Results Show Giving Prophylactic Tocilizumab Reduces CRS in Outpatient Delivery of Teclistamab, Talquetamab

Bringing bispecific antibodies to as many patients with multiple myeloma as possible will require giving them in community settings. And that means taking steps to avoid cytokine release syndrome (CRS), a well-known adverse event associated with these treatments, which was managed in clinical trials by giving stepped doses in the hospital.

Starting in August 2023, investigators opened the OPTec trial (NCT05972135), a phase 2 multicenter study based in community clinics to evaluate whether offering prophylactic tocilizumab would allow patients with relapsed/refractory multiple myeloma to avoid mandatory inpatient hospitalization when receiving their first dose of the BCMA x CD3–directed teclistamab (Tecvayli; Johnson & Johnson).¹ After encouraging early results, a separate arm for the GPRC5D x CD3–directed talquetamab (Talvey; Johnson & Johnson), called OPTal, was added in late 2024.²

At a session during the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, Peter Forsberg, MD, of the Colorado Blood Cancer Institute, presented results from OPTec/OPTal, which show that a single dose of prophylactic tocilizumab before step-up dosing of teclistamab or talquetamab reduced the incidence of CRS, and investigators found this had “no impact on safety or efficacy” of the bispecific therapies, supporting the administration of these therapies in the outpatient setting. So far, more data have accumulated for teclistamab than for talquetamab.³ And, investigators are opening a third arm of the trial to study the use of dexamethasone.

Background and Rationale

CRS has been the primary driver of inpatient hospitalization requirements for bispecific antibody step-up dosing, occurring in 72% of patients in the MajesTEC-1 teclistamab trial and 73% to 79% in MonumenTAL-1 with talquetamab.^4,5 Cohorts within both pivotal studies had previously demonstrated that a single prophylactic dose of tocilizumab could meaningfully reduce CRS rates—to 26% with teclistamab and 18% with talquetamab—without compromising safety or efficacy.

OTPec/OPTal has been testing the safety and efficacy of this strategy. As Forsberg explained during the session, this was “a multiarm community practice-based trial evaluating outpatient administration and step-up dosing for [teclistamab] and [talquetamab] across 15 sites in the United States,” noting that “most of these sites had limited experience of bispecific dosing prior to participating in the trial.”

Study Design and Safety Monitoring

The trial calls for a prophylactic dose of tocilizumab, 8 mg/kg, before step-up dose 1, with protocol safety requirements: Patients were required to live within 60 minutes of the treating clinic and have a competent adult caregiver available for 48 hours after each step-up and first full dose. Clinic check-ins were required daily on weekdays, with phone check-ins permitted on weekends. Home monitoring was deliberately kept accessible. "Patients needed to check their temperature and oxygen saturation twice a day," Forsberg said, noting, "there were no complex wearables or intensive monitoring.”

Results Show a Dramatic Reduction in CRS

As of January 6, 2026, 45 patients were enrolled in arm A (teclistamab) and 7 in arm B (talquetamab). Results show that the single dose of prophylactic tocilizumab before the first outpatient step-up of either bispecific reduced the incidence of CRS by approximately 5-fold compared with historical controls. Specifically:

• In arm A, only 4 of 45 patients (8.9%) experienced any CRS, all grade 1, and none required hospitalization.
• In arm B, 1 patient experienced a grade 2 CRS event requiring hospitalization, and a second patient had recurrent febrile events characterized as CRS; both resolved with standard management.
• No grade 3 CRS or immune effector cell–associated neurotoxicity syndrome events were observed in either arm.

Efficacy of Therapies Is Holding Strong

The CRS mitigation came without any detectable toll on response rates. Among 34 evaluable patients in arm A, the overall response rate was 69%, including stringent complete responses, complete responses, and very good partial responses.

At a median follow-up of 11.8 months, 75% of patients in arm A had not experienced disease progression. It’s still early, and Forsberg noted, “several responses are evolving, and some patients were early enough in dosing at the time of data cutoff to not be considered response-evaluable.”

Infection Rates and IVIG: An Evolving Protocol

Infections remained a notable concern, with 51% of arm A patients experiencing any-grade infection and 18% experiencing grade 3 or higher events. There was a single grade 5 sepsis-related death recorded.

During the question-and-answer period, Forsberg acknowledged that guidance on intravenous immunoglobulin (IVIG) prophylaxis had evolved over the course of the trial. “Our approach to IVIG evolved—we did update the protocol with firmer language around incorporation of IVIG for hypogammaglobulinemia." He said, “Firm guidelines around that are a critical component of dosing and broader uptake.”

Coverage, Caregivers, and Community Access

Over the past year, The American Journal of Managed Care^® (AJMC^®) has received diverse feedback about payer coverage for prophylactic tocilizumab with bispecifics for multiple myeloma. AJMC asked Forsberg whether the data might prompt more consistent payer coverage for prophylactic tocilizumab, which the National Comprehensive Cancer Network included in recommendations more than a year ago.⁶

In a written response, Forsberg expressed cautious optimism. “Using tocilizumab to enable outpatient startup dosing can help substantially reduce health care utilization and overall costs. Ideally, this is something that payers would recognize.”

AJMC also asked Forsberg to elaborate on the requirement that patients have a caregiver present. Forsberg described practical requirements. “Our experience has been that almost all caregivers do great and that we don’t need highly complex monitoring or management expectations to have safe outpatient startup dosing.”

New Arm Will Feature Additional Strategy With Dexamethasone

The trial has been amended to add arm C, evaluating prophylactic oral dexamethasone (24 mg divided into 3 doses of 8 mg each) as an alternative CRS prevention strategy with teclistamab. Forsberg described it as another "path to enable safe community-based outpatient administration.” Enrollment in arm C is actively ongoing.

References

1. Caffrey M. Preventing adverse events with bispecific antibodies in myeloma in the community setting. Am J Manag Care. 2024;30(spec 1):SP89.
2. Halpen L, Joszt L. Study of prophylactic tocilizumab may soon add talquetamab arm. Am J Manag Care. 2025;31(spec 1):SP55.
3. Forsberg P. Andorsky D, Rifkin RM, 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 (pts) with relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2026;44(suppl 16):7510. doi:10.1200/JCO.2026.44.16_suppl.7510
4. Usmani SZ, Garfall AL, van de Donk NWCJ, et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet. 2021;398(10301):665-674. doi:10.1016/S0140-6736(21)01338-6
5. Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244. doi:10.1056/NEJMoa2204591
6. Nierengarten MB. NCCN guidelines focus on treatment options for patients with multiple myeloma. Cancer. 2025;131(17):e70014. doi:10.1002/cncr.70014