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Objectives: This final post hoc analysis evaluated patient-reported outcomes from the Phase 3 MAIA study of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) after median 64.5-month follow-up in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), including patient subgroups., Methods: Key scales from the EORTC QLQ-C30 (global health status [GHS], physical functioning, pain, and fatigue) were assessed. Scores were evaluated every 3 months for 1 year, then every 6 months until disease progression., Results: The intent-to-treat population (n = 737) included 46.3% frail, 35.4% 70 to < 75 years old, and 43.6% ≥ 75 years old. D-Rd-treated patients showed improvements from baseline that were sustained over 5 years in the intent-to-treat population and across subgroups by age, frailty, and bone lesions. Greater proportions of patients treated with D-Rd versus Rd achieved minimally important changes for improvement at cycle 36 (year ~3) in GHS (odds ratio, 1.84 [95% CI, 1.16-2.91]), physical functioning (1.93 [1.18-3.14]), pain (1.41 [0.90-2.22]), and fatigue (2.00 [1.24-3.23]). Greater proportions of patients with bone lesions improved with D-Rd versus Rd on GHS and physical functioning., Conclusions: In transplant-ineligible patients with NDMM, D-Rd improved health-related quality of life over a 5-year period versus Rd., Trial Registration: ClinicalTrials.gov: NCT02252172., (© 2025 Johnson and Johnson. European Journal of Haematology published by John Wiley & Sons Ltd.)

Patients with relapsed/refractory multiple myeloma (RRMM) have a poor prognosis and a need remains for novel effective therapies. Belantamab mafodotin, an anti-B-cell maturation antigen antibody-drug conjugate, was granted accelerated/conditional approval for patients with RRMM who have received at least 4 prior lines of therapy, based on response rates observed in DREAMM-1/DREAMM-2. Despite the 41% response rate and durable responses observed with belantamab mafodotin in the Phase III confirmatory DREAMM-3 trial, the marketing license for belantamab mafodotin was later withdrawn from US and European markets when the trial did not meet its primary endpoint of superiority for progression-free survival compared with pomalidomide and dexamethasone. This review reflects on key lessons arising from the clinical journey of belantamab mafodotin in RRMM. It considers how incorporating longer follow-up in DREAMM-3 may have better captured the clinical benefits of belantamab mafodotin, particularly given its multimodal, immune-related mechanism of action with responses deepening over time. A non-inferiority hypothesis may have been more appropriate rather than superiority in the context of a monotherapy versus an active doublet therapy. Further, anticipation of, and planning for, non-proportional hazards arising from response heterogeneity may have mitigated loss of statistical power. With the aim of improving the efficacy of belantamab mafodotin, other Phase III trials in the RRMM development program (DREAMM-7 and DREAMM-8) proceeded to evaluate the synergistic potential of combination regimens in earlier lines of treatment. The aim was to increase the proportion of patients responding to belantamab mafodotin (and thus the likelihood of seeing a clear separation of the progression-free survival curve versus comparator regimens). Protocol amendments reflecting DREAMM-3 learnings could also be implemented prospectively on the combinations trials to optimize the follow-up duration and mitigate risk. The wider implications of the lessons learned for clinical research in RRMM and in earlier treatment settings are discussed., Competing Interests: Competing interests: PM, HAA, JBO, PP, and ER are employees of, and hold financial equities in GSK. SL reports grant funding and personal fees from Celgene and Takeda and personal fees from Novartis, Bristol-Myers Squibb, GSK, Amgen, Merck, and Janssen. KW has received honoraria from Abbvie, Amgen, Adaptive Biotech, AstraZeneca, BMS/Celgene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Stemline, and Takeda; consulting or advisory fees from Abbvie, Amgen, Adaptive Biotech, BMS/Celgene, Janssen, GSK, Karyopharm, Oncopeptides, Pfizer, Roche Pharma, Sanofi, and Takeda, and research funding from Abbvie, Amgen, BMS/Celgene, Janssen, GSK, and Sanofi. ST has received honoraria from Amgen Canada, Janssen Biotech, Pfizer, and Sanofi; has received grant funding from Amgen Inc, and Bristol-Myers Squibb, and has received research funding from Bristol-Myers Squibb, Genentech, GSK, Janssen, Pfizer and Roche; has acted as a consultant for Bristol-Myers Squibb, GSK, Roche, and Sanofi. MVM has received speakers fees from Amgen, Celgene, GSK, Janssen, Pfizer, Sanofi Pasteur, Takeda Oncology; participated in advisory boards for Celgene, GSK, Janssen, Pfizer, Regeneron Pharmaceuticals, and Sanofi Pasteur, and acted as a consultant for Hoffmann-La Roche, Kite Pharma, and Stemline Therapeutics. MAD has received fees from speaker’s bureau participation from Amgen, Beigene, BMS, Janssen, and Takeda., (© 2025. The Author(s).)

