Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC.

BACKGROUND: Among patients with resected, epidermal growth factor receptor (EGFR)-mutated, stage IB to IIIA non-small-cell lung cancer (NSCLC), adjuvant osimertinib therapy, with or without previous adjuvant chemotherapy, resulted in significantly longer disease-free survival than placebo in the ADAURA trial. We report the results of the planned final analysis of overall survival. METHODS: In this phase 3, double-blind trial, we randomly assigned eligible patients in a 1:1 ratio to receive osimertinib (80 mg once daily) or placebo until disease recurrence was observed, the trial regimen was completed (3 years), or a discontinuation criterion was met. The primary end point was investigator-assessed disease-free survival among patients with stage II to IIIA disease. Secondary end points included disease-free survival among patients with stage IB to IIIA disease, overall survival, and safety. RESULTS: Of 682 patients who underwent randomization, 339 received osimertinib and 343 received placebo. Among patients with stage II to IIIA disease, the 5-year overall survival was 85% in the osimertinib group and 73% in the placebo group (overall hazard ratio for death, 0.49; 95.03% confidence interval [CI], 0.33 to 0.73; P<0.001). In the overall population (patients with stage IB to IIIA disease), the 5-year overall survival was 88% in the osimertinib group and 78% in the placebo group (overall hazard ratio for death, 0.49; 95.03% CI, 0.34 to 0.70; P<0.001). One new serious adverse event, pneumonia related to coronavirus disease 2019, was reported after the previously published data-cutoff date (the event was not considered by the investigator to be related to the trial regimen, and the patient fully recovered). Adjuvant osimertinib had a safety profile consistent with that in the primary analysis. CONCLUSIONS: Adjuvant osimertinib provided a significant overall survival benefit among patients with completely resected, EGFR-mutated, stage IB to IIIA NSCLC. (Funded by AstraZeneca; ADAURA ClinicalTrials.gov number, NCT02511106.).

Not Waiting to Progress; How the COVID-19 Pandemic Nudged Neoadjuvant Therapy for Stage III Locally Advanced Melanoma Patients.

Background: Early-phase neoadjuvant trials have demonstrated promising results in the utility of upfront immunotherapy in locally advanced stage III melanoma and unresected nodal disease. Secondary to these results and the COVID-19 pandemic, this patient population, traditionally managed through surgical resection and adjuvant immunotherapy, received a novel treatment strategy of neoadjuvant therapy (NAT). Methods: Patients with node-positive disease, who faced surgical delays secondary to COVID-19, were treated with NAT, followed by surgery. Demographic, tumour, treatment and response data were collected through a retrospective chart review. Biopsy specimens were analysed prior to the initiation of NAT, and therapy response was analysed following surgical resection. NAT tolerability was recorded. Results: Six patients were included in this case series; four were treated with nivolumab alone, one with ipilimumab and nivolumab and one with dabrafenib and trametinib. Twenty-two incidents of adverse events were reported, with the majority (90.9%) being classified as grade one or two. All patients underwent surgical resection: three out of six patients following two NAT cycles, two following three cycles and one following six cycles. Surgically resected samples were histopathologically evaluated for the presence of disease. Five out of six patients (83%) had ≤1 positive lymph node. One patient showed extracapsular extension. Four patients demonstrated complete pathological response; two had persisting viable tumour cells. Conclusions: In this case series, we outlined how in response to surgical delays secondary to the COVID-19 pandemic, NAT was successfully applied to achieve promising treatment response in patients with locally advanced stage III melanoma.

Multicenter phase 2 study of oral azacitidine (CC-486) plus CHOP as initial treatment for PTCL.

