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The therapeutic landscape of multiple myeloma continues to evolve rapidly, with immunotherapies increasingly moving into earlier lines of therapy and novel agents expanding treatment options across plasma cell disorders. During the VJHemOnc Post-EHA Myeloma Highlights webinar chaired by Karthik Ramasamy, MBBS, MRCP, FRCPath, PhD, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, experts presented selected abstracts from the 2026 European Hematology Association (EHA) Congress. Here, we summarize five studies spanning relapsed and newly diagnosed multiple myeloma, high-risk smoldering myeloma, and AL amyloidosis that may help shape future clinical practice.
MonumenTAL-3: Talquetamab combinations improve survival outcomes in relapsed/refractory multiple myeloma?
T-cell engagers have reshaped the treatment landscape of relapsed/refractory (R/R) multiple myeloma, with several agents demonstrating deep and durable responses in heavily pretreated patients. Investigators have now begun evaluating these therapies in earlier lines of treatment to determine whether combining T-cell engagers with established backbone regimens can further improve long-term outcomes.1,2
During the Post-EHA Myeloma Highlights webinar, Meral Beksaç, MD, Ankara University, Ankara, Turkey, presented the pre-planned interim analysis of the Phase III MonumenTAL-3 study (NCT05455320) evaluating talquetamab, daratumumab and pomalidomide (Tal-DP), or talquetamab plus daratumumab (Tal-D), compared with daratumumab, pomalidomide and dexamethasone (DPd) in patients with R/R MM after at least one prior line of therapy.2
864 patients were randomized 1:1:1 to Tal-DP, (n=287), Tal-D, (n=287), or DPd (n=290). Most patients were refractory to lenalidomide (85.1%) or their last line of therapy (93.4%), and 30.9% of patients had high-risk cytogenetics.2
After a median follow-up of 24.6 months, both talquetamab-containing regimens significantly improved progression-free survival (PFS) compared with DPd, meeting the primary endpoint.
Hazard ratios (HR) for disease progression or death were 0.28 (95% CI: 0.20–0.40, p<0.0001) with Tal-DP and 0.33 (95% CI 0.24–0.46, p<0.0001) with Tal-D. Estimated 24-month PFS rates were 81.3% (95% CI: 75.8–85.7), 77.6% (95% CI: 71.7–82.5), and 51.2% (95% CI: 44.8–57.1), respectively. PFS benefit was consistent across clinically relevant subgroups.2
Overall response rates (ORR) were 88.2% with Tal-DP and 88.5% with Tal-D, compared with 77.6% with DPd. Complete response rate or better (≥CR) was achieved in 71.1% and 69.0% of patients receiving Tal-DP and Tal-D, compared with 34.5% in the DPd arm. Measurable residual disease (MRD)-negative ≥CR rates were significantly higher with talquetamab-containing regimens (52.3% and 46.3% versus 15.9%, respectively). Overall survival (OS) also favored both talquetamab arms compared with DPd (Tal-DP: HR 0.47 [95% CI: 0.30–0.73; p=0.0006], Tal-D: HR 0.51 [95% CI: 0.33–0.78; p=0.0015]).2
The safety profile was manageable and consistent with the known toxicities of the individual agents. Adverse events (AEs) leading to discontinuation of all study treatment occurred in 10.5% (Tal-DP), 8.0% (Tal-D), and 6.7% (DPd). Grade 3–4 infections occurred at similar or lower rates with talquetamab-containing regimens than with DPd (37.0% with Tal-PD, 27.7% with Tal-D, and 41.0% with DPd). GPRC5D-related AEs, including taste changes and weight loss, were predominantly Grade 1–2 and did not lead to treatment discontinuation.
The MonumenTAL-3 study represents the first Phase III trial to demonstrate significant improvements in both PFS and OS with a GPRC5D-directed bispecific antibody in a combination therapy.2 These findings support talquetamab-containing regimens as a potential new treatment option for patients with R/R MM from second-line therapy onwards.
