The use of ibrutinib in Italian CLL patients treated in a real-world setting (EVIDENCE): A preliminary report

Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs. chemo- and/or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in a real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3, 29.7, and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in the TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN =52.1%, R/R = 48.6%), while IGHV was unmutated in 35.0% (TN =33.3% and R/R = 36.15) and mutated in 15.0% (TN =14.6%, R/R = 15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs. R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%), and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7 vs. 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN =8, R/R = 24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN =17.2%, R/R = 18.7%) and it mostly occurred within the first 6 months. The main causes of discontinuation were toxicity (6.1%), PD (3.8%), and death (3.5%). Temporary interruptions (≤3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN =35.3%, R/R = 27.2%) and 37.7% (TN =37.5%, R/R = 37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1-27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2-86.1%] with no difference between TN 83.2% (95% CI, 75.2-89.4%) and R/R 81.2% pts (95% CI, 74.9-86.4%). EVIDENCE is the first realw rld study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL.

The Use of Ibrutinib in Italian CLL Patients Treated in a Real-World Setting (EVIDENCE): A Preliminary Report

Introduction Ibrutinib is the only once-daily Bruton's tyrosine kinase (BTK) inhibitor with significant survival benefit vs chemo- and /or immunotherapy in multiple phase 3 studies of patients (pts) with chronic lymphocytic leukemia (CLL). It has profoundly changed the treatment landscape of CLL with the longest follow-up. However, seven years (yrs) after ibrutinib was approved in Italy by regulatory agencies for CLL treatment, available data on the patterns of care of such pts in the setting of clinical practice is limited. Herein we present the first interim analysis (IA) of EVIdeNCE (ClinicalTrials.gov Identifier: NCT03720561), a multicenter, observational clinical study designed to describe the current management of pts receiving ibrutinib in real-world setting in Italy in terms of retention rate: the study's primary end point. Methods EVIDENCE 312 treatment-naïve (TN) 38% and relapsed/refractory (R/R) 62% pts with CLL according to the iwCLL diagnosis criteria observed at 39 Italian hematological institutions in the period between November 2018 and October 2019. Inclusion criteria were treatment with ibrutinib according to the European Summary of Product Characteristics as per routine clinical practice started within the previous 3 months. The purpose of this IA is to provide demographics and disease characteristics at baseline and a preliminary evaluation of ibrutinib retention rate after one year of follow-up, along with its safety profile. Results The median age of pts at the time of ibrutinib initiation was 71.0 yrs (range 41.0-89.0), with 60% ≥70 yrs, 63.2% male, and 90% with Eastern Cooperative Oncology Group (ECOG) performance 0-1. Baseline Rai stage 0-I, II, and III-IV accounted for 18.3%, 29.7% and 52.1% pts, respectively. Patients in stage IV were observed in 40% of the R/R and 27% in TN subgroup. Considering 120 pts with known mutational status, del(17p) and/or TP53 mutation were present in 50.0% of pts (TN=52.1%, R/R=48.6%), while IGHV was unmutated