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies. The International Myeloma Working Group conveyed panel of experts to review patient and disease-related factors affecting efficacy and safety of immunotherapy, summarize existing information on sequencing therapy and provide a series of core recommendations., Competing Interests: Competing interests: LJC: Honoraria (Amgen, Bristol-Myers-Squibb, AbbVie, Pfizer, Johnson & Johnson, Adaptive Biotechnologies, Sanofi, Genentech/Roche), Research Funding (Amgen, Bristol-Myers-Squibb, Johnson & Johnson, AbbVie, Caribou, Gracell, Genentech/Roche); RB: Honoraria (Bristol-Myers-Squibb, Pfizer, Adaptive Biotechnologies, Caribou, Genentech/Roche, GSK, Karyopharm, Legend Biotech, Johnson & Johnson, SparkCures), Research Funding (AbbVie, Bristol-Myers-Squibb, Johnson & Johnson, Novartis, Pack Health, Prothena, Sanofi); HM: Honoraria (Bristol-Myers-Squibb, Pfizer, GSK, Karyopharm, AbbVie) Research Funding (Pfizer); SB: Honoraria (AbbVie, Adaptive Biotechnologies, Bristol-Myers-Squibb, Johnson & Johnson, MJH Lifesciences); BD: Honoraria (Sanofi, Johnson & Johnson, Canopy, COTA, Bristol-Myers-Squibb) Research Funding (Amgen, GSK); CN: Honoraria (Johnson & Johnson); JR: Honoraria (Janssen, Bristol-Myers-Squibb, Pfizer, Karyopharm, Sanofi, Takeda, Genentech, AbbVie, Regeneron, Forus, Menarini, Adaptive Biotechnologies); KW:Honoraria (Abbvie, Amgen, Adaptive Biotech, Astra Zeneca, Beigene, BMS, Celgene, Janssen, GSK, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, Takeda) Research Funding (Amgen, BMS/Celgene, Janssen, Sanofi; GSK, Abbvie) Consultancy (Abbvie, Amgen, Adaptive Biotech, Beigene, BMS, Celgene, Janssen, GSK, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Takeda); MJF: Honoraria (Kite/Gilead, CMS, Novartis, Janssen, Legend, Cytoagents, SITC); JCY: Honoraria (Janssen, Sanofi, Bristol-Myers-Squibb, Regeneron, GSK, Pfizer, Menarini); NWCJvdD: Honoraria (Janssen, Amgen, Celgene, Novartis, Cellectis, Bristol-Myers-Squibb/Celgene, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive, Pfizer, AbbVie, Servier) Research Funding (Janssen, Amgen, Bristol-Myers-Squibb/Celgene, Novartis, Cellectis); NB: Honoraria (AbbVie, Amgen, Bristol-Myers-Squibb, Forus, Genentech, GlaxoSmithKline, Janssen, Pfizer, Sanofi, Takeda) Research Funding (Pfizer); RP: Honoraria (GSK, Pfizer, Janssen, Bristol-Myers-Squibb, Abbvie, Roche) Research Funding (GSK, Pfizer); W-JC: Honoraria (AbbVie, Amgen, Pfizer, Sanofi, Regeneron, GSK, Novartis) Research Funding (Bristol-Myers-Squibb, Janssen, Novartis); PJH: Advisory Board without honoraria (Antengene, Gilead, iTeos Therapeutics, GSK, Janssen, Pfizer), Research Funding: Novartis; GK: Honoraria (Janssen, Bristol-Myers-Squibb, Sanofi, Kite, Arcellx, Pfizer, Kedrion, Cellectar); PK: Research Funding (Takeda Pharmaceuticals, Celgene, Sanofi, AbbVie, Karyopharm Therapeutics, Sorrento Therapeutics, Ichnos Sciences, Amgen); FS: Honoraria (AbbVie, GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi, Bristol-Myers-Squibb, Novartis, SkyliteDX, Pfizer, Daiki-Sankyo,); JB: Honoraria (AstraZeneca, Bristol-Myers-Squibb, Caribou Biosciences, Galapagos, Janssen, K36 Therapeutics, Kite Pharma, Legend Biotech, Pfizer, Regeneron, Roche, Sanofi, Sebia, Takeda) Research Funding (2 Seventy Bio, Abbvie, Amgen, Bristol-Myers-Squibb, C4 Therapeutics, Caribou Biosciences, CARsgen, Cartesian Therapeutics, Celularity, CRISPR Therapeutics, Fate Therapeutics, Genentech, GSK, Ichnos Sciences, Incyte, Janssen, Juno Therapeutics, K36 Therapeutics. Karyopharm, Lilly, Novartis, Poseida, Roche, Takeda); HE: Honoraria (Bristol-Myers-Squibb, Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, Novartis, Roche), Research Funding (BMS/Celgene, Janssen, Sanofi; GSK, Amgen) Consultancy (Amgen, BMS, Celgene, Janssen, GSK, Novartis, Roche, Sanofi, Takeda); ADC: Honoraria (GSK; Bristol-Myers-Squibb, Janssen, AbbVie, Pfizer, iTeos, Ichnos, Arcellx, Legend; Genentech/Roche, Novartis, AstraZeneca, Kite); Research Funding (GSK, Genentech, Janssen, BMS); Patent (Novartis); JM: Honoraria (Amgen, Sanofi, Bristol-Myers-Squibb, Janssen, Takeda); YL: Honoraria (Janssen, Sanofi, NexImmune, Caribou, Bristol-Myers-Squibb, Pfizer, Regeneron, Genentech; Sanofi, Regeneron) Research Funding (Janssen, Bristol-Myers-Squibb); TGM: Honoraria (GSK, Sanofi, Amgen, Janssen); AC: Honoraria (AbbVie, Adaptive biotechnologies, Amgen, Angengene, Bristol-Myers-Squibb, Forus, Genentech/Roche, GSK, Janssen, Karyopharm, Millenium/Takeda, Sanofi). The remaining authors declare no conflict of interest. The work presented in this manuscript did not receive any financial or material support., (© 2025. The Author(s).)

