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In the phase 2 GRIFFIN trial (ClinicalTrials.gov identifier: NCT02874742), daratumumab added to lenalidomide, bortezomib, and dexamethasone (D-RVd) improved depth of response and progression-free survival (PFS) versus lenalidomide, bortezomib, and dexamethasone (RVd) alone in transplant-eligible (TE) patients with newly diagnosed multiple myeloma (NDMM). Here, we present patient-reported outcomes (PROs) collected using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30-item (QLQ-C30), EORTC Quality of Life Questionnaire Multiple Myeloma Module 20-item (QLQ-MY20), and EuroQol 5-Dimension 5-Level (EQ-5D-5L) tools on day 1 of cycles 1, 2, and 3; on day 21 of cycle 4 (end of induction therapy); on day 1 of cycle 5; on day 21 of cycle 6 (end of posttransplant consolidation therapy); and at months 6, 12, 18, and 24 of maintenance therapy. Meaningful improvements from baseline were seen in most of the PRO scales with both treatments after consolidation and were sustained for at least 2 years of maintenance treatment. Large reductions from baseline (~20 points) were especially observed in pain symptoms for both treatment groups, although these were numerically higher for patients receiving D-RVd during the majority of the time points. In addition, improvements in key scales, such as global health status, fatigue symptoms, and physical functioning, were also seen with both D-RVd and RVd. These improvements in health-related quality of life contribute to the totality of evidence supporting the improvement in clinical outcomes such as response rates and PFS with D-RVd in induction, consolidation, and maintenance therapy in TE patients with NDMM., (© 2024 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Due in part to racial disparities and underrepresentation in clinical studies, optimal therapies for Black patients with multiple myeloma remain undefined. This final analysis of GRIFFIN by race showed that the addition of daratumumab (D) to lenalidomide/bortezomib/dexamethasone (RVd) provides clinical benefit among both Black and White transplant-eligible newly diagnosed patients compared with RVd alone. However, Black patients were more likely to discontinue ≥1 drug due to treatment-emergent adverse events. In summary, these findings suggest a benefit of D-RVd front-line therapy among Black and White patients and underscore the importance of equitable treatment access for all patients., (© 2024 Janssen Scientific Affairs, LLC. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Daratumumab plus lenalidomide and dexamethasone (D-Rd) and bortezomib plus lenalidomide and dexamethasone (VRd) are commonly used treatment combinations for transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma (NDMM). D-Rd and VRd demonstrated superior efficacy relative to lenalidomide and dexamethasone (Rd) in the MAIA and SWOG S0777 trials, respectively, but have not been compared directly in a head-to-head trial. Naïve comparisons of efficacy across the two trials may be biased because MAIA enrolled only TIE patients (median age 73 years), whereas SWOG S0777 enrolled both TIE patients and transplant-eligible patients who chose to defer/refuse frontline stem cell transplantation (median age 63 years). The present study compared progression-free survival (PFS) in TIE patients with NDMM treated with D-Rd versus VRd based on an adjusted indirect treatment comparison (ITC) that leveraged individual patient-level data from MAIA and SWOG S0777., Methods: Harmonized inclusion/exclusion criteria (including age ≥ 65 years as a proxy for transplant ineligibility) and propensity-score weighting were used to balance the trial populations on measured baseline characteristics. After differences in trial populations were adjusted for, an anchored ITC was performed wherein within-trial PFS hazard ratios (HRs) for D-Rd versus Rd and VRd versus Rd were estimated and used to make indirect inference about PFS for D-Rd versus VRd., Results: PFS HRs were 0.52 (95% confidence interval [CI] 0.41-0.67) for D-Rd versus Rd based on MAIA data, 0.88 (95% CI 0.63-1.23) for VRd versus Rd based on SWOG S0777 data, and 0.59 (95% CI 0.39-0.90) for the Rd-anchored ITC of D-Rd versus VRd. Sensitivity and subgroup analyses produced results consistent with the primary results., Conclusion: This anchored ITC demonstrated a greater PFS benefit for D-Rd versus VRd in TIE patients with NDMM. In the absence of head-to-head trials comparing D-Rd and VRd, the present trial may help inform treatment selection in this patient population., (© 2024. The Author(s).)

