Prophylactic Tocilizumab Reduces CRS During Outpatient Teclistamab, Talquetamab Step-Up in R/R Myeloma

A single dose of prophylactic tocilizumab (Actemra) administered before outpatient step-up dosing of teclistamab-cqyv (Tecvayli) or talquetamab-tgvs (Talvey) reduced the incidence of cytokine release syndrome (CRS) in patients with relapsed/refractory multiple myeloma, according to data from the phase 2 OPTec/OPTal trial (NCT05972135) presented in a poster session at the 2026 Society of Hematologic Oncology (SOHO) Annual Meeting.¹

As of March 6, 2026, CRS occurred in 8.9% of patients in the teclistamab plus tocilizumab arm (n = 45) and 28.5% in the talquetamab plus tocilizumab arm (n = 7), translating to an overall CRS rate of 12.2%, an approximate 5-fold reduction in incidence, according to investigators. All 6 CRS events in the teclistamab arm were grade 1; in the talquetamab arm, 3 of 4 events were grade 1, and 1 was grade 2. No grade 3 or higher CRS or any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) events were reported in either arm.

“Data support administration of bispecific antibodies in the community-based, outpatient setting,” lead study author Peter Forsberg, MD, of the Colorado Blood Cancer Institute in Denver, and colleagues wrote in a poster presentation of the data.

How was the OPTec/OPTal trial designed?

CRS is among the most common adverse effects (AEs) of T-cell–redirecting therapies, including bispecific antibodies, in multiple myeloma, and the associated risk has historically supported a recommendation for inpatient hospitalization during step-up dosing.

Talquetamab currently holds FDA accelerated approval for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.² Teclistamab monotherapy received accelerated approval in the same indication in October 2022, and in March 2026, the FDA granted full approval to teclistamab plus daratumumab (Darzalex) for the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 1 prior line of therapy.^3,4

OPTec/OPTal is a two-arm, phase 2, community practice–based study being conducted across 15 US sites, evaluating outpatient administration and step-up dosing (SUD) monitoring of teclistamab and talquetamab, each preceded by a single 8-mg/kg dose of prophylactic tocilizumab on day 1.¹

Eligible patients were at least 18 years of age, had an ECOG performance status of 0 or 1, and had received at least 3 prior therapies, including a proteasome inhibitor, an immunomodulatory drug, and/or a CD38 monoclonal antibody. Outpatient safety monitoring included a requirement to remain within 60 minutes of the clinic and in the company of a competent adult for 48 hours following each SUD treatment, twice-daily home monitoring of temperature and oxygen saturation, and neurologic exams for the first 2 cycles.

In arm A, patients received teclistamab SUD1 at 0.06 mg/kg on day 1, SUD2 at 0.3 mg/kg on day 4, and the full 1.5-mg/kg dose on day 8, followed by weekly dosing for up to 12 cycles. In arm B, patients received talquetamab SUD1 at 0.01 mg/kg on day 1, SUD2 at 0.06 mg/kg on day 4, SUD3 at 0.4 mg/kg on day 8, and the full 0.8-mg/kg dose on day 15, followed by biweekly dosing for up to 6 cycles.

The primary end point was incidence of CRS from SUD1 through the end of cycle 2.

Patients in the teclistamab arm had a median age of 74.0 years (range, 53-87) and a median of 5.0 prior lines of therapy (range, 1-11); those in the talquetamab arm had a median age of 66.0 years (range, 58-83) and a median of 6.0 prior lines (range, 2-9). Triple-class exposure was reported in 88.9% and 100% of patients, respectively, and the respective penta-class exposure rates were 40.0% and 71.4%.

What did the efficacy analysis show?

The overall response rate (ORR) was 68.9% in the teclistamab arm and 71.4% in the talquetamab arm. In the teclistamab arm, best responses included a stringent complete response (sCR) or complete response (CR) in 24.4% of patients, a very good partial response (VGPR) in 26.7%, and a partial response (PR) in 17.8%, with a VGPR or better achieved in 51.1%. In the talquetamab arm, 28.6% of patients achieved an sCR or CR and 42.9% achieved a VGPR, with a VGPR or better achieved in 71.4%.

With a median follow-up of 11.8 months, 75.6% of patients in the teclistamab arm had not experienced disease progression, and no progression events had been reported in the talquetamab arm as of the data cutoff. Data continue to mature, with more than 10 patients remaining on active treatment.

What other safety data were reported?

The most common AEs across both arms were diarrhea (50%), nausea (35%), neutropenia (33%), fatigue (29%), cough (27%), and headache (27%). The most common grade 3 or higher AEs were neutropenia (n = 13), sepsis (n = 4; defined by positive blood culture results), and anemia (n = 4). One fatal AE, sepsis, occurred in the teclistamab arm.

Infections of any grade occurred in 51.1% of patients in the teclistamab arm and in 71.4% of patients in the talquetamab arm; grade 3 or higher infections occurred in 17.8% and 28.6% of patients, respectively.

A third arm, arm C, has been opened to assess whether prophylactic oral dexamethasone enables safe community-based outpatient administration of teclistamab.

References

1. Forsberg P, Andorsky D, Rifkin R, et al. OPTec/OPTal: a phase 2 study to evaluate outpatient (OP), step-up administration of teclistamab (Tec) or talquetamab (Tal) with prophylactic tocilizumab (prophyToci) in patients with relapsed/refractory multiple myeloma (RRMM). Presented at: 2026 Society of Hematologic Oncology Annual Meeting; September 9-12, 2026; Houston, TX. Abstract MM-1078.
2. U.S. FDA approves Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen. August 10, 2023. Accessed September 11, 2026. https://www.janssen.com/us-fda-approves-talveytm-talquetamab-tgvs-first-class-bispecific-therapy-treatment-patients-heavily
3. U.S. FDA approves Tecvayli (teclistamab-cqyv), the first bispecific T-cell engager antibody for the treatment of patients with relapsed or refractory multiple myeloma. News release. Johnson & Johnson. October 25, 2022. Accessed September 11, 2026.
4. FDA grants third approval under the national priority voucher program. FDA. March 5, 2026. Accessed September 11, 2026. https://www.fda.gov/news-events/press-announcements/fda-grants-third-approval-under-national-priority-voucher-program