Cevostamab Plus Pomalidomide/Dexamethasone Yields Durable, Deep Responses in BCMA-Naive Relapsed/Refractory Myeloma

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

Responses deepened over time across both evaluated dose levels of the FcRH5×CD3 T-cell–engaging bispecific antibody, and most patients who achieved a complete response (CR) or better went on to test negative for measurable residual disease (MRD). Neither median progression-free survival (PFS) nor median duration of response (DOR) had been reached at a median follow-up of approximately 20 months in either dose cohort, and investigators used these findings, together with the overall safety profile, to help select doses for phase 3 testing.

Patients were randomized 1:1 to 70-mg (n = 29) or 105-mg (n = 25) target-dose cevostamab plus pom-dex. At a median time on study of 20.2 (range, 12.7-27.5) and 20.4 (range, 3.3-27.3) months, respectively, the objective response rate (ORR) was 86.2% (95% CI, 71.9%-100%) with 70 mg and 88.0% (95% CI, 73.3%-100%) with 105 mg; rates of CR or better were 62.1% and 64.0%, and rates of very good partial response or better were 75.9% and 76.0%. Among MRD-evaluable patients with a CR or better, MRD negativity at the 10⁻⁵ threshold by next-generation sequencing (clonoSEQ) was achieved by 93.8% (95% CI, 81.9%-100%; n = 15 of 16) with 70 mg and 92.3% (95% CI, 77.8%-100%; n = 12 of 13) with 105 mg.

How was arm B of the CAMMA 1 trial designed?

Arm B of CAMMA 1 enrolled patients with RRMM who had received at least 1 prior line including an immunomodulatory drug and a proteasome inhibitor; pomalidomide-refractory patients were excluded. Patients were randomized 1:1 to a 70-mg or 105-mg cevostamab target dose, given intravenously on days 1 and 15 of each 28-day cycle after either a double (0.3/3.3 mg over 14 days) or triple (0.3/1.2/3.6 mg over 21 days) step-up pre-phase, with hospitalization for at least 48 hours after each infusion to monitor for cytokine release syndrome (CRS). Oral pomalidomide was dosed at 2 mg on days 1 through 21 each cycle—below the standard 4-mg pom-dex dose—and dexamethasone (20 mg) was given weekly through cycle 4, becoming optional from cycle 5; treatment continued until progression or unacceptable toxicity. Primary objectives were safety and selection of the recommended phase 2 dose (RP2D); secondary objectives were activity, pharmacokinetics, and pharmacodynamics.

Baseline characteristics were comparable between arms: median age was 65 years and median prior lines of therapy was 2 (range, 1-6) in both groups. Most patients were triple-class exposed (72.4% with 70 mg; 56.0% with 105 mg) and refractory to their last prior therapy (72.4% and 68.0%, respectively), and high-risk cytogenetics were more common with 105 mg (36.4% vs 15.0%).

Cevostamab is an FcRH5×CD3 T-cell–engaging bispecific antibody; phase 1 monotherapy data showed manageable safety and durable responses in heavily pretreated myeloma, with more pronounced activity in BCMA-naive patients.² Earlier CAMMA 1 arm B results, presented at the 2025 IMS Annual Meeting, similarly showed high response and MRD-negativity rates with this regimen.³ Andrew Spencer, MBBS, FRACP, FRCPA, DM, professor of haematology at Monash University and head of the Malignant Haematology, Transplantation and Cellular Therapies Service at The Alfred Hospital in Melbourne, Australia, presented the extended follow-up data.¹

What did the additional efficacy data show?

Responses deepened over time in both dose cohorts, with most patients who remained on treatment for 20 months or longer showing ongoing or deepening responses. The median DOR was not reached in either group: not reached ([NR] 95% CI, not estimable [NE]-NE) with 70 mg (n = 25) and NR (95% CI, 15.0 months-NE) with 105 mg (n = 22). The 18-month DOR rate was 74.0% (95% CI, 55.9%-92.0%) with 70 mg and 68.2% (95% CI, 48.7%-87.6%) with 105 mg. Median PFS also was NR in either arm: NR (95% CI, 15.6 months-NE) with 70 mg and NR (95% CI, 16.9 months-NE) with 105 mg, with 18-month PFS rates of 67.4% (95% CI, 49.8%-84.9%) and 66.0% (95% CI, 46.7%-85.3%), respectively.