in 35.0% (TN=33.3% and R/R=36.15) and mutated in 15.0% (TN=14.6%, R/R=15.3%). At baseline, 62.9% of pts had comorbidities and 30.6% presented with a history of cardiovascular diseases (CVDs). A CIRS score ≥6 was observed in 28.5% of pts. The median time from CLL diagnosis to the start of ibrutinib was 5.1 yrs (TN 1.75 yrs vs R/R 7.27 yrs). At least 1 treatment-emergent adverse event (TEAE) of any grade was experienced by 70.7% of pts. Frequencies were as follows: infections (30.8%;COVID-19 infections 3.2%), arthralgia (10.8%), neutropenia (9.3%), fatigue (8.4%), diarrhea (7.7%), atrial fibrillation (7.4%;grade 3-4, 4.2%), fever (7.1%), rash (6.4%), anemia (6.1%) and hypertension (4.2%). Mild bleeding TEAEs were reported in 16.1% of pts with no major bleeding event. TEAEs were more frequent in the elderly (≥65 yrs) while no significant differences in the rate of TEAEs were recorded in TN and R/R pts (69.7% vs 71.4%, respectively). Serious TEAEs were reported in 21.9% of pts. Overall in intention to treat (ITT), 32 deaths (10%) were observed (TN=8, R/R=24). The most common causes of death were infections (3.5%) and progressive disease (PD) (1.9%). Permanent discontinuation was observed in 56 (18%) of the pts (TN=17.2%, R/R=18.7%) and it mostly occurred within the first 6 months. Main causes of discontinuation were toxicity (6.1%), PD (3.8%) or death (3.5%). Temporary interruptions (≤ 3 months without therapy and/or dose modifications) during the whole observation period occurred in 30.3% (TN=35.3%, R/R=27.2%) and 37.7% (TN=37.5%, R/R=37.8%) of pts, respectively, mainly determined by toxicity and clinical judgment. Finally, in this first IA after 17.3 months (range 1.1 - 27.0) median follow-up, the ibrutinib retention rate (calculated as the ratio between the number of patients who retained ibrutinib treatment over the total number of patients at risk) at 1-year was 81.9% [95% confidence interval (CI), 77.2% - 86.1%] with no difference between TN 83.2% (95% CI, 75.2% - 89.4%) and R/R 81.2% pts (95% CI, 74.9% - 86.4%). Conclusions EVIDENCE is the irst real-world study of ibrutinib use in CLL clinical practice in Italy. Ibrutinib retention rate at one-year suggests a better knowledge and expertise of hematologists in the management of ibrutinib-related toxicities that may result in an improved long-term outcome of pts with CLL. Disclosures: Molica: Janssen: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astrazeneca: Honoraria. Scarfo: Astra Zeneca: Honoraria;Abbvie: Honoraria;Janssen: Honoraria, Other: Travel grants. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation;Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria;Janssen: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria. Frigeri: Celgene: Consultancy, Speakers Bureau;Abbvie: Speakers Bureau;Janssen: Consultancy, Speakers Bureau;Amgen: Speakers Bureau. Sanna: Janssen: Consultancy;Abbvie: Consultancy;Astra Zeneca: Consultancy. Coscia: Janssen: Honoraria, Other, Research Funding;AbbVie: Honoraria, Other;AstraZeneca: Honoraria;Gilead: Honoraria. Reda: Abbvie: Consultancy;Astra Zeneca: Consultancy;Beigene: Consultancy;Janssen: Consultancy. Tafuri: Novartis: Research Funding;Roche: Research Funding;Celgene: Research Funding. Grugnetti: Janssen: Current Employment. Magarotto: Janssen: Current Employment. Mauro: Tskeda: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Speakers Bureau;Abbvie: Consultancy, Honoraria, Speakers Bureau;Roche: Consultancy, Honoraria;Astra Zeneca: Consultancy, Honoraria, Speakers Bureau.

