Explore the vast range of titles available.

The addition of daratumumab to lenalinomide and dexamethasone in patients with previously untreated myeloma who were not eligible for high-dose chemotherapy and hematopoietic stem-cell transplantation resulted in a higher response rate, an increased depth of response, and longer progression-free survival than lenalidomide and dexamethasone alone.

In the primary analysis of the phase 3 MAIA trial (median follow-up 28·0 months), a significant improvement in progression-free survival was observed with daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in transplantation-ineligible patients with newly diagnosed multiple myeloma. Here, we report the updated efficacy and safety results from a prespecified interim analysis for overall survival. MAIA is an ongoing, multicentre, randomised, open-label, phase 3 trial that enrolled patients at 176 hospitals in 14 countries across North America, Europe, the Middle East, and the Asia-Pacific region. Eligible patients were aged 18 years or older, had newly diagnosed multiple myeloma, had an Eastern Cooperative Oncology Group performance status score of 0–2, and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation because of their age (≥65 years) or comorbidities. Patients were randomly assigned (1:1) using randomly permuted blocks (block size 4) by an interactive web response system to receive 28-day cycles of intravenous daratumumab (16 mg/kg, once per week during cycles 1–2, once every 2 weeks in cycles 3–6, and once every 4 weeks thereafter) plus oral lenalidomide (25 mg on days 1–21 of each cycle) and oral dexamethasone (40 mg on days 1, 8, 15, and 22 of each cycle; daratumumab group) or lenalidomide and dexamethasone alone (control group). Randomisation was stratified by International Staging System disease stage, geographical region, and age. Neither patients nor investigators were masked to treatment assignment. The primary endpoint was progression-free survival, which was centrally assessed, and a secondary endpoint was overall survival (both assessed in the intention-to-treat population). The safety population included patients who received at least one dose of the study treatment. The results presented here are from a prespecified interim analysis for overall survival, for which the prespecified stopping boundary was p=0·0414. This trial is registered with ClinicalTrials.gov, NCT02252172. Between March 18, 2015, and Jan 15, 2017, 952 patients were assessed for eligibility, of whom 737 patients were enrolled and randomly assigned to the daratumumab group (n=368) or the control group (n=369). At a median follow-up of 56·2 months (IQR 52·7–59·9), median progression-free survival was not reached (95% CI 54·8–not reached) in the daratumumab group versus 34·4 months (29·6–39·2) in the control group (hazard ratio [HR] 0·53 [95% CI 0·43–0·66]; p<0·0001). Median overall survival was not reached in either group (daratumumab group, 95% CI not reached–not reached; control group, 95% CI 55·7–not reached; HR 0·68 [95% CI 0·53–0·86]; p=0·0013). The most common (>15%) grade 3 or higher treatment-emergent adverse events were neutropenia (197 [54%] patients in the daratumumab group vs 135 [37%] patients in the control group), pneumonia (70 [19%] vs 39 [11%]), anaemia (61 [17%] vs 79 [22%]), and lymphopenia (60 [16%] vs 41 [11%]). Serious adverse events occurred in 281 (77%) patients in the daratumumab group and 257 (70%) patients in the control group. Treatment-related deaths occurred in 13 (4%) patients in the daratumumab group and ten (3%) patients in the control group. Daratumumab plus lenalidomide and dexamethasone increased overall survival and progression-free survival in patients ineligible for stem-cell transplantation with newly diagnosed multiple myeloma. There were no new safety concerns. Our results support the frontline use of daratumumab plus lenalidomide and dexamethasone for patients with multiple myeloma who are ineligible for transplantation. Janssen Research & Development.

