Background:Multiple myeloma (MM) is an incurable hematological malignancy with increasing prevalence. While randomized controlled trials have demonstrated survival improvements, they underrepresent older and comorbid patients. Real-world data from observational cohorts are therefore essential. Objective:To assess the comparability of patient, hospitalization and center characteristics for patients treated in centers included in the French Epidemiology of Multiple MYeloma (EmmY) cohort with those treated in centers of the French-speaking Intergroupe Francophone du Myélome (IFM) network (including EmmY) and those treated in all centers treating MM in France between 2017-2023. Methods:We analyzed French national hospital discharge data (PMSI) to identify adults hospitalized with MM (ICD-10 C90) between August 2017 and December 2023. Patient demographics, comorbidities, hospitalization characteristics, and center profiles were compared between the three cohorts using standardized differences. Results:We identified 69,276 patients (including 50,243 IFM and 33,785 EmmY), 1,871,369 hospitalizations (including 1,484,288 IFM and 1,022,462 EmmY), and 323 centers (including 118 IFM and 70 EmmY). EmmY centers were larger and treated a higher mean proportion of MM patients (2.7%) per center than IFM (2.4%) and all MM centers (1.3%). No clinically meaningful differences were observed between EmmY and IFM centers regarding patient age, sex, comorbidities, treatment patterns, or hospitalization outcomes. Conclusions:The EmmY cohort is highly comparable to patients treated in specialized MM centers and those within the broader French MM population, supporting its validity as a robust real-world data source. It is well-suited for evaluating treatment pathways and outcomes in real-world MM populations, including patients underrepresented in randomized controlled trials.

In previous analyses of MAIA, daratumumab plus lenalidomide/dexamethasone (D-Rd) significantly improved progression-free survival and overall survival (OS) versus lenalidomide/dexamethasone (Rd) in transplant-ineligible newly diagnosed multiple myeloma (NDMM). We report results on long-term OS and subsequent antimyeloma therapies from the MAIA final analysis. A protocol amendment (July 20, 2021) led to a long-term extension of MAIA, during which patients were followed for OS. A total of 737 patients were randomized to D-Rd (n = 368) or Rd (n = 369). At a median follow-up of 89.3 months (range, 0.0-102.2; interquartile range, 85.3-93.0), median OS was 90.3 months (95% confidence interval [CI], 80.8-not estimable [NE]) with D-Rd versus 64.1 months (56.0-70.8) with Rd (hazard ratio [HR], 0.67; 95% CI, 0.55-0.82); estimated 7-year OS rates were 53.1% (95% CI, 47.8-58.2) and 39.3% (34.1-44.5), respectively. Median time to subsequent antimyeloma treatment was not reached (95% CI, 84.1-NE) for D-Rd versus 42.4 months (33.5-50.6) for Rd (HR, 0.51; 95% CI, 0.41-0.63; P < 0.0001). Death due to adverse events occurred in 84 patients (D-Rd, n = 44/364 [12%]; Rd, n = 40/365 [11%]). With >7 years of follow-up, D-Rd demonstrated a new benchmark for median OS (7.5 years) in transplant-ineligible NDMM, further supporting frontline D-Rd use to maximize survival.

The combination of CD38 immunotherapy and proteasome inhibition has shown synergistic activity. Elderly relapsed or refractory multiple myeloma (RRMM) experience worse outcomes due to variabilities in fitness and higher rates of adverse events (AEs) and treatment discontinuations. The Intergroupe Francophone du Myélome (IFM) 2018-02 trial (NCT03757221) evaluated a dexamethasone-free regimen of daratumumab and ixazomib (I-Dara) in elderly frail RRMM. This prospective, phase 2 trial was conducted at 14 IFM centres. Patients aged ≥65 years with International Myeloma Working Group frailty score ≥2 and an Eastern Cooperative Oncology Group 0-2 in first or second relapse received daratumumab 16 mg/kg; ixazomib 4 mg weekly d1, d8, d15 in a 28-day cycle; and methylprednisolone. The primary end-point was ≥ very good partial response (VGPR) rate. Of 55 patients included, the median age was 82 years, with 90% aged over 75. VGPR or better was 32%. With a median follow-up of 35.3 months, the median progression-free survival time was 19.5 months. The median OS was not reached: 75% at 33.6 months. Grade ≥3 AEs occurred in 36 (67%) patients: cytopenias in 18 and infection in 8 (6 pneumonia). The IFM 2018-02 shows that I-Dara demonstrated an acceptable safety profile for this elderly frail RRMM patients' population. The response rates and survival outcomes were acceptable given the studied population.

