EHA 2026 Multiple Myeloma Highlights Have Worldwide Impact

At the 2026 EHA Annual Congress, several key presentations displayed the progress being made across different treatment settings in multiple myeloma, from precursor conditions to late-relapsed disease. The following highlights showcase key findings from across the meeting in multiple myeloma and smoldering myeloma, including promising data on new chimeric antigen receptor (CAR) T-cell therapy approaches and optimized bispecific antibody combinations.

Talquetamab Plus Daratumumab With or Without Pomalidomide Bests Standard of Care in R/R Myeloma

The phase 3 MonumenTAL-3 trial (NCT05455320) established a new benchmark in relapsed/refractory (R/R) multiple myeloma with talquetamab (Talvey) plus daratumumab (Darzalex) with or without pomalidomide (Pomalyst) demonstrating superior progression-free survival (PFS) over daratumumab plus pomalidomide and dexamethasone (DPd). With a median follow-up of 24.6 months, the 2-year PFS rates were 81.3% for the talquetamab, daratumumab, and pomalidomide (Tal-DP) arm and 77.6% for talquetamab plus daratumumab (Tal-D), compared with 51.2% for DPd. Median PFS was not reached in either experimental arm vs 24.4 months for DPd.

Tal-DP reduced the risk of progression or death by 72% vs DPd (HR, 0.28; 95% CI, 0.20-0.40; P <.001), and Tal-D reduced that risk by 67% (HR, 0.33; 95% CI, 0.24-0.46; P <.001). Overall response rates (ORRs) were 88.2% and 88.5% for Tal-DP and Tal-D, respectively, vs 77.6% for DPd (P <.001 for both). The rate of complete response (CR) or better was 71.1% and 69.0% vs 34.5%. Among patients treated at first relapse with lenalidomide (Revlimid)-refractory disease, PFS HRs were 0.19 and 0.23 for Tal-DP and Tal-D, respectively, vs DPd. The presenting investigator Peter Voorhees, MD, of Atrium Health Levine Cancer Institute, concluded that these data support talquetamab-based combinations as a new standard of care as early as the first relapse.¹

Cilta-Cel Benefit Linked to Quality of Bridging Therapy Response, Regardless of Cytogenetic Risk

A post hoc analysis of the phase 3 CARTITUDE-4 trial (NCT04181827) demonstrated that achieving at least a partial response (PR) to bridging therapy prior to ciltacabtagene autoleucel (Carvykti; cilta-cel) infusion was associated with improved 30-month PFS and overall survival (OS) outcomes in both high- and standard-risk cytogenetic subgroups among patients with lenalidomide-refractory multiple myeloma.

In the high-risk subgroup, 30-month PFS rates were 65.1% (95% CI, 51.4%-75.8%) for bridging therapy responders (n = 64) vs 51.2% (95% CI, 35.1%-65.2%) for nonresponders (n = 41), with a median PFS that was not reached (NR) vs 35.2 months, respectively. In the standard-risk subgroup, 30-month PFS rates were 85.0% (95% CI, 69.6%-93.0%) for responders (n = 40) vs 70.2% (95% CI, 40.9%-86.9%) for nonresponders (n = 19).

Notably, no cases of immune effector cell–associated parkinsonism occurred among patients who achieved PR or better to bridging therapy in either cytogenetic subgroup, and infections were a key contributor to nonrelapse mortality in patients without bridging response. The investigators concluded that well-controlled disease at the time of cilta-cel infusion predicted deeper and more durable benefit across cytogenetic risk strata.²

In Vivo CAR T Approach Eliminates Manufacturing Delays, Achieves Universal MRD Negativity

KLN-1010, an investigational in vivo anti–-B-cell maturation antigen (BCMA) chimeric CAR T-cell gene therapy, yielded a 100% ORR and universal minimal residual disease (MRD) negativity at 1 month in preliminary phase 1 data from the inMMyCar trial (NCT07075185)., presented at EHA 2026.

Among 18 patients with R/R multiple myeloma who had received a median of 3.5 prior lines of therapy, a single intravenous infusion of KLN-1010 produced responses by International Myeloma Working Group (IMWG) criteria in all evaluable patients, with 50% achieving a very good partial response (VGPR) or better. Among 6 patients with at least 4 months of follow-up, 67% achieved stringent complete response (sCR). All 14 patients with available 1-month data were MRD-negative at the 10^-5 sensitivity threshold, with responses sustained through 6 months and earliest-treated patients remaining in ongoing response beyond 9 months.

Unlike conventional ex vivo CAR T therapies, KLN-1010 requires no lymphodepleting chemotherapy and no weeks-long manufacturing process; median time from consent to treatment was 13 days. Cytokine release syndrome (CRS) occurred in most patients, but no grade 3 or higher CRS events were observed. The investigators noted that the favorable safety profile may enable ambulatory care delivery.³

GPRC5D-Targeted CAR T Shows High Response Rates in Earlier-Line R/R Myeloma

Arlocabtagene autoleucel (arlo-cel), an investigational GPRC5D-targeting CAR T-cell therapy, produced deep and durable responses in patients with previously treated R/R multiple myeloma who had received 1 to 3 prior lines of therapy, based on phase 1 data (NCT04674813). presented at EHA 2026.