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.5 months), transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR) and measurable residual disease (MRD)-negativity rate (10 -5 ). PFS favored D-Rd versus Rd in most subgroups, including patients aged ≥75 years (HR, 0.59; 95% CI, 0.44-0.79), frail patients (HR, 0.64; 95% CI, 0.48-0.85), patients with high-risk cytogenetics (HR, 0.59; 95% CI, 0.44-0.80), and patients with isolated gain(1q21) (HR, 0.36; 95% CI, 0.19-0.67). ORRs, MRD-negativity rates, and sustained (≥12 months) MRD-negativity rates were higher with D-Rd versus Rd across subgroups. In patients aged ≥75 years, rates of grade 3/4 and serious treatment-emergent adverse events (TEAEs) were similar for D-Rd and Rd, but discontinuation due to TEAEs was lower for D-Rd. Results support use of D-Rd for high-risk patients, supporting D-Rd as a standard of care for transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as NCT02252172., Competing Interests: Competing interests: PM served on an advisory board for and received honoraria from Janssen, Celgene, Amgen, AbbVie, Sanofi, and Oncopeptides. TF has nothing to disclose. SZU received research funding from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Merck, Pharmacyclics, Sanofi, Seattle Genetics, SkylineDx, and Takeda; served in a consulting role for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Edo Pharma, Genentech, Gilead, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, Seattle Genetics, Secura Bio, SkylineDx, Takeda, and TeneoBio; and served on a speakers bureau for Amgen, Bristol Myers Squibb, Janssen, and Sanofi. NB served in a consulting or advisory role for and received honoraria from AbbVie, Bristol Myers Squibb/Celgene, FORUS, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, and Takeda; and received research funding from Pfizer and Celgene. NR served as a consultant for Bristol Myers Squibb, Janssen, Takeda, Amgen, and GlaxoSmithKline; and received research funding from bluebird bio. TP served as an advisor for Janssen, Celgene, Takeda, Oncopeptides, Genentech, CSL Behring, and AbbVie; and received research support from Janssen, Genmab, Celgene, Takeda, Oncopeptides, Genentech, AbbVie, and Roche. RZO received research funding from Asylia Therapeutics, Biotheryx, Heidelberg Pharma, CARsgen, Celgene/Bristol Myers Squibb, Exelixis, Janssen, Sanofi-Aventis, and Takeda; received honoraria from and served as a member on a board of directors or advisory committee for AbbVie, Biotheryx, Bristol Myers Squibb, Janssen, Karyopharm, Meridian Therapeutics, Monte Rosa Therapeutics, Neoleukin, Oncopeptides, Regeneron, Sanofi-Aventis, and Takeda; and holds stock in Asylia Therapeutics. SB served as a consultant and on a speakers bureau for Sanofi, Pfizer, and Bristol Myers Squibb. HN is an employee of Genmab. CH received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, and AbbVie. HQ served as a consultant for and received research funding from AbbVie, Bristol Myers Squibb, Karyopharm, Amgen, GlaxoSmithKline, and Antengene. HG received grants and/or provisions of Investigational Medicinal Product from Amgen, Array BioPharma/Pfizer, Bristol Myers Squibb/Celgene, Chugai, Dietmar Hopp Foundation, Janssen, Johns Hopkins University, Mundipharma, and Sanofi; received research support from Amgen, Bristol Myers Squibb, Celgene, GlycoMimetics, GlaxoSmithKline, Heidelberg Pharma, Roche, Karyopharm, Janssen, Incyte, Millennium Pharmaceuticals, Molecular Partners, Merck Sharp & Dohme, MorphoSys AG, Pfizer, Sanofi, Takeda, and Novartis; served on an advisory board for Amgen, Bristol Myers Squibb, Janssen, Sanofi, and Adaptive Biotechnologies; received honoraria from Amgen, Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer; and received support for attending meetings and/or travel from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Sanofi, and Pfizer. MO served as a consultant for Janssen. AP received honoraria from AbbVie, Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Sanofi, and Takeda; served as a member on a board or advisory committee for Amgen, Celgene/Bristol Myers Squibb, GlaxoSmithKline, Janssen, Pfizer, and Takeda; and received research funding from Takeda. CPV received honoraria from Janssen, Bristol Myers Squibb, Sanofi, FORUS, Pfizer, AbbVie, GlaxoSmithKline, and Amgen. KW received research funding from Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Sanofi, Stemline, and Takeda; received honoraria from AbbVie, Amgen, Adaptive Biotechnologies, AstraZeneca, Bristol Myers Squibb/Celgene, BeiGene, Janssen, GlaxoSmithKline, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and received travel support from Janssen, GlaxoSmithKline, and Sanofi. MT has nothing to disclose. MM served on an advisory board for Celgene/Bristol Myers Squibb, Janssen, Takeda, Amgen, GlaxoSmithKline, and Sanofi; received research funding from Janssen and Takeda; and received accommodations from Janssen, Celgene/Bristol Myers Squibb, Takeda, Amgen, and Sanofi. LF received honoraria from Janssen, Sanofi, Amgen, and Takeda; and received funding from Janssen and Amgen. XL received honoraria, research support, and consulting fees from Amgen, Merck, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Oncopeptides, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutics, Regeneron, and iTeos. GW, HP, and FB are employees of Janssen and hold stock in Johnson & Johnson. MK and RC are employees of Janssen. SKK received research funding from AbbVie, Amgen, Allogene, AstraZeneca, Bristol Myers Squibb, CARsgen, GlaxoSmithKline, Janssen, Novartis, Roche-Genentech, Takeda, Regeneron, and Molecular Templates; participated in consulting or an advisory board (with no personal payments) for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Roche-Genentech, Takeda, AstraZeneca, bluebird bio, Epizyme, Secura Bio, Monte Rosa Therapeutics, Trillium, Loxo Oncology, K36, Sanofi, and Arcellx; and participated in consulting or an advisory board (with personal payments) for Oncopeptides, BeiGene, Antengene, and GLH Pharma., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Although survival rates for patients with newly diagnosed multiple myeloma (NDMM) have