19 lockdown and socioeconomic deprivation on the outcomes of gastric cancer - A National study

Background: COVID-19 has significantly disrupted cancer care. This has impacted on staging, management and survival of gastric cancer as health services worldwide had to adapt. Responding to the pandemic, the UK government declared a national lockdown on 23 March 2020. Our aim was to determine the impact of COVID-19 and socio-economic deprivation on patients with newly diagnosed gastric cancers. Method(s): This was a retrospective cohort study. Consecutive new patients presenting in NHS Scotland to five regional OG cancer MDTs covering 93.2% of the Scottish population between October 2019 and September 2020 were identified. Gastric cancers were included and electronic health records were reviewed. Patient's residential address was used to calculate Scottish Index of Multiple Deprivation (SIMD). Patients were divided into two groups: Most deprived (SIMD 1-5) and least deprived (SIMD 6-10) and results compared. The study period was divided into pre- and post-lockdown, based on the first UK national lockdown of 23 March 2020. Result(s): 269 patients were diagnosed with gastric cancer;4 (1.5%) were excluded due to unrecognised postcode. 173 (65.3%) were male and the median age was 73 years (range 29-94). 143 (54.0%) were in most deprived and 122 (46.0%) were in least deprived group. Deprivation and lockdown: Age, sex, ECOG performance status and route of referral were not significantly different. No clinically meaningful difference in median time to gastroscopy was observed (16.5 vs 17 days). Stage 4 cancer were more commonly observed in most deprived group (60.8% vs 52.1%). In whole cohort, the palliative care intent was higher post-lockdown (70% vs 83.2%, p=0.033). Palliative intent treatment increased in the most deprived group from 74.3% to 81.2% and in least deprived from 65.2% to 85.7% (p=0.092). The median survival for the whole cohort decreased post-lockdown (9.0 vs 6.9 months, p=0.14), but did not reach statistical significance. The medial survival did not change for the most deprived group (7.6 vs 7.1 months, p=0.840), however it decreased significantly for the least deprived group post-lockdown (11 vs 6.7 months, p=0.014). A test of heterogeneity between lockdown period and SIMD group supported the suggestion that the least deprived cohort did worse post-lockdown (HR 1.72, p=0.055). Conclusion(s): This national study highlights that the least deprived patients had survival advantage pre-lockdown, which has been completely lost post COVID-19 national lockdown. This disproportional impact on the least deprived patients could be because early cancers were not diagnosed in the least deprived population.

Stage Migration, Changed Treatment Profile and Survival Impact in Newly Diagnosed Oesophago-gastric Cancer in Scotland during the COVID-19 Pandemic - A National study

Background: COVID-19 has significantly disrupted cancer care. This may have impacted on staging, management and survival as health services worldwide had to adapt. Responding to the pandemic, the UK government declared a national lockdown on 23rd March 2020. This national study investigated the effect of the national response on oesophago-gastric (OG) cancers in Scotland, including time from referral to gastroscopy, staging at presentation, multidisciplinary team (MDT) treatment outcomes and overall survival. Method(s): This was a retrospective cohort study. Consecutive new patients presenting in NHS Scotland to five regional OG cancer MDTs covering 93.2% of the Scottish population between October 2019 and September 2020 were identified. Electronic health records were reviewed. The study period was divided into pre- and post-lockdown, based on the first UK national lockdown. Result(s): 931 patients with biopsy-proven OG cancer were identified;499 (53.6%) pre- and 432 (46.4%) post-lockdown. Median age was 71 years (range 25-95) and 66% were male. There were 252 (27.1%) gastric and 679 (72.9%) oesophageal cancers. No clinically meaningful difference in median time to gastroscopy was observed post-lockdown (19 days vs 15 days, P<0.001), however, patients were more likely to present as an emergency (11.1% vs 8.2%, p=0.014). Post-lockdown, patients tended to poorer ECOG PS (p=0.09), were more symptomatic (p=0.007), and presented with higher stage disease (stage 4;57.6% vs 49.3%). There was a significant shift to palliative intent treatment post-lockdown (76.2% vs 64.7%, p<0.001). Median overall survival post-lockdown was 7.6 months vs 10.1 months pre-lockdown (HR 1.24;95% CI 1.06-1.43, p=0.005). Conclusion(s): This national study highlights the impact of COVID-19 on OG cancer diagnosis and outcome in Scotland. Patients presented at a later stage and a shift towards palliative intent treatment was observed, with subsequent negative impact on overall survival. The reason for the observed stage migration of OG cancers is likely multifactorial, occurring prior to the diagnostic pathway and not simply due to a delay in performing gastroscopy.

Has the affluent oesophageal cancer population in Scotland fared worseduring the Covid-19 pandemic?