Psychological distress in outpatients with lymphoma during the covid-19 pandemic

Background: Cancer patients are a population at high risk of contracting COVID-19 and, also of developing severe complications due to the infection, which is especially true when they are undergoing immunosuppressive treatment. Despite this, they had still to go to hospital to receive chemotherapy during lockdown. Aims: In this context, we have evaluated the psychological status of onco-hematological outpatients receiving infusion and not deferrable anti-neoplastic treatment for lymphoproliferative neoplasms, with the aim of both measuring the levels of post-traumatic symptoms, depression, and anxiety during the pandemic and also of investigating the perception of risk of potential nosocomial infection. Methods: The Impact of Event Scale-Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS) were administered to all patients. Moreover, patients were investigated about their worries regarding the impact of COVID-19 on their lives as onco-hematologic patients. Since the 2nd to the 29th April 2020 (during the first phase of the lockdown period in Italy) outpatients affected by lymphoma and needing an infusional chemotherapy/ immunetherapy were evaluated in the study. A multi-disciplinary approach to the patient was then activated, in order to provide a psychological support during the next phases of pandemy. Results: 77 outpatients were prospectively evaluated. The mean age was 56.6 (range 22-85);39 (50.6 %) were male and 38 (49.4 %) female. Diagnoses were distributed as: cHL n. 25 (32.5%);aggressive NHLS n. 15 (19.5%), of whom n. 9 had diffuse large B-cell lymphoma (DLBCL), n 5 mantle cell lymphoma (MCL), and n. 1 primary mediastinal large B-cell lymphoma;indolent NHLs n. 37 (48%), distributed as follicular lymphoma (FL) n. 28, marginal zone lymphoma (MZL) n. 3, hairy cell leukemia (HCL) n. 3, lymphoplasmacytic lymphoma n. 1, CLL/SLL n. 3. N. 6 (7.8%) were treated inside of a clinical trial. N. 52 (67.5%) of patients received infusion chemotherapy or immune-chemotherapy and n. 25 (32.5%) received immunotherapy. According to the line of treatment, n. 38 (49.3%) received induction therapy, n. 6 (7.8%) second line therapy, n. 13 (16.9%) were at the third or higher line, and n. 20 (26%) were receiving maintenance therapy.The mean age was 56.6 (range 22-85). Authors found that 36% of patients had anxiety (HADS-A), 31% depression (HADS-D), and 43% were above the cut-off for the HADS-General Scale;36% fulfilled the diagnostic criteria for post-traumatic stress disorder (PTSD). Women and younger patients were found to be more vulnerable to anxiety and PTSD. In the subsequent months, Authors planned a more structured psychological support, based on a screening offered to outpatients with lymphoma. Summary/Conclusion: The study firstly analyzes the psychological impact of the COVID-19 pandemic on the frail population of patients affected by lymphoproliferative neoplasms, to underly the importance of screening patients for emotional and distress conditions and then offering them psychological support.