What did the safety analysis show?

Any-grade adverse effects (AEs) occurred in all patients in both cohorts, with grade 3/4 AEs in 82.8% (70 mg) and 96.0% (105 mg), and serious AEs in 58.6% and 60.0%, respectively. A grade 5 AE unrelated to progression occurred in each cohort: treatment-related septic shock with 70 mg and intracranial hemorrhage (not treatment-related) with 105 mg. AEs led to discontinuation of cevostamab in 6.9% and 8.0% of patients, of pomalidomide in 27.6% and 32.0%, and of dexamethasone in 0% and 8.0%, with 70 mg and 105 mg, respectively.

Rates of neutropenia (79.3% vs 84.0%), anemia (34.5% vs 40.0%), thrombocytopenia (24.1% vs 32.0%), cytokine release syndrome (CRS) (72.4% vs 68.0%, predominantly grade 1), and any-grade infections (75.9% vs 80.0%) were similar between the 70-mg and 105-mg groups, respectively, while rash was more common with 105 mg (56.0% vs 34.5%). No substantial skin, hair or nail changes, or mucosal toxicities occurred beyond rash, and immune effector cell–associated neurotoxicity syndrome was rare, limited to one grade 1 and one grade 2 case, both with 105 mg. Grade 3/4 infections (17.2% vs 40.0%) and serious infections (24.1% vs 40.0%) were less frequent with 70 mg, and episodic immunoglobulin (Ig) supplementation was used in 65.5% and 72.0% of patients, respectively. Unlike BCMA-targeted bispecific antibodies, cevostamab plus pom-dex did not cause a persistent decline in polyclonal IgG; median levels stayed above 4 g/L in later cycles, particularly with 70 mg, suggesting preserved humoral immunity.

CRS was less frequent and lower grade with triple step-up than double step-up dosing: any-grade CRS occurred in 61.5% (n = 16 of 26) vs 78.6% (n = 22 of 28), grade ≥2 CRS in 7.7% vs 21.4%, and no grade ≥3 CRS events occurred with triple step-up vs 3.6% with double step-up; tocilizumab (Actemra) use for CRS was also lower with triple step-up dosing (7.7% vs 35.7%).

What are the next steps for cevostamab in myeloma?

Based on the observed benefit-risk profile, investigators identified triple step-up dosing combined with the 70-mg cevostamab plus pom-dex regimen as the RP2D. This regimen is now being evaluated in the phase 3 CEVOLUTION trial (NCT07555938), a randomized, open-label study comparing cevostamab plus pom-dex with standard-of-care regimens in patients with RRMM who have received an anti-CD38 antibody and lenalidomide (Revlimid) 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-naïve patients with relapsed/refractory multiple myeloma (RRMM): CAMMA 1 Arm B extended follow-up data. Presented at: 23rd International Myeloma Society (IMS) Annual Meeting & Exposition; September 23-26, 2026; Glasgow, Scotland. Abstract OA-11.
2. Ryan C. Phase 1 data set the stage for further exploration of cevostamab in R/R myeloma. OncLive. Published August 4, 2026. Accessed September 23, 2026. https://www.onclive.com/view/phase-1-data-set-the-stage-for-further-exploration-of-cevostamab-in-r-r-myeloma
3. Wahner A. Cevostamab-based triplet delivers high response and MRD negativity rates in R/R myeloma. OncLive. Published January 21, 2026. Accessed September 23, 2026. https://www.onclive.com/view/cevostamab-based-triplet-delivers-high-response-and-mrd-negativity-rates-in-r-r-myeloma