Optec/Optal: A phase 2 study to evaluate outpatient, step-up administration of teclistamab or talquetamab with prophylactic tocilizumab in patients with relapsed/refractory multiple myeloma

Background:

Teclistamab (Tec), a B-cell maturation antigen (BCMA) Å~ cluster of differentiation 3 (CD3) bispecific antibody (bsAb), and talquetamab (Tal), a G protein-coupled receptor class C group 5 member D (GPRC5D) × CD3 bsAb, are approved for relapsed/refractory multiple myeloma (RRMM). Cytokine release syndrome (CRS) occurred in 72% and 73%–79% of patients in the MajesTEC-1 and Monumen-TAL-1 studies, respectively. In cohorts that received prophylactic tocilizumab (prophyToci), CRS rates were lower (26% in MajesTEC-1; 18% in MonumenTAL-1), with no negative impact on safety or efficacy.

Objectives:

Evaluate the impact of a single prophylactic dose of tocilizumab prior to step-up dose 1 of teclistamab or talquetamab on the incidence of CRS, safety, and efficacy in patients with RRMM treated in the outpatient setting.

Purpose:

To evaluate prophyToci in patients with RRMM treated with Tec/Tal using the approved step-up dose (SUD) schedule in the outpatient setting.

Study Design:

This was a nonrandomized, multicenter, prospective study.

Methods:

Patients provided informed consent. ProphyToci 8 mg/kg was administered before SUD1 of Tec/Tal. Safety recommendations (home monitoring, daily investigator assessments after SUD-phase treatments, and neurological examinations) and guidance (caregiving and travel) were provided. The primary endpoint was the incidence of anygrade CRS (cycles 1–2). Secondary endpoints were safety (grade [G] ≥2 CRS, recurrent CRS, infections, neurotoxicity, and neutropenia) and efficacy (intention-to-treat [ITT] population, overall response rate [ORR], best overall response, and progression-free survival [PFS]).

Results:

As of March 6, 2026, 45 patients were enrolled in the Tec group and 7 in the Tal group. Across both groups, the most common G ≥3 adverse events included neutropenia (n=13), sepsis (n=4), and anemia (n=4); one G5 event (sepsis) occurred with Tec. In the Tec group, the CRS rate was 9%, with 6 events reported in 4 patients (all G1). CRS was managed with dexamethasone. No immune effector cell-associated neurotoxicity syndrome (ICANS) events were reported. The infection rate was 51% (n=23 events), with 18% ≥G3 (n=8 events). ORR was 68.9%. After a median follow-up of 11.8 months, 75.6% of Tec patients had not progressed. In the Tal group, the CRS rate was 29%, with 4 events reported in 2 patients (G1, n=3 events; G2, n=1 event). G1 CRS was managed with dexamethasone and/or antibiotics; G2 CRS was managed with dexamethasone, fluid hydration, and Toci. G2 CRS resolved in <3 days. No ICANS events were reported. The infection rate was 71% (n=5 events), with 29% ≥G3 (n=2 events). ORR was 71.4%. Interpretation is limited by the small sample size.

Conclusion:

A single prophyToci dose before SUD1 of Tec/Tal reduced CRS without negatively impacting safety or efficacy, supporting outpatient administration. Per a protocol amendment, a third arm was added to evaluate the effect of prophylactic dexamethasone on CRS with Tec; enrollment is ongoing (NCT05972135).

Funding: Johnson & Johnson and Sarah Cannon Research Institute, Development Innovations.

Prior Presentations:

Presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, May 29–June 2, 2026, in Chicago, IL, USA; and the Society of Hematologic Oncology (SOHO) Annual Meeting, September 9–12, 2026, in Houston, TX, USA.

© 2026 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2026 ASCO Annual Meeting. All rights reserved.