improved over recent decades, multiple myeloma (MM) remains without a cure for most. There is increasing consensus that achievement of deep remissions, especially minimal residual disease negativity (MRD -), in frontline treatment is crucial and translates into improved survival. The standard of care (SOC) for NDMM consists at minimum of a triplet regimen of therapies, with or without an autologous stem cell transplant, or a doublet regimen for certain ineligible, particularly frail patients who may have specific limitations. Recently, anti-CD38 monoclonal antibodies (mAbs), such as daratumumab (Dara) or isatuximab (Isa), have been integrated into frontline SOC regimens. Seeking to further deepen and prolong responses, several clinical trials have commenced investigating the addition of anti-CD38 mAbs to carfilzomib, lenalidomide, and dexamethasone (KRd). These quadruplet regimens (Isa/Dara-KRd) are being evaluated in the context of evolving treatment considerations for the heterogeneous population of patients with NDMM. In clinical trials, the addition of Isa/Dara to KRd achieved high rates of deep responses and MRD - . Favorable outcomes were observed in patients with NDMM independent of age, transplant eligibility, and cytogenetic risk, while these treatments did not result in unexpected or emergent safety risks. The efficacy observed with intensified, yet well-tolerated therapy may offer further development of risk- and response-adapted therapy for individualized patient needs. This review summarizes the clinical outcomes of quadruplet-based therapy with Isa/Dara-KRd in NDMM., Competing Interests: Declarations. Ethics Approval: N/A. Consent: N/A Competing Interests: L.J.C. received research funding from Amgen, BMS, Caribou, Genentech, and Janssen; and honoraria from Adaptive Biotechnologies, Amgen, BMS, Janssen, and Pfizer. F.G. reports consulting fees from Amgen, BMS, Oncopeptides, Pfizer, and Roche; honoraria from AbbVie, Amgen, BMS, Janssen, Sanofi, and Takeda; and data safety monitoring or advisory board participation from AbbVie, Amgen, BMS, Janssen, Oncopeptides, Pfizer, Roche, Sanofi, and Takeda. O.L. acknowledges funding from Amgen, Celgene, FDA, Glenmark, IMF, Janssen, Karyopharm Therapeutics, LLS, MMRF, Myeloma Solutions Fund, NCI/NIH, Paula and Rodger Riney Foundation, Perelman Family Foundation, Rising Tide Foundation, Seattle Genetics, Takeda, and Tow Foundation; honoraria for scientific talks/participation in advisory boards for AbbVie, Adaptive, Amgen, Binding Site, BMS, Celgene, GSK, Janssen, Juno, and Pfizer; and serving on Independent Data Monitoring Committees (IDMCs) for international randomized trials by Janssen, Merck, Novartis, and Takeda. M-V.M. reports consulting fees from Amgen, GSK, Janssen, Seagen, and Takeda; honoraria and data safety monitoring or advisory board participation from AbbVie, Amgen, Celgene, GSK, Janssen, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, and Takeda. P.M. reports advisory board participation and honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Pfizer, Sanofi, and Takeda. C.T. received honoraria from and served in a consulting or advisory role for AbbVie, Amgen, Celgene, Janssen, and Takeda; and had travel, accommodations or other expenses paid or reimbursed by AbbVie, Amgen, Janssen, and Takeda. F.E., I.M., and R.N. are employees of Amgen. K.W. has served in a consulting or advisory role for Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Janssen-Cilag, Karyopharm Therapeutics, Oncopeptides, Roche, Sanofi, and Takeda; received travel, accommodations, and/or expenses from Amgen, BMS, Celgene, GSK, Janssen-Cilag, and Takeda; honoraria from AbbVie, Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Janssen-Cilag, Karyopharm Therapeutics, Novartis, Oncopeptides, Pfizer, Roche/Genentech, Sanofi, and Takeda; and research funding from Amgen, BMS, Celgene, GSK, Janssen-Cilag, and Sanofi., (© 2025. The Author(s).)

Objective: Analyze the outcomes of critically ill patients who developed new-onset organ dysfunction and received systemic chemotherapy during their ICU stay., Design: Retrospective cohort study., Setting: A tertiary medical center in Germany with an Intensive Care Medicine department consists of 11 intensive care units comprising 140 beds, serving all subspecialties of adult intensive care medicine., Patients: 167 patients receiving systemic oncological treatment from January 1st, 2015 to December 31st, 2021, with a data cut-off on December 31st, 2022., Interventions: None., Measurements and Main Results: A total of 167 patients were included. The primary reasons for ICU admission were respiratory failure and shock/sepsis, each accounting for 34% of cases, while complications associated with oncological therapy accounted for less than 8%. The median age of hematological patients (n = 129) was 62 years (IQR 50-70), and for solid tumor patients (n = 38), it was 60 years (IQR 52-65). Predominant disease entities included lymphoma (43%) and acute myeloid leukemia (29%) among hematological patients, and lung cancer (47%) and gastrointestinal malignancies (17%) among solid tumor patients. Hematological patients had a significantly higher median Simplified Acute Physiology Score II (47 vs. 39 points; p=0.013), a higher need for invasive mechanical ventilation (59% vs. 50%; p=0.3), renal replacement therapy (54% vs. 24%; p < 0.001), and a higher 1-year mortality rate (64% vs. 53%; p=0.2) compared to solid tumor patients. The hazard ratio for 1 year survival for male sex was 2.34 (1.31-3.49), for mechanical ventilation 2.01 (1.33-3.04), for vasopressor therapy 1.98 (1.27-3.10), and for renal replacement therapy 1.51 (1.03-2.23), respectively., Conclusion: Administering intravenous chemotherapy in an ICU setting remains challenging, and the experience to establish an indication for systemic chemotherapy is still challenging. However, the study demonstrates that, after careful interdisciplinary decision-making, a substantial number of patients can benefit from it., Competing Interests: The 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 © 2025 Karagiannis, Klingler, Arelin, Alsdorf, König, Roedl, Fiedler, Weisel, Kluge, Bokemeyer and Wichmann.)

