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Background: CASSIOPEIA part 1 demonstrated superior depth of response and prolonged progression-free survival with daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) alone as an induction and consolidation regimen in transplant-eligible patients newly diagnosed with myeloma. In CASSIOPEIA part 2, daratumumab maintenance significantly improved progression-free survival and increased minimal residual disease (MRD)-negativity rates versus observation. Here, we report long-term study outcomes of CASSIOPEIA., Methods: CASSIOPEIA was a two-part, open-label, phase 3 trial of patients done at 111 European academic and community-based centres. Eligible patients were aged 18-65 years with transplant-eligible newly diagnosed myeloma and an Eastern Cooperative Oncology Group performance status of 0-2. In part 1, patients were randomly assigned (1:1) to pre-transplant induction and post-transplant consolidation with D-VTd or VTd. Patients who completed consolidation and had a partial response or better were re-randomised (1:1) to intravenous daratumumab maintenance (16 mg/kg every 8 weeks) or observation for 2 years or less. An interactive web-based system was used for both randomisations, and randomisation was balanced using permuted blocks of four. Stratification factors for the first randomisation (induction and consolidation phase) were site affiliation, International Staging System disease stage, and cytogenetic risk status. Stratification factors for the second randomisation (maintenance phase) were induction treatment and depth of response in the induction and consolidation phase. The primary endpoint for the induction and consolidation phase was the proportion of patients who achieved a stringent complete response after consolidation; results for this endpoint remain unchanged from those reported previously. The primary endpoint for the maintenance phase was progression-free survival from second randomisation. Efficacy evaluations in the induction and consolidation phase were done on the intention-to-treat population, which included all patients who underwent first randomisation, and efficacy analyses in the maintenance phase were done in the maintenance-specific intention-to-treat population, which included all patients who were randomly assigned at the second randomisation. This analysis represents the final data cutoff at the end of the study. The trial is registered with ClinicalTrials.gov, NCT02541383., Findings: Between Sept 22, 2015 and Aug 1, 2017, 1085 patients were randomly assigned to D-VTd (n=543) or VTd (n=542); between May 30, 2016 and June 18, 2018, 886 were re-randomised to daratumumab maintenance (n=442) or observation (n=444). At the clinical cutoff date, Sept 1, 2023, median follow-up was 80·1 months (IQR 75·7-85·6) from first randomisation and 70·6 months (66·4-76·1) from second randomisation. Progression-free survival from second randomisation was significantly longer in the daratumumab maintenance group than the observation-alone group (median not reached [95% CI 79·9-not estimable (NE)] vs 45·8 months [41·8-49·6]; HR 0·49 [95% CI 0·40-0·59]; p<0·0001); benefit was observed with D-VTd with daratumumab maintenance versus D-VTd with observation (median not reached [74·6-NE] vs 72·1 months [52·8-NE]; 0·76 [0·58-1·00]; p=0·048) and VTd with daratumumab maintenance versus VTd with observation (median not reached [66·9-NE] vs 32·7 months [27·2-38·7]; 0·34 [0·26-0·44]; p<0·0001)., Interpretation: The long-term follow-up results of CASSIOPEIA show that including daratumumab in both the induction and consolidation phase and the maintenance phase led to superior progression-free survival outcomes. Our results confirm D-VTd induction and consolidation as a standard of care, and support the option of subsequent daratumumab monotherapy maintenance, for transplant-eligible patients with newly diagnosed multiple myeloma., Funding: Intergroupe Francophone du Myélome, Dutch-Belgian Cooperative Trial Group for Hematology Oncology, and Janssen Research & Development., Competing Interests: Declaration of interests PM served on advisory boards for and received honoraria from Janssen, Bristol Myers Squibb, Amgen, Takeda, AbbVie, Sanofi, and Pfizer. CH received honoraria from Janssen, Bristol Myers Squibb, Amgen, AbbVie, and Pfizer. AP served in a consulting or advisory role for Bristol Myers Squibb, Janssen, and Pfizer; and received research funding from Bristol Myers Squibb, Sanofi, and Takeda. BA received research funding (paid to institution) from Bristol Myers Squibb; received honoraria from Janssen, Bristol Myers Squibb, Sanofi, and GSK; received travel funding from Janssen, Bristol Myers Squibb, and Sanofi; and served on an advisory board for Janssen, Bristol Myers Squibb, and Takeda. KB has a direct financial relationship with Janssen, Bristol Myers Squibb, Amgen, Sanofi, and Pfizer. SZ received research support from Janssen and Takeda; and served on advisory boards for Janssen, Bristol Myers Squibb, Sanofi, Oncopeptides, Amgen, and Takeda. MD received honoraria from and served in a consulting or advisory role for Amgen, Bristol Myers Squibb, Janssen, Sanofi, and Stemline; and received research funding from Janssen. CS received consulting fees or honoraria from Takeda, Bristol Myers Squibb, Janssen, Amgen, Sanofi, and Pfizer. MMo received honoraria from Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Celgene, Janssen, Takeda, Novartis, and Sanofi; and received research funding from Celgene, Janssen, and Sanofi. LK received honoraria from, served on advisory boards for, or received travel funding from AbbVie, Amgen, Janssen, Celgene/Bristol Myers Squibb, Pfizer, Sanofi, and Takeda. MMa received honoraria from and served in a consulting or advisory role for Janssen, Bristol Myers Squibb/Celgene, Sanofi, and Takeda; received research funding from Janssen and Takeda; and received travel, accommodations, or expenses from Janssen and Sanofi. FO-P served on boards for Janssen, Sanofi, and Pfizer. MR served on an advisory board for Janssen and Pfizer; received research funding from Bristol Myers Squibb, Janssen, and Sanofi; gave lectures for Amgen, Bristol Myers Squibb, Janssen, and Takeda; and had travel, accommodations, or other expenses paid or reimbursed by Amgen, Bristol Myers Squibb, GSK, Janssen, Pfizer, Sanofi, and Takeda. JMSdC served on an advisory board and received honoraria from Janssen, Sanofi, GSK, and AbbVie; and received accommodations from Pfizer and Amgen. NWCJvdD received research support from Janssen, Amgen, Celgene, Novartis, Cellectis, and Bristol Myers Squibb; and serves on advisory boards for Janssen, Amgen, Celgene, Bristol Myers Squibb, Sanofi, Takeda, Roche, Novartis, Bayer, Adaptive, Merck, Pfizer, AbbVie, and Servier (all paid to institution). AB served on advisory boards for Janssen, Sanofi, Amgen, and Bristol Myers Squibb. CT served on an advisory board for and received honoraria from Janssen. NM served on an advisory board for Janssen. M-CV received travel support from Janssen and Sanofi. M-DL received travel expenses from Janssen. WH is an employee of Cytel and is a contractor for Johnson & Johnson. JW, CdB, MR, VV, RC, and JV are employees of Janssen and hold stock in Johnson & Johnson. AT is an employee of Janssen. JC served on advisory boards for Sanofi and Bristol Myers Squibb; served as a consultant for Janssen, Sanofi, Bristol Myers Squibb, Pfizer, and Adaptive; received research support from Sanofi and Bristol Myers Squibb; and received travel support from Janssen, Sanofi, Bristol Myers Squibb, and Pfizer. PS served on an advisory board for Amgen, Bristol Myers Squibb, Celgene, Janssen, Karyopharm, and Pfizer; and received research funding from Amgen, Bristol Myers Squibb, Celgene, Janssen, and Karyopharm. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Chimeric antigen receptor T-cell therapy idecabtagene vicleucel (ide-cel) showed significantly improved progression-free survival compared with standard regimens in adults with relapsed and refractory multiple myeloma who had received two to four previous regimens in the ongoing phase 3 KarMMa-3 trial (NCT03651128). This study analysed patient-reported outcomes (PROs), a KarMMa-3 secondary endpoint., Methods: In the randomised, open-label, phase 3 KarMMa-3 trial, 386 patients in hospitals (≥18 years of age, with measurable disease and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who had received two to four previous regimens-including an immunomodulatory agent, a proteasome inhibitor, and daratumumab-and had documented disease progression after receiving their last dose of the last therapy) were randomly assigned to ide-cel (n=254) or standard regimens (daratumumab, pomalidomide, and dexamethasone; daratumumab, bortezomib, and dexamethasone; ixazomib, lenalidomide, and dexamethasone; carfilzomib and dexamethasone; or elotuzumab, pomalidomide, and dexamethasone; n=132). Patients were expected to complete the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire (QLQ-C30), Multiple Myeloma Module (QLQ-MY20), EQ 5 dimensions (EQ-5D), and EQ-5D visual analogue scale (VAS) at baseline and follow-up timepoints (data cutoff April 18, 2022). PROs included nine prespecified primary domains: EORTC QLQ-C30 GHS-quality of life (QoL), physical functioning, cognitive functioning, fatigue, and pain; QLQ-MY20 disease symptoms and side effects of treatment; and five-level EQ-5D (EQ-5D-5L) index score and EQ-5D visual VAS. Differences in overall least-squares mean changes from baseline to month 20 were analysed using post-hoc constrained longitudinal data analysis. Time to confirmed improvement or deterioration from baseline was analysed using Cox proportional hazard models., Findings: Patients were randomly assigned between May 6, 2019, and April 8, 2022. Overall, the median age was 63 years (IQR 55-68); 151 (39%) patients were female; and 250 (65%) patients were White, 36 (9%) Black or African American, 19 (5%) Hispanic or Latino, 12 (3%) Asian, and seven (2%) of other race. The median follow-up was 18·6 months (IQR 14·0-26·4). PRO compliance was higher than 75% throughout. Overall least-squares mean changes from baseline favoured ide-cel with Hedges' g effect sizes from 0·3 to 0·7 for most domains. Patients in the ide-cel group showed statistically significant and clinically meaningful improvements across the primary PRO domains of interest, with the exception of QLQ-MY20 disease symptoms, side effects of treatment, and EQ-5D-5L index score, which showed improvement across assessment visits but did not exceed the within-group minimally important difference thresholds. The ide-cel group had shorter times to clinically meaningful improvement than the standard regimens group in QLQ-C30 domains except in role functioning, diarrhoea, and financial difficulties; in QLQ-MY20 domains except body image; and in EQ-5D-VAS., Interpretation: Ide-cel offers improved health-related quality of life compared with standard regimens for patients with relapsed and refractory multiple myeloma after previous lines of therapy. The PRO data highlight the extended QoL benefits of a one-time infusion with ide-cel compared with continuous treatment with standard regimens in the treatment of triple-class exposed patients with relapsed and refractory multiple myeloma., Funding: 2seventy bio and Celgene, a Bristol Myers Squibb Company., Competing Interests: Declaration of interests MD reports payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from Amgen, Bristol Myers Squibb, GSK, Janssen, Sanofi, Stemline, and Takeda. KP reports consulting fees from AbbVie, Arcellx, Bristol Myers Squibb, Caribou Science, Cellectis, Genentech, Janssen, Karvopharm, Legend Biotech, Merck, Oncopeptides, Pfizer, and Precision Biosciences. BA reports consulting fees from Amgen, Bristol Myers Squibb, and Janssen; and honoraria for presentations, support for attending meetings or travel, and participation on advisory boards for Bristol Myers Squibb, Janssen, and Sanofi. MC reports consulting fees from Bristol Myers Squibb, Janssen, and Sanofi; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events for AbbVie, Bristol Myers Squibb, and Takeda. AN reports honoraria and participation on advisory boards for Adaptative Biotechnologies, Amgen, BeyondSpring Pharmaceuticals, Bristol Myers Squibb, Cellectar Biosciences, GSK, Janssen, Karyopharm, Oncopeptides, ONK Therapeutics, Pfizer, Sanofi, Secura Bio, and Takeda; research funding to the institution from Aduro Biotech, Amgen, Arch Oncology, Bristol Myers Squibb, Cellectis, Genentech, GSK, Janssen, Karyopharm Therapeutics, Kite Pharmaceuticals, Merck, Pfizer, and Takeda; and grants and research support for investigator-initiated studies from Amgen, GSK, Janssen, Merck, and Takeda. SM reports participation on advisory boards for AbbVie, Amgen, Bristol Myers Squibb, GSK, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, and Takeda. SG reports grants or contracts from Amgen, Actinuum, Bristol Myers Squibb, Johnson & Johnson, Miltenyi, Omeros, and Takeda; leadership or fiduciary role on other board, society committee or advocacy group, paid or unpaid, for Amgen, Actinuum, Bristol Myers Squibb, Kite Pharmaceuticals, Janssen, Jazz Phamaceuticals, Johnson & Johnson, Novartis, Spectrum Pharmaceuticals, and Takeda; and ownership of stock in Bristol Myers Squibb. HE reports consulting fees, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, support for attending meetings or travel, and participation on a data safety monitoring board or advisory board for Amgen, Bristol Myers Squibb, GSK, Janssen, Novartis, Sanofi, and Takeda; research funding to the institution from Amgen, Bristol Myers Squibb, GSK, Janssen, and Sanofi; and ownership of stock in Bristol Myers Squibb. SA reports consulting fees from BeiGene, Bristol Myers Squibb, Cellectar Biosciences, GSK, Janssen, Pfizer, Sanofi, and Takeda; and research funding to the institution from AbbVie, Amgen, Ascentage, Bristol Myers Squibb, Cellectar Biosciences, GSK, Janssen, Pharmacyclics, and Sanofi. PR-O reports consulting fees from AbbVie, Bristol Myers Squibb, GSK, H3 Pharmaceuticals, Janssen, Oncopeptides, Pfizer, Roche, and Sanofi; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AbbVie, Bristol Myers Squibb, GSK, Janssen, and Sanofi; support for attending meetings or travel from Pfizer; and participation on a data safety monitoring board or advisory board for Bristol Myers Squibb and Janssen. LE, DD, TSM, and MPM are employee of Bristol Myers Squibb. LS and SG are employees of Evidera. NC declares no competing interests. MC is an employee of Celgene, a Bristol Myers Squibb Company., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) report significantly lower HRQoL compared with patients with newly diagnosed MM and experience further deterioration in HRQoL with each relapse and subsequent treatment. Therefore, consideration of the impact of treatment on HRQoL in addition to clinical outcomes is vital., Patients and Methods: In the phase I/II MajesTEC-1 (NCT03145181, NCT04557098) study, patients with RRMM who received teclistamab, an off-the-shelf, T-cell redirecting BCMA × CD3 bispecific antibody, had deep and durable responses with manageable safety. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30-item and the EuroQol 5 Dimension 5 Level descriptive questionnaire. Changes over time from baseline were measured with a repeated measures mixed-effects model. Proportions of patients with clinically meaningful improvement after starting treatment and time to clinically meaningful worsening were assessed., Results: Compliance was maintained throughout the study. Compared with baseline, positive changes were observed for pain, global health status, and emotional functioning with treatment; other assessments were largely unchanged from baseline. Post hoc analysis showed patients with deeper clinical response generally reported improved HRQoL outcomes. Following an initial decline in HRQoL in some scales, the proportion of patients reporting clinically meaningful improvements increased, while the proportion reporting clinically meaningful worsening decreased over time. Clinically meaningful improvements in pain were reported in ≥40% of patients at most assessment time points., Conclusions: These results complement previously reported clinical benefits and support teclistamab as a promising therapeutic option for patients with RRMM., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Teclistamab is the first approved B cell maturation antigen × CD3 bispecific antibody with precision dosing for the treatment of triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). We compared the effectiveness of teclistamab in MajesTEC-1 versus real-world physician's choice of therapy (RWPC) in patients from the prospective, non-interventional LocoMMotion and MoMMent studies., Methods: Patients treated with teclistamab from MajesTEC-1 (N = 165) were compared with an external control arm from LocoMMotion (N = 248) or LocoMMotion + MoMMent pooled (N = 302). Inverse probability of treatment weighting adjusted for imbalances in prognostic baseline characteristics. The relative effect of teclistamab versus RWPC for overall response rate (ORR), very good partial response or better (≥ VGPR) rate, and complete response or better (≥ CR) rate was estimated with an odds ratio using weighted logistic regression transformed into a response-rate ratio (RR) and 95% confidence interval (CI). Weighted proportional hazards regression was used to estimate hazard ratios (HRs) and 95% CIs for duration of response (DOR), progression-free survival (PFS), and overall survival (OS)., Results: Baseline characteristics were well balanced between treatment cohorts after reweighting. Patients treated with teclistamab had significantly improved outcomes versus RWPC in LocoMMotion: ORR (RR [95% CI], 2.44 [1.79-3.33]; p < 0.0001), ≥ VGPR (RR 5.78 [3.74-8.93]; p < 0.0001), ≥ CR (RR 113.73 [15.68-825.13]; p < 0.0001), DOR (HR 0.39 [0.24-0.64]; p = 0.0002), PFS (HR 0.48 [0.35-0.64]; p < 0.0001), and OS (HR 0.64 [0.46-0.88]; p = 0.0055). Teclistamab versus RWPC in LocoMMotion + MoMMent also had significantly improved outcomes: ORR (RR 2.41 [1.80-3.23]; p < 0.0001), ≥ VGPR (RR 5.91 [3.93-8.88]; p < 0.0001), ≥ CR (RR 132.32 [19.06-918.47]; p < 0.0001), DOR (HR 0.43 [0.26-0.71]; p = 0.0011), PFS (HR 0.49 [0.37-0.66]; p < 0.0001), and OS (HR 0.69 [0.50-0.95]; p = 0.0247)., Conclusion: Teclistamab demonstrated significantly improved effectiveness over RWPC in LocoMMotion ± MoMMent, emphasizing its clinical benefit as a highly effective treatment for patients with TCE RRMM., Trial Registration: MajesTEC-1, ClinicalTrials.gov NCT03145181 (phase 1) and NCT04557098 (phase 2); LocoMMotion, ClinicalTrials.gov NCT04035226; MoMMent, ClinicalTrials.gov NCT05160584., (© 2023. The Author(s).)

