IMS 2026 Day 4 Recap: MRD-Guided Regimens Highlight Final Sessions

The final day of the 23rd International Myeloma Society (IMS) Annual Meeting, held September 23 to 26, 2026, in Glasgow, Scotland, closed with 6 oral abstract sessions built around minimal residual disease (MRD)–guided treatment strategies, real-world evidence for a commercially available CAR T-cell therapy, and updated safety data on chimeric antigen receptor (CAR) T-cell–associated neurotoxicity.

Saturday's data spanned newly diagnosed, high-risk, and relapsed/refractory multiple myeloma (RRMM), reinforcing MRD negativity as both a trial end point and, increasingly, a live decision point for intensifying or de-escalating therapy.

CEPHEUS Update Reinforces Daratumumab Quadruplet in Transplant-Ineligible NDMM

An updated MRD analysis of the phase 3 CEPHEUS trial (NCT03652064), presented by Sonja Zweegman, MD, PhD, of Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, showed that daratumumab (Darzalex) plus bortezomib (Velcade), lenalidomide, and dexamethasone (DVRd) continued to outperform VRd alone in transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM).¹

At a median follow-up of 76 months among 395 patients (DVRd, n = 197; VRd, n = 198), overall MRD-negativity rates (10⁻⁵) were 61.4% with DVRd vs 39.9% with VRd in the intention-to-treat population (OR, 2.36; P < 0.0001). Rates of sustained MRD negativity (10⁻⁵) for at least 24 months were also higher with DVRd vs VRd in the MRD-evaluable population (87.5% vs 63.0%; OR, 3.30; P = 0.0342). Median progression-free survival (PFS) favored DVRd in the overall intention-to-treat population (HR, 0.59; 95% CI, 0.44–0.80) and among patients with 12-month sustained MRD negativity in both the intention-to-treat (HR, 0.65; 95% CI, 0.34–1.26) and TIE (HR, 0.75; 95% CI, 0.35–1.60) populations.

DREAMM-8 Update Links Sustained MRD Negativity With Improved PFS in RRMM

A long-term update from the phase 3 DREAMM-8 trial (NCT04484623), led by Suzanne Trudel, MD, of Princess Margaret Cancer Centre, University of Toronto, and colleagues including senior author Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens, showed that patients with RRMM treated with belantamab mafodotin (Blenrep) plus pomalidomide (Pomalyst) and dexamethasone (BPd) were more than 4 times as likely to achieve sustained MRD negativity as those treated with pomalidomide, bortezomib, and dexamethasone (PVd).²

At a data cutoff of July 7, 2025 (median follow-up, 35.8 months), 27.7% of patients in the intention-to-treat BPd arm (n = 155) achieved complete response (CR) or better plus MRD negativity, compared with 6.1% in the PVd arm (n = 147); sustained MRD-negativity rates were 15.5% vs 2.7%, respectively. Patients with sustained MRD negativity had durable outcomes in both arms, with only 1 of 24 BPd-treated and 0 of 4 PVd-treated patients experiencing a PFS event; among patients without sustained MRD negativity, median PFS was 21.1 months with BPd vs 10.2 months with PVd (HR, 0.04; 95% CI, 0.01–0.32).

MRD-Guided Bispecific Intensification Deepens Responses in High-Risk NDMM

In a late-breaking abstract, Paula Rodríguez-Otero, MD, of Clínica Universidad de Navarra, and colleagues reported early results from the phase 2 GEM-TECTAL trial (NCT05849610), evaluating an MRD-guided, transplant-free approach for newly diagnosed high-risk multiple myeloma (ND-HRMM).³

Patients received 4 induction cycles of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRd), followed by 6 cycles of teclistamab (Tecvayli) plus daratumumab (Tec-D) intensification; patients who achieved MRD negativity moved to Tec-D maintenance, while those with persistent MRD positivity received early rescue with talquetamab (Talvey) plus daratumumab. Among the first 30 patients enrolled (median age, 70 years; 70% meeting ultra-high-risk criteria), overall response rate (ORR) rose from 76.7% after D-VRd induction to 93.3% after Tec-D intensification, with a CR-or-better rate of 80%. The primary end point of MRD-negative CR by next-generation flow (10⁻⁶) was met in 73% (22 of 30) of patients in the intention-to-treat population. During Tec-D intensification, grade 3 or higher infections occurred in 14.3% of patients and cytokine release syndrome (CRS) occurred in 25%, all grade 1.