BELA-DRD: Belantamab mafodotin quadruplet demonstrates encouraging frontline activity in transplant-ineligible myeloma
Daratumumab combined with lenalidomide and dexamethasone (DRd) is an established first-line treatment option for transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM).3 The activity of belantamab mafodotin (belamaf) in R/R MM has provided the rationale for evaluating its addition to DRd in the frontline setting, with the aim of improving the depth and durability of response.4
During EHA 2026 and the Post-EHA Myeloma Highlights webinar, Evangelos Terpos, MD, PhD, University of Athens, Athens, Greece, presented updated results from the open-label, Phase Ib/II BELA-DRD study (EUCT-2021-006792-42) evaluating belamaf in combination with DRd in transplant-ineligible patients with NDMM.4
During the initial dose-finding phase, which assessed the safety and tolerability of two belamaf dose levels (1.9 and 1.4 mg/kg every eight weeks [Q8W]), 24 patients were enrolled. This phase of the trial established belamaf 1.9 mg/kg Q8W, subsequently extended to every 12 weeks, as the recommended Phase II dose (RP2D) for the dose-expansion phase. The study then expanded with an additional cohort of 12 patients treated at the RP2D.4
Clinical activity was demonstrated across both study phases. ORR was 91.7% in both the dose-finding and expansion cohorts. In the dose-finding phase, 70% achieved ≥CR. In MRD-evaluable patients, MRD negativity was observed in 81.3% of the dose-finding cohort and in 71.4% of the expansion cohort.
Median time to at least a partial response (≥PR) was 1.1 months in both phases. At the time of analysis, estimated 18-month PFS was 91.7% in the overall study population and 87.5% among patients treated with RP2D. At a median follow-up of 17.9 months in the expansion cohort, 91.7% of patients remained on treatment and one patient discontinued due to progressive disease.4
The safety profile was consistent with previous experience of belamaf. Fatigue was the most common Grade ≥3 non-ocular AE, occurring in 54.2% of patients during the dose-finding phase and 50.0% of patients treated with the RP2D, which was largely attributed to lenalidomide. Ocular AEs remained the principal toxicity, although Grade ≥3 best-corrected visual acuity decline was infrequent (10.4% of ocular assessments in part 1 and 3.9–5.3% in part 2), while Grade ≥3 keratopathy was rare (0.6% in part 1 and not observed in part 2). These events resolved rapidly, with median resolution times of approximately one month. Similar rates of ocular AEs were observed when dose modifications were guided by hematologists using the Vision-Related Anamnestic (VRA) tool or by ophthalmologists, supporting the feasibility of both monitoring approaches.4
The BELA-DRD study demonstrated rapid, deep responses together with high MRD negativity rates and PFS rates in transplant-ineligible patients with NDMM. These findings support continued evaluation of belamaf-containing quadruplets in randomized studies of frontline myeloma.
EMN30/MajesTEC-4: Fixed-duration teclistamab maintenance deepens responses following autologous stem cell transplantation
Maintenance therapy following autologous stem cell transplantation (ASCT) has become a key component of treatment for patients with NDMM, with lenalidomide remaining the standard maintenance therapy for most patients.3 Given the efficacy of teclistamab in heavily pretreated myeloma, investigators are now assessing whether its earlier use as fixed-duration maintenance following ASCT can further improve outcomes.5
During EHA 2026 and the Post-EHA Myeloma Highlights webinar, Niels van de Donk, MD, PhD, VU University Medical Center, Amsterdam, The Netherlands, presented updated safety run-in results from the ongoing Phase III EMN30/MajesTEC-4 study (NCT05243797) evaluating teclistamab, alone or in combination with lenalidomide, as fixed-duration maintenance following ASCT.5
Ninety-four patients who had achieved ≥PR following induction therapy and ASCT were enrolled across three safety run-in cohorts evaluating teclistamab plus lenalidomide in Cohort 1 (n=32) and Cohort 2 (n=32), or teclistamab alone in Cohort 3 (n=30). At the latest safety analysis, median follow-up was 32.7 months in Cohort 1, and 21.2 months in Cohorts 2 and 3. Following the initial step-up dosing schedule, patients in Cohorts 2 and 3 received teclistamab every four weeks from Cycle 2 onwards.5
