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Simple Summary: Immune checkpoint inhibitors (ICIs) are a type of immunotherapy used to treat a variety of cancers by helping a patient's own immune system to kill cancer cells. ICIs received their regulatory approval based on the results of large, randomized clinical trials. However, certain patient groups were excluded from these trials, so their outcomes are unknown. We performed a multicenter, retrospective study of real-world data in the United States in patients who had received at least one cycle of ICI treatment to evaluate the efficacy and safety of ICIs in patient groups underrepresented in clinical trials. Unique patient groups included age > 75 years, non-White race, positive smoking history, poor performance status, obesity, autoimmune diseases, chronic viral infections, multiple previous cancer therapies, or >three metastatic sites. Overall, ICIs were safe and efficacious in these patient groups. We noted that poor performance status and a history of multiple cancer therapies were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer immune-related adverse events. Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%—smokers, 30.4%—non-White, 22.8%—elderly, 20.8%—ECOG PS ≥ 2, 15.7%—history of AIDs, and 4.7%—history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs. [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of this study was to determine the prevalence of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) meeting high-risk criteria for early relapse after CD19 CAR T-cell therapy (CART) who have disease encompassable in a standard radiation therapy (RT) plan (defined as <5 malignant lesions) and may benefit from bridging RT prior to CD19 CART., Materials and Methods: This is a single-center, retrospective study of patients with R/R NHL who received CD19 CART from 2018 to 2022. Eligible patients had pre-apheresis radiologic studies available. All patients were classified by number of lesions and history of high-risk disease criteria: bulky disease ≥10 cm, ≥1 extranodal (EN) sites, LDH ≥normal, or ≥1 lesion with SUVmax ≥10., Results: A total of 81 patients with R/R NHL were evaluated. Based on our definition, 40 (49%) patients would have been eligible for bridging RT, including 38 patients who met high-risk criteria: 31 with ≥1 EN site, 19 had ≥1 lesion with SUVmax ≥10, 16 with bulky disease, and 3 with elevated LDH. At 3 months after CART, ORRs in high-risk patients with <5 lesions, ≥5 lesions, and no lesions on pre-apheresis studies were 76% (CR 69%, PR 7%), 70% (CR 60%, PR 10%), and 80% (CR 80%), respectively., Conclusion: Approximately 47% (38/81) of patients were classified as at high risk of relapse after CART with disease encompassable in a standard radiation plan and eligible for bridging RT studies., Competing Interests: KA: RefleXion Medical: Employee, Stock, and Stock Options. TF: Abbvie: Consultancy, Advisory Board, Speakers Bureau; ADC Therapeutics: Consultancy, Advisory Board; Astrazeneca: Consultancy, Advisory Board, Research Funding; Celgene/BMS: Speakers Bureau, Research Funding; Corvus: Research Funding; Daiichi Sakyo: Consultancy, Advisory Board, Research Funding; Eisai: Research Funding; Genmab: Consultancy, Advisory Board, Research Funding; Janssen Biotech, Inc.: Speakers Bureau; Juno: Research Funding; Karyopharm: Consultancy, Advisory Board; Kite, a Gilead Company: Consultancy, Advisory Board; Kymera: Research Funding; MorphoSys: Consultancy, Advisory Board; Research Funding; Pharmacyclics LLC: Speakers Bureau; Portola: Research Funding; Poteligeo: Speakers Bureau; SecuraBIO: Consultancy, Advisory Board; Seattle Genetics: Speakers Bureau, Research Funding; Takeda: Speakers Bureau; Tessa: Research Funding; Genomic Testing Cooperative: Other: Equity holder in privately-traded company. AG: Janssen: Membership on an entity’s Board of Directors, Advisory Board, Research Funding; Advisory Board, Honoraria; AbbVie/Pharmacyclics: Advisory Board, Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity’s Board of Directors, Advisory Board, Research Funding; AstraZeneca: Advisory Board, Honoraria, Research Funding to Institution, Membership on an entity’s Board of Directors; Acerta: Membership on an entity’s Board of Directors, Honoraria, Research Funding; Bristol Meyers Squibb/Celgene: Advisory Board, Consultancy, Honoraria, Research Funding; Constellation: Research Funding; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment, Research Funding; Hoffman la Roche: Consultancy, Research Funding, Honoraria; Infinity/Verastem: Research Funding; Karyopharm: Research Funding; Xcenda: Honoraria, Consultancy; Vincerx: Honoraria, Advisory Board; Michael J Hennessey Associates INC: Honoraria; OncLive Peer Exchange: Honoraria; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privatelyheld company, Membership on an entity’s Board of Directors, Other: Leadership role; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity’s Board of Directors, Other: Leadership role; Practice Update Oncology: Consultancy, Honoraria; Physicians’ Education Resource: Honoraria, Consultancy; Novartis: Honoraria; Clinical Advances in Hematology/Oncology: Honoraria; 3rd GCC Hematoogy Expert Forum: Consultancy; Alloplex: Advisory Board, Honoraria; Peer Review: Membership on an entity’s Board of Directors. AI: Merck: Current holder of stock options in a privately-held company; COTA: Current holder of stock options in a privately-held company; MJH Life Sciences: Honoraria; TG Therapeutics: Consultancy, Advisory Board; Secura Bio: Consultancy, Advisory Board; AstraZeneca: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genomic Testing Cooperative: Other: Equity holder in privatelytraded company. SR: ReAlta Life Sciences: Consultancy; SIR-Pant Immunotherapeutics: Advisory Board; COTA: Stock; Genomic Testing Cooperative: Stock. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Danish, Della Pia, Fogel, Alkhatatneh, Zhao, Varughese, Al Feghali, Pascual, Sinclaire, Marafelias, Zenreich, Kuo, Feldman, Zhang, Goy, Ip and Rowley.)

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients ( n  = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1-21) and ibrutinib 560 mg (days 1-28) of 28-day cycles. The MTD for lenalidomide was 20 mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92 months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67 > 30%). R2I was safe and tolerable in patients with R/R MCL.