IMS Day 2 Recap: MRD-Guided Maintenance, Novel Bispecific Data in Myeloma

About half of patients who discontinued maintenance therapy after 2 years of sustained minimal residual disease (MRD) negativity in the phase 3 GEM2014MAIN trial remained alive and progression-free at a 7-year landmark, according to long-term data presented at the 23rd International Myeloma Society (IMS) Annual Meeting.¹ The findings were among several MRD- and dosing-focused updates presented on day 2 of the meeting.

Also presented were first-year results of intensified maintenance in MRD-positive patients from the phase 3 MIDAS trial, a patient-reported ocular safety analysis from the phase 1 DREAMM-9 study of belantamab mafodotin, extended follow-up of cevostamab plus pomalidomide and dexamethasone from the CAMMA 1 study, and an early update on the trispecific antibody ramantamig.^2-5

GEM2014MAIN: MRD-Guided Maintenance Discontinuation

The phase 3 GEM2014MAIN trial (NCT02406144) evaluated MRD-guided discontinuation of maintenance therapy in patients with newly diagnosed multiple myeloma (MM) who had completed induction, transplant, and consolidation in the GEM2012MENOS65 trial (NCT01916252).¹ Patients were randomly assigned to maintenance with lenalidomide (Revlimid) plus dexamethasone (Rd) or Rd plus ixazomib (Ninlaro; IRd); those who were MRD negative by next-generation flow cytometry (10⁻⁶ sensitivity) after 2 years discontinued therapy, while MRD-positive patients continued Rd for 3 additional years.

At a median follow-up of 9.5 years, MRD negativity at any time point independently predicted longer progression-free survival (PFS; hazard ratio [HR], 0.13; P < .001), as did high-risk cytogenetics (HR, 1.56; P = .012) and International Staging System stage. Of 271 patients who completed 2 years of maintenance, 165 (49.7%) were MRD negative and discontinued treatment; their median PFS was not reached, vs 3.5 years for MRD-positive patients who continued therapy (P < .001). Among those who discontinued, 84 of 165 (51%) remained alive and progression-free at a 7-year landmark, with only 3 progressions and 1 nonprogression death.

CAMMA 1: Modified Cevostamab Dosing in BCMA-Naive Patients

In arm A of the phase 1b CAMMA 1 study (NCT04910568), a modified, fixed-duration cevostamab regimen induced durable responses in BCMA-naive patients with R/R MM, including responses that continued after treatment completion.² The regimen was designed to intensify target dosing in early cycles and reduce it in later cycles, compared with the 160-mg every-3-weeks schedule evaluated in a prior phase 1 study (NCT03275103).

Cevostamab was started with a single 3.6-mg step-up dose on cycle 1, day 1, followed by the 90-mg target dose weekly in cycles 1 and 2, every 2 weeks in cycles 3 through 6, and every 4 weeks in cycles 7 through 13.

As of January 23, 2026, 24 BCMA-naive patients were enrolled, with a median age of 66.5 years and a median of 4 prior lines. Overall, 87.5% were refractory to their last line, 62.5% were triple-class refractory, and 37.5% were penta-drug refractory. High-risk cytogenetics were present in 33.3% of evaluable patients (7/21), and 8.3% had extramedullary disease.

At a median follow-up of 47.5 months, the ORR was 70.8%, with a very good partial response (VGPR) or better rate of 58.3% and a CR or better rate of 33.3%. The median duration of response (DOR) was 46.5 months (95% CI, 9.0-not estimable), and the median PFS was 12.4 months (95% CI, 2.8-not estimable). Eleven patients with a partial response or better completed all 13 planned cycles. Ten patients had responses lasting at least 40 months after initiation, 7 of whom were in CR or better at the end of treatment.

Grade 3 or 4 adverse events (AEs) occurred in 70.8% of patients, most commonly neutropenia (54.2%) and anemia (29.2%). Grade 3 or 4 infections occurred in 33.3%, and 37.5% of patients received intravenous immunoglobulin (IVIG). CRS occurred in 75.0% of patients (grade 1, 50.0%; grade 2, 20.8%; grade 3, 4.2%) and was limited to the step-up dose and initial target dose. Two patients discontinued cevostamab due to AEs, and 2 grade 5 AEs, sepsis and cerebrovascular accident, were assessed as unrelated to treatment.

“This fixed-duration modified regimen led to a respectable overall response rate…and this is something that compares favorably to the first improvement study, where similar response rates and VGPR rates were seen,” said Ravi Vij, MD, MBA, professor of medicine at Washington University. “These data support the continued evaluation of fixed-duration dosing regimens in future studies of cevostamab.”

MIDAS: Isatuximab-Iberdomide Maintenance in MRD-Positive NDMM

In the phase 3 MIDAS trial (NCT04934475), patients with transplant-eligible newly diagnosed MM who remained MRD positive after 6 cycles of isatuximab (Sarclisa), carfilzomib (Kyprolis), lenalidomide, and dexamethasone induction received intensified maintenance with isatuximab plus iberdomide (Isa-Iber) for 3 years following single or tandem autologous stem cell transplantation (ASCT).³ Iberdomide, an investigational CELMoD, was dosed at 1 mg/day on days 1 through 21 of each 28-day cycle.