Background: COVID-19 has significantly disrupted cancer care. This has impacted on staging, management and survival of oesophageal cancer as health services worldwide had to adapt. Responding to the pandemic, the UK government declared a national lockdown on 23rd March 2020. Our aim was to determine the impact of COVID-19 and socio-economic deprivation on patients with oesophageal cancers. Method(s): Thiswas a retrospective cohort study.Consecutivenewpatients presenting in NHS Scotland to five regional OG cancer MDTs covering 93.2% of the Scottish population between October 2019 and September 2020 were identified. Electronic health records were reviewed. Patient's residential address was used to calculate Scottish Index of Multiple Deprivation (SIMD). Patients were divided into two groups: Most deprived (SIMD 1-5) and least deprived (SIMD 6-10) and results compared. The study period was divided into pre- and post-lockdown, based on the first UK national lockdown on 23rd March 2020. Result(s): 728 patients with were identified, 5 were excluded due to unrecognised postcode. 365 (50.5%) were in the more deprived and 358 (49.5%) were in least deprived group. 488 (67.0%) were male and the median age was 71 years (range 25-95). Deprivation and lockdown: Age, sex, WHO performance status and route of referral was not significantly different. No clinically meaningful difference in median time to gastroscopy was observed. Palliative intent treatment increased in the most deprived from 67.0% to 71.4% and in least deprived from 54.0% to 74.0% (p=0.002). The overall survival for the whole cohort decreased post-lockdown (11.3 vs 7.8 months, p=0.001). Pre-lockdown the median survival for most deprived group was 8.9 vs 15 months for the least deprived group (p=0.001). Post-lockdown the median survival was similar irrespective of socioeconomic status (7.8 vs 6.9 months, p=0.99). The medial survival did not changed post-lockdown for the most deprived group (8.9 vs 7.8 months, p=0.480). However, the median survival for the least deprived group significantly decreased post lockdown (15 vs 6.9 months, p<0.001). A test of heterogeneity between lockdown period and SIMD group supported the suggestion that least deprived group did worse post-lockdown (HR 1.45, p=0.035). Conclusion(s): This national study highlights that the least deprived patients had survival advantage pre-lockdown, which has been completely lost due to the lockdown. This disproportionate impact on the least deprived patients could be because early cancers were not diagnosed in the least deprived population.

Daratumumab (Dara), Cyclophosphamide, Thalidomide and Dexamethasone for Transplant Eligible Newly Diagnosed Multiple Myeloma (Te Ndmm) Patients: Response Rate Impacts on Pfs

Background: The four-drug combo has becoming one of the main induction treatment for TE NDMM patients (pts). We conducted a phase 2 study to assess the safety and preliminary efficacy of Cyclophosphamide (C), thalidomide (T), dexamethasone (d)-(CTd) and Dara combination. MAXDARA study has shown in the primary analysis with 21 included patients (pts), 4 and 8 pts MRD negativity after four induction cycles and two consolidation cycles post transplant, respectively. (Crusoe E et al ASH 2020, 2416 poster presentation). In the present analysis we evaluate the effect of deep response rate on PFS. Method(s): This is a phase II, open-label single-center clinical trial. The main inclusion criteria were: TE NDMM, creatinine clearance > 30 ml/min, normal cardiac, renal and liver function and the ECOG performance status = 0 - 2. The protocol was Dara-CTd for up to four 28-day induction cycles: C-500mg oral (PO) on days 1,8 and 15, T at 100-200mg PO on days 1 to 28, (d) at 40mg PO on days 1,8,15 and 22 and Dara at 16mg/Kg/dose intravenous (IV) on days 1,8,15 and 22 during cycles 1 - 2 and every other week in cycles 3 - 4, followed by ASCT. All pts received up to four 28-day consolidation cycles that was started at D+30 after ASCT: Dara at 16mg/Kg and (d) at 40mg every other week, associated with T at 100mg PO on days 1 - 28. Dara at 16mg/Kg was used monthly as maintenance until progression or limiting toxicity. The MRD was evaluated by next-generation flow (NGF) 10-6 and PET-CT was performed when the patient obtained NGF negativity or finished consolidation. PFS outcome was estimated using Kaplan-Meier method and PFS analysis were performed based on the different response rates. (Data cut-off was April 2022) Results: A total of 24 pts were included. The median age being 58 (range 37- 67 years), 15 (62.5%) pts were female, 22 (92%) were non-white, 6 (25%) had an R-ISS = 1, 12 (50%) had an R-ISS = 2 and 4 (16%), an R-ISS = 3. Sixteen (66.7%) pts were IgG isotype and Six (25%) had high-risk chromosomal abnormalities [1q+, del17p, t(4;14) or t(14;16)]. To date, 23 pts have completed induction, 21 performed transplant and 14 are still in treatment after one year of dara maintenance. By ITT analysis, 22 pts (91.6%) achieved (> PR) after 4 induction cycles. One pts achieved SD, one MR and one sCR. Eleven (39%) pts achieved PR, and 10 (35.7%) VGPR. After two consolidation cycles, ORR was 68%, 8 (28.6%) and 11 (39.3%) pts obtained sCR and VGPR, respectively. The best response during any time of the treatment were PR in 3 (12.5%) pts, VGPR in 12 pts (50%) and sCR in 8 (33.3%) pts. In a ITT analysis, NGF MRD 10-6 negativity were observed in 4(16.6%) after four induction cycles, and in 17 (70.8%) pts after two consolidation cycles post-ASCT. In a ITT analysis, after a median follow up (FU) of 26 months, the PFS was 37months for the entire group. The median PFS comparing sCR vs < VGPR were 37m vs 27m (p = 0.021), respectively, and comparing MRD negative by NGF vs no, had impacted even more on PFS with a median of 37m vs 16m (p = 0.004), respectively. The OS was not yet achieved and 83% of the patients still alive after a median FU of 27m. Four pts died from infection, two of them related with covid infection (one before transplant and one during maintenance). Another case post-transplant, considered not related to the investigational agent and one after consolidation, related to the investigational agent. Summary/Conclusion: The Daratumumab - CTd protocol is an active and safe regimen capable of producing deep and sustainable responses. The deeper response rate impacted on PFS, confirm that MRD negativity is critical to patient outcome. Copyright © 2022