Background: In CARTITUDE-4, ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (primary endpoint; previously reported) versus standard of care in patients with relapsed, lenalidomide-refractory multiple myeloma. We report here patient-reported outcomes., Methods: In the ongoing, phase 3, open-label CARTITUDE-4 study, patients were recruited from 81 sites in the USA, Europe, Asia, and Australia, and were randomly assigned 1:1 to cilta-cel (target, 0·75 × 10 6 CAR-T cells/kg) or standard of care (daratumumab, pomalidomide, and dexamethasone; pomalidomide, bortezomib, and dexamethasone). Eligible patients had relapsed, lenalidomide-refractory multiple myeloma, received one to three previous treatment lines including a proteasome inhibitor and an immunomodulatory drug, and had an ECOG performance status of 0 or 1. Secondary endpoints reported here include time to sustained worsening of symptoms (Multiple Myeloma Symptom and Impact Questionnaire [MySIm-Q]; a key secondary endpoint) and change in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core C30 (intention-to-treat population) and EuroQol 5-Dimension 5-Level (EQ-5D-5L; intention-to-treat population). This study is registered with ClinicalTrials.gov number NCT04181827 and is ongoing., Findings: Patients were enrolled from July 10, 2020, to Nov 17, 2021, and 419 of 516 screened patients were randomly assigned (cilta-cel, n=208; standard of care, n=211; median follow-up, 15·9 months [IQR 12·4 to 17·8]); median age was 61 years. 191 (92%) of 208 patients in the cilta-cel group and 190 (91%) of 209 evaluable patients in the standard- of-care group completed baseline assessments. MySIm-Q compliance post-baseline was 70 to 81% (cilta-cel) and 79 to 89% (standard of care). MySIm-Q median time to sustained symptom worsening with cilta-cel versus standard of care was 23·7 versus 18·9 months (HR 0·42; 95% CI 0·26 to 0·68). 12-month mean changes for EORTC global health status (GHS) were +10·1 (95% CI 7·0 to 13·1) and -1·5 (95% CI -5·3 to 2·3) points and were +8·0 (95% CI 5·2 to 10·7) and +1·4 (95% CI -1·9 to 4·7) points for EQ-5D-5L visual analogue scale (VAS). Rates of clinically meaningful improvements in GHS and VAS were higher with cilta-cel than with standard of care., Interpretation: Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease., Funding: Janssen Research & Development, Legend Biotech USA., Competing Interests: Declaration of Interests RM reports a consulting or advisory role or honoraria for Amgen, BMS–Celgene, GSK, Janssen, Menarini-Stemline, Pfizer, Sanofi, and Takeda. HY reports honoraria for Astellas. WA reports honoraria, research funding, or travel expenses from Affimed, BioNTech, GSK, Immatics, and Janssen. MCM reports consulting or advisory roles, honoraria, speaker's bureau, or research funding from BeiGene, CDR life, GSK, Pfizer, Siemens, and Janssen Medicine, and hospitality from Janssen. LS reports consulting or advisory roles for BMS and Johnson & Johnson. II reports a consulting role for AbbVie, ADC Therapeutics, Beam Therapeutics, Genmab, Gilead, and Incyte; and holds equity in Gilead. SJH reports consulting or advisory roles, honoraria, research funding, or speaker's bureau for AbbVie, Amgen, Celgene–BMS, Eusa, F Hoffmann-La Roche–Genentech, GSK, Haemalogix, Janssen, Novartis, and Terumo BCT. UAS reports research funding from BMS, and Janssen and consulting or advisory roles with BMS, Janssen, and Sanofi. JMS has stock and other ownership interests in Johnson & Johnson; and is employed by Janssen. MV is employed by Janssen. NL has stock options in Janssen; and is employed by Janssen. KSG has equity and stock options in Janssen and is employed by Janssen. EGK has equity and stock options in Janssen and is employed by Janssen. AS has equity and stock options in Janssen and is employed by Janssen. CL is employed by Janssen. JG is employed by Janssen. QL is employed by Janssen. WD is employed by Janssen. OCF has equity in Legend and is employed by Legend. EF is employed by Legend. NP has equity in Legend; and is employed by Legend. LK reports a consulting role or honoraria for AbbVie, Amgen, Celgene, GSK, Janssen, Sanofi, and Takeda. KW reports a consulting role, honoraria, or research funding for AbbVie, Amgen, Adaptive Biotech, AstraZeneca, BeiGene, BMS–Celgene, GSK, Janssen, Karyopharm, Menarini, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda. AKM and HM declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The complex and heterogeneous genomic landscape of multiple myeloma (MM) and many of its clinical and prognostic implications remains to be understood. In other cancers, such as breast cancer, using whole-exome sequencing (WES) and molecular signatures in clinical practice has revolutionized classification, prognostic prediction, and patient management. However, such integration is still in its early stages in MM. In this study, we analyzed WES data from 35 MM patients to identify potential mutational signatures and driver mutations correlated with clinical and cytogenetic characteristics. Our findings confirm the complex mutational spectrum and its impact on previously described ontogenetic and epigenetic pathways. They show TYW1 as a possible new potential driver gene and find no significant associations of mutational signatures with clinical findings. Further studies are needed to strengthen the role of mutational signatures in the clinical context of patients with MM to improve patient management.