Peripheral T-cell lymphomas (PTCL) with T-follicular helper phenotype (PTCL-TFH) has recurrent mutations affecting epigenetic regulators, which may contribute to aberrant DNA methylation and chemoresistance. This phase 2 study evaluated oral azacitidine (CC-486) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as initial treatment for PTCL. CC-486 at 300 mg daily was administered for 7 days before C1 of CHOP, and for 14 days before CHOP C2-6. The primary end point was end-of-treatment complete response (CR). Secondary end points included safety and survival. Correlative studies assessed mutations, gene expression, and methylation in tumor samples. Grade 3 to 4 hematologic toxicities were mostly neutropenia (71%), with febrile neutropenia uncommon (14%). Nonhematologic toxicities included fatigue (14%) and gastrointestinal symptoms (5%). In 20 evaluable patients, CR was 75%, including 88.2% for PTCL-TFH (n = 17). The 2-year progression-free survival (PFS) was 65.8% for all and 69.2% for PTCL-TFH, whereas 2-year overall survival (OS) was 68.4% for all and 76.1% for PTCL-TFH. The frequencies of the TET2, RHOA, DNMT3A, and IDH2 mutations were 76.5%, 41.1%, 23.5%, and 23.5%, respectively, with TET2 mutations significantly associated with CR (P = .007), favorable PFS (P = .004) and OS (P = .015), and DNMT3A mutations associated with adverse PFS (P = .016). CC-486 priming contributed to the reprograming of the tumor microenvironment by upregulation of genes related to apoptosis (P < .01) and inflammation (P < .01). DNA methylation did not show significant shift. This safe and active regimen is being further evaluated in the ALLIANCE randomized study A051902 in CD30-negative PTCL. This trial was registered at www.clinicaltrials.gov as #NCT03542266.

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse.

INTRODUCTION: Treatment of patients with multiple myeloma (MM) in first relapse remains a challenge. This phase II study combined elotuzumab (Elo) with carfilzomib, lenalidomide, and dexamethasone (KRd) for treatment of MM in first relapse with the aim of improving efficacy. METHODS: Enrolled patients received Elo-KRd induction for 4 cycles, and Elo-lenalidomide maintenance until progression. The primary endpoint was VGPR or better (≥VGPR) postinduction. Secondary endpoints were MRD by flow cytometry, OS, PFS, and safety. Correlatives included characterization of the impact of Elo-KRd on NK and T cell subsets via flow cytometry. Target accrual of 40 patients was not met due to COVID-19 pandemic. RESULTS: Of 15 patients enrolled, 10 (67%) had high-risk features (del17p, t[4;14], t[14;16], 1q gain/amplification, plasma cell leukemia, extramedullary MM, or functional high risk), 12 (80%) were lenalidomide-refractory, and 5 (33.3%) bortezomib-refractory. Postinduction ≥VGPR was 7/15 (46.7%) and MRD-negative (10-5) rate 20%. Overall response during study was 80%, including ≥VGPR as best response of 53.3%. At median follow-up of 28.2 (range, 3.8 to 44.2) months, the median PFS was 11.5 months (95% CI 1.9, 18), and median OS not reached (95% CI 10.1, NA). No new safety concerns were reported. Elo-KRd treatment did not augment NK cell distribution or activity in blood or bone marrow. Effector CD4+ and CD8+ T cells significantly decreased postinduction, with concomitant acquisition of T central memory phenotype, particularly at a high rate in ≥VGPR group. CONCLUSION: A short course of Elo-KRd induction followed by Elo-lenalidomide maintenance demonstrated activity in predominantly lenalidomide-refractory and / or high-risk MM. The results with this well-tolerated combination are comparable to other contemporary approved triplet combinations.

Impact of triple intrathecal prophylaxis in acute lymphoblastic leukemia adults receiving HyperCVAD: A COVID-19 practice change.