Overall, 219 patients (108 after single ASCT, 111 after tandem ASCT) initiated Isa-Iber maintenance, and 203 completed the first year. MRD negativity at the 10⁻⁶ threshold improved from 40% post-consolidation to 58% after 1 year in the single-ASCT arm, and from 32% to 48% in the tandem-ASCT arm; at 10⁻⁵, rates rose from 67% to 76% and 62% to 70%, respectively. The most common adverse events during maintenance were neutropenia (46% any grade; 42% grade ≥3) and infections (72%; 18% grade ≥3). Five progressions and 1 death occurred in each arm during the first year.

DREAMM-9: Ocular Tolerability With Extended Belantamab Mafodotin Dosing

A patient-reported outcomes analysis of the phase 1 DREAMM-9 trial (NCT04091126) found that longer dosing intervals of belantamab mafodotin (belamaf; Blenrep) reduced ocular toxicity in transplant-ineligible newly diagnosed MM.³ The trial evaluated belamaf across 8 induction/maintenance dosing cohorts combined with bortezomib, lenalidomide, and dexamethasone, building on a prior report that higher induction dose intensity produced deeper responses while longer dosing intervals required fewer dose modifications.

Among 118 patients enrolled as of June 2, 2025, 92% of grade 2 or higher ocular events resolved. Patients dosed every 9 to 12 weeks or every 12 weeks had the lowest rates of severe or very severe blurred vision (25%-32%), compared with 58% for every-6-to-8-week dosing and 67% to 92% for every-3-to-4-week dosing. Vision-related functioning generally stayed below the threshold for clinically important difference in the longer-interval groups, with between-group differences narrowing after week 24. An induction/maintenance dosing strategy is now being used in the ongoing phase 3 DREAMM-10 (NCT06679101) and PrE1005 (NCT04484623) trials.

“Extended dosing interval with belamaf improves oculator ability while maintaining efficacy and quality of life, with no impact on vision-related functioning,” concluded Hang Quach, MBBS(Hons), FRACP, FRCPA, MD, professor of hematology at the University of Melbourne and director of clinical haematology and clinical hematology research at St.Vincent's Hospital, during the presentation.

Ramantamig: Updated RP2D Data and Outpatient Dosing

In an expanded cohort from the first-in-human phase 1 study (NCT05652335) of ramantamig (Ram; JNJ-5322), a T-cell–redirecting trispecific antibody targeting BCMA and GPRC5D, updated data continued to show deep, durable responses at the recommended phase 2 dose (RP2D) in triple-class exposed relapsed/refractory MM, with feasible outpatient dosing (OPD).⁵ The RP2D is a single 5-mg step-up dose (SUD) followed by 100 mg subcutaneously every 4 weeks.

As of April 2026, 56 patients (median age, 68 years; median 3 prior lines [range, 1-11]; 41.9% with high-risk cytogenetics) had received Ram at the RP2D, including 47 who were naive to prior T-cell–redirecting therapy. Infections occurred in 80.4% of patients (25.0% grade 3/4), and cytokine release syndrome (CRS) occurred in 39.3%, nearly all grade 1 or 2. In the 30-patient OPD cohort, 93.3% received the SUD and 79.3% received the first treatment dose outpatient with prophylactic tocilizumab (Actemra; 96.6% of patients); CRS in this setting was low-grade (10.0% at SUD, 6.7% at dose 1, all grade 1), though 4 patients required hospitalization within 2 days of outpatient dosing. Among T-cell–redirecting-naive patients, the overall response rate was 93.6% (≥CR, 76.6%), all MRD-evaluable patients were MRD negative at 10⁻⁵ by next-generation sequencing, and 18-month duration of response and PFS rates were 90.7% and 84.6%, respectively.

“…This is a very feasible approach that I think lays the groundwork for studying outpatient prompting administration,” said Jeffrey Matous, MD, member physician at the Colorado Blood Cancer Institute and part of the Plasma Cell Diseases Group, during the presentation.

REFERENCES

1. Moreno DF et al. Discontinuation of maintenance therapy guided by minimal residual disease in newly diagnosed multiple myeloma: long-term results of the GEM2014MAIN study. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; September 23-26, 2026; Glasgow, Scotland.

2. Krishan A et al. A Fixed-Duration, Modified Cevostamab Dosing Regimen Induces Durable Remissions That Continue After Completion in BCMA-Naïve Pts With Relapsed/Refractory Multiple Myeloma (RRMM): CAMMA 1 Arm A Results. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; September 23-26, 2026; Glasgow, Scotland.

3. Usmani SZ et al. DREAMM-9 patient-reported vision-related function with extended belantamab mafodotin dosing intervals with bortezomib, lenalidomide, dexamethasone (BVRd) in transplant ineligible multiple myeloma. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; September 23-26, 2026; Glasgow, Scotland.

4. Spencer A et al. Cevostamab plus pomalidomide (Pom) and dexamethasone (Dex) induces durable remissions in BCMA-naive patients with relapsed/refractory multiple myeloma (RRMM): CAMMA 1 arm B extended follow-up data. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; September 23-26, 2026; Glasgow, Scotland.

5. Matous JV et al. Updated safety and efficacy of ramantamig (Ram; JNJ-5322) at the recommended phase 2 dose (RP2D), demonstrating feasibility of outpatient dosing (OPD) in relapsed/refractory multiple myeloma (RRMM). Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; September 23-26, 2026; Glasgow, Scotland.