Clinical, Laboratory Profile, Treatment and Outcome Of Primary Amyloidosis in the Era Of Novel Agents: An Experience from a Tertiary Care Hospital

Introduction: Diagnosis of AL amyloidosis requires demonstration of amyloid in affected tissues along with clonal plasma cells in bone marrow or presence of monoclonal light chains in blood. With the availability of serum light chain assay and immunophenotyping by flow cytometry, more cases of AL amyloidosis are being diagnosed. Here we present our experience of AL amyloidosis diagnosis and treatment in the era of modern diagnostics and therapy. Aims & Objectives: We aimed to describe the clinical presentations, laboratory features, treatment and outcomes of patients with AL amyloidosis in a single center using standard diagnostic tests and treatment with novel agents. Material(s) and Method(s): A retrospective analysis of AL amyloidosis patients, diagnosed in our hospital, a tertiary care center from January 2016 to June 2022 was conducted. The data was collected from departmental database. All statistical analyses were done by SPSS version 17. Result(s): Diagnosis of AL amyloidosis was done in 31 patients. Median age of presentation was 61 years. 25 (80.6%) were males. Major symptoms were pedal edema (38.7%) and shortness of breath (32.3%). Twenty four (77.4%) presented with ECOG PS >= 2. Most common systems involved were cardiac (54.8%) and renal (54.8%). Fourteen (45.2%) had two or more systems involvement while 17 (54.8%) had single system involvement. Lambda monoclonal light chain was present in 83.9% and kappa monoclonal light chain in 16.1%. Median M-protein was 0.59 g/dL (range 0-2 g/dL) and median bone marrow plasma cells were 6% (range-1-18%). Eighteen patients were treated;cyclophosphamide, bortezomib and dexamethasone (CyBORD) in 12/18 (66.7%) and bortezomib + dexamethasone in 6/18 (33.3%). Among 18 patients followed up with median follow up of 9 months (range 1-64 months), six expired;three due to COVID, two due to cardiac arrhythmia (during first cycle) and one due to relapse and rest 12 were alive. Among the 12 patients who were alive 6 were in complete hematological response. Conclusion(s): Our study presents the spectrum of clinical manifestations, management and outcomes of primary amyloidosis in Indian context. There is a need to increase the awareness among the physicians about amyloidosis so that early diagnosis can be made and timely treatment can be done with novel agents to improve the dismal historical results.

Mantle Cell Lymphoma: A Single Centre Experience from a Tertiary Care Centre in North India

Introduction: Mantle cell lymphoma (MCL) is an aggressive lymphoma with an incidence of 2.4-6% among all non-Hodgkin's lymphoma. Though with the addition of rituximab to standard chemotherapy backbone with autologous stem cell transplant (ASCT) consolidation and novel small molecule inhibitors, the outcome of MCL has improved, however, not many patients undergo ASCT due to financial constraints. Aims & Objectives: To study the clinical profile of all patients of MCL over a period of 6 years and assess their outcome. Material(s) and Method(s): This study was a retrospective cohort study which included all patients diagnosed with mantle cell lymphoma, between January 2016 to January 2022, conducted in the Department of Haematology, Sanjay Gandhi Institute of Medical Sciences, Lucknow, India. A total of 53 cases were included in the study. SPSS-23 was used for the data analysis. Result(s): The median age was 59 years (ranging from 39-81 years), with a male to female ratio of 5.3:1. The ECOG performance status was of 0-2 was seen in 85.2%. The median haemoglobin, leukocyte count and platelet count at presentation was 10.6 g/dL, 7400/mm3 and 1,52,000/mm3 respectively. Of the 53 patients, 48% presenting with B symptoms. The median Lactate dehydrogenase levels were 521 (ranging from 220-1230). 72% patients presented with stage IV disease and MIPI score was high, intermediate and low risk in 43.4%, 32.1% and 24.5% low risk. 48% patients received RCHOP/RDHAP regimen, 36% received RCHOP and 16% received R-Benda. 5 patients underwent ASCT. 13 patients relapsed, 1 was refractory and 1 died post-transplant due to Covid sepsis. The third patient, who had relapsed, received R Benda, was found to have multiple myeloma 1 year after therapy, and succumbed to sepsis. 63% were put on Rituximab maintenance. Conclusion(s): MCL is a rare, aggressive B cell lymphoma with a lesser incidence in Indian population compared to the world. While aggressive chemotherapy with monoclonal antibody has improved the response rate of patients with nodal MCL, wait and watch strategy remains the backbone of management of leukaemic NNMCL.