Background: Daratumumab, a monoclonal antibody targeting CD38, has been approved for use with standard myeloma regimens. An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients with newly diagnosed multiple myeloma is needed., Methods: In this phase 3 trial, we randomly assigned 709 transplantation-eligible patients with newly diagnosed multiple myeloma to receive either subcutaneous daratumumab combined with VRd induction and consolidation therapy and with lenalidomide maintenance therapy (D-VRd group) or VRd induction and consolidation therapy and lenalidomide maintenance therapy alone (VRd group). The primary end point was progression-free survival. Key secondary end points were a complete response or better and minimal residual disease (MRD)-negative status., Results: At a median follow-up of 47.5 months, the risk of disease progression or death in the D-VRd group was lower than the risk in the VRd group. The estimated percentage of patients with progression-free survival at 48 months was 84.3% in the D-VRd group and 67.7% in the VRd group (hazard ratio for disease progression or death, 0.42; 95% confidence interval, 0.30 to 0.59; P<0.001); the P value crossed the prespecified stopping boundary (P = 0.0126). The percentage of patients with a complete response or better was higher in the D-VRd group than in the VRd group (87.9% vs. 70.1%, P<0.001), as was the percentage of patients with MRD-negative status (75.2% vs. 47.5%, P<0.001). Death occurred in 34 patients in the D-VRd group and 44 patients in the VRd group. Grade 3 or 4 adverse events occurred in most patients in both groups; the most common were neutropenia (62.1% with D-VRd and 51.0% with VRd) and thrombocytopenia (29.1% and 17.3%, respectively). Serious adverse events occurred in 57.0% of the patients in the D-VRd group and 49.3% of those in the VRd group., Conclusions: The addition of subcutaneous daratumumab to VRd induction and consolidation therapy and to lenalidomide maintenance therapy conferred a significant benefit with respect to progression-free survival among transplantation-eligible patients with newly diagnosed multiple myeloma. (Funded by the European Myeloma Network in collaboration with Janssen Research and Development; PERSEUS ClinicalTrials.gov number, NCT03710603; EudraCT number, 2018-002992-16.)., (Copyright © 2023 Massachusetts Medical Society.)