Treatment of acute lymphoblastic leukemia (ALL) requires both systemically and locally directed therapies to prevent central nervous system (CNS) recurrence. In response to restrictions brought on by the COVID-19 pandemic, our institution adopted triple intrathecal (IT) chemotherapy for CNS prophylaxis during HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). We retrospectively reviewed records of newly diagnosed adult all patients who were consecutively treated with HyperCVAD between January 2011 and July 2022. Outcomes of patients who received triple IT chemotherapy and standard of care (SOC) CNS prophylaxis were compared. The primary endpoint was CNS relapse-free survival (RFS) while secondary endpoints included cumulative incidence of relapse, overall survival, number of outpatient, and total ITs per patient, and CNS treatment-related toxicities. A total of 37 patients including 21 in the triple IT and 16 in the SOC cohorts were evaluated. There were no differences between the triple IT and SOC cohorts with respect to CNS-RFS (89.6% vs. 80.4%; HR, 1.55; 95% CI, 0.45-5.39; p = .49), cumulative incidence of relapse (8.9% vs. 19.6%; HR, 1.14; 95% CI, 0.3-5.3; p = .87), and overall survival (89.6% vs. 85.7%; HR, 0.91; 95% CI, 0.20-4.21; p = .90) at 2-years. Significantly fewer IT doses were administered in the triple IT cohort (p = .011) and the number of additional outpatient appointments to administer IT chemotherapy were markedly reduced as 98.6% of IT doses were administered during scheduled admissions compared to 76.8% (p < .001). The adoption of triple IT chemotherapy did not increase CNS treatment-related toxicities but rather, the inverse was observed. Triple IT chemotherapy during HyperCVAD represents a feasible alternative to SOC CNS prophylaxis, especially during times of resource restriction and when minimization of patient exposures is desired.

The prognostic impact of monocyte fluorescence, immunosuppressive monocytes and peripheral blood immune cell numbers in HIV-associated Diffuse Large B-cell Lymphoma.

INTRODUCTION: Diffuse large B-cell lymphoma (DLBCL) is a high grade non-Hodgkin lymphoma which is common among immunodeficient people. Derangements of peripheral blood immune cells have been described to have a prognostic impact in DLBCL in high income countries, including a monocytosis, the ratios of lymphocytes to both monocytes (L:M) and neutrophils (N:L), as well as the numbers of regulatory T-cells (Tregs) and immunosuppressive monocytes (HLA-DRlow monos). To date, the impact of these variables has not been assessed in the setting of HIV-associated DLBCL (HIV-DLBCL), which is among the most common malignancies seen in people living with HIV. In this study, we assessed these factors in a cohort of South African patients with DLBCL and a high HIV-seropositivity-rate. In addition, we evaluated the prognostic value of monocyte activation (as reflected by monocyte fluorescence (MO-Y) on a Sysmex haematology analyser). This parameter has to date not been assessed in the setting of DLBCL. METHODS: A full blood count and differential count as well as flow cytometry for HLA-DRlow monocyte and Treg enumeration were performed in patients with incident DLBCL referred to the Chris Hani Baragwanath Academic Hospital in Johannesburg, South Africa between November 2019 and May 2022. Additional clinical and laboratory data were recorded from the patient charts and laboratory information system. RESULTS: Seventy-six patients were included, of whom 81.3% were people living with HIV with a median CD4 count of 148 cells/ul. Most patients had advanced stage disease (74.8%) and were predominantly treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy (without Rituximab). At a median follow-up period of 19 months, the median survival time was 3.5 months, with a 12-month survival rate of 27.0%. All of the immune-cell-related variables (with the exception of the CD4 count) were similar between the people living with HIV and the HIV-negative individuals. In contrast to previous studies, a high monocyte count, the L:M and increased numbers of HLA-DRlow monocytes were not significantly associated with survival in HIV-DLBCL, while a neutrophilia (>8 x 109/L), the N:L (>6:1), high numbers of Tregs (≥5.17% of CD4s) and lymphopenia (<1.3 x 109/L) were. In addition, increased monocyte fluorescence (MO-Y >115.5) was associated with superior outcomes, which we speculate to reflect a more robust antitumour immune response among individuals with high levels of monocyte activation. On Cox Proportional hazard analysis, immune-cell factors independently associated with survival included a CD4 count <150 cells/ul and a neutrophilia. CONCLUSION: The monocyte count, L:M and the number of HLA-DRlow monos are not strong prognostic indicators in HIV-DLBCL, while a low CD4 count and neutrophilia are. Elevation of the MO-Y shows some promise as a potential biomarker of antitumour immunity; further study in this regard would be of interest.

Bendamustine and rituximab is well-tolerated and efficient in the treatment of indolent non-Hodgkin's lymphoma and mantle cell lymphoma in elderly: A single center observational study.