Alternate-day hypofractionated radiotherapy for radical treatment of head & neck cancer during the COVID-19 pandemic: A single institute experience

Background: Managing head and neck squamous cell carcinoma (HNSCC) requires a prolonged course of concurrent chemoradiotherapy and other supportive care measures. Such a multidisciplinary approach was significantly hampered during the emergence of the COVID-19 pandemic which necessitated divergence of health resources towards treating the infected patients thereby compromising cancer care. Therefore, we adopted an alternate-day hypofractionated radiotherapy (ADH RT) schedule, aiming to decrease patients' hospital visits daily without compromising the oncological outcomes. This study assesses the response and toxicity of the ADH RT schedule in HNSCC patients. Method(s): Retrospective analysis of all histopathologically proven HNSCC patients treated with ADH RT regimen during April - October 2020 in our institute. Hypofractionation dose schedule: 63Gy/21 fractions, 3Gy/fraction was delivered on alternate days without concurrent chemotherapy after patients' consent. Weekly radiation toxicity assessment and post-radiotherapy response assessment by CECT face and neck at 3 and 6 months. Result(s): A total of 26 patients were planned for ADH RT. Most (96%) of them were males with a median age of 60 years and ECOG PS <=2. The most common tumor site was the oropharynx (58%), the stage was IVA (54%) followed by stage IVB (27%). 93% of patients had a history of tobacco smoking. Only 23 patients completed the treatment and were included in the final assessment. Mucositis and dermatitis grade 1, 2 and 3 was observed in 44%, 52%, 4% and 78%, 18%, and 4% patients, respectively. At three months of follow-up, 5 patients were lost to follow-up and 4 patients expired due to COVID/disease-related complications. Complete response (CR) was observed in 10 patients (71.4%) and partial response in 4 patients. At 6 months, CR was observed in 7 (64.5%) patients. Conclusion(s): Most of the patients were able to tolerate and complete treatment. At analysis, around half of the patients either expired or were lost to follow-up which is the major limitation of this study. Among the available patients, a good response was observed. The practical applicability of this regimen needs to be tested further with a larger sample size and longer follow-up. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2022

The clinical significance of COVID-19 in patients with lung cancer and other thoracic malignancies

The COVID-19 pandemic has posed significant challenges to healthcare systems worldwide. Patients with cancer, and particularly those with lung malignancies, represent a highrisk group for COVID-19 since they are more susceptible to infection and have a higher risk of severe outcomes. However, the restructuration of the healthcare environment, the development of guidelines for treatment and surveillance, and the improvement of vaccination coverage allowed adequate patient shielding and continuity of oncological care of cancer patients. By shedding light on the characteristics of COVID-19 patients with thoracic malignancies, recent studies also contributed to the development of personalized therapeutic strategies. Accordingly, several determinants were identified to predict disease outcomes. These include the ECOG performance status, the levels of C-reactive protein, neutrophils and procalcitonin, the disease stage, and the presence of pneumonia. COVID-19 vaccines are safe in patients with lung cancer. In order to obtain adequate immunization, the booster dose is recommended in these patients. Copyright © PROFESSIONAL PUBLISHING HUNGARY.

Causes of unplanned hospitalizations and factors associated with in-hospital mortality among patients receiving chemotherapy treatment

Background: Hospitalizations during cancer treatment are common, can impact quality of life and the progress of the treatment. We aimed to investigate the main causes of hospitalizations and factors associated with in-hospital mortality for patients receiving chemotherapy. Methods: This retrospective study included patients (pts) with solid tumors, who received outpatient chemotherapy in the 30-day period before unplanned admission to a cancer center in Brazil, from February to December of 2021. Patients with COVID-19 diagnosis were excluded. We retrieved clinical and laboratory data from health records. Logistic regression univariable and multivariable models were performed to analyze the association of the variables and in-hospital mortality as dependent outcome. Results: 784 pts were included, median age at hospitalization was 60 (IQR 49-68), and 57% were female. Most patients had ECOG 0-1 (61%) and nearly 70% had metastatic disease at admission. The most common primary tumors were colorectal (21.6%), breast (20.1%), lung (8.6%), and gastric (8.6%). Over half (56%) received platin-based regimens, usually in association with fluoropyrimidines or taxanes. Pain (33%), nausea (23%) and fever (16%) were the most referred symptoms at admission. The main diagnosis at were infection (32%), followed by disease progression (DP) (29%), and chemotherapy associated toxicity (26%). A total of 174 (22%) pts required intensive care unit support during hospital stay. The in-hospital overall mortality rate was 18%. Univariable analysis revealed poor ECOG-PS, grade 3 anemia, grade 3 thrombocytopenia and DP associated with in-hospital mortality. In the final multivariable model, ECOG ≥ 2 (OR 1.99, CI 95% 1.33 - 2.99, p <0.001), DP (OR 4.62, CI 95% 3.07 - 7.00, p <0.001) and grade 3 anemia (OR 2.38, CI 95% 1.45 - 3.87, p<0.001) remained statistically associated with in-hospital mortality. Conclusions: A substantial percentage of unplanned admissions after chemotherapy treatment are due to toxicity. Poor performance status, progression of disease on admission and severe anemia are associated with worse in-hospital prognosis. Grade 3 anemia on admission was the only toxicity associated with in-hospital mortality. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R.C. Bonadio: Personal, Expert Testimony: AstraZeneca, Ache;Personal, Research Grant: Novartis;Personal, Roche. All other authors have declared no conflicts of interest.