Introduction/background: Multiple myeloma (MM) is considered an incurable cancer. Patients with newly diagnosed MM (NDMM) are at risk for relapse within 1 year of frontline therapy. The immunomodulatory agent lenalidomide combined with dexamethasone (Rd) may be used as treatment for NDMM or relapsed MM, including in patients ineligible for autologous stem cell transplant., Patients: This subanalysis of the phase III FIRST trial characterized patients with transplant-ineligible NDMM who experienced relapse while receiving Rd therapy by relapse timing (early [<12 months] versus late [≥12 months]) and type (CRAB vs. non-CRAB)., Methods: The Kaplan-Meier product limit method was used to estimate time-to-event endpoints, including progression-free survival (PFS) and overall survival (OS). Factors associated with the odds of late relapse were identified by logistic regression with univariate and multivariate analyses using a binary outcome (relapse at <12 vs. ≥12 months) in patient-, disease-, and treatment-specific baseline variables., Results: Patients with early refractory relapse had functionally high-risk disease and inferior outcomes. In patients with early relapse versus those with late relapse, median OS (95% CI) was 26.8 months (21.9-32.8) versus 63.9 months (57.0-78.0), median OS from disease progression to death was 19.9 months (16.0-25.5) versus 36.4 months (27.9-47.0), and median PFS from randomization to second progression was 19.1 months (17.3-22.5) versus 42.1 months (37.4-44.9). Lactate dehydrogenase, baseline β2 microglobulin, and myeloma subtype were shown to predict time to relapse., Conclusions: Clinicians could use these factors to consider more aggressive treatment regimens for those at highest risk of early relapse., Competing Interests: Disclosure SM serves on data safety monitoring boards/advisory boards for AbbVie, Adaptive Biotechnology, Amgen, Celgene/Bristol Myers Squibb, GSK, Janssen, Novartis, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, and Takeda. MeD has received honoraria for participation in advisory boards for Amgen, Bristol Myers Squibb, BeiGene, Takeda, and Janssen. CH has received honoraria from Celgene/Bristol Myers Squibb, Janssen, Amgen, AbbVie, and Takeda. XL has received honoraria from Janssen, Bristol Myers Squibb, Takeda, Sanofi, Pfizer, Amgen, Roche, and Gilead. MiD has received research funding from Bristol Myers Squibb and Janssen; consulting fees from Amgen, Bristol Myers Squibb, Janssen, Takeda, and Sanofi; honoraria from Amgen, Bristol Myers Squibb, Janssen, Takeda, and Sanofi; and support for meeting attendance/travel expenses from Amgen, Bristol Myers Squibb, Janssen, Takeda, and Sanofi. KW has received research funding from Amgen, Adaptive Biotech, AstraZeneca, Celgene/Bristol Myers Squibb, BeiGene, Janssen, GSK, Sanofi, Stemline, and Takeda; honoraria from AbbVie, Amgen, Adaptive Biotech, AstraZeneca, Celgene/Bristol Myers Squibb, BeiGene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche, Sanofi, Stemline, and Takeda; and support for travel expenses from Janssen, GSK, and Sanofi. JM, BC, and MS are employees of Bristol Myers Squibb and have received meeting attendance/travel expenses and stock or stock options from Bristol Myers Squibb. TF declares no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: There is an increased risk of second primary malignancies (SMPs) in patients with multiple myeloma (MM). This multinational 'real-world' retrospective study analyzed the characteristics and outcomes of MM patients that developed SPMs., Results: 165 patients were analyzed: 62.4% males; 8.5% with a prior cancer; 113 with solid SPMs, mainly ≥stage 2; and 52 with hematological SPM (hemato-SPM), mainly MDS/AML. Patients with hemato-SPM were younger ( p = 0.05) and more frequently had a prior AutoHCT ( p = 0.012). The time to SPM was shorter in the older (>65 years) and more heavily pretreated patients. One hundred patients were actively treated at the time of SPM detection. Treatment was discontinued in 52, substituted with another anti-MM therapy in 15, and continued in 33 patients. Treatment discontinuation was predominant in the patients diagnosed with hemato-SPM (76%). The median OS following SPM detection was 8.5 months, and the main cause of death was SPM. A poor ECOG status predicted a shorter OS (PS 3 vs. 0, HR = 5.74, 2.32-14.21, p < 0.001), whereas a normal hemoglobin level (HR = 0.43, 0.19-0.95, p = 0.037) predicted longer OS., Conclusions: With the continuing improvement in OS, a higher proportion of MM patients might develop SPM. The OS following SPM diagnosis is poor; hence, frequent surveillance and early detection are imperative to improve outcomes.

We used a modified Delphi approach to establish areas of consensus and nonconsensus regarding the utility of determining measurable residual disease (MRD) to assess multiple myeloma (MM) treatment response, which may inform disease management and design of future clinical trials. This modified Delphi study incorporated 2 iterative rounds of surveys to evaluate the opinions of an expert panel of 61 practicing hematological oncologists from across 14 countries in Europe concerning the use of MRD testing in MM management. Survey 1 assessed experts' opinions on MRD testing in different clinical situations and associated challenges. Survey 2 focused on the lack of consensus areas identified in survey 1. Consensus to an individual question was defined a priori as 75% agreement or disagreement by the panel. From the 2 rounds of surveys, the experts reached consensus agreement that MRD testing should be performed in newly diagnosed or relapsed patients who achieved complete response (CR) or better after transplantation. In transplant-ineligible patients, experts recommended MRD testing in those who are ≤70 years old and in CR. If a patient was previously positive on positron-emission tomography and computed tomography (PET/CT), both MRD and PET/CT should be assessed at CR. MRD testing should be performed ≤6 months after transplantation and every 6-12 months in continuously treated patients in CR. There was no consensus on making treatment decisions based on MRD status. MRD testing is an important component of clinical management in MM. Additional data will further clarify the role of MRD in guiding treatment decisions., Competing Interests: KR: Has served as an advisor for and received honoraria from Janssen, Adaptive Biotechnologies, Amgen, Takeda, Abbvie, Oncopeptides, Celgene – Bristol Myers Squibb, Pfizer, and GSK. Has received grant funding from Janssen, Amgen, Takeda, GSK and Celgene – Bristol Myers Squibb. HA-L: Has served as an advisor for and received honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, GSK, Takeda, and Adaptive Biotechnologies. CHB: Has served as an advisor for and received honoraria from Amgen, Bristol Myers Squibb, Takeda, Sanofi, GSK, and Adaptive Biotechnologies. MD: Has served as an advisor for and received honoraria from Amgen, Celgene – Bristol Myers Squibb, GSK, Janssen, Sanofi, and Takeda. FG: Has served as an advisor for Janssen, Amgen, Celgene – Bristol Myers Squibb, Adaptive Biotechnologies, Roche, Abbvie, GSK, Takeda, Bluebird Bio, Oncopeptides, Pfizer, and Sanofi. Has received honoraria from Janssen, Amgen, Celgene – Bristol Myers Squibb, GSK, Takeda, and Sanofi. SM: Has served as an advisor for Abbvie, Adaptive Biotechnologies, Amgen, Celgene – Bristol Myers Squibb, GSK, Janssen, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, and Takeda. JM-L: Has served as an advisor for and received honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, GSK, Incyte, Roche, Pfizer, Novartis and Adaptive Biotechnologies. MVM: Has served as an advisor for and received honoraria from Janssen, Celgene – Bristol Myers Squibb, Takeda, Amgen, Adaptive Biotechnologies, Oncopeptides, Sanofi, Roche, Regeneron, and Pfizer. MM: Has received honoraria from Amgen, Astellas, Bristol Myers Squibb, Celgene, Gilead, Janssen, Jazz, Takeda, Novartis, Pfizer, Sanofi, and Adaptive Biotechnologies. Has received research funding from Celgene, Janssen, Jazz, and Sanofi. NWCJvdD: Has served as an advisor for Janssen Pharmaceuticals, Amgen, Adaptive Biotechnologies, Celgene, Bristol Myers Squibb, Novartis, Roche, Takeda, Bayer, and Servier. Has received grant funding from Janssen Pharmaceuticals, Amgen, Celgene, Cellectis, and Bristol Myers Squibb. KW: Has served as an advisor for Amgen, Adaptive Biotechnologies, Bristol Myers Squibb, Celgene, GSK, Janssen, Karyopharm, Oncopeptides, Sanofi, and Takeda. Has received honoraria from Amgen, Adaptive Biotechnologies, Bristol Myers Squibb, Celgene, GSK, Janssen, Karyopharm, Oncopeptides, Sanofi, Takeda, and Roche. Has received grant funding from Amgen, Janssen, Celgene, and Sanofi (to the institution)., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association.)

Background: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy., Methods: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib., Results: The median follow-up from maintenance start was 44 months. Three-year progression-free survival (PFS) was 52% (48%-57%) for no EMD, 56% (44%-69%) for paraskeletal involvement, and 45% (22%-68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three-year overall survival (OS) was 81% (77%-84%), 88% (80%-96%), and 68% (47%-89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD., Conclusion: Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