Bendamustine and rituximab (BR) is a preferred first-line therapy for indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL); however, few reports on BR performance in elderly patients are available to date. We compared safety and efficacy of BR in patients ≥70 years (elderly) vs <70 years (younger) treated at our institution. Among 201 patients, 113 were elderly (median age: 77 years), including 38 patients ≥80 years, and 88 were younger (median age: 62 years). Elderly patients had more bone marrow involvement by lymphoma, anemia, ECOG status 3 and high-risk disease follicular lymphoma (P < .05 for all). Fifty-four percent of elderly received full dose of bendamustine vs 79.5% of younger patients. More elderly patients (54%) vs younger (43.2%) experienced treatment delay. Less elderly proceeded to rituximab maintenance. Overall, the number of adverse events per patient and transformed B-Cell lymphoma/secondary malignancies were similar between groups. Elderly patients had less febrile neutropenia, rituximab-associated infusion reactions, but more herpes zoster reactivation. There were more deaths in the elderly (37.2%) vs younger (10.2%) groups (P < .001), mainly due to non-lymphoma-related causes. With median follow-up of 42 months [4.0-97.0] disease-free survival for the elderly was similar to younger patients. There was no difference between patients <80 and ≥80 years (P = .274). In conclusion, the real-world elderly patients have more advanced disease and higher ECOG status. BR is well-tolerated; elderly patients had lower incidence of febrile neutropenia. Dose reduction and treatment delays are common, but BR efficacy was not affected even in very old patients (≥80 years).

In search for optimal induction chemotherapy for advanced nasopharyngeal cancer: Standard dosing of Docetaxel, Platinum, and 5-Fluorouracil (TPF) followed by chemoradiation.

OBJECTIVES: A phase II = design is used to evaluate the efficacy and feasibility of full dose docetaxel, platinum, and 5-fluorouracil (TPF) in a sequential chemoradiation treatment locally advanced (LA) or oligometastatic (OM) NPC patients. MATERIALS AND METHODS: Twenty patients with LANPC (M0 cohort) and six patients with OMNPC (M1 cohort) received induction standard dose T (75 mg/m2) P (75 mg/m2) F (750 mg/m2 IVCI x 5days) x 3 followed by weekly cisplatin (40 mg/m2) or carboplatin (AUC 1.5) x 6 concurrent with radiation therapy of 70 Gy over 6.5-7 weeks. The first five patients received bevacizumab as part of an exploratory objective of hypoxia modification using correlative fluoromisonidasole (18F-MISO) PET CT scanning. RESULTS: The 18F-MISO imaging failed to reveal adequate levels of baseline hypoxia necessary to evaluate for changes with chemotherapy and bevacizumab. Ninety percent of M0 patients and 83% of M1 patients received the full-intended TPF and radiation dose. Eighty-five percent of M0 patients and all M1 patients received at least 60% of the full-intended concurrent platinum dose. The 2-year progression free survival (PFS) rate for the M0 cohort was 90% (95% CI: 77.8%- 100%), and was sustained at 5 years. The 2-year PFS rate for the M1 cohort was 66.7% (95% CI: 37.9%- 100%). The 2-year overall survival (OS) rates for the M0 and M1 cohorts were 100% and 83.3% (95% CI: 58.3%- 100%), respectively. At five years, OS was 94.4% for the M0 cohort. CONCLUSION: Administration of standard-dose TPF as induction chemotherapy in this NPC patient population is both feasible and effective when coupled with definitive concurrent chemoradiation. CLINICALTRIALS.GOV IDENTIFIER: NCT00896181.

Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review.