Predictors of in-hospital mortality after unplanned admissions among adults with cancer aged 80 years and older

Background: Patients older than 80 years with cancer are more likely to be late-diagnosed, and less likely to receive optimal cancer treatment, compared to younger geriatric patients. Understanding the factors that influence these patient's outcomes is essential to guide their management and proper choice of assistance. Methods: A retrospective cohort of patients with solid tumors older than 80 years admitted to a tertiary, publicly-funded, cancer center in Brazil, from February 1st to December 31st, 2021. COVID-19 diagnoses were excluded. We collected data on staging, body mass index (BMI), comorbidities, ECOG-PS, symptoms, admission diagnoses, and in-hospital mortality. The age-adjusted Charlson Comorbidity Index [CCI] was further calculated. We investigated the association between collected variables of interest and in-hospital mortality with uni and multivariable logistic regression models. Results: Of 440 patients, the median age was 84 (IQR 81-87) and 58% were men. Prevalent cancer diagnoses were prostate (22%), breast (12%), colon (9.5%), and lung cancer (8.1%). Before admission, 42% of patients had distant metastasis, while 21% had no evidence of disease. Two-thirds of patients had poorer ECOG-PS (≥2), and the median CCI was 10 (IQR 8-11). Comorbidities included cardiovascular disease (29%), chronic renal disease (13%), dementia (9.5%) and COPD (9.1%). Pain (27%), dyspnea (18%), and altered level of consciousness (16%) were the most prevalent complaints. During hospitalization, 35% had an infection diagnosis and 26% had progression of disease. The overall in-hospital mortality rate was 25%. Higher CCI (OR 1.24, 95%CI 1.11-1.38), poorer ECOG-PS (OR 2.17, 95%CI 1.29-3.77), and progression of disease (OR 2.77, 95%CI 1.62-4.75) were associated with in-hospital mortality after univariable regression and remained all statistically significant in the multivariable model. BMI and age were not associated with poorer outcomes. Conclusions: Hospitalized patients with cancer aged 80 years and older have a high mortality rate. The Charlson Comorbidity Index, a comorbidity burden score that includes cancer staging, correlates with in-hospital mortality and therefore could guide supportive care decisions for older adults. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R.C. Bonadio: Financial Interests, Personal, Expert Testimony: AstraZeneca, Ache;Financial Interests, Personal, Research Grant: Novartis;Financial Interests, Personal, Sponsor/Funding: Roche. All other authors have declared no conflicts of interest.

HER2 copy number variation in non-small cell lung cancer (NSCLC)

Background: The value of increased HER2 gene copy number (GCN) in NSCLC is unclear. In this study we defined its frequency and characterized a cohort of patients harboring it. Methods: Patients with stage IIIB/IV NSCLC enrolled in the Gustave Roussy MSN study (NCT02105168) between Oct. 2009 and Feb. 2016 were screened by FISH (positivity defined as HER2 GCN to centromeres ratio ≥ 2) and tested for other molecular alterations. Descriptive analyses of clinical-pathological data were performed, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: HER2 FISH tested positive in 22 of 250 screened patients (9%). Median age was 60 years (range 47-80), 68% (n=15) were male, 91% (n=20) were current or former tobacco smokers (median exposure 47 pack-year), 64% (n=14) had adenocarcinoma, 18% (n=4) squamous cell and 18% (n=4) large cell carcinoma. 91% (n=20) had an ECOG PS of 0 or 1. Stage IV with extra-thoracic involvement was the most common clinical presentation (64%, n=14). Overall, 95% of patients (n=21) had 1 or 2 metastatic sites at diagnosis (bone 32%, lung 27%, nodes 18%, liver 18%, brain 18%). In 9 patients (41%) 12 concurrent molecular alterations were detected: 5 KRAS mutation (3 G12C, 1 G12D, 1 G61H), 2 HER2 exon 20 insertion, 1 EGFR exon 19 deletion, 1 BRAF V600E mutation, 1 ALK rearrangement, 1 FGFR1 and 1 MET amplification. 18 patients received first-line platinum-based chemotherapy, with 33% (95% CI 16-56) objective response rate and 83% (95% CI 61-94) disease control rate. After a median follow-up of 28 months (95% CI 23-45), median PFS and OS were 5.9 (95% CI 3.4-11.0) and 15.3 (95% CI 10.3-NR) months, respectively. Median PFS was longer in patients with higher GCN. As further line of treatment, 5 patients received trastuzumab: 4 in combination with chemotherapy and 1 as monotherapy, with 1 stabilization of disease as best response. 3 patients received nivolumab (1 partial response and 1 stable disease) and 3 a targeted therapy (anti ALK, EGFR, BRAF). Conclusions: Increased HER2 GCN was found in 9% of patients with unresectable NSCLC, was not correlated to particular clinical characteristics, but frequently occurred with other molecular alterations. Its clinical actionability and the correlation with protein expression deserve further characterization. Clinical trial identification: NCT02105168. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: M. Tagliamento: Other, Personal, Other, Travel grants: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly;Other, Personal, Writing Engagements, Honoraria as medical writer: Novartis, Amgen. E. Auclin: Financial Interests, Personal, Advisory Board: Amgen, Sanofi. E. Rouleau: Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche, Amgen, GSK;Financial Interests, Institutional, Invited Speaker: Clovis, BMS;Financial Interests, Institutional, Funding, Data base: AstraZeneca. A. Bayle: Non-Financial Interests, Institutional, Other, Principal/Sub-Investigator of Clinical Trials: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd, Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi;Financial Interests, Institutional, Other, drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. D. Planchard: Financial I terests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. All other authors have declared no conflicts of interest.