T-cell redirecting bispecific antibodies (BsAbs) and chimeric antigen receptor T cells (CAR T cells) have revolutionised multiple myeloma therapy, but adverse events such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenias, hypogammaglobulinaemia, and infections are common. This Policy Review presents a consensus from the European Myeloma Network on the prevention and management of these adverse events. Recommended measures include premedication, frequent assessing for symptoms and severity of cytokine release syndrome, step-up dosing for several BsAbs and some CAR T-cell therapies; corticosteroids; and tocilizumab in the case of cytokine release syndrome. Other anti-IL-6 drugs, high-dose corticosteroids, and anakinra might be considered in refractory cases. ICANS often arises concomitantly with cytokine release syndrome. Glucocorticosteroids in increasing doses are recommended if needed, as well as anakinra if the response is inadequate, and anticonvulsants if convulsions occur. Preventive measures against infections include antiviral and antibacterial drugs and administration of immunoglobulins. Treatment of infections and other complications is also addressed., Competing Interests: Declaration of interests HL reports honoraria for lectures and for advisory boards from Celgene-BMS, Janssen-Cilag, Takeda, Amgen, Sanofi, AbbVie, and Pfizer; and research funding from Amgen and Sanofi. ET reports grants from Amgen, Janssen, GSK, Takeda, and Sanofi; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Amgen, ASTRA, BMS, GSK, Integris, Pfizer, Sanofi, and Takeda; support for attending meetings or travel from Amgen, Takeda, and Eusa Pharma; and participation on a data safety monitoring board or advisory board from BMS, GSK, Sanofi, Takeda, Eusa Pharma, Janssen, ASTRA, and Amgen. NvdD reports research support from Janssen, Amgen, Celgene, Novartis, Cellectis, and BMS; and participation on a data safety monitoring board or advisory board from Janssen, Amgen, Celgene, BMS, Takeda, Roche, Novartis, and Adaptive. M-VM reports honoraria derived from lectures and participation in advisory boards from Janssen, BMS-Celgene, Takeda, Amgen, GSK, AbbVie, Pfizer, Regeneron, Roche, Sanofi, and Oncopeptides. PMo reports honoraria for advisory boards and symposia from Celgene, Janssen, Pfizer, and Abbvie; and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Celgene, Takeda, Amgen, AbbVie, Sanofi, and GSK. M-AD reports participation in advisory boards for Amgen, Takeda, BMS, Janssen, Beigene, and Sanofi. MD reports grants from Janssen and BMS; consulting fees from Amgen, BMS, Janssen, Sanofi, Stemline, and Takeda; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from BMS and Janssen; and participation on a data safety monitoring board or advisory board for BMS and Takeda. PR-O reports honoraria for lectures from BMS, Janssen, Sanofi, GSK, Amgen, Regeneron, and Takeda; and participation in advisory boards for BMS, Janssen, Sanofi, Kite Pharma, AbbVie, Oncopeptides, Takeda, Pfizer, and GSK. JS-M reports consulting fees from Takeda, Janssen, Celgene, BMS, Amgen, Sanofi, and GSK; honoraria from Takeda, Janssen, Celgene, Amgen, BMS, Sanofi, and GSK; and participation in scientific advisory boards for Takeda, Janssen, Celgene, Novartis, Amgen, BMS, Sanofi, GSK Roche, and Regeneron. KY reports consulting fees from Sanofi, and Janssen; speaker bureaus from Sanofi, Amgen, Takeda, and Pfizer; honoraria from Sanofi, Janssen, Amgen, Takeda, and Pfizer; and research funding from Sanofi, Janssen, Amgen, Takeda, and BMS. FG reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Amgen, Sanofi, BMS, Takeda, GSK, Roche, and AbbVie; and participation on a data safety monitoring board or advisory board from Janssen, Amgen, Sanofi, BMS, Takeda, GSK, Roche, AbbVie, Oncopeptides, Pfizer, and Adaptive. HE reports consulting fees, payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events; and support for attending meetings or travel from Janssen, BMS–Celgene, Amgen, GSK, Sanofi, Takeda, and Novartis. RM reports consulting fees from Janssen, Takeda, and Sanofi; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Celgene, Takeda, Amgen; and participation on an advisory board for Janssen, Celgene, Takeda, BMS, and Amgen. JC reports grants from Janssen; consulting fees from Janssen and Sanofi; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Amgen; support for attending meetings or travel from Gilead; and a patent planned, issued, or pending: 20175032.0: anti-CD38 single-domain antibodies in disease monitoring and treatment. ME reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, BMS, Takeda, Amgen, GSK, and Sanofi; and support for attending meetings or travel from Janssen, BMS, Takeda, and Amgen. GC reports research funding from Takeda and BMS; consulting fees from Takeda, BMS, AbbVie, Roche, Pfizer, Janssen, Karyopharm, and Amgen; and speaker bureau for Janssen, Takeda, AbbVie, and Amgen. KW reports honoraria and participation on advisory boards from AbbVie, Adaptive, Amgen, Bristol Myers Squibb, Celgene, Janssen, GSK, Karyopharm, Novartis, Oncopeptides, Pfizer, Roche Pharma, Takeda, and Sanofi; and reports research funding from Amgen, Celgene, Janssen, and Sanofi. AB reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from BMS, Sanofi, Janssen, and Amgen. MBe reports participation on advisory boards for Amgen, Bristol-Myers Squibb, Janssen, Sanofi, Takeda, and Oncopeptides. JB reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Takeda, and Amgen; payment for expert testimony from Janssen and Amgen; support for attending meetings or travel from Janssen and Takeda; and a leadership or fiduciary role in other board, society, committee, or advocacy group, paid or unpaid, in the Serbian Myeloma Group and the Balkan Myeloma Study Group. FS reports grants or contracts from Celgene, Janssen, Oncopeptides, Sanofi, GSK, and Targovax; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Amgen, BMS, Takeda, AbbVie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, Pfizer, Daiki-Sankyo, and GSK; and participation on a data safety monitoring board or advisory board for AbbVie, GSK, Celgene, Takeda, Janssen, Oncopeptides, Sanofi, and BMS. MC reports consulting fees from Glaxo Smith Kline, Janssen, Sanofi, Roche, Amgen, Takeda, AbbVie, Bristol Myers Squibb, Celgene, and Pfizer; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Sanofi, and Bristol Myers Squibb; and participation on a data safety monitoring board or advisory board from Glaxo Smith Kline, Janssen, Sanofi, Roche, Amgen, Takeda, AbbVie, Bristol Myers Squibb, Celgene, and Pfizer. RH reports grants or contracts paid to institution from Janssen, Amgen, Celgene, BMS, Novartis, and Takeda; consulting fees from Janssen, Amgen, Celgene, AbbVie, BMS, Novartis, PharmaMar, and Takeda; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing, or educational events from Janssen, Amgen, Celgene, BMS, PharmaMar, and Takeda; support for attending meetings or travel from Amgen, Celgene, Takeda, and Janssen; and participation in a data safety monitoring board or advisory board for BMS, Takeda, Amgen, Oncopeptides, Sanofi, Janssen, and GSK. CT reports consulting fees from AbbVie, Janssen, and Pfizer; payment for lectures from Janssen and BMS; support for attending meetings or travel from Janssen; and participation in advisory boards for Janssen, Pfizer, and BMS. MBo reports honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb, and AbbVie; participation in an advisory board for Janssen and GSK; and research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, BMS, and Mundipharma. PS reports participation in an advisory board for and research funding from Amgen, BMS, Celgene, Janssen, Karyopharm, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: To understand the long-term experience of patients receiving ide-cel chimeric antigen receptor T (CAR T) cell therapy for relapsed or refractory multiple myeloma in the pivotal phase 2 KarMMa trial., Methods: This qualitative study analyzed semi-structured patient interviews 6-24 months after ide-cel infusion. Thematic analysis with quantitative and longitudinal analyses explored patient perceptions of ide-cel treatment experience, advantages and disadvantages, and long-term health-related quality of life impact. Patient journeys were developed from narrative analysis of perceived treatment benefits with known remission length., Results: Interviews with 45 patients 6-24 months postinfusion were analyzed; all reported ≥ 1 ide-cel treatment advantage, most often related to efficacy (n = 42/45, 93%), few or no side effects (n = 35/45, 78%), and avoidance of other treatments (n = 34/45, 76%). Patients generally reported 6-month improvements in physical health, functioning, emotional well-being, social life, and outlook on the future; these improvements mostly remained "stable" through 18 and 24 months. The most common patient journeys comprised physical, functioning, or emotional benefit with remission < 2 years., Conclusions: Longitudinal analysis of patient experiences showed sustained benefits and preference for ide-cel up to 24 months after treatment. Trial Registration Number and Date: NCT03361748. December 5, 2017., Competing Interests: Declaration of Competing Interest MD has received research funding and honoraria from Amgen, Celgene, Janssen, Karyopharm, and Sanofi. PRO has served as a consultant for and received honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, Kite Pharma, Oncopeptides, and Sanofi; has served as a consultant for Takeda; and has served on the board of directors or advisory committee and speakers bureau for Amgen, Bristol Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Regeneron, and Sanofi. NS has worked in an advisory role for Allogene Therapeutics, Amgen, CareDx, CSL Behring, GlaxoSmithKline, Indapta Therapeutics, Karyopharm, Kite Pharma, Oncopeptides, and Sanofi; has received research funding from bluebird bio, Bristol Myers Squibb/Celgene, Janssen, Nektar, Poseida, Precision Biosciences, Sutro Biopharma, and Teneobio; and is an employee and stockholder of AstraZeneca. OM, SL, MM, and HG are employees of ICON plc. JD is an employee and stockholder of ICON plc. JB, DSD, and TBC are employees and stockholders of Bristol Myers Squibb. NCM has served as a consultant for AbbVie, Adaptive, Amgen, Bristol Myers Squibb, Janssen, Legend, Novartis, Pfizer, and Takeda; has served as a consultant for, holds stock, patents and royalties in, and is a member on a board of directors or advisory committee for Oncopeptides; and is an employee of Dana Farber Cancer Institute., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6-12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE-RRMM) have a poor prognosis and limited treatment options. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, was studied in patients with TCE-RRMM in the single-arm MajesTEC-1 study. To assess the relative effectiveness of teclistamab versus real-world physician's choice of therapy (RWPC), adjusted comparisons were performed using individual patient data from MajesTEC-1 and LocoMMotion, a prospective study of patients with TCE-RRMM., Methods: An external control arm for MajesTEC-1 was created from patients in LocoMMotion (n = 248; clinical cut-off: November 2, 2021) and compared with treated patients (n = 165) from MajesTEC-1 (teclistamab 1.5 mg/kg weekly; clinical cut-off: March 16, 2022). Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints [overall response rate (ORR), very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR)], relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), and overall survival (OS)]., Results: After weighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, teclistamab-treated patients were 2.3-fold, 5.2-fold and 148.3-fold, more likely to reach ORR [response-rate ratio (RR) = 2.31, 95% CI 1.77-2.85, p < 0.0001], ≥ VGPR (RR = 5.19, 95% CI 3.26-7.12, p < 0.0001) and ≥ CR (RR = 148.25, 95% CI 20.63-1065.40, p < 0.0001), respectively, versus patients receiving RWPC. Following adjustment, DOR (HR 0.32, 95% CI 0.19-0.54, p < 0.0001) and PFS (HR 0.48, 95% CI 0.35-0.65, p < 0.0001) were significantly longer with teclistamab versus RWPC. OS was numerically better with teclistamab versus RWPC [HR 0.77 (0.55-1.09), p = 0.1419]., Conclusion: Teclistamab demonstrated improved effectiveness versus RWPC, highlighting its clinical benefit as a novel and effective treatment for patients with TCE-RRMM., Trial Registration: Majest TEC-1, ClinicalTrials.gov NCT04557098; LocoMMotion, ClinicalTrials.gov NCT04035226., (© 2023. The Author(s).)

Background: Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma., Methods: In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150×10 6 to 450×10 6 CAR-positive T cells) or one of five standard regimens. The primary end point was progression-free survival. Key secondary end points were overall response (partial response or better) and overall survival. Safety was assessed., Results: A total of 386 patients underwent randomization: 254 to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class-refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95% confidence interval, 0.38 to 0.65; P<0.001). A response occurred in 71% of the patients in the ide-cel group and in 42% of those in the standard-regimen group (P<0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Adverse events of grade 3 or 4 occurred in 93% of the patients in the ide-cel group and in 75% of those in the standard-regimen group. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and investigator-identified neurotoxic effects occurred in 15%, with 3% having an event of grade 3 or higher., Conclusions: Ide-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. The toxicity of ide-cel was consistent with previous reports. (Funded by 2seventy bio and Celgene, a Bristol-Myers Squibb company; KarMMa-3 ClinicalTrials.gov number, NCT03651128.)., (Copyright © 2023 Massachusetts Medical Society.)

