New Teclistamab Study in Multiple Myeloma Shows Improved Tolerance, Responses

A new study of teclistamab (Teclavy; Janssen)-based inductions in patients with newly diagnosed multiple myeloma (NDMM) showed improvements in tolerability and responses, including minimal residual disease (MRD) at 10^-5 and 10^-6 levels, according to data presented at the 22nd International Myeloma Society Annual Meeting. The multicohort phase 2 study (MajesTEC-5; NCT05243797) evaluated teclistamab in combination with daratumumab (DARA)-based induction regimens in 50 patients with transplant-eligible (TE) NDMM.

Teclistamab is the first drug of its kind targeting bispecific B-cell maturation antigen (BCMA) proteins on myeloma cells. It was approved in 2022 by the FDA specifically for patients whose MM returns after they have received 4 other types of myeloma treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Study Methodology

Researchers looked at the safety and efficacy of teclistamab in combination with daratumumab-based induction (with or without bortezomib) for the different study arms, as shown in the table below.¹

A total of 50 patients were enrolled and 49 treated across the 3 arms: 10 patients in arm A, 20 in arm A1, and 19 in arm B. The age range was 30 to 68 years, with an average age of 58. All arms included a 2-step step-up dosing phase for teclistamab in cycle 1.

All patients received 1800 mg of daratumumab SC weekly in cycles 1 and 2 and every 2 weeks (Q2W) in cycles 3 to 6, and 25 mg of lenalidomide on days 1 to 21 of cycles 2 to 6.

Arm A received 1.5 mg/kg of teclistamab once a week (QW) in cycles 2 to 6 and 20 mg of dexamethasone in cycles 1-4. Arm 1A received 3.0 mg/kg every 4 weeks (Q4W) in cycles 2 to 6 and 20 mg of dexamethasone in cycles 1 and 2. Arm B had the same treatment cycle as Arm 1A, plus 1.3 mg/m² every week in cycles 1 to 6. Administration routes included subcutaneous (SC), oral (PO), and intravenous (IV).

A total of 8 patients stopped taking lenalidomide, 2 stopped bortezomib, and 1 stopped teclistamab, with most citing treatment-related toxicities as their reason. Still, 47 patients proceeded to stem cell collection, and 46 had successful mobilization.

This was the first trial to assess teclistamab as a front-line treatment with a steroid-sparing approach.

Patient Responses and Outcomes

Teclistamab showed highly promising results in this study, with 100% of patients demonstrating a response rate post-induction and 100% showing MRD-negativity (10^-5 after cycles 3 and 6, 10^-6 after cycle 6).¹

Of the 46 patients who had a successful stem cell mobilization, the median stem cell yield was 8.1 × 106/kg.

Nearly all patients (89.8%) reported some kind of adverse event, primarily hematologic, rising to grade 3 or 4. Over one-third (34.7%) also reported grade 3 or 4 infections, and 65.3% reported cytokine release syndrome during the step-up phase. However, and notably, no incidents of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.

What Do These Results Mean for Pharmacists?

The tolerability, deep MRD responses, and preserved stem cell mobilization show the benefit of teclistamab as a first-line treatment in NDMM; indeed, MRD responses at these levels are tantamount to a functional cure and have implications for overall survival and long-term prognosis.¹

However, pharmacists should caution patients to closely monitor any symptoms of infection or hematologic toxicity and look for opportunities to integrate supportive care options for patients.

REFERENCES

1. Raab M, Weinhold N, Martin Kortüm K, et al. Post-Induction Outcomes and Updated Minimal Residual Disease Analysis from GMMG-HD10/DSMM-XX (MajesTEC-5): A Study of Teclistamab-based Induction Regimens in Newly Diagnosed Multiple Myeloma (NDMM). Abstracts of the 22nd International Myeloma Society Annual Meeting. Abstract OA-13.