Three-years real-world evidence of adjuvant dabrafenib plus trametinib (DT) in patients with resected melanoma in Spain (GEM 1901 - DESCRIBE-AD)

Background: DT combination has shown efficacy in the adjuvant setting for BRAF-mutated melanoma (BMM) patients (pts) in clinical trials. Previous reports from DESCRIBE-AD resulted in promising overall survival (OS) rates at 12 months. Methods: An observational retrospective study was carried out in 25 GEM sites in Spain. Histologically confirmed and resected BMM pts previously treated with DT according to standard clinical practice in the adjuvant setting were included. Only surgical resection was allowed as a prior treatment to DT. DT discontinuation rate and time to treatment discontinuation were the primary objective. Secondary objectives included safety and efficacy of the combination. Here, we report 3-year results for OS. Results: From 10/2020 to 03/2021, 65 pts were included. Median age was 58 years, 55% were male and 60%, 25%, and 14% had an ECOG PS 0/1/Uk respectively, one patient presented ECOG 3. Allocation of stage IIIA, IIIB and IIIC according to TNM AJCC 7th edition was 29%, 26% and 32%, respectively. There were 3 pts diagnosed at stage I/II but considered of risk, and 2 pts with stage IV but completely resected, all considered for adjuvant DT. Ulceration was present in 40%, Breslow ≥2 mm in 71%, and nodes were microscopically and macroscopically affected in 39% and 22% of pts, respectively. Only 9.2% of pts discontinued DT prematurely due to toxicity and 21.2% had dose reductions to manage toxicity. After a median follow-up of 36.2 m (range: 13-51.1), the overall OS rate at 3-years was 83.5% (95% CI: 74.5-93.5). According to AJCC 7 stage at diagnosis, the 3-years OS rate was 95.2% (95% CI: 86.6-100), 75% (56-100), and 76.8% (60.7-97.2) for stage I-II-IIIA, IIIB, and IIIC-IV respectively. Throughout the study period 11 (16.9%) pts died, of which 10 died due to disease progression and one due to COVID-19 infection. Conclusions: Adjuvant treatment with DT for melanoma achieved good treatment compliance and has proven efficacy in the real world. Adjuvant DT has a clinical impact in survival in line with previous clinical trial COMBI-AD. Editorial acknowledgement: We acknowledge Mfar Clinical Research staff for their assistance in the development of this . Legal entity responsible for the study: Grupo Español Multidisciplinar en Melanoma (GEM). Funding: Grupo Español Multidisciplinar en Melanoma (GEM) as Sponsor with Industry partner NOVARTIS. Disclosure: P. Cerezuela-Fuentes: Financial Interests, Personal, Other, Consultancy, conference,congress attendance/infrastructure: BMS, MSD, Pierre Fabre, Roche, Sanofi, SunPharma. J. Martín-Liberal: Financial Interests, Personal, Other, Lecture fees: Astellas, MSD;Financial Interests, Personal, Other, Lecture fees, advisory fees: Bristol Myers Squibb, Novartis, Pierre Fabre, Pfizer, Roche, Sanofi;Non-Financial Interests, Personal, Member, membership or affiliation: ASCO, ESMO, SEOM, GEM, EORTC, SOGUG, GEIS. L.A. Fernández-Morales: Financial Interests, Personal, Invited Speaker, Speak at sponsored meetings: BMS, MSD, Pierre-Fabre, Roche;Financial Interests, Personal, Other, Speak at sponsored meetings and advisory role: Novartis. J. Medina Martinez: Financial Interests, Personal, Other, Speaker, consultancy or advisory role or similar activity: Novartis, Roche, Pierre Fabre, BMS, MSD, Sanofi. M. Quindós: Financial Interests, Personal, Other, speaker, consultancy and advisory: AstraZeneca, GSK, Merck Sharp & Dohme, Novartis, PharmaMar, Roche, Bristol Myers Squibb, Pierre Fabre;Financial Interests, Institutional, Other, Clinical trials: Merck Sharp & Dohme, Roche, Bristol Myers Squibb. A. García Castaño: Non-Financial Interests, Advisory Role: Bristol, MSD, Novartis. T. Puértolas: Financial Interests, Personal, Invited Speaker, Speaker and advisory role: BMS, Novartis;Financial Interests, Personal, Invited Speaker: Roche, MSD, Sun-Pharma;Financial Interests, Personal, Other, Speaker and advisory role: Pierre-Fabre;Financial Interests, Personal, Advisory Role: Sanofi;Financial Interests, Institutional, Other, Clinical trial: Roche, BMS, Apexi en Inc, Aduro Biotech, Alkermes Inc;Non-Financial Interests, Institutional, Other, congresses inscriptions: Lilly, Sun-Pharma, Novartis, Roche, MSD;Non-Financial Interests, Institutional, Leadership Role, Vocal: GEM (Grupo Español Multidisciplinar de Melanoma);Non-Financial Interests, Institutional, Affiliate: SEOM (Sociedad Española de Oncología Médica), GEM (Grupo Español Multidisciplinar de Melanoma). P. Ayala de Miguel: Financial Interests, Personal, Invited Speaker, Public speaking: Novartis, Merck Sharp & Dohme, Sanofi, Pierre-Fabré. B. Campos: Financial Interests, Personal, Other, Speaker or advisory role: Roche, BMS, Sanofi, Novartis, Pierre-Fabre, Sun Pharma;Financial Interests, Personal, Other, Speaker role: AstraZeneca, Merck, ROVI, Leo Pharma. E. Espinosa: Financial Interests, Personal, Advisory Role, Advisory: BMS, MSD;Financial Interests, Personal, Other, Advisory, educational activities: Novartis;Financial Interests, Personal, Invited Speaker, Advisory, educational activities: Pierre Fabre;Financial Interests, Personal, Funding, Funding for translational investigation: Roche;Non-Financial Interests, Personal, Member, Vicepresident: Grupo Español Multidisciplinario de Melanoma. A. Rodríguez-Lescure: Financial Interests, Personal, Advisory Role: Pfizer, Novartis, ROCHE, AstraZeneca, Daiichi Sankyo, Seagen;Financial Interests, Personal, Invited Speaker, Public speaking: Pierre-Fabre;Financial Interests, Institutional, Research Grant, Grant for Clinical Trials: BMS, Lilly, Roche, Novartis, Amgen, Pzifer, Zimeworks, AstraZeneca, G1 Therapeutics, Bayer. L. Espasa Font: Financial Interests, Personal, Full or part-time Employment: Novartis. G. Belaustegui Ferrández: Financial Interests, Personal, Full or part-time Employment: Novartis. All other authors have declared no conflicts of interest.