Efficacy and Safety of Front-Line Venetoclax and Rituximab (VenR) for the Treatment of Young Patients with Chronic Lymphocytic Leukemia and an Unfavorable Biologic Profile. Preliminary Results of the Gimema Study ‘Veritas‘

Fixed-duration treatment with venetoclax (Ven), a highly selective Bcl-2 inhibitor combined with an anti-CD20 monoclonal antibody, showed high efficacy inducing high rates of deep responses with undetectable minimal residual disease (uMRD) in patients with previously treated and untreated chronic lymphocytic leukemia (CLL). The efficacy and safety of the Ven and rituximab (VenR) combination have been investigated in a multicenter, prospective study of the GIMEMA group that included young patients with previously untreated CLL (LLC 1518, VERITAS, NCT03455517). The primary endpoint of this study was the CR rate assessed according to the iwCLL criteria. Inclusion criteria were: treatment requirement per iwCLL criteria, age ≤65 years, cumulative Illness rating scale score ≤6, creatinine clearance ≥30 mL/min, and an unfavorable biologic profile with IGHV unmutated and or TP53 disruption. Treatment consisted of the Ven dose ramp-up (from 20 to 400 mg daily, during 5-weeks) followed by Ven 400 mg daily, combined with R for six 28-day courses (375 mg/m2, course 1;500 mg/m2, courses 2-6). Patients continued with Ven single agent, 400 mg daily, until month 13. Tumor lysis syndrome (TLS) prophylaxis measures included hydration, allopurinol, or rasburicase. All patients received Pneumocystis Jirovecii prophylaxis. G-CSF was given in patients with recurrent and severe granulocytopenia. Adverse events (AEs) were graded according to the CTCAE criteria v.5, TLS events were classified according to Howard's criteria. Response was assessed at months 7 and 15 and included clinical examination, PB evaluation, BM aspirate, BM biopsy, and CT scan. MRD was checked centrally in the PB and BM by a 6/4-color flow-cytometry assay with a sensitivity of at least 10-4 according to the internationally standardized European Research Initiative on CLL. Quantitative MRD results assessed by flow-cytometry were categorized as uMRD (uMRD4;<10-4), intermediate MRD, or high MRD (≥10-2). MRD was further evaluated by allele-specific oligonucleotide PCR with a sensitivity up to 10-5 in the PB and BM of patients who showed uMRD4 by flow-cytometry. During the follow-up, MRD was monitored every 6 months. Between October 2018 and May 2020, 77 patients with CLL were included in this study. Two patients were off study before the start of treatment (withdrawal of consent, 1;Covid-19 infection, 1) and were not included in the analysis. The median age was 53.5 years (range 38-65). Binet stage B/C was present in 84% of patients, increased beta-2 microglobulin in 41%. Seventy-one (96%) of patients were IGHV unmutated, while 3 (4%) were IGHV mutated and showed TP53 mutation (Table 1). At the data cutoff of June 30, 2020, 65 (87%) patients completed the ramp-up phase. The planned 400 mg dose of Ven was reached within 5 weeks in 78.5% of patients. Response was assessed in 34 patients at the end of the VenR combination therapy. A response was achieved by 32 (94%) patients. Responses included 20 (59%) CRs, 1 CRi (3%) and 11 (32%) PRs due to residual enlarged nodes (median maximum size, 1.9 cm). Treatment failure due to toxicity was recorded in 2 (6%) patients. Overall, a response with uMRD4 by flow-cytometry in the PB was observed in 26 (76.5%) cases, and in the PB and BM, in 17 (50.0%). The rates of patients with CR and uMRD4 by flow-cytometry in the PB, and both in the PB and BM, were 44%, and 35%, respectively (Table 2). No detectable disease by PCR, both in the PB and BM, was observed in 4 (12%) patients. With a median follow-up of 4.5 months from the start of therapy, no patient has progressed or died. Fifty-three percent of patients were hospitalized during the first seven days of the Ven ramp-up phase. A transient laboratory TLS was observed in 3 patients. Treatment was discontinued after the first dose of Ven in 1 patient with evidence of laboratory TLS associated with severe neurologic toxicity due to the concomitant administration of fentanyl. Selected grade ≥3 AEs included neutropenia in 10 patients (ramp-up phase, 5) and neutropenic fever in 4. Gra e ≥3 infection was recorded in 3 patients and was the reason for treatment discontinuation in 1 who developed COVID-19 pneumonia. In conclusion, the preliminary results of this study demonstrate the high efficacy of the front-line VenR combination, which resulted in a high proportion of CRs and responses with uMRD4 in young patients with CLL and an unfavorable biologic profile. [Formula presented] Disclosures: Mauro: Astrazeneca: Membership on an entity's Board of Directors or advisory committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jannsen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Octopharma: Consultancy. Reda: Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees. Trentin: Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Shire: Honoraria;Takeda: Membership on an entity's Board of Directors or advisory committees;Octapharma: Membership on an entity's Board of Directors or advisory committees. Coscia: Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;Karyopharm Therapeutics: Research Funding;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Sportoletti: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Laurenti: Roche: Membership on an entity's Board of Directors or advisory committees;AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gaidano: Astrazeneca: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Sunesys: Membership on an entity's Board of Directors or advisory committees. Marasca: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Shire: Honoraria;Roche: Membership on an entity's Board of Directors or advisory committees. Murru: Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rigolin: Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Scarfo: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AstraZeneca: Honoraria;Gilead: Membership on an entity's Board of Directors or advisory committees. Marchetti: Pfizer: Membership on an entity's Board of Directors or advisor committees;Takeda: Membership on an entity's Board of Directors or advisory committees;Amgen: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees. Levato: Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Galieni: Celgene: Honoraria;Takeda: Honoraria;AbbVie: Honoraria;Janssen: Honoraria. Liberati: Verastem: Research Funding;Onconova: Research Funding;Janssen: Honoraria, Research Funding;Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding;Abbvie: Honoraria, Research Funding;Pfizer: Research Funding;Karyopharm: Research Funding;Morphosys: Research Funding;Novartis: Research Funding;GSK: Research Funding;Incyte: Honoraria;Oncopeptides: Research Funding;Takeda: Research Funding. Molica: Roche: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Visentin: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Gilead: Membership on an entity's Board of Directors or advisory committees, SpeakersBureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vitale: Janssen: Honoraria. Del Giudice: Janssen: Other: grant for meeting participation;Tolero: Membership on an entity's Board of Directors or advisory committees;Roche: Other: grant for meeting partecipation;AstraZeneca: Membership on an entity's Board of Directors or advisory committees. Cuneo: Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Astra Zeneca: Honoraria;Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foà: Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Incyte: Speakers Bureau;Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Membership on an entity's Board of Directors or advisory committees;Novartis: Speakers Bureau;Roche: Membership on an entity's Board of Directors or advisory committees.

