Etentamig Clears the Bar Against Standard Therapy in Triple-Class Exposed Myeloma

Etentamig significantly outperformed physician's choice of standard therapy in triple-class exposed relapsed/refractory multiple myeloma (RRMM), according to primary results from the phase 3 CERVINO trial (NCT06158841).

Presented at the 23rd International Myeloma Society Annual Meeting, the data add a fourth BCMA×CD3 bispecific to a field already crowded by the FDA approved agents teclistamab (Tecvayli; Johnson & Johnson), elranatamab (Elrexfio; Pfizer Inc), and linvoseltamab (Lynozyfic; Regeneron Pharmaceuticals).^1-4

A Different Dosing Philosophy

Data from a phase 1 trial (NCT03933735), first presented at the American Society of Hematology in 2023, established that etentamig has a low-affinity CD3-binding domain and high-avidity, bivalent BCMA-binding domain. This allows for less frequent, higher-dose administration than its bispecific competitors, without a step-up dosing period stretched across multiple weeks.⁵

CERVINO was designed to test whether that dosing convenience translated into a genuine efficacy advantage, not just a logistical one. A total of 393 patients were randomly assigned 1:1 to etentamig monotherapy or the investigator’s choice of carfilzomib plus dexamethasone, elotuzumab plus pomalidomide and dexamethasone, or selinexor plus bortezomib and dexamethasone.¹

The results answered that question decisively. Overall response rate was approximately 74.0% with etentamig compared to 45.7% with standard therapy (P < .0001), and median progression-free survival was not reached with etentamig versus 6.2 months with standard therapy (HR, 0.40; P < .0001). Perhaps most notable for a bispecific trial this early in follow-up, 12-month overall survival (OS) numerically favored etentamig (87.9% vs 72.0%; HR, 0.48); however, the prespecified statistical boundary for declaring a survival benefit was not yet crossed at this interim analysis.¹

What This Means for Infusion Clinics

For pharmacists, the dosing schedule is a practical difference. Patients received a single 2-mg step-up dose before moving to full 60-mg monthly dosing—a considerably shorter ramp-up than the multi-week step-up regimens required for teclistamab or elranatamab.² This translated into a cytokine release syndrome (CRS) rate under 40% (nearly all grades 1 or 2) and an immune effector cell-associated neurotoxicity syndrome rate of just 3.6%. Among those who received only the single step-up dose, CRS fell further to 28.3%, with no grade 3 or higher events observed.¹

Notably, for infection-prophylaxis protocols, grades 3 and 4 infections ran modestly higher with etentamig than with standard therapy (27.7% vs 19.2%), which is consistent with the class-wide infection signal seen across BCMA-directed bispecifics.⁶ Discontinuations due to treatment-related adverse events were less frequent with etentamig (3.6% vs 9.6%), suggesting the once-monthly schedule may also support better long-term tolerability and adherence in an outpatient setting.¹

What Does Access Look Like?

The manufacturer has not yet filed for FDA approval of etentamig, and CERVINO's OS data remain immature. But if the survival trend holds up with longer follow-up, this randomized, active-comparator design could give etentamig an advantage that its already-approved competitors—which are all cleared on earlier-phase, single-arm data—do not have.

For health-system and specialty pharmacists building or revising BCMA-bispecific formulary and site-of-care protocols, CERVINO is worth tracking closely as the field moves from “Does this work?” to “Which one, and on what schedule?”

REFERENCES

1. Voorhees P, Mateos MV, Costa L, et al. CERVINO: phase 3 results of etentamig vs investigator's choice of standard available therapies in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

2. Talvey (talquetamab-tgvs) [prescribing information]. Horsham, PA: Janssen Biotech Inc; 2023. Accessed September 17, 2026. www.accessdata.fda.gov/drugsatfda_docs/label/2025/761342s016lbl.pdf

3. Elrexfio (elranatamab-bcmm) [prescribing information]. New York, NY: Pfizer Inc; 2023. Accessed September 17, 2026. https://labeling.pfizer.com/ShowLabeling.aspx?id=19669

4. FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma. FDA. July 2, 2025. Accessed September 25, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-linvoseltamab-gcpt-relapsed-or-refractory-multiple-myeloma

5. Vij R, Kumar SK, D'Souza A, et al. Updated safety and efficacy results of ABBV-383, a BCMA x CD3 bispecific T-cell redirecting antibody, in a first-in-human phase 1 study in patients with relapsed/refractory multiple myeloma. Blood. 2023;142(Supplement 1):3378. doi:10.1182/blood-2023-182388

6. Lee H, Ahn S, Maity R, et al. Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma. Nat Med. 2023;29(9):2295-2306. doi:10.1038/s41591-023-02491-5