Real-World Data Affirm Equecabtagene Autoleucel Activity in Heavily Pretreated RRMM

A multicenter Chinese real-world analysis of 281 patients with RRMM treated with equecabtagene autoleucel (eque-cel), a fully human BCMA-directed CAR T-cell therapy, across 65 centers since its June 2023 commercial launch, reported an ORR of 95.9% (256 of 267 response-evaluable patients), according to data presented by Jin Lu, MD, of Peking University People's Hospital.⁴

Among evaluable patients, 77.2% achieved a CR or stringent CR, and MRD negativity was reported in 94.1%. At a median follow-up of 10.97 months, median PFS and overall survival (OS) had not been reached; 12-month PFS and OS rates were 71.5% and 87.8%, respectively. The cohort was heavily pretreated (median, 3 prior lines) and high risk (82.4% high-risk cytogenetics; 47.0% extramedullary disease). Outcomes were largely consistent across subgroups, including patients older than 70 years and those with prior anti-CD38 exposure, though patients with high prelymphodepletion CAR-HEMATOTOX risk scores had a lower 12-month PFS rate (60.3%) than those with low-risk scores (86.9%).

Novel Dual-Targeting CAR T-Cell Therapy Shows Early Activity in RRMM

BMS-986453, an investigational autologous CAR T-cell therapy targeting both BCMA and GPRC5D, produced an ORR of 83% across all doses in a phase 1 dose-escalation and expansion study (NCT06153251), according to data presented by Doris Hansen, MD, of Moffitt Cancer Center. Among 58 treated patients (median age, 67 years; 33% high-risk cytogenetics; median, 4 prior lines), ORR was 94% at the 2 highest doses combined (75 million and 150 million CAR T cells; n = 35), with a CR rate of 71%.⁵

Grade 3/4 treatment-emergent adverse events occurred in 98% of patients, most commonly neutropenia (88%) and thrombocytopenia (48%). CRS occurred in 78% of patients (grade 3, 3.4%), and on-target, off-tumor toxicities affecting skin, nails, or oral mucosa occurred in 50%, nearly all grade 2 or lower. One treatment-related death from CRS occurred in the highest-dose (300 million cell) cohort; maximum tolerated dose was not reached.

Prophylactic Cyclophosphamide Fails to Reduce Cilta-Cel-Associated Neurotoxicity

A prospective, single-center comparative study from Mayo Clinic, presented by Christoph Schaefers, MD, found that prophylactic cyclophosphamide administered at peak absolute lymphocyte count (ALC) did not reduce rates of delayed neurotoxicity (DNT) or parkinsonism syndrome (PKS) following ciltacabtagene autoleucel (cilta-cel) in patients with a high postinfusion ALC—a subgroup with an established 25% to 30% risk for these toxicities.⁶

Among 39 of 101 high-ALC patients who received prophylactic cyclophosphamide, DNT and PKS rates were 26% and 8%, respectively—similar to a historical cohort without prophylaxis (22% DNT, 8% PKS) and a cohort that received prophylactic dexamethasone (23% DNT, 9% PKS). Cyclophosphamide also did not significantly alter ALC expansion kinetics compared with dexamethasone prophylaxis. Investigators noted that 3 of 4 PKS events in the cyclophosphamide cohort were clinically mild and that no PKS-related deaths occurred in that cohort, compared with a 36% (n = 5 of 14) PKS-associated mortality rate in the comparator cohorts combined—an observation the investigators said supports further study of biologically informed, risk-adapted prevention strategies rather than a single prophylactic agent.

The meeting closed with a "Highlights of the 2026 Annual Meeting" session recapping basic science, translational, and clinical data from all 4 days, followed by the formal closing ceremony.

REFERENCES

1. Zweegman S et al. The benefit of daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) on depth and durability of response in the phase 3 CEPHEUS trial: updated minimal residual disease analysis. Abstract OA-69. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

2. Trudel S et al. Long-term outcomes with sustained minimal residual disease (MRD) negativity in belantamab mafodotin–treated patients (pts) with relapsed/refractory multiple myeloma (RRMM): an update from DREAMM-8. Abstract OA-38. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

3. Rodríguez-Otero P et al. MRD-guided frontline T-cell redirection therapy for newly diagnosed high-risk multiple myeloma using teclistamab-daratumumab intensification and talquetamab-daratumumab early rescue intervention. Abstract LBA-08. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

4. Lu J et al. BCMA CAR T-cell therapy (equecabtagene autoleucel, eque-cel) for multiple myeloma in Chinese clinical practice: a large real-world evidence of 281 patients. Abstract OA-09. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

5. Hansen D et al. BMS-986453, a dual-targeting BCMA × GPRC5D autologous CAR T cell therapy in patients (pts) with relapsed/refractory multiple myeloma (RRMM): initial results from a phase 1 trial. Abstract OA-10. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

6. Schaefers C et al. Mitigating cilta-cel-associated delayed neurotoxicity in patients with high lymphocyte expansion: a prospective observational comparative study of prophylactic cyclophosphamide. Abstract OA-41. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.