Background: Few studies have addressed the cost patterns of patients with multiple myeloma (MM) before and after first relapse. This US claims analysis evaluated, from a US health plan perspective, patterns of total direct costs of care from treatment initiation to progression for patients with MM treated with novel agents, using time to next therapy (TTNT) as a proxy measure for progression., Methods: A retrospective study was conducted using a large US claims database, evaluating patients with claims for MM between 2006 and 2013. Patients with claims for stem cell transplant (SCT) were excluded. The analysis focused on patients receiving lenalidomide (LEN) or bortezomib (BORT) based treatment, for whom complete claim history was available through initiation of subsequent treatment. Average patient monthly direct costs were determined, including medical and pharmacy costs, and total cost patterns over quarterly time periods were calculated., Results: The study population comprised 2843 patients with newly diagnosed MM (NDMM) and 1361 with relapsed MM. Total monthly cost for patients with NDMM declined steadily, from $15,734 initially to $5082 at 18+ months after therapy. Upon initiation of second-line therapy, total monthly costs rose to $13,876 and declined to $6446 18 months later. Although NDMM cost levels for individual ordinal months were similar between the LEN and BORT groups, TTNT was longer for LEN-based treatments (37 months). The BORT-treated cohort had higher average monthly total costs for NDMM and for the common time period through 37 months after initiation of therapy ($7534 vs $10,763 for LEN and BORT, respectively). Key limitations of this study, in addition to the lack of mortality and staging information available from claims data, include the definition of TTNT based on change in treatment or a defined gap in therapy prior to retreatment, which may differ from actual time of progression in some patients., Conclusions: For patients with NDMM receiving either LEN- or BORT-based treatment without SCT, followed until TTNT, total direct monthly costs (drug + medical) declined steadily over time. Monthly costs returned to near initial levels when patients began second-line therapy and then followed a similar pattern of decline. Due to the longer TTNT for patients initiated on LEN and the associated longer period of below-average costs, patients initiated with LEN-based treatments had mean monthly total costs >$3200 lower than total costs for patients initiated on BORT during the first 3 years after starting treatment, cumulating to nearly $120,000 in lower costs for patients initiated on LEN.

Lenalidomide and dexamethasone with bortezomib (VRd) or carfilzomib (KRd) are commonly used induction regimens in the U.S. This single-center, retrospective study evaluated outcomes and safety of VRd and KRd. Primary endpoint was progression-free survival (PFS). Of 389 patients with newly diagnosed multiple myeloma, 198 received VRd and 191 received KRd. Median PFS was not reached (NR) in both groups; 5-year PFS was 56% (95%CI, 48–64%) for VRd and 67% (60–75%) for KRd (P = 0.027). Estimated 5-year EFS was 34% (95%CI, 27–42%) for VRd and 52% (45–60%) for KRd (P < 0.001) with corresponding 5-year OS of 80% (95%CI, 75–87%) and 90% (85–95%), respectively (P = 0.053). For standard-risk patients, 5-year PFS was 68% (95%CI, 60–78%) for VRd and 75% (65–85%) for KRd (P = 0.20) with 5-year OS of 87% (95%CI, 81–94%) and 93% (87–99%), respectively (P = 0.13). For high-risk patients, median PFS was 41 months (95%CI, 32.8–61.1) for VRd and 70.9 months (58.2-NR) for KRd (P = 0.016). Respective 5-year PFS and OS were 35% (95%CI, 24–51%) and 69% (58–82%) for VRd and 58% (47–71%) and 88% (80–97%, P = 0.044) for KRd. Overall, KRd resulted in improved PFS and EFS with a trend toward improved OS compared to VRd with associations primarily driven by improvements in outcome for high-risk patients. [ABSTRACT FROM AUTHOR]