Importance: Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 × 109/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. CLL is associated with an immunocompromised state and an increased rate of complications from infections. Observations: At the time of diagnosis, the median age of patients with CLL is 70 years, and an estimated 95% of patients have at least 1 medical comorbidity. Approximately 70% to 80% of patients with CLL are asymptomatic at the time of diagnosis, and one-third will never require treatment for CLL. Prognostic models have been developed to estimate the time to first treatment and the overall survival, but for patients who are asymptomatic, irrespective of disease risk category, clinical observation is the standard of care. Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). There is no evidence that starting either class before the other improves outcomes. The covalent BTK inhibitors are typically used indefinitely. Survival rates are approximately 88% at 4 years for acalabrutinib, 94% at 2 years for zanubrutinib, and 78% at 7 years for ibrutinib. Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up). A noncovalent BTK inhibitor, pitobrutinib, has shown an overall response rate of more than 70% after failure of covalent BTK inhibitors and venetoclax. Phosphoinositide 3'-kinase (PI3K) inhibitors (idelalisib and duvelisib) can be prescribed for disease that progresses with BTK inhibitors and venetoclax, but patients require close monitoring for adverse events such as autoimmune conditions and infections. In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents. Conclusions and Relevance: More than 200 000 people in the US are living with a CLL diagnosis, and CLL causes approximately 4410 deaths each year in the US. Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.

Ruxolitinib and methylprednisolone for treatment of patients with relapsed/refractory multiple myeloma.

Although Janus kinase (JAK) inhibitors have demonstrated efficacy for treating autoimmune disorders and myeloproliferative neoplasms, their efficacy in treating other types of cancer has not been clearly demonstrated. We evaluated oral ruxolitinib (15 mg twice daily) with oral methylprednisolone (40 mg every other day) for multiple myeloma (MM) patients with progressive disease who had received a proteasome inhibitor, lenalidomide, glucocorticosteroids and three or more prior regimens. All of the planned 29 patients had been enrolled with follow-up until 28 April 2022. Median lines of prior therapy were 6 (range 3-12). Cytogenetics and fluorescent in situ hybridization were evaluable in 28 patients; 9 (32%) and 17 (70%) patients showed high-risk cytogenetics and/or 1q+, respectively. The overall response rate was 31%. The median duration of response was 13.1 (range 2.8-22.0) months. Median progression-free survival rate was 3.4 (range 0.5-24.6) months, Overall, the treatment was well tolerated. The combination of ruxolitinib and methylprednisolone demonstrated significant clinical activity among previously heavily-treated MM patients, and responses were achieved among patients who had high-risk cytogenetics. This is the first clinical study to show activity of JAK inhibitors in combination with steroids for MM patients and expands the potential use of these drugs to those with cancers other than myeloproliferative neoplasms.

Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma.

BACKGROUND: In a pilot study involving patients with cutaneous squamous-cell carcinoma, a high percentage of patients had a pathological complete response with the use of two doses of neoadjuvant cemiplimab before surgery. Data from a phase 2 study are needed to confirm these findings. METHODS: We conducted a phase 2, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab as neoadjuvant therapy in patients with resectable stage II, III, or IV (M0) cutaneous squamous-cell carcinoma. Patients received cemiplimab, administered at a dose of 350 mg every 3 weeks for up to four doses, before undergoing surgery with curative intent. The primary end point was a pathological complete response (the absence of viable tumor cells in the surgical specimen) on independent review at a central laboratory, with a null hypothesis that a pathological complete response would be observed in 25% of patients. Key secondary end points included a pathological major response (the presence of viable tumor cells that constitute ≤10% of the surgical specimen) on independent review, a pathological complete response and a pathological major response on investigator assessment at a local laboratory, an objective response on imaging, and adverse events. RESULTS: A total of 79 patients were enrolled and received neoadjuvant cemiplimab. On independent review, a pathological complete response was observed in 40 patients (51%; 95% confidence interval [CI], 39 to 62) and a pathological major response in 10 patients (13%; 95% CI, 6 to 22). These results were consistent with the pathological responses determined on investigator assessment. An objective response on imaging was observed in 54 patients (68%; 95% CI, 57 to 78). Adverse events of any grade that occurred during the study period, regardless of whether they were attributed to the study treatment, were observed in 69 patients (87%). Grade 3 or higher adverse events that occurred during the study period were observed in 14 patients (18%). CONCLUSIONS: Neoadjuvant therapy with cemiplimab was associated with a pathological complete response in a high percentage of patients with resectable cutaneous squamous-cell carcinoma. (Funded by Regeneron Pharmaceuticals and Sanofi; ClinicalTrials.gov number, NCT04154943.).