Introduction: This phase 1 trial assessed the safety, pharmacokinetics, and preliminary antitumor activity of RO7297089, an anti-BCMA/CD16a bispecific antibody., Methods: RO7297089 was administered weekly by intravenous infusion to patients with relapsed/refractory multiple myeloma. The starting dose was 60 mg in this dose-escalation study utilizing a modified continual reassessment method with overdose control model., Results: Overall, 27 patients were treated at doses between 60 and 1850 mg. The maximally administered dose was 1850 mg due to excipients in the formulation that did not allow for higher doses to be used. The maximum tolerated dose was not reached. The most common adverse events irrespective of grade and relationship to the drug were anemia, infusion-related reaction, and thrombocytopenia. Most common treatment-related grade ≥ 3 toxicities were ALT/AST increase and reduced lymphocyte count. Pharmacokinetic studies suggested non-linear pharmacokinetics and target-mediated drug disposition, with a trend of approaching linear pharmacokinetics at doses of 1080 mg and higher. Partial response was observed in two patients (7%), minimal response in two patients (7%), and stable disease in 14 patients (52%)., Conclusions: RO7297089 was well tolerated at doses up to 1850 mg, and the efficacy data supported activity of RO7297089 in multiple myeloma. Combination with other agents may further enhance its potential as an innate immune cell engager in multiple myeloma., Trial Registration: ClinicalTrials.gov: NCT04434469; Registered June 16, 2020; https://www., Clinicaltrials: gov/ct2/show/NCT04434469 ., (© 2023. Genentech, Inc.)

Introduction: Given the rapid increase in novel treatments for patients with multiple myeloma (MM), this patient preference study aimed to establish which treatment attributes matter most to MM patients and evaluate discrete choice experiment (DCE) and swing weighting (SW) as two elicitation methods for quantifying patients' preferences., Methods: A survey incorporating DCE and SW was disseminated among European MM patients. The survey included attributes and levels informed by a previous qualitative study with 24 MM patients. Latent class and mixed logit models were used to estimate the DCE attribute weights and descriptive analyses were performed to derive SW weights. MM patients and patient organisations provided extensive feedback during survey development., Results: 393 MM patients across 21 countries completed the survey ( M years since diagnosis =6; M previous therapies =3). Significant differences (p<.01) between participants' attribute weights were revealed depending on participants' prior therapy experience, and their experience with side-effects and symptoms. Multivariate analyses showed that participants across the three MM patient classes identified via the latent class model differed regarding their past number of therapies ( F =4.772, p =.009). Patients with the most treatments (class 1) and those with the least treatments (class 3) attached more value to life expectancy versus quality of life-related attributes such as pain, mobility and thinking problems. Conversely, patients with intermediary treatment experience (class 2) attached more value to quality of life-related attributes versus life expectancy. Participants highlighted the difficulty of trading-off between life expectancy and quality of life and between physical and mental health. Participants expressed a need for greater psychological support to cope with their symptoms, treatment side-effects, and uncertainties. With respect to patients' preferences for the DCE or SW questions, 42% had no preference, 32% preferred DCE, and 25% preferred SW., Conclusions: Quality of life-related attributes affecting MM patients' physical, mental and psychological health such as pain, mobility and thinking problems were considered very important to MM patients, next to life expectancy. This underscores a need to include such attributes in decision-making by healthcare stakeholders involved in MM drug development, evidence generation, evaluation, and clinical practice. This study highlights DCE as the preferred methodology for understanding relative attribute weights from a patient's perspective., 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 © 2022 Janssens, Lang, Vallejo, Galinsky, Morgan, Plate, De Ronne, Verschueren, Schoefs, Vanhellemont, Delforge, Schjesvold, Cabezudo, Vandebroek, Stevens, Simoens and Huys.)

Objective: To understand the experience of patients with relapsed and refractory multiple myeloma (RRMM) receiving idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, in the pivotal, phase 2 KarMMa trial., Methods: Optional semi-structured interviews before leukapheresis (pre-treatment) captured expectations and after ide-cel infusion (1, 2, and 3 months post-treatment), assessed treatment experience, ide-cel advantages/disadvantages, and health and well-being. In a mixed-method analysis, treatment experiences were categorized by clinical response status, health and well-being, and self-reported recovery after infusion., Results: Pre-treatment interviews indicated unmet treatment needs. In post-treatment interviews, most patients reported the positives of ide-cel outweighed negatives (69%, n = 27/39). Most common advantages of ide-cel were efficacy (18-64%), favorable side-effect profile (46-68%), and recovery time (13-18%); most common disadvantages were related to side effects (13-20%). When analyzed by clinical response, patients most often had stringent complete or very good partial response and improved health and well-being with mild or severe recovery from the infusion (27/58, 47%). Most patients with minimal clinical response reported mild infusion recovery (5/6, 83%)., Conclusions: Patient interviews before ide-cel treatment showed unmet needs in triple-class exposed RRMM. Post-treatment experiences generally favored ide-cel versus previously received treatments., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma., Methods: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better)., Results: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2)., Conclusions: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.)., (Copyright © 2022 Massachusetts Medical Society.)

Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0-1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1-20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2-36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9-5.6) and 12.4 months (95% CI: 10.3-NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action., (© 2022. The Author(s).)

With the introduction of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, major improvements have been achieved in the treatment of multiple myeloma (MM), with a significant impact on the outcome of this disease. Different treatment combinations are now in use and other therapies are being developed. Based on an extensive review of the recent literature, we propose practical recommendations on myeloma management, to be used by hematologists as a reference for daily practice.

Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor T cell therapy, showed deep, durable responses in patients with triple-class exposed, relapsed and refractory multiple myeloma (RRMM) in the phase 2 KarMMa (Efficacy and Safety Study of bb2121 in Subjects With Relapsed and Refractory Multiple Myeloma) trial. We assessed health-related quality of life (HRQoL) among KarMMa patients. The European Organization for Research and Treatment of Cancer Quality of Life C30 Questionnaire and its supplementary 20-item multiple myeloma module, as well as the EuroQol 5-dimension 5-level instrument, were administered at screening, baseline (≤72 hours before or same day as lymphodepletion), day of ide-cel treatment, and after ide-cel treatment. Mean changes from baseline that exceeded the predetermined threshold of minimally important difference were deemed clinically meaningful. The proportions of patients experiencing clinically meaningful changes in HRQoL were assessed using within-patient change thresholds. Time to stable improvement (≥2 consecutive visits with clinically meaningful HRQoL improvements) was analyzed by using the Kaplan-Meier method. A total of 126 (98%) of 128 patients treated with ide-cel were included in the HRQoL analysis. Pretreatment baseline RRMM burden was high and meaningfully worse than that in the age- and sex-weighted general population. Statistically significant and clinically meaningful improvements from baseline were observed by month 1 for pain (-8.9) and disease symptoms (-10.2), and by month 2 for fatigue (-7.2), physical functioning (6.1), cognitive functioning (6.7), and global health status/QoL (8.0). Clinically meaningful improvements in fatigue, pain, and physical functioning were most prominent at months 9, 12, and 18, respectively, and were sustained through 15 to 18 months after ide-cel treatment. For triple-class exposed patients with RRMM with a poor prognosis and few treatment options, a single ide-cel infusion provides early, sustained, statistically significant, and clinically meaningful improvements in HRQoL. This study was registered at Clinicaltrials.gov as #NCT03361748., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Patients with multiple myeloma frequently present with substantial immune impairment and an increased risk for infections and infection-related mortality. The risk for infection with SARS-CoV-2 virus and resulting mortality is also increased, emphasising the importance of protecting patients by vaccination. Available data in patients with multiple myeloma suggest a suboptimal anti-SARS-CoV-2 immune response, meaning a proportion of patients are unprotected. Factors associated with poor response are uncontrolled disease, immunosuppression, concomitant therapy, more lines of therapy, and CD38 antibody-directed and B-cell maturation antigen-directed therapy. These facts suggest that monitoring the immune response to vaccination in patients with multiple myeloma might provide guidance for clinical management, such as administration of additional doses of the same or another vaccine, or even temporary treatment discontinuation, if possible. In those who do not exhibit a good response, prophylactic treatment with neutralising monoclonal antibody cocktails might be considered. In patients deficient of a SARS-CoV-2 immune response, adherence to measures for infection risk reduction is particularly recommended. This consensus was generated by members of the European Multiple Myeloma Network and some external experts. The panel members convened in virtual meetings and conducted an extensive literature research and evaluated recently published data and work presented at meetings, as well as findings from their own studies. The outcome of the discussions on establishing consensus recommendations for COVID-19 vaccination in patients with multiple myeloma was condensed into this Review., Competing Interests: Declaration of interests HL declares research funding from Amgen and Takeda, and speaker's honoraria from and participation on advisory boards for Amgen, Takeda, Sanofi, Janssen, Celgene-Bristol Myers Squibb, and Seattle Genetics. PS declares research funding from Amgen, Celgene-Bristol Myers Squibb, Janssen, SkylineDx, and Takeda, and honoraria from and participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, Janssen, SkylineDx, and Takeda. TF declares participation on advisory boards for Janssen, Bristol Myers Squibb, Takeda, Amgen, Roche, Karyopharm, Oncopeptides, and Abbvie, and speaker's honoraria from Janssen and Bristol Myers Squibb. JS-M declares consulting fees from and participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline, Regeneron, SecuraBio, and Karyopharm. M-VM declares honoraria from and participation on advisory boards for Janssen, Celgene-Bristol Myers Squibb, Takeda, Amgen, Sanofi, Oncopeptides, GlaxoSmithKline, Adaptive, Pfizer, Regeneron, Roche, Sea-Gen, and Blu Bird bio. PM declares honoraria from and participation on advisory boards for Janssen, Celgene-Bristol Myers Squibb, Amgen, Sanofi, and Abbvie. MC declares honoraria from Janssen, Celgene-Bristol Myers Squibb, GlaxoSmithKline, Amgen, Takeda, AbbVie, and Sanofi, and participation on advisory boards for Janssen, Celgene-Bristol Myers Squibb, GlaxoSmithKline, Amgen, Takeda, AbbVie, and Sanofi. CP declares consultancy fees from Amgen, Takeda, Celgene-Bristol Myers Squibb, and Sanofi; travel support from Amgen, Takeda, Janssen, and Celgene-Bristol Myers Squibb; and honoraria from Janssen, Celgene-Bristol Myers Squibb, and Sanofi. SZ declares research funding from Takeda and Janssen, and participation on advisory boards for Takeda, Janssen, Sanofi, Bristol Myers Squibb, and Oncopeptides. ME declares honoraria from and participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, GlaxoSmithKline, Janssen, Karyopharm, Sanofi, and Takeda, and research funding from Amgen, Celgene-Bristol Myers Squibb, Janssen, Karyopharm, and Takeda. GC declares honoraria from and participation on advisory boards for Celgene-Bristol Myers Squibb, Takeda, GlaxoSmithKline, Sanofi, Amgen, Janssen, and Oncopeptides, and research funding from GlaxoSmithKline and Takeda. MAD declares participation on advisory boards for Amgen, Takeda, Bristol Myers Squibb, Janssen, and Beigene. FG declares honoraria from Amgen, Janssen, Takeda, Celgene-Bristol Myers Squibb, AbbVie, and GlaxoSmithKline, and participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, Janssen, Takeda, AbbVie, GlaxoSmithKline, Roche, Adaptive Biotechnologies, Oncopeptides, and Bluebird Bio. HE declares honoraria from Amgen, Celgene-Bristol Myers Squibb, Janssen, Takeda, GlaxoSmithKline, Sanofi, Novartis; consultancy fees from and participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, Janssen, Takeda, GlaxoSmithKline, Sanofi, and Novartis; and research funding from Amgen, Celgene-Bristol Myers Squibb, Janssen, Sanofi, and GlaxoSmithKline. MD declares speaker's honoraria and research funding from Amgen, Celgene-Bristol Myers Squibb, Janssen, Sanofi, and Takeda. KW declares research funding from Amgen, Celgene-Bristol Myers Squibb, Janssen, and Sanofi, and honoraria from Amgen, Abbvie, Adaptive Biotech, Celgene-Bristol Myers Squibb, Janssen, Karyopharm, Novartis, Oncopeptides, Roche Pharma, Takeda, and Sanofi. GJ declares speaker's honoraria from and participation on advisory boards for Celgene-Bristol Myers Squibb, Takeda, GlaxoSmithKline, Sanofi, Amgen, Johnson & Johnson, and Oncopeptides, and research funding from Celgene-Bristol Myers Squibb and Takeda. LG declares participation on advisory boards for Amgen, Takeda, Celgene-Bristol Myers Squibb, and Janssen. NvdD declares research funding from Janssen Pharmaceuticals, Amgen, Celgene-Bristol Myers Squibb, Novartis, and Cellectis, and participation on advisory boards for Janssen Pharmaceuticals, Amgen, Celgene-Bristol Myers Squibb, Takeda, Roche, Novartis, Bayer, Servier, GlaxoSmithKline, and Sanofi. XL declares honoraria from Janssen-Cilag, Celgene-Bristol Myers Squibb, Amgen, Novartis, Takeda, Sanofi, Abbvie, Merck, Roche, Karyopharm Therapeutics, Carsgen Therapeutics, Oncopeptides, and GlaxoSmithKline; consulting and advisory roles for Janssen-Cilag, Celgene-Bristol Myers Squibb, Amgen, Takeda, Novartis, Merck, Gilead Sciences, Abbvie, Roche, Karyopharm Therapeutics, Oncopeptides, Carsgen Therapeutics, and GlaxoSmithKline; travel fees from Accommodations; and expenses from Takeda. HG declares grants and provision of Investigational Medicinal Product Amgen, Celgene-Bristol Myers Squibb, Chugai, Janssen, and Sanofi; research support from Amgen, Celgene-Bristol Myers Squibb, Chugai, Janssen, Incyte, Molecular Partners, MSD, Sanofi, Mundipharma GmbH, Takeda, and Novartis; participation on advisory boards for Adaptive Biotechnology, Amgen, Celgene-Bristol Myers Squibb, Janssen, Sanofi, and Takeda; and honoraria from Amgen, Celgene-Bristol Myers Squibb, Chugai, GlaxoSmithKline, Janssen, Novartis, and Sanofi. MeB declares participation on advisory boards for Amgen, Celgene-Bristol Myers Squibb, Janssen, Sanofi, Takeda, and Oncopeptides, and speaker's honoraria from Amgen, Celgene-Bristol Myers Squibb, Janssen, Sanofi, and Takeda. IN declares Advisory Boards and Honoraria: Amgen, Janssen, Celgene-Bristol Myers Squibb. MS declares speaker's honoraria and participation on advisory boards for Celgene-Bristol Myers Squibb, Amgen, Takeda, Janssen, and GlaxoSmithKline. NA declares research funding from Celgene-Bristol Myers Squibb, Amgen, Janssen, and Takeda. RH declares consultancy fees from and participation on advisory boards for Janssen, Amgen, AbbVie, Bristol Myers Squibb, Novartis, PharmaMar, and Takeda; honoraria from Janssen, Amgen, Bristol Myers Squibb, PharmaMar, and Takeda; and research funding from Janssen, Amgen, Bristol Myers Squibb, Novartis, and Takeda. NZ declares speaker's honoraria and participation on advisory boards for Celgene-Bristol Myers Squibb, Amgen, Takeda, Janssen, and Sanofi. EK declares consultancy fees and honoraria from and participation on advisory boards for Amgen, Genesis Pharma, Takeda, Janssen, and Pfizer Sanofi. AB declares honoraria from and participation on advisory boards for Amgen, Janssen, Celgene-Bristol Myers Squibb, and Sanofi. FS declares honoraria from Amgen, Celgene, Janssen, MSD, Novartis, Oncopeptides, Sanofi, SkyliteDX, and Takeda, and membership on an entity's advisory committees for Amgen, Celgene-Bristol Myers Squibb, Janssen, MSD, Novartis, Oncopeptides, Sanofi, and Takeda. MaB declares honoraria from Sanofi, Celgene-Bristol Myers Squibb, Amgen, Janssen, Novartis, and AbbVie; participation on advisory boards for Janssen and GlaxoSmithKline; and research funding from Sanofi, Celgene-Bristol Myers Squibb, Amgen, Janssen, Novartis, and Mundipharma. ET declares consultancy fees and honoraria from Amgen, Celgene-Bristol Myers Squibb, Janssen, Takeda, Genesis Pharma, GlaxoSmithKline, and Sanofi, and research support from Amgen, Janssen, Celgene-Bristol Myers Squibb, Genesis Pharma, GlaxoSmithKline, and Sanofi. HA-L, MM, CD, and JC declare no competing interests., (Crown Copyright © 2021 Published by Elsevier Ltd. All rights reserved.)

Background: CASSIOPEIA part 1 showed superior depth of response and significantly improved progression-free survival with daratumumab, bortezomib, thalidomide, and dexamethasone (D-VTd) versus bortezomib, thalidomide, and dexamethasone (VTd) as induction and consolidation in patients with autologous stem-cell transplant (ASCT)-eligible newly diagnosed multiple myeloma. In part 2, we compared daratumumab maintenance versus observation only., Methods: CASSIOPEIA is a two-part, open-label, randomised, phase 3 trial of patients aged 18-65 years with newly diagnosed multiple myeloma and Eastern Cooperative Oncology Group performance status 0-2, done in 111 European academic and community practice centres. In part 1, patients were randomly assigned (1:1) to induction and consolidation with D-VTd or VTd. Patients still on study who had a partial response or better were randomly assigned (1:1) by an interactive web-response system to daratumumab 16 mg/kg intravenously every 8 weeks (a reduced frequency compared with standard daratumumab long-term dosing) or observation only for up to 2 years. Stratification factors were induction treatment and depth of response in part 1. The part 2 primary endpoint was progression-free survival from second randomisation. This preplanned interim analysis of progression-free survival was done after 281 events and shall be considered the primary analysis of progression-free survival. Sponsor personnel and designees who were involved in the analysis were masked to treatment group until the independent data monitoring committee recommended that the preplanned interim analysis be considered the main analysis of progression-free survival in part 2. Otherwise, treatment assignments were unmasked. The interaction between induction and consolidation and maintenance was tested at a two-sided significance level of 0·05 by a stratified Cox regression model that included the interaction term between maintenance treatment and induction and consolidation treatment. Efficacy analyses were done in the maintenance-specific intention-to-treat population, which comprised all patients who underwent second randomisation. Safety was analysed in all patients in the daratumumab group who received at least one dose and all patients randomly assigned to observation only. This trial is registered with ClinicalTrials.gov, NCT02541383. Long-term follow-up is ongoing and the trial is closed to new participants., Findings: Between May 30, 2016, and June 18, 2018, 886 patients (458 [84%] of 543 in the D-VTd group and 428 [79%] of 542 in the VTd group) were randomly assigned to daratumumab maintenance (n=442) or observation only (n=444). At a median follow-up of 35·4 months (IQR 30·2-39·9) from second randomisation, median progression-free survival was not reached (95% CI not evaluable [NE]-NE) with daratumumab versus 46·7 months (40·0-NE) with observation only (hazard ratio 0·53, 95% CI 0·42-0·68, p<0·0001). A prespecified analysis of progression-free survival results showed a significant interaction between maintenance and induction and consolidation therapy (p<0·0001). The most common grade 3 or 4 adverse events were lymphopenia (16 [4%] of 440 patients in the daratumumab group vs eight [2%] of 444 patients in the observation-only group), hypertension (13 [3%] vs seven [2%]), and neutropenia (nine [2%] vs ten [2%]). Serious adverse events occurred in 100 (23%) patients in the daratumumab group and 84 (19%) patients in the observation-only group. In the daratumumab group, two adverse events led to death (septic shock and natural killer-cell lymphoblastic lymphoma); both were related to treatment., Interpretation: Daratumumab maintenance every 8 weeks for 2 years significantly reduced the risk of disease progression or death compared with observation only. Longer follow-up and other ongoing studies will shed further light on the optimal daratumumab-containing post-ASCT maintenance treatment strategy., Funding: Janssen Research & Development, the Intergroupe Francophone du Myélome, and the Dutch-Belgian Cooperative Trial Group for Hematology Oncology., Competing Interests: Declaration of interests PM reports personal fees from Celgene, Amgen, Takeda, Janssen, and AbbVie, outside the submitted work. CH reports personal fees from Janssen, AbbVie, Amgen, and Celgene, outside the submitted work. AP reports personal fees from Celgene, Amgen, Janssen, Sanofi, and Takeda, outside the submitted work. BA reports grants from Amgen, Celgene, Sanofi, and Janssen, during the conduct of the study; personal fees from Amgen, Celgene/Bristol Myers Squibb, Sanofi, GlaxoSmithKline, Takeda, and Janssen, outside the submitted work; and advisory board participation from Amgen, Celgene/Bristol Myers Squibb, Sanofi, GlaxoSmithKline, and Janssen, outside the submitted work. KB reports grants from Celgene outside the submitted work; personal fees from Celgene, Janssen, Takeda, and Amgen, outside the submitted work; and non-financial support from Celgene, AbbVie, and Takeda, outside the submitted work. SZ reports grants from Celgene, Janssen, and Takeda, during the conduct of the study. MD reports grants from Celgene and Janssen during the conduct of the study; participation on an advisory board for Celgene, Takeda, Janssen, Sanofi, and Oncopeptides, outside the submitted work. TD reports grants from Celgene and Janssen, during the conduct of the study; and personal fees and advisory board participation from Celgene, Takeda, Janssen, and Amgen, outside of the submitted work. CD reports personal fees from Janssen, outside the submitted work. TF reports personal fees from Janssen, Bristol Myers Squibb, Takeda, Amgen, Roche, Karyopharm, Sanofi, and Oncopeptides, outside the submitted work. CS reports personal fees from Celgene, outside the submitted work. MMo reports grants from Stemline, BMS, Amgen, Jazz Pharmaceuticals, Novartis, Takeda, Janssen, GSK, Sanofi, and Celgene; non-financial support from Stemline, BMS, Amgen, Jazz Pharmaceuticals, Novartis, Takeda, Janssen, GSK, Sanofi, and Celgene; and personal fees from Stemline, BMS, Amgen, Jazz Pharmaceuticals, Novartis, Takeda, Janssen, GSK, Sanofi, and Celgene, outside the submitted work. LK reports personal fees from Amgen, Janssen, Celgene, Takeda, and AbbVie, outside the submitted work. XL reports personal fees from Janssen, outside the submitted work. MMa reports personal fees from and advisory board participation for Amgen, Celgene, Janssen, and Takeda, outside the submitted work. A-MS reports personal fees from Celgene outside the submitted work. NWCJvdD reports grants from Amgen, Bristol Myers Squibb, Celgene, Janssen, and Novartis, during the conduct of the study; and personal fees from Amgen, Bristol Myers Squibb, Celgene, Janssen, Novartis, Bayer, Roche, Servier, and Takeda, outside the submitted work. AB reports personal fees from Amgen, Celgene, Janssen, and Bristol Myers Squibb, outside the submitted work. CT reports personal fees from Janssen, outside the submitter work. MR reports grants from Janssen, during the conduct of the study; personal fees and travel support from Celgene, Amgen, Sanofi, Takeda, and Janssen, outside the submitted work. M-DL reports grants from AbbVie, Amgen, Janssen, Roche, and Takeda, during the conduct of the study; and personal fees and advisory board participation from AbbVie, Janssen, Roche, and Takeda, outside the submitted work. TA reports employment and equity ownership from Genmab. MK reports employment with Janssen. KZ reports employment with Janssen. CdB reports employment and equity ownership from Janssen. SV reports employment with Janssen. TK reports employment with Janssen. VV reports employment with Janssen. JV reports employment with Janssen. HA-L reports grants from Celgene and Janssen, during the conduct of the study; and personal fees from Celgene, Amgen, Bristol-Myers Squibb, Sanofi, and Janssen, outside the submitted work. PS reports personal fees from Celgene and Janssen, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Idecabtagene vicleucel (ide-cel, bb2121), a chimeric antigen receptor (CAR) T cell therapy, has been investigated in patients with relapsed and refractory multiple myeloma (RRMM) who have received an immunomodulatory drug, proteasome inhibitor, and anti-CD38 antibody in the single-arm phase 2 KarMMa clinical trial. Two therapies with distinct mechanisms of action - selinexor plus dexamethasone (Sd) and belantamab mafodotin (BM) - are currently approved in the United States for heavily pretreated patients, including those who are triple-class refractory. To compare ide-cel versus Sd and ide-cel versus BM, matching-adjusted indirect comparisons were performed. Ide-cel extended progression-free survival (PFS) and overall survival (OS) versus both Sd and BM (hazard ratio (HR); 95% confidence interval (CI)). PFS: ide-cel versus Sd, 0.46; 0.28-0.75; ide-cel versus BM, 0.45; 0.27-0.77. OS: ide-cel versus Sd, 0.23; 0.13-0.42; ide-cel versus BM, 0.35; 0.14-0.87. These results suggest ide-cel offers clinically meaningful improvements over currently approved regimens for patients with heavily pretreated RRMM.