SummaryBackgroundPatients with frailty and newly diagnosed multiple myeloma have worse outcomes due to higher rates of adverse events (AEs) and treatment discontinuation. This study evaluated a dexamethasone-sparing regimen of daratumumab plus lenalidomide versus lenalidomide plus dexamethasone in frail patients with newly diagnosed multiple myeloma. MethodsIn this prospective, randomised, open-label trial, conducted at 61 active Intergroup Francophone of Myeloma centres, patients aged 65 years or older with newly diagnosed multiple myeloma and an Eastern Cooperative Oncology Group proxy frailty score of 2 or more were randomly assigned 2:1 to receive daratumumab (1800 mg subcutaneously) plus oral lenalidomide (25 mg daily for 21 days of a 28 day cycle) and dexamethasone (20mg weekly) for two cycles (dexamethasone-sparing group) or lenalidomide (25 mg daily) and oral dexamethasone (20 mg weekly; control group), with stratification by International Staging System, age, and centre. The primary endpoint was progression-free survival. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients exposed to at least one dose of randomised intervention. This trial is registered with ClinicalTrials.gov, NCT03993912, and is complete. FindingsFrom Oct 18, 2019 to July 20, 2021, 335 patients were screened, of whom 295 patients were randomly assigned (200 to lenalidomide plus daratumumab, 95 to lenalidomide plus dexamethasone). The median age was 81 years (IQR 77–84), with 180 (61%) aged older than 80 years, and 151 (51%) patients were female and 144 (49%) were male. Median follow-up was 46·3 months (IQR 46·0–52·7). Median progression-free survival was 53·4 months (95% CI 35·3–not reached) in the dexamethasone-sparing group versus 22·5 months (16·5–39·0) in the control group (hazard ratio [HR] 0·51, 95% CI 0·37–0·70, p<0·0001). The most common grade 3–5 AEs were neutropenia (110 [55%] of 200 patients in the dexamethasone-sparing group vs 23 [24%] of 95 patients in the control group), and infection (38 [19%] vs 20 [21%]). Serious adverse events occurred in 126 patients (63%) in the dexamethasone-sparing group and 66 patients (69%) in the control group. AEs leading to death occurred in 23 patients (12%) in the dexamethasone-sparing group and 12 patients (13%) in the control group, with 4 (2%) and 2 (2%) grade 5 treatment-emergent adverse events, respectively. InterpretationIn the IFM2017-03 trial, use of lenalidomide plus daratumumab, with dexamethasone limited to the first 2 treatment cycles, reduced the risk of progression or death compared with lenalidomide plus dexamethasone, with no additional safety concerns. Lenalidomide plus daratumumab could therefore be considered as a treatment option for older patients with frailty and newly diagnosed multiple myeloma. FundingThe study was funded by Johnson & Johnson.

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.

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. 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. 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). 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. 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.

Aims/Background Recent agents have profoundly reshaped the multiple myeloma (MM) landscape. Their real‐world impacts need to be assessed over the long term. Methods EMMY is a non‐interventional, prospective dynamic cohort, conducted in France, since 2017, with 900 patients enrolled each year. Newly diagnosed MM (NDMM) who initiated a treatment from 2017 to 2020 are here described. Results A total of 1036 non‐transplant eligible (NTE) patients (median age: 74.9 years) and 561 patients who received autologous stem cell transplantation (ASCT) (median age: 60.6 years) were enrolled. For ASCT patients, a shift in induction treatment from bortezomib‐thalidomide‐dexamethasone (VTd) (29.1%) to bortezomib‐lenalidomide‐dexamethasone (VRd) (55.1%) marked the period. Maintenance treatment with R after ASCT became a standard (75% of patients). In NTE patients, R‐based regimens were increasingly used from 29.4% in 2017 (of whom Rd.: 17.0%, VRd: 10.6%) to 73.3% in 2020 (of whom Rd.: 21.8%, VRd: 48.5%). Median progression‐free survival (mPFS) was 46.5 months (95% CI: 37.8–50.6) and 18.7 months (95% CI: 16.3–20.8) in ASCT and NTE patients, respectively. In the ASCT group, patients treated with and without R maintenance had a mPFS of 51.8 (95% CI: 44.1–NA) and 29.6 months (95% CI: 21.8–40.9), respectively. In the NTE group, the mPFS was 26.3 (95% CI: 21.9–30.9) and 14.6 months (95% CI: 11.9–17.7) in patients who received an R‐based and non‐R‐based regimen, respectively. The estimated 48‐month overall survival rates were 89% (95% CI: 84.5–92.2) and 63% (95% CI: 58.5–67.1) for ASCT and NTE patients, respectively. Conclusions The 2017–2020 period was marked by the expansion of R use in both NDMM ASCT and NTE patients. A total of 1036 non‐transplant eligible (NTE) patients and 561 patients who received autologous stem cell transplantation (ASCT) were enrolled in Emmy. In the ASCT group, patients treated with and without R maintenance had a mPFS of 51.8 (95% CI: 44.1–NA) and 29.6 months (95% CI: 21.8–40.9), respectively. In the NTE group, the mPFS was 26.3 (95% CI: 21.9–30.9) and 14.6 months (95% CI: 11.9–17.7) in patients who received an R‐based and non‐R‐based regimen, respectively. The 2017–2020 period was marked by the expansion of R use in both NMDD ASCT and NTE patients.

Hairy cell leukaemia (HCL) diagnosis is based on the morphologic detection of circulating abnormal hairy cells in the peripheral blood and/or bone marrow, an HCL immunological score of 3 or 4 based on the expression of the CD11c, CD25, CD103 and CD123 and also the presence of a BRAF V600E activating mutation in the B‐raf proto‐oncogene (BRAF gene) (7q34). When using new generation sequencing of 21 targeted genes in 124 HCL patients, we identified a cohort of 6/124 (2%) patients with unusual BRAF mutations: two patients presented non‐V600 mutations (BRAF F595L, BRAF W604L respectively) and four other patients silent BRAF mutations. When using droplet digital PCR (ddPCR) three of the four patients with concomitant BRAF V600E and silent mutation were negative. The respective role of these mutations in the occurrence of HCL or its progression remains to be clarified, but BRAF sequencing is necessary in case of negative BRAF V600E by ddPCR.