Among 31 evaluable patients treated with a single infusion of arlo-cel at the recommended phase 2 dose of 150 × 10⁶ CAR T cells, the ORR was 94%, including a CR or better in 71%. The median time to response was 0.99 months (IQR, 0.95-1.68), and the 18-month duration of response rate was 64.6%. Among 20 patients with evaluable MRD data, the MRD-negative CR rate was 65% (95% CI, 40.8%-84.6%). The 12-month and 18-month PFS rates were 73.0% (95% CI, 53.2%-85.5%) and 62.6% (95% CI, 42.7%-77.3%), respectively, whereas OS was 100% at both time points.

No grade 3 or higher CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) events were observed. On-target, off-tumor events were predominantly grade 1/2 and most resolved. Study investigator Susan Bal, MD, of University of Alabama at Birmingham, stated in her presentation that these results support arlo-cel as a potentially effective early-line treatment option in patients with R/R multiple myeloma.⁴

Quadruplet Without Transplant Achieves Deep Remissions in Smoldering Myeloma

Data from the phase 2 ASCENT trial (NCT03289299) demonstrated that a limited-duration quadruplet regimen of carfilzomib (Kyprolis), lenalidomide, daratumumab, and dexamethasone (DKRd) produced high rates of deep remission in patients with high-risk smoldering multiple myeloma, with no autologous stem cell transplantation (ASCT) required.

Among 86 evaluable patients, the ORR was 98%, including 94% with a VGPR or better and a sCR rate of 52%. MRD negativity per IMWG criteria was achieved by 60% of patients, and 87% had at least 1 undetectable disease assessment in the marrow. MRD negativity increased incrementally from 8.1% at the end of induction to 47.7% at the end of maintenance. The median PFS was not reachedNR; 10 patients experienced exclusively biochemical progression events, and the 3-year PFS rate was 89.9% (95% CI, 82.3%-98.3%). Median follow-up for living patients was 52 months. Presenting investigator Shaji Kumar, MD, noted that the regimen’s toxicity profile was similar to what has been observed with DKRd in newly diagnosed multiple myeloma and emphasized the importance of longer follow-up to assess whether durable cure is achievable in a subset of patients.⁵

Belantamab Mafodotin Quadruplet Yields Durable Remissions in Transplant-Ineligible NDMM

A phase 1/2 study (NCT05280275) evaluated belantamab mafodotin-blmf (Blenrep) combined with daratumumab, lenalidomide, and dexamethasone (BelaDRd) in patients with newly diagnosed multiple myeloma (NDMM) who were ineligible for transplant and classified as intermediate-fit or frail per IMWG criteria.

In part 1 of the study (n = 16 evaluable), 81.3% of patients achieved MRD negativity for a median duration of 14.1 months. Among 7 evaluable patients in part 2, 71.4% achieved MRD-negative status. The ORR was 91.7% across parts 1 and 2, with CR or better rates of 66.7% and 58.3%, respectively. The 18-month PFS rate was 91.7% (95% CI, 76.4%-97.2%) in the overall population, and model-based median PFS estimates ranged from 78.7 months to 133.9 months. Ocular toxicity was manageable; grade 3 or higher best corrected visual acuity decline was reported in 10.4% of assessments in part 1. Most grade 2 or higher ocular events resolved to grade 1 or lower. Study investigator Evangelos Terpos, MD, PhD, characterized the results as warranting a phase 3 study of this quadruplet combination.⁶

REFERENCES

1. Voorhees PM, Mina R, Rodríguez-Otero P, et al. Phase 3, randomized study of talquetamab plus daratumumab ± pomalidomide vs daratumumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: MonumenTAL-3. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S100.

2. van de Donk NWCJ, Mina R, Touzeau C, et al. Ciltacabtagene autoleucel in lenalidomide-refractory multiple myeloma responding to bridging therapy: CARTITUDE-4 cytogenetic subgroup analysis. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF767.

3. Spencer A, Harrison S, Lim SL, et al. Successful in vivo CAR-T generation and MRD clearance with KLN-1010 across diverse baseline T-cell phenotypes in relapsed/refractory multiple myeloma. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S185.

4. Bal S, Htut M, Berdeja J, et al. Arlocabtagene autoleucel, a GPRC5D-targeted CAR T-cell therapy for patients with relapsed/refractory multiple myeloma: updated phase 1 safety and efficacy results in patients with 1-3 prior regimens. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S200.

5. Kumar S, Laplant B, Badros A, et al. Aggressive smoldering curative approach evaluating novel therapies (ASCENT): a phase 2 trial of induction, consolidation, and maintenance in high-risk smoldering multiple myeloma. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S207.

6. 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. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S204.