Background: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM., Methods: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders., Results: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores., Conclusion: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach., Trial Registration: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015., (© 2021. The Author(s).)

Background: Investigational and marketed drugs for the treatment of multiple myeloma (MM) are associated with a range of characteristics and uncertainties regarding long term side-effects and efficacy. This raises questions about what matters most to patients living with this disease. This study aimed to understand which characteristics MM patients find most important, and hence should be included as attributes and levels in a subsequent quantitative preference survey among MM patients. Methods: This qualitative study involved: (i) a scoping literature review, (ii) discussions with MM patients ( n = 24) in Belgium, Finland, Romania, and Spain using Nominal Group Technique , (iii) a qualitative thematic analysis including multi-stakeholder discussions. Results: MM patients voiced significant expectations and hopes that treatments would extend their lives and reduce their cancer signs and symptoms. Participants however raised concerns about life-threatening side-effects that could cause permanent organ damage. Bone fractures and debilitating neuropathic effects (such as chronic tingling sensations) were highlighted as major issues reducing patients' independence and mobility. Patients discussed the negative impact of the following symptoms and side-effects on their daily activities: thinking problems, increased susceptibility to infections, reduced energy, pain, emotional problems, and vision problems. MM patients were concerned with uncertainties regarding the durability of positive treatment outcomes, and the cause, severity, and duration of their symptoms and side-effects. Patients feared short-term positive treatment responses complicated by permanent, severe side-effects and symptoms. Conclusions: This study gained an in-depth understanding of the treatment and disease-related characteristics and types of attribute levels (severity, duration) that are most important to MM patients. Results from this study argue in favor of MM drug development and individual treatment decision-making that focuses not only on extending patients' lives but also on addressing those symptoms and side-effects that significantly impact MM patients' quality of life. This study underscores a need for transparent communication toward MM patients about MM treatment outcomes and uncertainties regarding their long-term efficacy and safety. Finally, this study may help drug developers and decision-makers understand which treatment outcomes and uncertainties are most important to MM patients and therefore should be incorporated in MM drug development, evaluation, and clinical practice., 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 © 2021 Janssens, Lang, Vallejo, Galinsky, Plate, Morgan, Cabezudo, Silvennoinen, Coriu, Badelita, Irimia, Anttonen, Manninen, Schoefs, Vandebroek, Vanhellemont, Delforge, Stevens, Simoens and Huys.)

Introduction: This study aims to develop and validate a simple score to estimate survival in the older population suffering from malignant hemopathies., Methods: We prospectively recruited 285 patients, aged ≥65 years, admitted to receive chemotherapy. At inclusion, a geriatric assessment was performed. Cox proportional hazards models were performed to assess correlations between vulnerabilities and one-year survival. We developed a frailty score, HEMA-4, based on the most powerful prognostic factors. It was externally confirmed with an independent cohort., Results: In the development cohort, 206 patients were evaluable. Mean age was 76 years (range 65-90). The HEMA-4 score was created based on four independent predictive factors for survival: cognitive impairment (MMSE<27), comorbidities (≥2 on Charlson comorbidity index), CRP (≥10 mg/L) and low albumin level (<35 g/L). The population was stratified into three groups: good prognosis (score = 0-1, n = 141), intermediate prognosis (score = 2, n = 37) and poor prognosis (score = 3-4, n = 28). Their respective one-year survival was 74%, 51% (HR = 2.30; 95% CI =1.31-4.05; p < 0.01) and 36% (HR = 3.95; 95% CI =2.23-6.98; p < 0.01). In the validation cohort (n = 25), the one-year survival was 78% in the good prognosis group (n = 9) and 50% in the intermediate prognosis group (n = 6). The poor prognosis group had a median survival of four months in the development cohort and six months in the validation cohort (n = 10)., Conclusion: The HEMA-4 score is a simple score that combines cognitive impairment, comorbidities, inflammation and low albumin level. Our data suggest that it predicts survival among older patients suffering from malignant hemopathies referred to receive chemotherapy regardless of their chronological age., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

To understand the profile of best responders (complete response or better [≥CR]) to carfilzomib, we described the characteristics, progression-free survival (PFS), overall survival (OS) data, and the safety of patients who achieved ≥CR to carfilzomib-based treatment in ASPIRE and ENDEAVOR. In post hoc analyses from ASPIRE and ENDEAVOR, median PFS and OS were longer for ≥CR patients versus those who achieved a very good partial response or partial response (VGPR/PR). In the carfilzomib arm of ASPIRE, median PFS was 50.4 months for ≥CR versus 22.1 months for VGPR/PR; median OS was 67.0 versus 44.2 months, respectively. In the carfilzomib arm of ENDEAVOR, median PFS was 34.0 for ≥CR versus 20.4 months for VGPR/PR; median OS was non-estimable. Despite the longer treatment duration, fewer patients with ≥CR versus VGPR/PR experienced treatment-emergent adverse events that led to discontinuation of carfilzomib-based treatment in ASPIRE or ENDEAVOR. Low serum lactate dehydrogenase was the only factor associated with achieving ≥CR vs patients not achieving CR in ASPIRE in multivariate regression analyses. No association was found between cytogenetic risk status and reaching ≥CR. Carfilzomib treatment may lead to rapid and deep responses, irrespective of most patient characteristics.

Introduction : Impressive therapeutic progress is being made in the management of multiple myeloma (MM). his progress is related to the introduction of several new classes of therapeutic agents including proteasome inhibitors, immunomodulatory drugs (IMiDs) and monoclonal antibodies (MoAbs). Areas covered : In this manuscript, the role of the IMiDs thalidomide and lenalidomide in the management of newly diagnosed MM is discussed. The mode of action of IMiDs and their role in the management of newly diagnosed MM patients is highlighted. In addition, clinical data on how MoAbs such as the anti-CD38 antibody daratumumab can further increase the efficacy of IMiD-based first-line anti-myeloma regimens are provided. A database search in PubMed was carried out. Expert Opinion : Immunomodulation has become an indispensable part of successful anti-myeloma regimens both at relapse and at diagnosis. The combination of lenalidomide plus dexamethasone with an anti-CD38 MoAb such as daratumumab and a proteasome inhibitor such as bortezomib is currently one of the most potent first-line treatment regimens for MM. A better understanding on how IMiDs synergize with existing and new anti-myeloma treatments can further improve the outcome for patients. Optimal first-line therapy will continue to benefit the long-term outcome of a growing population of young and elderly MM patients.

Background: Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic effects in patients with relapsed and refractory multiple myeloma., Methods: In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 10 6 to 450 × 10 6 CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses)., Results: Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10 -5 nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion., Conclusions: Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.)., (Copyright © 2021 Massachusetts Medical Society.)

