IMS 2026: Key Updates Across The Multiple Myeloma Paradigm

The 23rd Annual International Myeloma Society (IMS) Meeting & Exposition featured a full poster hall alongside its plenary and oral sessions. Several presentations offered real-world and evidence-synthesis perspectives that speak directly to everyday treatment decisions, including how much benefit venetoclax (Venclexta) delivers in t(11;14)-positive disease, what patients experience on daratumumab (Darzalex) regimens, and whether the clinical-trial edge of quadruplet induction holds up in routine practice.

Here are the key takeaways of select poster presentations from the meeting:

How beneficial is venetoclax in t(11;14)-positive relapsed multiple myeloma?

Venetoclax is widely used off label in patients with relapsed/refractory multiple myeloma who harbor the t(11;14) translocation, despite the lack of FDA approval and conflicting randomized data. In a systematic review and meta-analysis, investigators pooled 298 patients from 2 randomized phase 3 trials, CANOVA (NCT03539744) and BELLINI (NCT02755597), to quantify the efficacy of venetoclax-based therapy vs standard of care in this population.¹

Venetoclax-based therapy was associated with a directionally favorable improvement in progression-free survival (PFS), with a pooled hazard ratio (HR) of 0.40 (95% CI, 0.08-1.91), and a trend toward prolonged time to deterioration in disease-related symptoms (TTDDS; HR, 0.70; 95% CI, 0.46-1.05). No pooled overall survival (OS) benefit was observed (HR, 1.15; 95% CI, 0.78-1.71). None of the pooled efficacy outcomes reached statistical significance, and substantial heterogeneity was observed for PFS (I² = 88.8%), while heterogeneity was minimal for OS and TTDDS (I² = 0%).

“Venetoclax-based therapy demonstrates a directionally favorable effect on PFS and TTDDS in t(11;14)-positive [relapsed/refractory multiple myeloma],” lead study investigator Vasu Malhotra, DO, of Lakeland Regional Health in Lakeland, Florida, wrote with coauthors in the poster.¹ “Future trials should prioritize t(11;14) populations and consider non-inferiority or combination-based comparator designs. The lack of statistical significance in pooled outcomes likely reflects differences in trial design and treatment backbone rather than absence of biological activity.”

How do QOL outcomes with daratumumab translate to real-world settings?

Daratumumab is highly utilized across newly diagnosed (NDMM) and relapsed/refractory multiple myeloma, but prospective, real-world data on health-related quality of life (HRQOL) with daratumumab regimens remain limited. In a prospective, multicenter, observational study across 4 US centers including Yale, Mayo Clinic, University of Alabama at Birmingham, and Vanderbilt, investigators enrolled 152 patients receiving standard-of-care daratumumab regimens and assessed HRQOL using the EORTC QLQ-C30 at baseline and at 3, 6, and 12 months.² The population included 89 patients with NDMM and 63 with relapsed/refractory disease.

Among 137 patients evaluable for HRQOL, global health status increased significantly and linearly from a baseline score of 60.7 to 66.3 at 3 months (P = .006) and 71.4 at 6 months (P <.001), exceeding the minimally important difference of 10 points, and was maintained at 69.4 at 12 months (P <.001). Patients with NDMM had a greater increase in physical (P = .03) and role (P = .02) functioning and a larger decrease in pain (P = .009) at 3 months than those with relapsed/refractory disease. Significant improvement was seen across all functional and symptom scales except constipation/diarrhea and financial difficulties.

The overall response rate was 89.5% in NDMM and 64.2% in relapsed/refractory disease, with a very good partial response or better in 71.1% and 47.2%, respectively. At a median follow-up of 11.6 months, the 12-month progression rate was 8.6% in patients with NDMM vs 17.9% in those with relapsed/refractory multiple myeloma, and the 12-month mortality rate was 3.9% vs 9.0%. Hematologic adverse events were most common (anemia, 64%; leukopenia, 38.7%; lymphopenia, 33.0%), while the infection rate was low (3.3%; 1.3% grade 3).

“In this prospective, observational trial we saw clinically meaningful improvements in global health status, functioning, and symptom scales with [daratumumab] regimens in both NDMM and [relapsed/refractory multiple myeloma],” lead study investigator Sabrina L. Browning, MD, an assistant professor of Medicine (Medical Oncology and Hematology) at Yale School of Medicine and Yale Cancer Center, wrote with coauthors.² “[Daratumumab] regimens were both efficacious and tolerable across the myeloma disease spectrum.”

How does quadruplet induction compare with triplet therapy in transplant-eligible disease?

Quadruplet induction with daratumumab plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (DVRd) has demonstrated superior PFS over the triplet bortezomib, lenalidomide, and dexamethasone (VRd) in randomized trials and is now a standard for transplant-eligible multiple myeloma. However, real-world comparative evidence remains limited. Using a target trial emulation of the Flatiron Health Research Database, investigators compared PFS and OS between patients who initiated first-line DVRd or VRd from September 2019 to October 2024, applying inverse probability of treatment weighting and estimating treatment effects with restricted mean survival time (RMST) because the proportional hazards assumption was violated.³

Among 2493 eligible transplant-eligible patients, including 948 who received DVRd and 1545 who received VRd, with a median follow-up of 24.2 months, DVRd was associated with a significantly longer PFS. The 36-month PFS rate was 75.2% with DVRd vs 64.4% with VRd, an RMST difference of 1.5 months (P = .003). OS was similar between groups, with a 36-month OS of 84.0% vs 84.4% (RMST difference, −0.1 months; P = .89). Notably, the PFS difference was more pronounced among patients who did not receive an upfront transplant (36-month PFS, 68.2% vs 51.4%) than among those who did (81.7% vs 76.1%). Use of DVRd rose from 4.1% of eligible patients in 2019 to 78.5% in 2024.

“In a large real-world cohort of transplant-eligible patients with [NDMM], we observed findings consistent with prior trials: DVRd was associated with longer PFS than VRd but no difference was observed with OS,” lead investigator Amandeep Godara, MD, an associate professor in the Division of Hematology & Hematologic Malignancies at the Huntsman Cancer Institute of the University of Utah, wrote with coauthors in the poster.³ “Longer follow-up is needed to determine whether the PFS benefit ultimately translates into an OS advantage.”

References

1. Malhotra V, Patel SG, Carter M, et al. Efficacy of venetoclax-based therapy in t(11;14)-positive relapsed/refractory multiple myeloma. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract PA-170.
2. Browning S, Li F, Parker T, et al. Patient-reported quality of life and real-world outcomes with use of daratumumab regimens in newly diagnosed and relapsed/refractory multiple myeloma: a multicenter study. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract PA-341.
3. Tan CJ, Meraz M, Maxwell L, et al. Comparative effectiveness of quadruplet vs triplet induction regimen in transplant-eligible newly diagnosed multiple myeloma: a target trial emulation. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract PA-106.