Background Multiple myeloma (MM) is a chronic hematologic malignancy characterized by complex therapeutic strategies, repeated relapses, and substantial information and psychosocial needs. Advances in oral therapies and outpatient management have shifted greater responsibility to patients and caregivers, emphasizing the need for accessible, high-quality educational resources. Therapeutic patient education (TPE) aims to empower patients to understand and manage their condition more effectively. Digital education tools such as massive open online courses (MOOCs) represent an innovative approach to deliver structured, interactive, and scalable learning experiences to large patient populations. However, few MOOCs have been specifically designed for patients with oncological or hematological disorders, and even fewer have been rigorously evaluated for their educational impact. Objective This study aimed to develop and evaluate a MOOC co-designed with patients, caregivers, and health care professionals to improve knowledge, skills, and empowerment among patients living with MM and their relatives. Secondary objectives included assessing participant satisfaction, engagement, and the feasibility of this digital education model at a national scale. Methods The MOOC “Understanding and Living with Myeloma” was jointly developed by the French Association of Patients with Multiple Myeloma (AF3M) and the French-Speaking Myeloma Intergroup (IFM). The program consisted of 5 thematic modules delivered over 8 weeks, covering disease mechanisms, diagnosis, treatment options, side-effect management, and daily-life adaptation. Content combined educational videos, self-assessment quizzes, peer-tutoring forums, and live web conferences with experts. Participants self-assessed their knowledge using a 52-item questionnaire rated from 1 (poor) to 5 (excellent) before and after completing the program. Descriptive and inferential analyses were performed using the Wilcoxon signed-rank test (2-sided α=.05). Results During the first session, 254 participants registered for the course. Among them, 76 (30%) completed all modules and both evaluations. The mean global knowledge score increased from 3.06/5 before to 4.21/5 after the MOOC (mean gain + 1.15, + 38%; P<.001). Improvements were consistent across all knowledge domains, including understanding of treatments (+40%), recognition of warning signs (+35%), and self-management skills (+39%). Overall, 98% (74/76) of respondents reported being satisfied or very satisfied with the course, and 99% (75/76) would recommend it to other patients. Since 2018, the MOOC has been conducted 6 times at different periods, enrolling a cumulative total of 2400 participants, confirming its sustainability and scalability. Conclusions Participation in this co-designed, patient-centered MOOC was associated with a statistically and educationally significant improvement in knowledge among patients with MM and their caregivers. The program was highly valued by users and demonstrates the feasibility of large-scale digital patient education in oncology. As a freely accessible, repeatable, and peer-supported resource, this MOOC complements medical consultations and traditional TPE programs. Its design and outcomes may serve as a model for future digital health education initiatives targeting other chronic diseases.

ABSTRACT:The prognostic heterogeneity of multiple myeloma is mainly driven by the genomic features of myeloma cells. The International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) recently proposed a high-risk (HR) genomic model to have a consensus definition of genomic risk. We performed next-generation sequencing in the form of a panel on samples from 6528 patients with newly diagnosed multiple myeloma (NDMM) and 1583 patients at first relapse between 2019 and 2024. We observed that 22.4% of patients at diagnosis and 36.7% of patients at first relapse were classified as high risk according to the Consensus Genomic Staging. Clinical data were available for 2695 patients at diagnosis. After a median follow-up of 35 months, the median progression-free survival (PFS) was 30 months for patients with HR NDMM and 51 months for standard-risk (SR) patients (P< .0001). The HR cytogenetic criteria from the Revised- International Staging System score were not able to differentiate between HR and SR patients based on the IMS/IMWG genomic subgroups. Looking at each criterion independently, we found that the presence of del(17p), TP53 mutation, biallelic del(1p32), or the combination of intermediate-risk cytogenetics (gain 1q, del(1p32), t(4;14), t(14;16), t(14;20)) significantly reduced the PFS when compared with SR patients. Moreover, patients with several cumulating criteria had an even worse prognosis. Among SR patients, classified according to the genomic definition with normal creatinine, the median PFS for those with high β2-microglobulin was not significantly different from that of patients with normal β2-microglobulin level. This study validated the IMS/IMWG genomic definition of HR myeloma in a large cohort of patients diagnosed from 2019 onwards.