Objectives: The seroprevalence of antibodies against Cytomegalovirus (CMV) is an established poor prognostic factor for patients receiving an allogeneic stem cell transplantation. However, the impact of CMV serology on outcome after autologous stem cell transplantation remains unknown., Methods: Here, we analyzed the CMV immunoglobulin (Ig) serology of 446 newly-diagnosed multiple myeloma (MM) patients of the GMMG-MM5 phase III trial with a median follow-up of 58 months., Results: CMV IgG and IgM positivity was seen in 51% and 6% of the patients, respectively. In multivariate analysis CMV IgG and CMV IgM serology show an age-depending effect for PFS. We identified positive CMV IgG/positive CMV IgM serology as an age-depending beneficial factor on PFS., Discussion: Younger patients with a positive CMV IgG/positive CMV IgM serology experienced a favorable effect on PFS, whereas a positive CMV IgG/positive CMV IgM serology at older age has a disadvantageous effect on PFS.

Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.1-35.0). Patients (N  =  248) had received median 4 prior LOT (range, 2-13) at enrollment. 91 unique regimens were used in index LOT. Overall response rate was 31.9% (95% CI, 26.1-38.0), median progression-free survival (PFS) was 4.6 months (95% CI, 3.9-5.6) and median overall survival was 13.8 months (95% CI, 10.8-17.0). 152 patients (61.3%) had subsequent LOTs with 134 unique regimens, of which 78 were used in first subsequent LOT. Median PFS2 (from start of study through first subsequent LOT) was 10.8 months (95% CI, 8.4-13.0). 158 patients died on study, 67.7% due to progressive disease. Additional subgroup analyses and long-term safety summaries are reported. The high number of RWCP treatment regimens utilized and poor clinical outcomes confirm a lack of standardized treatment for TCE patients with RRMM, highlighting the need for new treatments with novel mechanisms., Competing Interests: Competing interests: M-VM has received honoraria from or served on the board of directors/advisory committees for AbbVie, Adaptive Biotechnologies, Amgen, BMS/Celgene, GSK, Janssen, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Seagen, and Takeda. KW has served as a consultant and received honoraria from Adaptive Biotechnologies, Karyopharm, and Takeda; has received honoraria from Roche; and has received honoraria and served as a member on boards of directors and/or advisory committees for Amgen, BMS, Celgene, GSK, Janssen, Oncopeptides, and Sanofi. VDS has served on an advisory board or speakers’ bureaus and received honoraria from AbbVie, Alexion, AOP Health, argenx, BMS, GSK, Grifols, Leo Pharma, Novartis, Novo Nordisk, Sanofi, SOBI, and Takeda. HG has served as a consultant for Amgen, Novartis, and Takeda; has served as a consultant and received honoraria, grants, and/or provision of investigational medicinal product and research funding from Amgen, BMS, Celgene, Chugai, Janssen, and Sanofi; has received research funding from Incyte, Molecular Partners, MSD, Mundipharma, and Novartis; and has received other grants from Dietmer Hopp Foundation. MD has received honoraria from Amgen, BMS, GSK, and Janssen; and has served on the speakers’ bureau for Janssen. MM has received honoraria from Adaptive Biotech, Amgen, Astellas, BMS, Gilead, Novartis, Pfizer, and Takeda; and has received honoraria/research funding from Celgene and Sanofi. JL-H has no relationships to disclose. DD is an employee/consultant/honoraria/member of board of directors/advisory committees for Janssen Cilag; and a member of the board of directors/advisory committees/received research funding from Celgene. EA has no relationships to disclose. LV has served on the advisory board of BMS, Janssen, and Takeda. AP has received honoraria from or has served in a consulting/advisory role for AbbVie, Amgen, BMS, Janssen, Pfizer, Sanofi, and Takeda. RB has received honoraria/research funding from Allogene, BMS, Gilead, Janssen, and Servier. NWCJvdD has received research funding from AbbVie, Amgen, BMS, Celgene, Cellectis, Janssen Pharmaceuticals, and Novartis; and has served in a consulting/advisory role for Adaptive, Amgen, Bayer, BMS, Celgene, Janssen, Novartis, Pfizer, Roche, Sanofi, Servier, and Takeda. EMO has received honoraria from or has served in a consulting/advisory role for AbbVie, Amgen, BMS, GSK, Janssen, Karyopharm, Menarini, Oncopeptides, Pfizer, Sanofi, and Takeda. TR is a former Janssen employee. JMS is a Janssen employee. SK is a Janssen employee. IH is a Janssen employee. VS is a Janssen employee. LM is a Janssen employee. JB is a Janssen employee. OCF is an employee of Legend Biotech USA Inc. HE has received research funding or honoraria and has served in a consulting/advisory role for Amgen, BMS/Celgene, GSK, Janssen, and Sanofi. PM has received honoraria and/or served on advisory boards for AbbVie, Amgen, Celgene, Janssen, Sanofi, and Takeda., (© 2024. The Author(s).)