Psychological well-being in cancer outpatients during COVID-19

Purpose: The psychological status of cancer outpatients receiving anti-neoplastic treatment during the lockdown in a Italian non-COVID Cancer Center, was been investigated with the following aims: to measure the levels of post-traumatic stress symptoms, depression and anxiety;to compare patients with different cancer sites;to compare the anxiety and depression levels measured in this emergency period between cancer and non-cancer patients and between cancer patients before and after the emergency. Methods: The following questionnaires were used: The Hospital Anxiety and Depression Scale (HADs) and the Impact of Event Scale-Revised (IES-R).Worries regarding the COVID-19 on patients' lives, socio-demographic and clinical details were collected using a brief structured questionnaire. Results: One-hundred seventy-eight outpatients were enrolled. We found that 55% of patients were above the cut-off for HADS general scale and 23.7% had severe level of PTSD. The 68% of patients declared that their worries have increased during the pandemic especially for women. Patients with lung cancer have higher general distress compared with patients with breast cancer and lymphoma. The non cancer sample had values significantly higher both for the IES-R scales and for HADS Depression subscale. Finally, cancer patients who experienced the health emergency showed higher levels of anxiety than those measured 2 years ago. Conclusion: Cancer out-patients of the present sample have severe post-traumatic stress symptoms and psychological distress, those with lung cancer are at higher risk and may need special attention. Non-oncological subjects have higher depression levels than cancer patients.

Updated results of the fil “miro” study, a multicenter phase II trial combining local radiotherapy and MRD-driven immunotherapy in early-stage follicular lymphoma

Background: Early-stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), allowing a complete and long lasting eradication of the disease only in 40-50% of patients (pts). The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying pts unlikely to be cured by IFRT, for whom an immunotherapy consolidation could improve outcome. Methods: 110 pts with stage I/II FL were enrolled and treated with 24 Gy IFRT. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the FIL (Fondazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories. In BCL2/IGH+ pts at baseline by both nested PCR (NEST) and RQ-PCR (RQ) in BM a/o PB, MRD was analyzed after IFRT and every 6 months over a 3-year period. Pts with MRD+ by both NEST and RQ in BM a/o PB after IFRT or who became MRD+ during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab (OFA). The primary objective of the study was to define the efficacy of immunotherapy in obtaining a negative MRD. Results: Of the 106 evaluable pts, 50 were males. Median age was 55 y (29-83). The FLIPI score was 0 in 59% of pts, 1 in 35%, 2 in 6%. 68% of pts had inguinal site involvement. At baseline, 30% of pts had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in BM a/ o PB;the concordance between compartments was 90%. All but one pt achieved a clinical response after IFRT;one additional pt died soon after IFRT of unrelated causes. MRD evaluation after IFRT revealed the persistence of BCL2/IGH+ cells in PB a/o BM in 60% of pts. MRD + pts, either after IFRT (n = 18) or in case of conversion to MRD+ during the follow-up (n = 6), received OFA, obtaining a conversion to MRD-in 22/24 pts (91.7%-CI 73.0-99.0), significantly superior to the expected 50% (Fig). After a median F-U of 38 m, 17 pts who achieved a MRD-with OFA are still negative;5 converted to MRD+ (2 received OFA retreatment, achieving a second MRD-;2 pts were not re-treated due to Sars-Cov2 pandemic;1 relapsed). A clinical relapse or progression was observed in 23 pts: 18 (24.6%) among the 73 “no marker” pts and 5 (15.6%) among the 32 BCL2/IGH+ at baseline (p = 0.3), with no significant difference in PFS (p = 0.25). Two early relapses were observed among the 12 pts who became MRD-after IFRT and 3 among the 24 treated at least once with OFA (1 MRD+, 1 MRD-, 1 converted from MRD-to MRD+). Only 1 Pt relapsed while MRD-after OFA. Conclusions: MRD data indicate that RT alone is often insufficient to eradicate the disease, inducing a MRD-only in 40% of pts, notably long-lasting only in half of them. The primary objective of this study-MRD conversion after immunotherapy-was largely achieved. The strategy of an immunotherapy consolidation after IFRT in MRD+ pts allowed increasing molecular responses. However, this strategy is applicable only to 30% of enrolled pts. A clinical advantage of the MRD driven treatment strategy is suggested although not significan.