Frontline high-dose therapy (HDT) is, in 2025, the standard of care for patients with multiple myeloma (MM) who are eligible for autologous stem cell transplantation (ASCT). Prior to high-dose melphalan, induction therapy with quadruplet combinations is also proposed systematically when possible. Lenalidomide maintenance until progression is also recommended per international guidelines. This strategy has been developed over recent decades, based on results of phase 3 trials designed and conducted by different academic groups. With these therapeutic advances, the median overall survival (OS) for patients with MM has increased from 5 years in the 1990s, to over 15 years at present. Here, we present the contribution of the French myeloma cooperative group Intergroupe Francophone du Myélome (IFM) to these advances in the newly diagnosed transplant-eligible (NDTE) setting.

BACKGROUND:Measurable residual disease (MRD) is a major prognostic factor in newly diagnosed multiple myeloma. An assessment of an MRD-guided consolidation strategy in patients who are eligible for autologous stem-cell transplantation (ASCT) may be useful. METHODS:In this phase 3 trial, we randomly assigned transplantation-eligible patients with newly diagnosed myeloma who had completed induction therapy with isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) to receive consolidation therapy according to their MRD status. Patients who were MRD-negative at 10-5 sensitivity (i.e., <1 cancer cell per 100,000 normal cells, as assessed by next-generation sequencing) were assigned to undergo ASCT and receive Isa-KRd for two cycles (ASCT group) or to receive Isa-KRd for six cycles (Isa-KRd group). Patients who were MRD-positive at 10-5 sensitivity were assigned to undergo tandem ASCT (two ASCTs within a short period; tandem ASCT group) or to undergo ASCT and receive Isa-KRd for two cycles (single ASCT group). The primary end point was an MRD-negative status at 10-6 sensitivity before maintenance therapy. RESULTS:Among 485 patients who were MRD-negative at 10-5 sensitivity after induction, a premaintenance MRD-negative status at 10-6 sensitivity occurred in 86% in the ASCT group and in 84% in the Isa-KRd group (adjusted relative risk, 1.02; 95% confidence interval [CI], 0.95 to 1.10; P = 0.64). Among 233 patients who were MRD-positive at 10-5 sensitivity after induction, a premaintenance MRD-negative status at 10-6 sensitivity occurred in 32% in the tandem ASCT group and in 40% in the single ASCT group (adjusted relative risk, 0.82; 95% CI, 0.58 to 1.15; P = 0.31); 15% of the patients in the tandem ASCT group did not undergo a second ASCT. During consolidation, disease progression occurred in 5 patients and death unrelated to disease progression occurred in 2 patients - all were in the Isa-KRd or tandem ASCT groups. No new safety signals were observed. The median follow-up was 16.8 months in the ASCT and Isa-KRd groups and 16.3 months in the tandem ASCT and single ASCT groups. CONCLUSIONS:Among patients who were MRD-negative at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with ASCT than with Isa-KRd. Among patients who were MRD-positive status at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with tandem ASCT than with single ASCT. (Funded by Intergroupe Francophone du Myélome and others; MIDAS ClinicalTrials.gov number, NCT04934475.).

INTRODUCTION:Anti-CD38 monoclonal antibodies (aCD38) are increasingly used in early lines of therapies in multiple myeloma (MM). Retreatment with aCD38-based regimen is a widely used practice in later lines. However, data coming from clinical trials are currently limited. EMMY is a noninterventional, prospective dynamic cohort study conducted in 73 centers in France to assess the real-life management of MM in France and which can explore the efficacy of aCD38-based retreatment. METHODS:Patients who initiated a second line of treatment with aCD38-based combinations after a first exposure to aCD38 were identified and described and the outcomes of progression-free survival (PFS) and overall survival (OS) were estimated. RESULTS:In the EMMY cohort, 286 patients received 2 lines of treatment including aCD38. For all aCD38-retreated patients, median PFS was estimated at 5.1 months. Median PFS was 23.6 m in patients sensitive to aCD38 and 4.6 in nonsensitive patients, P = .0003. Median OS was estimated at 17.3 months for all patients,14.8 months in patients nonsensitive to aCD38, and not reached (NR) in sensitive patients, P = .0004. No significant differences in PFS or OS were observed between the refractory and nonrefractory to aCD38 groups. CONCLUSION:These results of aCD38 retreatment in a large sample of real-life patients (n = 286) in extensively pretreated patients show that retreatment may be a meaningful strategy for aCD38 sensitive patients. These findings need to be investigated further while the use of aCD38 is emerging as a first-line treatment for newly diagnosed patients.