Responses deepened during maintenance treatment. CR rates increased across all three cohorts, rising from 46.9%, 40.6%, and 60.0% following ASCT, to 100%, 96.9%, and 96.7% in Cohorts 1, 2, and 3, respectively. Among MRD-evaluable patients, MRD-negative ≥CR rates also increased during maintenance, reaching 100% in Cohorts 1 and 2, and 90% in Cohort 3 at 12 months. In addition, the estimated 24-month PFS rate was 96.6% in Cohort 1, and estimated 18-month PFS rates were 93.8% and 96.4% in Cohorts 2 and 3, respectively.5
The safety profile remained consistent with previous teclistamab experience. Grade 3–4 neutropenia was the most common hematologic toxicity across Cohorts 1, 2 and 3 (93.8%, 78.1%, and 63.3%, respectively), while Grade 3–4 infections were reported in 37.5%, 34.4%, and 26.7% of patients. Cytokine release syndrome (CRS) was reported in 44.7% of patients and was limited to Grade 1 or 2 events, with no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) observed. TEAEs led to treatment discontinuation in nine patients, and two fatal TEAEs occurred in Cohort 2, including one infection-related death.5
Taken together, these updated safety run-in results suggest that fixed-duration teclistamab-based maintenance can deepen responses following ASCT. The ongoing randomized phase of the EMN30/MajesTEC-4 trial will determine whether these initial findings translate into improved long-term outcomes compared with standard lenalidomide maintenance.5
ImmunoPRISM: Early intervention with teclistamab deepens responses in high-risk smoldering myeloma
Patients with high-risk smoldering multiple myeloma (HR-SMM) have a substantial risk of progression to symptomatic disease. As a result, interest is growing in early therapeutic intervention before progression occurs.6 Based on the efficacy of the BCMA×CD3 bispecific antibody teclistamab in R/R MM, investigators are now assessing whether earlier BCMA-directed T-cell redirection can induce deep responses and delay disease progression to active myeloma.7
During EHA 2026 and the Post-EHA Myeloma Highlights webinar, Omar Nadeem, MD, Dana-Farber Cancer Institute, Boston, MA, presented results from the multicenter, randomized, Phase II ImmunoPRISM trial (NCT05469893), comparing teclistamab with lenalidomide plus dexamethasone (Rd) in patients with HR-SMM.7
The study enrolled 59 patients (teclistamab, n=45; Rd, n=14). Baseline characteristics were balanced, with 41% of patients exhibiting high-risk cytogenetic abnormalities and 64% meeting the 20-2-20 criteria for high-risk disease.7
Teclistamab produced statistically significant deeper responses than Rd. CR or stringent CR (sCR) was achieved in 73% of teclistamab-treated patients compared with 0% of patients receiving Rd (p<0.001), while a very good partial response or better (≥VGPR) was achieved in 87% versus 14% of patients, respectively (p<0.001). Among MRD-evaluable patients, MRD negativity at 10-5 was achieved in 81% of patients receiving teclistamab and was sustained in all patients, whereas no patients receiving Rd became MRD negative. At a median follow-up of 23.4 months, teclistamab also significantly improved PFS, with an estimated two-year PFS rate of 92% compared with 51% for Rd (p=0.007).7
Summarizing the findings, Dr Nadeem commented: “This is the first randomized trial of teclistamab compared to a control arm in high-risk smoldering myeloma…We saw much higher response rates and complete response rates with teclistamab, translating into improved progression-free survival.”
The safety profile compared favorably with previous teclistamab studies in relapsed disease. CRS occurred in 71.1% of patients but was exclusively Grade 1–2, with no ICANS reported. Grade ≥3 infections occurred in 20.0% of teclistamab-treated patients and 21.4% of Rd-treated patients.7
The ImmunoPRISM study provides randomized trial evidence supporting BCMA-directed bispecific antibody therapy in HR-SMM. These findings support continued investigation of fixed-duration immune-interception strategies in this earlier disease setting.