Selinexor in Patients from Argentina with Multiple Myeloma Treated with Multiple Prior Therapies: A Case Series.

BACKGROUND Numerous treatment options are available for patients with multiple myeloma (MM). Because of the course of the disease, most patients will experience serial relapse or the MM will become refractory to most of these treatments, leaving patients with few or no treatment options over time. Selinexor, a treatment with a novel mechanism of action, is an oral selective inhibitor of nuclear export (SINE) compound that blocks exportin 1, the major nuclear exporter of tumor suppressor proteins. CASE REPORT In this case series, we report on treatment with the weekly oral administration of selinexor combined with bortezomib and dexamethasone (XVd) in 3 patients from Argentina who were heavily treated (5-7 prior therapies) for MM that relapsed or was refractory to each previous treatment. Two patients had the high-risk cytogenetic abnormality del(17p). All 3 patients experienced efficacy with XVd reaching a best response of partial response or very good partial response. These responses were consistent with those of patients from the BOSTON study who were treated with XVd but were less heavily pretreated (1-3 prior therapies) and had a shorter median time since diagnosis of MM (7 years vs 3.7 years). The 3 patients experienced adverse events (AEs) that included nausea, thrombocytopenia, asthenia, and fatigue, which were similar to the most commonly reported AEs associated with selinexor treatment. CONCLUSIONS With its oral administration, novel mechanism of action, and responses in heavily pretreated patients, selinexor may help to address an important clinical need in the treatment of patients with relapsed/refractory MM.

Safety and efficacy of induction immunochemotherapy with rituximab, methotrexate, ifosfamide, and vincristine (R-MIV) in patients with primary CNS lymphoma including recent COVID-19 pandemic experience.

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real-world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID-19 pandemic. In particular, treatment with high-dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R-MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high-dose methotrexate (3.5 g/m2 ) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n = 46/63), with an additional 17.5% (n = 11/63) patients without measurable disease at baseline. Grade 3-4 haematological toxicity was low for R-MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment-related toxicity. Co-existence of SARS-CoV-2 infection with cytomegalovirus reactivation and the varicella-zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression-free and overall survival were not reached (median follow-up: 44 months). In conclusion, the R-MIV regimen is feasible in routine practice, effective and safe, even during the COVID-19 pandemic.

Time and productivity loss associated with immunotherapy infusions for the treatment of melanoma in the United States: a survey of health care professionals and patients.

INTRODUCTION: A new dosing schedule for the oncology immunotherapy pembrolizumab, every 6 weeks (Q6W), has been approved by the U.S. FDA, reducing the frequency of visits to infusion centers. We quantified the time spent by oncologists, nurses, patients, and caregivers per melanoma-related immunotherapy infusion visit to evaluate its potential impact. METHODS: Surveys were self-completed by 100 oncologists, 101 oncology nurses, and 100 patients with melanoma across the U.S. to quantify the time spent per infusion visit with pembrolizumab (Q3W or Q6W), nivolumab (Q2W or Q4W), or nivolumab+ipilimumab (nivolumab in combination: Q3W; nivolumab maintenance: Q2W or Q4W). Time measures included traveling, waiting, consultation, infusion, post-treatment observation, and caregiving. Respondents were also surveyed regarding the impact of the COVID-19 pandemic on infusion treatments. RESULTS: Responses deemed valid were provided by 89 oncologists, 93 nurses, and 100 patients. For each new [returning] patient treated with pembrolizumab, nivolumab or nivolumab+ipilimumab, oncologists reported to spend an average of 90 [64], 87 [60] and 101 [69] minutes per infusion visit (p-value for between-group difference = 0.300 [0.627]). For first [subsequent] treatment cycles, nurses reported spending 160 [145] average minutes per visit for nivolumab+ipilimumab, versus roughly 120 [110] for the single agents (p-value for between-group difference = 0.018 [0.022]). Patients reported to spend an average of 263, 382, and 224 minutes per visit at the center for pembrolizumab (N = 47), nivolumab (n = 34), and nivolumab+ipilimumab (n = 15) respectively (p-value for between-group difference = 0.0002). Patients also reported that their unpaid (N = 20) and paid caregivers (N = 41) spent with them an average of 966 and 333 minutes, respectively, from the day before to the day after the infusion visit. CONCLUSION: Less frequent immunotherapy infusion visits may result in substantial time savings for oncologists, nurses, patients, and caregivers.