Competing Interests: MAD reported consultancy and honoraria from Janssen, Celgene, Takeda, Amgen and Bristol Myers Squibb. PM reported honoraria from Celgene, Janssen, Takeda, Amgen and Abbvie. ET reported honoraria from Bristol Myers Squibb, Janssen, Celgene, Takeda, Genesis Pharma, Amgen, Sanofi and Novartis and research funding from Janssen, Amgen, Takeda, Sanofi and Genesis Pharma. MVM reported honoraria from lectures and boards from Janssen, Celgene, Amgen, Takeda, Abbvie, GlaxoSmithKline, Adaptive, Roche and Seattle Genetics. SZ reported participation in advisory boards for Takeda, Celgene, Janssen, Sanofi and Oncopeptides and research funding from Celgene, Janssen and Takeda. GC reported being a member of speaker bureau for Takeda, Bristol Myers Squibb, Celgene, Amgen, Sanofi and Janssen and has received research grants from Bristol Myers Squibb, Celgene and Takeda. MD reported honoraria from Abbvie, Adaptive Biotechnologies, Amgen, Bristol Myers Squibb, Celgene, Janssen, Karyopharm, Sanofi and Takeda and has received research funding from Bristol Myers Squibb, Celgene, Janssen and Takeda. RH reported consultant or advisory roles for Janssen, Amgen, Celgene, AbbVie, Bristol Myers Squibb, Novartis, PharmaMar and Takeda; honoraria from Janssen, Amgen, Celgene, Bristol Myers Squibb, PharmaMar and Takeda and has received research grants from Janssen, Amgen, Celgene, Bristol Myers Squibb, Novartis and Takeda. FS reported honoraria from Amgen, Celgene, Bristol Myers Squibb, Takeda, Abbvie, Janssen, Novartis, SkyliteDX, Oncopeptides, Sanofi, GlaxoSmithKline, Adaptive and Merck Sharp & Dohme. MC reported honoraria from Janssen, Celgene, Amgen, Bristol Myers Squibb, Takeda, AbbVie, Sanofi and Adaptive Biotechnologies and speaker’s bureau membership for Janssen and Celgene. HG reported grants from Amgen, Bristol Myers Squibb, Celgene, Chugai, Dietmar-Hopp-Foundation, Janssen, John Hopkins University and Sanofi; research support from Amgen, Bristol Myers Squibb, Celgene, Chugai, Janssen, Incyte, Molecular Partners, Merck Sharp & Dohme, Sanofi, Mundipharma, Takeda and Novartis; participation in advisory boards for Adaptive Biotechnology, Amgen, Bristol Myers Squibb, Celgene, Janssen, Sanofi, Takeda; honoraria from Academy2 GmbH & Co. KG, Amgen, ArtTempi, Bristol Myers Squibb, Celgene, Chop GmbH, Chugai, FomF GmbH, GlaxoSmithKline, GWT Forschung und Innovation Dresden, InVo Institut für Versorgungsforschung in der Onkologie GbR, Janssen, Kompetenznetz Maligne Lymphome (KML), MedConcept GmbH, Medical Communication GmbH, New Concept Oncology, Novartis, Omnia Med Deutschland, Sanofi. TF reported speaker and advisory roles for Janssen, Bristol Myers Squibb, Takeda, advisory role for Roche, Sanofi, Karyopharm and Oncopeptides and Speaker for Amgen. HE reported consulting and advisory roles for Bristol Myers Squibb, Celgene, Janssen, Amgen, Takeda, Sanofi and GlaxoSmithKline; research funding from Bristol Myers Squibb, Celgene, Janssen, Amgen, GlaxoSmithKline and Sanofi; honoraria from Bristol Myers Squibb, Celgene, Amgen, Takeda, Sanofi and GlaxoSmithKline. MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb and AbbVie; has served on the advisory boards for Janssen and GlaxoSmithKline; has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol Myers Squibb and Mundipharma. JS-M reported consultancy for Amgen, Bristol Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, GlaxoSmithKline, Takeda, Sanofi and Roche. PS reported honoraria and advisory roles for Celgene, Janssen, Amgen, Takeda, Bristol Myers Squibb and Skyline and research funding from Celgene, Amgen, Janssen and Takeda. UM reported honoraria from Celgene, Janssen, Amgen, Takeda, AbbVie, Bristol Myers Squibb and Sanofi.

Objective : The aim of this study was to evaluate the administration of intravenous immunoglobulin (IVIg) solutions (5% vs. 10%) in hematological patients suffering from a secondary immunodeficiency (SID) to optimize infusion duration and hospitalization time. Design : A monocentric, observational study in 30 patients with secondary hypogammaglobulinemia due to a lymphoproliferative disorder currently under IVIg 5% treatment. A sequential approach was followed with observations during IVIg 5% and 10% administration 3 to 4 weeks later. Infusion time, time spent at the day clinic, IVIg-related adverse events and number of actions taken by the nursing staff were evaluated and compared between the 5% and 10% infusions. Questionnaires for patients and nursing staff were obtained after IVIg 10% to assess their satisfaction with the change of infusion. Results : Average infusion time was reduced from 4.92 h to 2.29 h (p < 0.0001). Time spent at the day clinic was 5.87 h for the 5% IVIg administration and 4.56 h for the 10% (p = 0.0005). IVIg-related adverse events rose from 0 to 0.43 per patient. No serious adverse events were reported. Nursing actions per patient decreased from 1.03 to 0.67. Patient and nursing satisfaction were respectively 83% and 96% in favor of IVIg 10%. Conclusion : A 10% IVIg solution can significantly reduce infusion time and overall duration of the day clinic visit. Care must be taken to minimize new infusion-related adverse events. Switching to a 10% IVIg administration increases patient and nursing satisfaction but also requires additional workflow changes to further shorten the day clinic visit.

Purpose: To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study., Patients and Methods: PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs., Results: A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score., Conclusion: D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.

We analyzed newly diagnosed multiple myeloma patients with del(17p) and/or t(4;14) undergoing either upfront single autologous (auto), tandem autologous (auto-auto) or tandem autologous/reduced-intensity allogeneic (auto-allo) stem cell transplantation. 623 patients underwent either auto (n = 446), auto-auto (n = 105), or auto-allo (n = 72) between 2000 and 2015. 46% of patients had t(4;14), 45% had del(17p) while 9% were reported having both abnormalities. Five-year overall survival (OS) was 51% (95% confidence interval [CI], 45-58%) for single auto, 60% (95% CI, 49-72%) for auto-auto, and 67% (95% CI, 53-80%) for auto-allo (p = 0.187). Five-year progression-free survival (PFS) was 17% (95% CI, 12-22%), 33% (95% CI, 22-43%), and 34% (95% CI, 21-38%; p = 0.048). Five-year relapse rate was 82, 63, and 56%, while non-relapse mortality was 1, 4, and 10%. In multivariable analysis, in t(4;14) with single auto as reference, auto-auto (hazard ratio [HR], 0.44; p = 0.007) and auto-allo (HR, 0.45; p = 0.018) were associated with better PFS. In terms of t(4;14) and OS, auto-auto appeared to improve outcome compared with single auto (HR, 0.49; p = 0.096). In del(17p), outcome in PFS was similar between single auto and auto-auto, while auto-allo appeared to improve PFS (HR, 0.65; p = 0.097). No significant difference in OS was identified between the groups in patients with del(17p).

Vaccination is one of the most successful medical interventions that has saved the life of millions of people. Vaccination is particularly important in patients with multiple myeloma, who have an increased risk of infections due to the disease-inherent immune suppression, and because of the immune suppressive effects of therapy. Hence, all appropriate measures should be exploited, to elicit an effective immune response to common pathogens like influenza, pneumococci, varicella zoster virus, and to those bacteria and viruses (haemophilus influenzae, meningococci, and hepatitis) that frequently may pose a significant risk to patients with multiple myeloma. Patients after autologous, and specifically after allogeneic transplantation have severely reduced antibody titers, and therefore require a broader spectrum of vaccinations. Response to vaccination in myeloma often is less vigorous than in the general population, mandating either measurement of the postvaccination antibody titers and/or repeating the vaccination. Here, we compile the existing data on vaccination in multiple myeloma and provide recommendations for clinical practice.

Multiple myeloma (MM), is a heterogeneous disease in which chromosomal abnormalities are important for prognostic risk stratification. Cytogenetic profiling with FISH on plasma cells from bone marrow samples (BM-PCs) is the current gold standard, but variable infiltration of plasma cells or failed aspiration can hamper this process. Ultra-low coverage sequencing (ULCS) of circulating cell-free DNA (ccfDNA) may offer a minimally invasive alternative for the work-up of these cases. We compared ULCS, aCGH and FISH on selected BM-PCs in a routine setting with ULCS of ccfDNA for the detection of somatic copy number aberrations (CNAs) in MM., Methods: Purified CD138+ BM-PCs of 23 MM patients at initiation of their treatment were subjected to aCGH, FISH and ULCS. Paired samples of peripheral blood-ccfDNA obtained at diagnosis were analyzed by ULCS and compared to the results found in BM-PCs., Results: Using ULCS of ccfDNA, cytogenetic markers were identified in 18 out of 23 patients; five cases could not be analyzed due to low (≤3%) tumor fraction (TF). High similarity between CNA profiles of BM-PCs and ccfDNA was found. Moreover, 78% of the ccfDNA profiles resulted in the same risk classification as the routine FISH and/or BM-PCs ULCS and aCGH. Chromothripsis was detected in five patients; these had the highest TF values (range 7.1% to 42%) in our series and their profiles showed other high-risk anomalies., Conclusion: This proof-of-principle study indicates that ULCS of ccfDNA can reveal CNAs in MM and should be explored further as a cost-efficient alternative, especially in cases where BM-PC purification fails., (Copyright © 2021. Published by Elsevier Ltd.)

In medicine, not everything is what it seems and sometimes you need all the pieces of the puzzle in order to complete the diagnosis. This is a case of a disease with two different faces and a review of its respiratory impact. https://bit.ly/2SDKwE5., Competing Interests: Conflict of interest: M. Vandebotermet has nothing to disclose. Conflict of interest: F. Staels has nothing to disclose. Conflict of interest: S. Giovannozzi has nothing to disclose. Conflict of interest: M. Delforge has nothing to disclose. Conflict of interest: T. Tousseyn has nothing to disclose. Conflict of interest: T. Steelandt has nothing to disclose. Conflict of interest: A. Corveleyn has nothing to disclose. Conflict of interest: I. Meyts has nothing to disclose. Conflict of interest: J. Maertens has nothing to disclose. Conflict of interest: J. Yserbyt has nothing to disclose. Conflict of interest: R. Schrijvers has nothing to disclose., (Copyright ©ERS 2020.)