CARES: Anselamimab improves survival in patients with κ light-chain AL amyloidosis
Although plasma cell-directed therapy has substantially improved outcomes in systemic AL amyloidosis, treatments capable of directly removing established amyloid deposits remain an important unmet clinical need.8 Anselamimab is a monoclonal antibody designed to target deposited amyloid fibrils, complementing standard anti-plasma cell therapy.8,9
During EHA 2026 and the Post-EHA Myeloma Highlights webinar, Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, University College London, London, UK, presented results from the Phase III CARES studies (NCT04512235; NCT04504825), evaluating anselamimab plus anti-plasma cell therapy compared with placebo in patients with newly diagnosed Mayo stage 3 AL amyloidosis.9
Across the combined studies, 406 patients were randomized 2:1 to receive anselamimab or placebo in addition to standard therapy. The primary endpoint combined all-cause mortality and cardiovascular (CV) hospitalizations using a hierarchical win-ratio analysis. The median duration of treatment was 21.4 months in the anselamimab arm and 21.1 months in the placebo arm. Daratumumab was used in 79.3% and 83.7% of the anselamimab and placebo arms, respectively.
Although the primary composite endpoint was not met in the overall study population, prespecified subgroup analyses demonstrated statistically significant benefit among patients with κ light-chain disease. In this subgroup, anselamimab reduced the risk of all-cause mortality by 62% (HR 0.38; 95% CI: 0.17–0.86; nominal p=0.012) and reduced CV hospitalizations by 71% compared with placebo (HR 0.29; 95% CI: 0.1–0.9). No corresponding benefit was observed among patients with λ light-chain disease.9
Safety findings were comparable between treatment groups, with no new safety concerns identified. AEs were consistent with the underlying disease and similar between patients receiving anselamimab and placebo.9
These findings suggest that anselamimab may represent the first therapy to demonstrate a survival benefit through direct targeting of amyloid deposits in patients with κ light-chain AL amyloidosis. Further studies will help to define the role of this novel approach alongside plasma cell-directed therapy.
From bispecific antibodies moving into earlier lines of therapy and maintenance settings, to immune interception approaches for HR-SMM, and therapies designed to directly target amyloid deposits, the breadth of innovation presented at EHA 2026 and the Post-EHA Myeloma Highlights webinar illustrates how treatment paradigms continue to expand.
References
- Devasia AJ, Chari C, Lancman G. Bispecific antibodies in the treatment of multiple myeloma. Blood Cancer J. 2024;14(1):158.
- Voorhees P, Mina R, Rodríguez-Otero P, et al. Phase 3, randomized study of talquetamab (Tal) plus daratumumab (Dara) ± pomalidomide (Pom) vs dara plus pom and dexamethasone (DPD) in relapsed/refractory multiple myeloma (RRMM): MONUMENTAL-3. Abstract S100. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- Dimopoulos MA, Terpos E, Boccadoro M, et al. EHA-EMN evidence-based guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma. Nat Rev Clin Oncol. 2025;22(9):680–700.
- Terpos E, Ntanasis-Stathopoulos I, Gavriatopoulou M, et al. High MRD negativity rates and prolonged PFS with belantamab mafodotin plus daratumumab, lenalidomide, and dexamethasone in transplant ineligible newly-diagnosed myeloma: Results of the BELA-DRD study. Abstract S204. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- van de Donk NWCJ, Silzle T, Špička I, et al. Teclistamab (tec) +/- lenalidomide (len) versus len alone as maintenance therapy post-transplant in newly diagnosed multiple myeloma (NDMM): Updated safety run-in (sri) results from EMN30/MAJESTEC-4. Abstract S197. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- Ntanasis-Stathopoulos I, Filippatos C, Malandrakis P, et al. Observation or treatment for smoldering multiple myeloma? A systematic review and meta-analysis of randomized controlled studies. Blood Cancer J. 2025;15(1):104.
- Nadeem O, Cordas dos Santos D, Magidson S, et al. Teclistamab improves depth of response and PFS versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: Results from the Phase 2 IMMUNOPRISM trial. Abstract LB5008. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
- Ioannou A. Recent developments in systemic light-chain amyloidosis prognosis and treatment. Future Cardiol. 2025;21(10):815–827.
- Wechalekar A, Dispenzieri A, Sanchorawala V, et al. Phase 3 randomized trial of anselamimab demonstrates improvement in all-cause mortality in Κ light-chain amyloidosis. Abstract S206. Presented at the European Hematology Association (EHA) 2026 Congress; June 11–14 2026; Stockholm, Sweden.