Aberrant alternative splicing (AS) is a prominent hallmark of cancer. AS can perturb protein-protein interactions (PPIs) by adding or removing interface regions encoded by individual exons. Identifying prognostic exon-exon interactions (EEIs) from PPI interfaces can help discover AS-affected cancer-driving PPIs that can serve as potential drug targets. Here, we assessed the prognostic significance of EEIs across 15 cancer types by integrating RNA-seq data with three-dimensional (3D) structures of protein complexes. By analyzing the resulting EEI network we identified patient-specific perturbed EEIs (i.e., EEIs present in healthy samples but absent from the paired cancer samples or vice versa) that were significantly associated with survival. We provide the first evidence that EEIs can be used as prognostic biomarkers for cancer patient survival. Our findings provide mechanistic insights into AS-affected PPI interfaces. Given the ongoing expansion of available RNA-seq data and the number of 3D structurally-resolved (or confidently predicted) protein complexes, our computational framework will help accelerate the discovery of clinically important cancer-promoting AS events., (© The Author(s) 2024. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

The growing use of frontline lenalidomide treatment in multiple myeloma (MM) is increasing the proportion of lenalidomide-refractory patients, which may limit the efficacy of subsequent lines of treatment (LOT). This systematic literature review (January 2008-October 2023) of clinical trials (CT) and real-world studies (RW) assessed treatment outcomes in adults with relapsed/refractory MM (RRMM) who were previously treated with ≥1 LOT, progressed and were lenalidomide-refractory. Medline, EMBASE and additional electronic databases were searched for articles published in English. Primary outcomes included progression-free survival (PFS), overall survival (OS) and overall/objective response rate (ORR); 24 CT and 19 RW were included. For CT, the population-weighted mean of median PFS (CT = 14) and OS (CT = 6) were shorter in the lenalidomide-refractory cohort (months: 8.8 [n = 2699] and 21.7 [n = 1066], respectively) than the intent-to-treat population (months: 13.8 [n = 5380] and 35.9 [n = 2264], respectively); the population-weighted (N = 2142) mean ORR for lenalidomide-refractory patients (CT = 18) was 56.0%. RW reported considerable variation in PFS (RW = 7), OS (RW = 8) and ORR (RW = 8); and median PFS (RW = 2; months) was lower in lenalidomide/bortezomib-refractory (5.5/5.5; n = 81/n = 25) versus lenalidomide-refractory (7.3/8.0; n = 81/n = 61) patients. These data provide evidence that clinical trials and real-world outcomes are suboptimal in lenalidomide-refractory patients with RRMM, highlighting the need to improve treatment options for this population., (© 2024 GSK and The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Measurement of overall survival (OS) remains the gold standard for interpreting the impact of new therapies for multiple myeloma in phase 3 trials. However, as outcomes have improved, it is increasingly challenging to use OS as the primary endpoint if timely approval of novel agents is to be ensured to enable maximum benefit for patients. Surrogate endpoints of OS, such as progression-free survival (PFS) and response to treatment, have contributed to approval decisions by the Food and Drug Administration (FDA) and European Medicines Agency as endpoints demonstrating clinical benefit, and the FDA has recently supported the use of minimal residual disease (MRD) as an accelerated approval endpoint in multiple myeloma. This review aims to address situations in which the use of PFS as a surrogate endpoint warrants careful interpretation especially for specific subgroups of patients and considers ways to ensure that studies can be designed to account for possible discordance between PFS and OS. The utility of subgroup analyses, including the potential for those not pre-specified, to identify target populations for new agents is also discussed., (© 2024. The Author(s).)

Background: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM., Methods: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles., Results: Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed., Conclusions: The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www., Clinicaltrials: gov as NCT03848845., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Chimeric antigen receptor (CAR) T-cell therapy has shown promise in patients with late-line refractory multiple myeloma, with response rates ranging from 73 to 98%. To date, three products have been approved: Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which are approved by the US Food and Drug Administration, the European Medicines Agency, Health Canada (ide-cel only), and Brazil ANVISA (cilta-cel only); and equecabtagene autoleucel (eque-cel), which was approved by the Chinese National Medical Products Administration. CAR T-cell therapy is different from previous anti-myeloma therapeutics with unique toxic effects that require distinct mitigation strategies. Thus, a panel of experts from the International Myeloma Working Group was assembled to provide guidance for clinical use of CAR T-cell therapy in myeloma. This consensus opinion is from experts in the field of haematopoietic cell transplantation, cell therapy, and multiple myeloma therapeutics., Competing Interests: Declaration of interests YL received consultancy fees from Janssen, Sanofi, NexImmune, Caribou, Bristol Myers Squibb (BMS), Pfizer, Regeneron, and Genentech; research fees from Janssen and BMS; serves on advisory boards for Janssen, Sanofi, BMS, Regeneron, and Genentech; serves on scientific advisory boards for NexImmune and Caribou; and serves on the