Pomalidomide Treatment in Relapsed/Refractory Multiple Myeloma Patients-Real-World Data From Hungary.

Pomalidomide is a third generation immunomodulatory drug in the treatment of refractory and relapsed multiple myeloma patients. Our aim was to investigate the efficacy and safety of pomalidomide therapy in a real world setting. Eighty-six Hungarian patients were included, 45 of whom received pomalidomide ± an alkylating agent, while in 38 of them pomalidomide was combined with a proteasome inhibitor. 56 patients (65%) showed any response to the treatment with 18 complete or very good partial remissions and 38 partial remissions. At a median duration of follow-up of 18.6 months, the median progression-free survival (PFS) was 9.03 months, while the median overall survival (OS) was 16.53 months in the whole cohort. Patients with early stage disease (R-ISS 1 and 2) had better survival results than those with stage 3 myeloma (p = 0.002). Neither the number of prior treatment lines, nor lenalidomide refractoriness had a significant impact on PFS. PFS was found similar between the cohort of patients with impaired renal function and the cohort without kidney involvement. During the study, eight mortal infections and two fatal bleeding complications occurred, however, mild hematologic and gastrointestinal toxicities were identified as the most frequent adverse events. The results of our investigations confirm that pomalidomide is an effective treatment option for relapsed/refractory MM, besides, the safety profile is satisfactory in subjects with both normal and impaired renal function.

Early efficacy and safety of obinutuzumab with chemotherapy in previously untreated patients with follicular lymphoma: A real-world retrospective report of the Polish Lymphoma Research Group.

BACKGROUND: The first-line obinutuzumab-based immunochemotherapy improves the outcome of patients with follicular lymphoma (FL) compared with rituximab-based regimens. However, infusion-related reactions occur in almost half of patients during the 1st obinutuzumab administration. OBJECTIVES: The study aimed to evaluate the early effectiveness and safety of obinutuzumab-based induction regimens in a real-world setting. MATERIAL AND METHODS: Outcomes of patients diagnosed with FL and treated with obinutuzumab between January 2020 and September 2021 were analyzed. RESULTS: The study group included 143 treatment-naïve patients with FL. The median age was 52 years (range: 28-89 years); 45.1% of patients had a high-risk disease as assessed using the Follicular Lymphoma International Prognostic Index (FLIPI). Induction chemotherapy included: O-CVP (obinutuzumab, cyclophosphamide, vincristine, prednisolone) in 49.0% of patients, O-CHOP (O-CVP plus doxorubicin) in 28.7% and O-BENDA (obinutuzumab, bendamustine) in 22.4%. Complete response (CR) and partial response (PR) rates were 69.9% and 26.5%, respectively. There was no difference in response rates between different regimens (p = 0.309). Maintenance was started in 115 patients (85.2%). In the 1st cycle, obinutuzumab was administered as a single 1000-milligram infusion in 47.9% of patients, whereas in 52.1%, initial infusions were split over 2 days (100 mg/900 mg). Infusion-related reactions were reported only during the 1st administration of obinutuzumab in 9.1% of patients, with a similar incidence in those receiving the total dose on a single day or split over 2 days (p = 0.458). The most common adverse events were hematological. Five patients died from coronavirus disease 2019 (COVID-19). CONCLUSION: The early responses to induction regimens and adverse events profile were similar for every type of induction treatment. The infusion-related reactions were rare and limited to the 1st dose of obinutuzumab.

The impact of recent chemotherapy on immunity in 2 COVID-19 cases with gastrointestinal tumors: A case report.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.