Background Venous thromboembolism (VTE) events remain a major concern for patients with newly diagnosed multiple myeloma (nMM) undergoing therapy. Objectives Evaluate the incidence and risk factors for VTE. Methods Post hoc analysis of the randomized phase 3 BENEFIT trial (NCT04751877) evaluating 257 patients aged 65 to 79 years with transplant-ineligible nMM who received isatuximab/bortezomib/lenalidomide/dexamethasone or isatuximab/lenalidomide/dexamethasone. Results In the whole cohort, the 6-month cumulative incidence of VTE was 4.8% (95% CI, 2.7%-8.1%), 0.8% (95% CI, 0.1%-5.6%) in patients receiving low-dose direct oral anticoagulants (DOACs) compared with 5.6% (95% CI, 1.9%-16.7%) in those who received prophylactic-dose heparin, and 9.8% (95% CI, 3.9%-24.75%) in patients receiving aspirin. Only 1 VTE occurred beyond the 6-month period. The most frequently used thromboprophylaxis agents were DOACs (n = 127, 55.2%), low-molecular-weight heparins (n = 54, 23.5%), and aspirin (n = 40, 17.4%). We noted that one-third of patients who experienced VTE had not received thromboprophylaxis. Among the different thromboprophylaxis regimens used, only low-dose DOAC was associated with a significant reduction in the risk of VTE. In multivariate analysis, proteinuria ≥ 0.44 g/L (hazard ratio [HR], 5.8; 95% CI, 1.7-26.8) and monoclonal protein concentration ≥ 22 g/L (HR, 4.9; 95% CI, 1.3-31.9) were significantly associated with an increased risk of VTE, while low-dose DOAC was associated with a decreased risk of VTE (HR, 0.13; 95% CI, 0.007-0.67). Conclusion In summary, the cumulative incidence of VTE remains high in patients with transplant-ineligible nMM. DOACs could be the most effective option for preventing VTE.

In the MAIA study, daratumumab plus lenalidomide and dexamethasone (D-Rd) improved progression-free survival (PFS) and overall survival (OS) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). We report updated efficacy and safety from MAIA (median follow-up, 64.5 months), including a subgroup analysis by patient age (<70, ≥70 to <75, ≥75, and ≥80 years). Overall, 737 transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint, PFS, was improved with D-Rd versus Rd (median, 61.9 vs 34.4 months; hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.45–0.67; P < 0.0001). Median OS was not reached in the D-Rd group versus 65.5 months in the Rd group (HR, 0.66; 95% CI, 0.53–0.83; P = 0.0003); estimated 60-month OS rates were 66.6% and 53.6%, respectively. D-Rd achieved higher rates of complete response or better (≥CR; 51.1% vs 30.1%), minimal residual disease (MRD) negativity (32.1% vs 11.1%), and sustained MRD negativity (≥18 months: 16.8% vs 3.3%) versus Rd (all P < 0.0001). D-Rd demonstrated clinically meaningful efficacy benefits across age groups. No new safety concerns were observed. Updated results (median follow-up, >5 years) continue to support frontline use of D-Rd in transplant-ineligible patients with NDMM.

Managing multiple myeloma (MM) patients receiving advanced (four or more) lines of treatment is a complex challenge. Therefore, real-world data are essential to better understand and address the medical need of this challenging population. We used the EMMY cohort, a French longitudinal real-world study, to describe the characteristics and outcomes of 2127 MM patients receiving advanced-line treatments between 2017 and 2020. A wide variety of treatments were used without a predominant combination showing an evolution over time. Patients exhibited median time to next treatment and overall survival ranging from 7.8 months (95% CI: 6.7-7.8) and 19.4 months (95% CI: 17.4-22.5) in Line 4 (L4) to 4.8 months (95% CI: 3.5-6) and 12.6 months (95% CI: 8.7-16.6) in L8, respectively. The EMMY study provides valuable insights into the real-world application of advanced-line treatments, demonstrating rapid disease progression and poor outcomes in these patients before the novel anti-B-cell maturation antigen (BCMA) directed therapies. These findings highlight the critical need for novel therapies in this population.