data safety monitor board for Pfizer. LQ received consultancy fees from Beigene, Xi'an, Janssen, Pfizer, Sanofi, and AstraZeneca; and is on the speaker board for Beigene, Xi'an, Janssen, Pfizer, Sanofi, AstraZeneca, and Roche. SU receives consultancy fees from AbbVie, Amgen, BMS, EdoPharma, Genentech, Gilead, GlaxoSmithKline (GSK), Janssen, Karyopharm Therapeutics, Merck, Oncopeptides, Sanofi, Seagen, Secura Bio, SkylineDx, and Takeda; and received research funding from AbbVie, Amgen, Array Biopharma, BMS, EdoPharma, Genentech, Gilead, GSK, Janssen, Merck, Moderna, Pharmacyclics, Seagen, Sanofi, SkylineDx, Takeda, and TeneoBio. CWJ received honoraria from AbbVie, Amgen, BMS, Pfizer, Sanofi, Regeneron, GSK, and Janssen; and research funding from Novartis, Janssen, and BMS Celgene. LC received research grants from Amgen, Janssen, BMS, Genentech, Caribou, and AbbVie; and honoraria from Amgen, Janssen, AbbVie, Pfizer, Sanofi, and Adaptive Biotechnologies. BD received advisory board and consulting fees from Janssen and COTA; research fees from GSK and Amgen; honoraria from the Multiple Myeloma Research Foundation and Plexus Communications; and is an independent reviewer for BMS. HE has an advisory role for and received consulting fees from BMS Celgene, Janssen, Amgen, GSK, and Sanofi; and received research funding from BMS Celgene, Janssen, Amgen, GSK, and Sanofi. CFdL received institutional grants from BMS, Janssen, and Amgen; honoraria from Amgen, Jassen, BMS, GSK, and Sanofi; support for attending meetings or travel from Janssen, BMS, GSK, and Amgen; is on data safety monitoring or advisory boards for Janssen, BMS, Amgen, Pfizer, and Sanofi; and received funding from the Spanish Institute of Health, the Asociación Española Contra el Cancer (AECC), the “La Caixa” Foundation, and AGAUR. RH received grants from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda; consulting fees from Janssen, Amgen, Celgene, BMS, Novartis, Takeda, AbbVie, PharmaMar, Oncopeptides, Sanofi, and GSK; and honoraria from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda. PJH serves on advisory boards (honoraria not accepted) for Antengene, Gilead, iTeos Therapeutics, Janssen, Novartis, and Pfizer. EK received honoraria from Janssen, Pfizer, GSK, and Prothena; and research support to the institution from GSK, Janssen, and Pfizer. JM-L received consultancy fees from Janssen, BMS, Sanofi, GSK, Novartis, Menarini, Incity, Roche, Gilead, Pfizer, and Karyopharm; and research funding from BMS, Janssen, Incity, Amgen, and Pfizer. M-VM received honoraria for serving on advisory boards and received fees for lectures from Janssen, BMS Celgene, Novartis, GSK, Sanofi, Amgen, Pfizer, AbbVie, and Regeneron. JM received consultancy fees from Amgen, BMS, Janssen, Sanofi, and Takeda; and research funding from BMS Clinical Trial. PM serves on advisory boards and received honoraria from Janssen and BMS Celgene. CN received consultancy fees from Janssen, BMS, Sanofi, GSK, Pfizer, Amgen, AstraZeneca, and DKSH; and research funding from Janssen and Amgen. AN serves on advisory boards and received honoraria from Adaptive Biotechnologies, Amgen, BMS, Cellectar Biosciences, GSK, Janssen, K36 therapeutics, ONK therapeutics, Pfizer, Sanofi, and Takeda; received research grants from Aduro Biotech, Amgen, Arch Oncology, BMS, Cellectis, Genentech, GSK, Janssen, Karyopharm, Kite Pharma, Merck, Pfizer, and Takeda; and received grants for investigator initiated studies from Amgen, GSK, Janssen, Merck, and Takeda. FS received consultancy fees from AbbVie, GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi, and BMS; honoraria from Amgen, BMS, Takeda, AbbVie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, Pfizer, Daiki-Sankyo, and GSK; and research grants from Celgene, Janssen, Oncopeptides, Sanofi, GSK, and Targovax. SS received research grants from Magenta Therapeutics, BMS, Allogene, Jansse, Novartis, AbbVie, Sanofi, Oncopeptides, Takeda, Kite, and Regeneron; and consultancy fees from Magenta Therapeutics, BMS, Janssen, AbbVie, Sanofi, Oncopeptides, Takeda, Kite, and Regeneron. NWCJvdD received research grants from Janssen, Amgen, Celgene, Novartis, Cellectis, and BMS; and serves on advisory boards for Janssen, Amgen, Celgene, BMS, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive, Pfizer, AbbVie, and Servier (all paid to institution). KW received research grants from AbbVie, Amgen, BMS Celgene, Janssen, GSK, Sanofi, and Takeda; honoraria from AbbVie, Amgen, Adaptive Biotech, Astra Zeneca, BMS Celgene, BeiGene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Stemline, Takeda, and Menarini; and consulting fees from AbbVie, Amgen, Adaptive Biotech, BMS Celgene, BeiGene, Janssen, GSK, Karyopharm, Oncopeptides, Pfizer, Roche Pharma, Sanofi, Takeda, and Menarini. SZ serves on advisory boards for Janssen, BMS, Takeda, Sanofi, Oncopeptides, and Amgen (no personal fees). PRO received honoraria for consulting or advisory board from BMS Celgene, Janssen, Roche, AbbVie, Pfizer, GSK, Sanofi, H3Biomedicine; travel grants from Pfizer; serves on steering committees for BMS Celgene, Regeneron, and Janssen; and is on the speakers bureau for Janssen, BMS Celgene, GSK, Sanofi, and AbbVie. LDA received consulting fees and serves on advisory boards for Janssen, Celgene, BMS, Amgen, GSK, AbbVie, Beigene, Cellectar, Sanofi, and Prothena. SK received consultancy fees from Oncopeptides, AbbVie, Celgene, Janssen, Takeda, Adaptive, KITE, and MedImmune AstraZeneca; and research grants from AbbVie, Celgene, Janssen, Takeda, Adaptive, KITE, MedImmune AstraZeneca, Merck, Novartis, Roche, and Sanofi. TM received research funding from Sanofi. All other authors declare no competing interests. IMWG are listed in the appendix (pp 9–21)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)