FP06.04 Psychological Distress in Outpatients with Lymphoma, Lung and Breast Cancer during COVID-19 pandemic

Introduction: The psychological impact of the lockdown experienced during the COVID-19 pandemic has been found detrimental for the general population, but it has still not been evaluated in cancer patients. We have investigated the psychological status of outpatients receiving anti-neoplastic treatmentduring the lockdown in a non-COVID Cancer Center, with the following aims: to measure the levels of post-traumatic stress symptoms, depression and anxiety, to compare patients with different diagnosis. A further objective was to compare the anxiety and depression levels between cancer patients before and after the emergency assuming an increase in distress in cancer patients in this period due to the health emergency. Methods: Outpatients attending the IRCCS "Giovanni Paolo II" in Bari for their therapy were asked to complete these questionnaires: The Hospital Anxiety and Depression Scale (HADs) and the Impact of Event Scale-Revised (IES-r).Worries regarding the COVID-19 on patients’ lives, socio-demographic and clinical details were investigated using a brief structured questionnaire. Results: One-hundred seventy-six outpatients (n.59 with lung cancer, n.40 with breast cancer, n.77 with lymphoma) were enrolled. Mean age was 57.9 y.o. (SD ±14);48% were male. We found that 54,4% of patients were above the cut-off (score≥16) for HADS general scale. The mean-IES-R score of patients was 25 (SD±17), with 22.8% indicating severe level of PTDS. The HADS-D has been found significantly correlated with IES-R (r= 0.35;p<0.005). The 70% of patients declared that their worries have increased during the pandemic;their bigger concerns were: the risk of getting infected while at hospital (51.4%);the risk of infecting relatives coming back home (38.7%), andthe risk of delaying therapy (35.3%).When comparing the level of anxiety and depression in different diagnosis it has been found that patients with lung cancer have higher distress(HADs-general scale) than patients with lymphoma (F=17.3, p<0.005) and breast cancer (F=8.86, p<0.005). Finally, cancer patients who experienced the health emergency showed higher levels of anxiety Hads-A, t (237) = 3.73 p<0.001), and general distress (Hads-G, t (237) = 2.51) than those measured 2 years ago (fig 1). Conclusion: This study focused on the psychological aspects of cancer patients during the COVID-19 pandemic, finding that one quarter of patients has severe post-traumatic stress symptoms, and has psychological distress. Patients with lung cancer have higher distress compared to the other groups. This condition risks being overlooked by clinical concerns, so we underline the importance to place even more attention to the psychological needs of patients. Keywords: cancer, COVID, Psychological distress

Psychological distress in outpatients with lymphoma, lung and breast cancer during covid-19 pandemic

Background: The psychological impact of the lockdown experienced during the COVID-19 pandemic has been found detrimental for the general population, but it has still not been evaluated in cancer patients. We have investigated the psychological status of outpatients receiving anti-neoplastic treatmentduring the lockdown in a non-COVID Cancer Center, with the following aims: to measure the levels of post-traumatic stress symptoms, depression and anxiety, to compare patients with different diagnosis. An additional aim was to offer a psychological on-line support to patients who need it. Material and methods: Outpatients attending the IRCCS 'Giovanni Paolo II' in Bari for their therapy were asked to complete these questionnaires: The Hospital Anxiety and Depression Scale (HADs) and the Impact of Event Scale-Revised (IES-r).Worries regarding the COVID-19 on patients' lives, socio-demographic and clinical details were investigated using a brief structured questionnaire. Results: One-hundred seventy-six outpatients (n.59 with lung cancer, n.40 with breast cancer, n.77 with lymphoma) were enrolled. Mean age was 57.9 y.o. (SD ±14);48% were male. We found that 54,4% of patients were above the cut-off (score≥16) for HADS general scale. The mean-IES-R score of patients was 25 (SD±17), with 22.8% indicating severe level of PTDS. The HADS-D has been found significantly correlated with IES-R (r= 0.35;p<0.005). The 70% of patients declared that their worries have increased during the pandemic;their bigger concerns were: the risk of getting infected while at hospital (51.4%);the risk of infecting relatives coming back home (38.7%), andthe risk of delaying therapy (35.3%).When comparing the level of anxiety and depression in different diagnosis it has been found that patients with lung cancer have higher distress(HADs-general scale) than patients with lymphoma (F=17.3, p<0.005) and breast cancer (F=8.86, p<0.005). Conclusions: This study focused on the psychological aspects of cancer patients during the COVID-19 pandemic, finding that one quarter of patients has severe post-traumatic stress symptoms, and has psychological distress. Patients with lung cancer have higher distress compared to the other groups. This condition risks being overlooked by clinical concerns, so weunderline the importance to place even more attention to the psychological needs of patients, especially for those who have symptoms similar to COVID-19 as in lung cancer, in order to offer adequate support.