7500 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). Results from the IsaKRD induction phase have been previously published (Perrot et al., Blood, 2025). Here, we present the results from the MRD-driven consolidation phase of the trial. Methods: MIDAS is a multicenter, open-label, randomized phase 3 trial involving transplant-eligible patients aged 18-65 with NDMM. Patients achieving post-induction MRD negativity at a threshold of 10⁻⁵ by next-generation sequencing (NGS) were randomized to either 6 additional cycles of IsaKRD (Arm A) or autologous stem cell transplantation (ASCT) followed by 2 cycles of IsaKRD (Arm B), followed by lenalidomide maintenance. MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance. Randomization was stratified by cytogenetic risk and center for both comparisons, and by MRD negativity at 10⁻⁶ post-induction for the Arm A vs. Arm B comparison. The primary endpoint was MRD negativity at 10⁻⁶ (by NGS) prior to maintenance for both comparisons. Results: A total of 485 patients with post-induction MRD negativity were randomized to Arm A (n=243) or Arm B (n=242). The pre-maintenance MRD negativity rates at 10⁻⁶ were 84% in Arm A and 86% in Arm B (Odds Ratio [OR] 1.17, 95% confidence interval [CI] 0.64–2.76, p=0.64). Additionally, 233 MRD-positive patients (10⁻⁵) were randomized to Arm C (n=109) or Arm D (n=124), with 19 patients (15%) not receiving the planned tandem ASCT. Pre-maintenance MRD negativity rates at 10⁻⁶ were 40% in Arm C and 32% in Arm D (OR 0.73, 95% CI 0.42–1.25, p=0.31). During the consolidation phase, 5 patients experienced disease progression (2 in Arm A, 0 in Arm B, 0 in Arm C, 3 in Arm D), and 2 patients died without progression in Arm A. No new safety signals were identified compared to the induction phase. The study is ongoing. With a median follow-up of 16.8 months in Arms A/B and 16.3 months in Arms C/D, sustained MRD negativity and progression-free survival (PFS) data are not yet available. Conclusions: After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10 -5 , tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶ before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy. Clinical trial information: NCT04934475 .

In patients with transplant-eligible newly diagnosed multiple myeloma, induction therapy with a quadruplet regimen prior to autologous transplant is the standard of care. The phase III IFM2020-02-MIDAS study (NCT04934475) assessed a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD). Here, we report safety and efficacy outcomes of six 28-day cycles of IsaKRD. Between December 2021 and July 2023, 791 patients were enrolled across 72 centers. The median age was 59 years; 13% had ISS-stage III, 5% had R-ISS-stage III, and 8% had high-risk cytogenetics (IFM Linear Predictor cytogenetic score >1). Overall, 96% (N=757) of patients completed induction. The median CD34+ cell yield was 7 × 106/Kg, with 94% of patients able to proceed with a potential tandem transplant. The best overall response rate was 95%. In the intent-to-treat population, 91% achieved a very good partial response or better after induction, with MRD-negativity rates of 63% at 10-5 and 47% at 10-6. MRD-negativity rates differed across ISS stages and cytogenetic subgroups. During induction, 7 patients experienced disease progression, and 5 died due to disease progression (N=1), cardiac events (N=2), or other causes (N=2). The most common grade 3/4 adverse events were neutropenia (25%), thrombocytopenia (5%), and infections (7%); only 13% of patients reported any grade peripheral neuropathy. IsaKRD induction yielded deep responses and high MRD-negativity rates while ensuring successful stem cell collection, with no new safety signals. Continued follow-up of this ongoing study is required to confirm these findings.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.5 months), transplant-ineligible patients with NDMM were randomized 1:1 to D-Rd or Rd. The primary endpoint was PFS; secondary endpoints included overall response rate (ORR) and measurable residual disease (MRD)–negativity rate (10–5). PFS favored D-Rd versus Rd in most subgroups, including patients aged ≥75 years (HR, 0.59; 95 www.clinicaltrials.gov as NCT02252172.