Cevostamab Combo Shows Durable Responses in R/R Multiple Myeloma

Cevostamab plus pomalidomide (Pomalyst) and dexamethasone (pom-dex) induced enduring responses in BCMA-naive patients with relapsed/refractory multiple myeloma, according to extended follow-up from the Arm B dose-expansion portion of the phase 1b CAMMA 1 trial (NCT04910568) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹

What were the response and survival outcomes?

At a median follow-up of approximately 20 months, the FcRH5/CD3 bispecific antibody plus pom-dex produced an overall response rate (ORR) of 86.2% (95% CI, 71.9%-100%) at the 70-mg cevostamab target dose and 88.0% (95% CI, 73.3%-100%) at the 105-mg target dose.

Response rates were comparable across the 2 dose cohorts. In the 70-mg cohort (n = 29), the rate of complete response (CR) or better was 62.1% and the rate of very good partial response (VGPR) or better was 75.9%, including a stringent CR (sCR) in 44.8%. In the 105-mg cohort (n = 25), the rate of CR or better was 64.0%, and the rate of VGPR or better was 76.0%, including an sCR in 44.0%.

Among measurable residual disease (MRD)–evaluable patients with a CR or better, MRD-negative CR rates at a sensitivity of 10⁻⁵ were 93.8% (n = 15/16) in the 70-mg cohort and 92.3% (n = 12/13) in the 105-mg cohort; across all patients, MRD-negative CR rates were 55.2% (n = 16/29) and 52.0% (n = 13/25), respectively. After a median follow-up of approximately 20 months, the median duration of response (DOR) and median progression-free survival (PFS) were not reached in either cohort. The 18-month DOR rates were 74.0% (95% CI, 55.9%-92.0%) with 70 mg and 68.2% (95% CI, 48.7%-87.6%) with 105 mg, and the 18-month PFS rates were 67.4% (95% CI, 49.8%-84.9%) and 66.0% (95% CI, 46.7%-85.3%), respectively.

What was the safety profile of the combination?

Grade 3/4 adverse events (AEs) occurred in 82.8% of the 70-mg cohort and 96.0% of the 105-mg cohort, and serious AEs occurred in 58.6% and 60.0%, respectively. Two grade 5 AEs excluding disease progression occurred, including a treatment-related septic shock event in the 70-mg cohort and an intracranial hemorrhage not attributed to treatment in the 105-mg cohort.

Cytokine release syndrome occurred in approximately 70% of patients in both cohorts, and immune effector cell–associated neurotoxicity syndrome was uncommon, limited to single grade 1 and grade 2 cases in the 105-mg cohort. Neutropenia (79.3% and 84.0%) and infections (75.9% and 80.0%) were the most common AEs of interest in the 70-mg and 105-mg cohorts.

AEs led to pomalidomide discontinuation in 27.6% and 32.0% of patients, almost exclusively due to neutropenia, while cevostamab discontinuations were lower (6.9% and 8.0%). The investigators reported a low rate of severe infections and preservation of humoral immunity in the 70-mg cohort.

“Cevostamab plus pomalidomide and dexamethasone induces deep and durable responses in BCMA-naive patients with relapsed [multiple] myeloma with a high ORR,” lead study investigator Andrew Spencer, MBBS, FRACP, FRCPA, DM, head of the Malignant Haematology, Transplantation and Cellular Therapy Service at The Alfred Hospital, a professor of Haematology at Monash University, and head of the Myeloma Research Group in Melbourne, Australia, stated in the presentation.¹

What was the CAMMA 1 Arm B design and population?

Arm B of CAMMA 1 is a randomized dose-expansion portion of the phase 1b study that enrolled patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy, including an immunomodulatory drug and a proteasome inhibitor; patients refractory to pomalidomide were excluded.² Patients were randomly assigned 1:1 to a 70-mg or 105-mg cevostamab target dose, with cevostamab initiated using a double or triple step-up dosing regimen, administered every 2 weeks for 6 cycles and then every 4 weeks, plus pomalidomide and dexamethasone.

The primary end points were safety and identification of the recommended phase 2 dose (RP2D). Secondary end points included activity, pharmacokinetics, and pharmacodynamics. Across the 70-mg and 105-mg cohorts, the median number of prior lines of therapy was 2; most patients were triple-class exposed (72.4% and 56.0%) and refractory to their last prior therapy (72.4% and 68.0%).

What is cevostamab, and what comes next?

Cevostamab is an FcRH5/CD3 T-cell–engaging bispecific antibody. FcRH5 is expressed on multiple myeloma cells independent of BCMA and GPRC5D, and phase 1 monotherapy data have shown more pronounced activity in patients without exposure to BCMA-directed agents. Based on the observed benefit-risk profile, the investigators identified the triple step-up dosing regimen and the 70-mg cevostamab plus pom-dex regimen as the RP2Ds. The 70-mg cevostamab plus pom-dex regimen is now being investigated in the phase 3 CEVOLUTION trial (NCT07555938) in patients with relapsed/refractory multiple myeloma who have received an anti-CD38 antibody and lenalidomide as part of 1 to 3 prior lines of therapy; enrollment is ongoing.

References

1. Spencer A, Mian HS, Kim K, 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; Glasgow, Scotland. Abstract OA-11.
2. A study evaluating the safety, pharmacokinetics, and activity of cevostamab in participants with relapsed or refractory multiple myeloma (CAMMA 1). ClinicalTrials.gov. Updated September 17, 2026. Accessed September 24, 2026. https://tinyurl.com/ypa4nhcn