Neoadjuvant cemiplimab in patients (pts) with stage II–IV (M0) cutaneous squamous cell carcinoma (CSCC): Primary analysis of a phase II study

Background: CSCC is highly immune-responsive;a prior pilot study demonstrated a high rate of pathologic complete response (pCR) or major pathologic response (MPR, ≤10% viable tumor), using cemiplimab anti-programmed death 1 (PD-1) therapy in the neoadjuvant setting. Here, we present the primary analysis of a confirmatory, open-label, multicenter, Phase 2, single-arm trial of neoadjuvant cemiplimab in pts with resectable Stage II–IV (M0) CSCC. Methods: Pts received cemiplimab 350 mg IV q3W for up to 4 doses before surgery. The primary endpoint was pCR rate per independent central pathologic review (ICPR). Key secondary endpoints included MPR rate per ICPR, objective response rate (ORR;complete response [CR] + partial response [PR]) per RECIST v1.1, investigator-assessed pCR and MPR, safety and tolerability. Results: At data cutoff date of 01 Dec 2021, 79 pts were enrolled (67 male;median age 73.0 yrs [range, 66.0–81.0];ECOG performance status 0 (n=60) and 1 (n=19) with stage II (n=5), III (n=38), or IV(M0) (n =36) disease;62 pts received all 4 doses (median number of doses given (Q1:Q3), 4 (4:4);70 pts underwent surgery. The study met its primary endpoint: pCR was observed in 40 (50.6%) pts (95% confidence interval [CI], 39.1–62.1%). MPR was observed in an additional 10 (12.7%) pts (95% CI, 6.2–22.0%). ORR was 68.4% (95% CI, 56.9–78.4) (5 CR, 49 PR, 16 stable disease, 8 progressive disease (PD), 1 non evaluable. Reasons 9 pts did not have surgery: 3 responders declined surgery, 2 lost to follow-up or noncompliance, 2 had inoperable PD, 2 due to AE. Fourteen (17.7%) pts experienced Grade ≥3 AE. Four pts died due to AEs: 1 exacerbation of cardiac failure, 2 myocardial infarctions, and 1 COVID-19 pneumonia. The most common AEs regardless of attribution (all grades) were fatigue (30.4%), rash maculo-papular (13.9%), diarrhea (13.9%) and nausea (13.9%). Conclusions: The pCR + MPR of 63.3% by ICPR in pts with Stage II–IV (M0) CSCC is the highest observed in a multicenter anti-PD-1 neoadjuvant monotherapy study for any solid tumor type. The safety profile of neoadjuvant cemiplimab is consistent with previous anti-PD-1 monotherapy experience. Ongoing follow-up will describe disease-free survival. Clinical trial identification: NCT04154943. Editorial acknowledgement: Medical writing support was provided by John G Facciponte, PhD, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Legal entity responsible for the study: Regeneron Pharmaceuticals, Inc., and Sanofi. Funding: Regeneron Pharmaceuticals, Inc., and Sanofi. Disclosure: N. Gross: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Board: PDS Biotechnology, Shattuck Labs and Genzyme;Financial Interests, Personal, Advisory Role: PDS Biotechnology, Shattuck Labs and Genzyme. D.M. Miller: Financial Interests, Personal, Advisory Role: Castle Biosciences, EMD Serono, Merck KGaA, Merck Sharpe & Dome, Pfizer, Regeneron, Sanofi Genzyme;Financial Interests, Personal, Ownership Interest: Checkpoint Therapeutics;Financial Interests, Personal, Research Grant: Kartos Therapeutics, NeoImmune Tech, Inc., Regeneron Pharmaceuticals, Inc. N. Khushanlani: Financial Interests, Personal, Research Grant: Regeneron Pharmaceuticals, Inc., Bristol Myers Squibb, HUYA Bioscience International, Merck, Novartis, GlaxoSmithKline, Celgene, Amgen;Financial Interests, Personal, Advisory Board: EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, Array Biopharma, Jounce Therapeutics, Immunocore, Bristol Myers Squibb, HUYA Bioscience International;Financial Interests, Personal, Other, honoraria: Sanofi;Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals, Mazor Robotics, Amarin, Transenetrix. V. Divi: Financial Interests, Institutional, Research Grant: Genentech. E.S. Ruiz: Financial Interests, Personal, Advisory Board: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Int rests, Personal, Advisory Role, consulting fees: Genentech, Leo Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Sanofi;Financial Interests, Personal, Member of the Board of Directors: Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Other, Advisory board and consulting fees: Bristol Myers-Squibb, Eisai, Genentech, Immunocore, Instil Bio, MacroGenics, Merck, Natera, Nektar Therapeutics, Odonate Therapeutics, OncoSec, Pfizer, Rain Therapeutics, Regeneron, Sanofi;Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Merck, Regeneron. F. Meier: Financial Interests, Personal, Other, Travel support, speaker’s fees or advisor’s honoraria: Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and Sanofi;Financial Interests, Personal, Research Grant: Novartis and Roche. P.L. Swiecicki: Financial Interests, Institutional, Research Grant: Ascentage Pharma, Pfizer;Financial Interests, Personal, Advisory Board: Prelude Therapeutics, Elevar Therapeutics, Regeneron Pharmaceuticals. J.L. Atlas: Financial Interests, Personal, Advisory Role: Regeneron Pharmaceuticals, Inc., Sanofi, and Bristol Myers Squibb. J.L. Geiger: Financial Interests, Institutional, Research Grant: Alkermes, Debio, Merck, Regeneron Pharmaceuticals, Inc., and Roche/Genentech;Financial Interests, Personal, Advisory Role: Exelixis, Merck and Regeneron Pharmaceuticals, Inc. A. Hauschild: Financial Interests, Personal and Institutional, Other, Institutional grants, speaker’s honoraria and consultancy fees: Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche;Financial Interests, Institutional, Other, Institutional grants and consultancy fees: EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Advisory Role: OncoSec Medical. J.H. Choe: Financial Interests, Personal, Advisory Role: Exelixis, Coherus Biosciences, Regeneron Pharmaceuticals, Inc. B.G.M. Hughes: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche;Financial Interests, Institutional, Research Grant: Amgen. S. Yoo: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. K. Fenech: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.D. Mathias: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. H. Han: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M.G. Fury: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.;Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. D. Rischin: Financial Interests, Institutional, Research Grant: Regeneron Pharmaceuticals, Inc., Genentech, Sanofi, Kura Oncology, Roche, Merck Sharp & Dohme, Merck KGaA, Bristol Myers Squibb, GlaxoSmithKline, ALX Oncology;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc., Sanofi, GlaxoSmithKline, Bristol Myers Squibb. All other authors have declared no conflicts of interest.