Magrolimab is a monoclonal antibody that blocks CD47, a 'do not eat me' signal overexpressed on tumor cells. CD47 is overexpressed in multiple myeloma (MM), which contributes to its pathogenesis. Preclinical studies have shown that CD47 blockade induces macrophage activation, resulting in elimination of myeloma cells, and that there is synergy between magrolimab and certain anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This phase II study investigates magrolimab in combination with commonly used myeloma therapies in patients with relapsed/refractory MM and includes a safety run-in phase followed by a dose-expansion phase. Primary end points include the incidence of dose-limiting toxicities and adverse events (safety run-in) and the objective response rate (dose expansion). Magrolimab is a therapy that blocks a 'do not eat me' signal overexpressed by certain cancers, including multiple myeloma (MM) cells. Studies have shown that blocking this signal leads to destruction of myeloma cells and that this cancer-killing effect may be increased by combining magrolimab with certain additional anticancer therapies. These findings suggest that magrolimab-based combinations may have a therapeutic benefit in MM. This study is investigating magrolimab in combination with commonly used myeloma therapies in patients with MM who have persistent disease despite prior treatment. Goals of the trial include assessing safety and response to treatment. Clinical Trial Registration:NCT04892446 (ClinicalTrials.gov) This phase II study investigates safety and treatment response to #magrolimab, an antibody that enhances phagocytosis of cancer cells, combined with commonly used therapies in patients with #multiplemyeloma. [ABSTRACT FROM AUTHOR]

Background and Objective: Ciltacabtagene autoleucel (cilta-cel) is a novel agent being investigated in the single-arm CARTITUDE-1 trial (NCT03548207) for patients with relapsed or refractory multiple myeloma who are triple-class exposed to an immunomodulatory drug, proteasome inhibitor, and an anti-CD38 monoclonal antibody. The objective of this study was to evaluate the comparative efficacy of cilta-cel vs physician's choice of treatment, as no head-to-head trials have been conducted. Methods: An external control arm for CARTITUDE-1 was created from patients in the long-term follow-up for three clinical trials of daratumumab (POLLUX, CASTOR, and EQUULEUS) who satisfied the eligibility criteria of CARTITUDE-1. These patients received physician's choice of treatment following the discontinuation of study drugs. Inverse probability of treatment weighting was used to align the external control and CARTITUDE-1 populations on important baseline characteristics. Overall response rate, complete response or better rate, progression-free survival, time to next treatment, and overall survival were assessed. Several sensitivity analyses were conducted. Results: After propensity score weighting, baseline characteristics were comparable between cohorts. Patients showed improved results with cilta-cel vs physician's choice of treatment: overall response rate (relative risk: 2.95 [95% confidence interval (CI) 2.27, 3.84; p < 0.0001]), complete response or better (relative risk: 111.70 [95% CI 29.08, 429.06; p < 0.0001]), progression-free survival (hazard ratio [HR]: 0.24 [95% CI 0.15, 0.37; p < 0.0001]), time to next treatment (HR: 0.14 [95% CI 0.09, 0.22; p < 0.0001]), and overall survival (HR: 0.21 [95% CI 0.13, 0.35; p < 0.0001]). Results were consistent across all sensitivity analyses. Conclusions: Cilta-cel showed superior efficacy compared with physician's choice of treatment, making it a promising new treatment option for patients with triple-class exposed relapsed or refractory multiple myeloma. [ABSTRACT FROM AUTHOR]

The article focuses on the role of Daratumumab, pomalidomide and dexamethasone (Pd) combination therapy for the treatment of relapsed and refractory multiple myeloma. It mentions the addition of daratumumab to the Pd backbone (DaraPd) for the patients with relapsed and refractory multiple myelom and also discussions on daratumumab that depletes levels of CD38 (cluster of differentiation 38).