CLINICAL, LABORATORY PROFILE, TREATMENT AND OUTCOME OF PRIMARY AMYLOIDOSIS IN THE ERA OF NOVEL AGENTS: AN EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN INDIA

Background: Diagnosis of AL amyloidosis requires demonstration of amyloid in affected tissues along with clonal plasma cells in bone marrow or presence of monoclonal light chains in blood. With increasing awareness among physicians and availability of proper diagnostics, more cases of AL amyloidosis are being diagnosed. Here we present our experience of AL amyloidosis diagnosis and treatment in the era of modern diagnostics and therapy with novel agents. Aims: We aimed to describe the clinical presentations, laboratory features and outcomes of patients with AL amyloidosis in a single center using standard diagnostic tests and treatment with novel agents. Methods: A retrospective analysis of AL amyloidosis patients, diagnosed in our hospital, a tertiary care center in India from January 2016 to December 2021. The data was collected from departmental database. All statistical analyses were done by SPSS version 17. Results: Diagnosis of AL amyloidosis was done in 27 patients. Median age of presentation was 59 years. 22 (81.5%) were males. Major symptoms were pedal edema (37%), shortness of breath (22.2%), frothy urine (11.1%) and fatigue (11.1%). Twenty two (81.5%) presented with ECOG PS ≥ 2. Most common system involved was renal in 16 (59.2%), followed by cardiac in 13 (48.1%) and gastro-intestinal in 9 (33.3%). Fifteen (55.6%) had two or more system involvement while 12 (44.4%) had single system involvement. Lambda monoclonal light chain was present in 22/27 (81.5%) and kappa monoclonal light chain was present in 5/27 (18.5%). Median Hb was 11.6 g/dl (range 6.7- 14.8 g/dl), median M-protein was 0.69 g/dL (range 0-2 g/dL) and median bone marrow plasma cells were 7% (range- 1-18%). Fourteen patients were treated;cyclophosphamide, bortezomib and dexamethasone (CyBORD) in 10/14 (71.4%) and bortezomib + dexamethasone in 4/14 (28.6%). Among 14 patients followed up with median follow up of 13 months (range 6-60 months), 5 expired;3 due to COVID, one due to cardiac arrhythmia (during first cycle) and one due to relapse and rest 9 were alive. Among the 9 patients who were alive 6 were in complete hematological response and 3 were in partial response after 6 cycles of therapy. Summary/Conclusion: Our study presents the spectrum of clinical manifestations, management and outcomes of primary amyloidosis in Indian context. There is a need to increase the awareness among the physicians about amyloidosis so that early diagnosis can be made and timely treatment can be done with novel agents to improve the dismal historical results.