Biologics License Application Submitted to FDA for Teclistamab in Relapsed/Refractory Multiple Myeloma


Patients with relapsed or refractory multiple myeloma may benefit from treatment with teclistamab, for which a biologics license application was submitted to the FDA.

A biologics license application for teclistamab was submitted to the FDA for the treatment of patients with relapsed/refractory multiple myeloma, according to a press release from developer Janssen.1

It was reported that the application is supported by results from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098). Updated results from the study were presented at the 2021 Annual Society of Hematology Annual Meeting & Symposium, which showed that, after a median follow-up of 7.8 months, patients had an overall response rate of 62.0% (95% CI, 53.7-69.8). Additionally, the median time to first response was 1.2 months. At a threshold of 10-5, patients had a minimal residual disease (MRD) rate of 24.7% (95% CI, 18.0%-32.4%), and 16.7% (95% CI, 11.1%-23.6%) at a threshold of 10-6. For those who achieved a complete response or greater, the MRD-negativity rate was 41.9%.2

“Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had," Peter Lebowitz, MD, PhD, global therapeutic area head, Oncology, at Janssen Research & Development, LLC, said in the press release.

The pivotal cohort consisted of 165 patients, 40 of whom were included in phase 1 and 125 in phase 2, with both groups receiving 1.5 mg/kg of teclistamab. The median duration of treatment was 5.9 months for patients included in the primary safety analysis. In total, 46.7% of patients received 6 months of treatment or more and 16.4% received 9 months of treatment or more. No patient in either group needed a dose reduction.

In terms of patient characteristics, investigators reported a median age of 64.0 years, 14.5% of whom were 75 years of age or older. Ninety six patients were male. A total of 25.9% of patients had high-risk cytogenetics, and 52.5% had an international staging system score of 1. Additionally, 73.3% of patients had a baseline renal function of 60 or more mL/min/1.73 m. The median time since diagnosis was 6.0 years. Patients also had a median of 5.0 lines of prior therapy, and 81.8% had prior stem cell transplantation. All patients were triple-class exposed, and 77.6% of patients were triple-class refractory. Moreover, 89.7% of patients were refractory to their last line of therapy.

At the clinical cut off, responders had a median follow-up of 8.0 months and 91.4% had 6 months or more of follow-up. The median duration of response and overall survival were not reached. Responders had a 6-month event-free survival rate of 92.5% (95% CI, 80.6%-97.2%), and 85.9% (95% CI, 70.0%-93.7%) at 9 months. Additionally, the progression-free survival rate was 64.4% (95% CI, 56.0%-71.7%) at 6 months and 58.5% (95% CI, 48.8-67.0) at 9 months.

A total of 88.2% of patients were alive without the need for subsequent treatment at the data cut off. Eleven of the 93 responders had progressed or died, and 1 responder was off treatment and still responding. During this time, 19 patients switched to less frequent dosing.

One patient discontinued treatment due to adverse effects (AEs), and 88 experienced serious AEs. A total of 35.2% of patients experienced injection site reactions, and 63% developed infections, 35.2% of which were grade 3/4. Investigators reported that 72.1% of patients showed evidence of hypogammaglobulinemia. In total, 9 patients died from AEs, but none were related to treatment with teclistamab. Grade 3/4 hematologic AEs included neutropenia (n = 94), anemia (n = 57), thrombocytopenia (n = 35), and lymphopenia (n = 53). The most common nonhematologic grade 3/4 AEs were diarrhea (n = 4) and fatigue (n = 3).

A total of 71.5% of patients experienced grade 1/2 cytokine release syndrome, with 1 patient experiencing a grade 3 event. All cytokine release syndrome events were resolved and no patients discontinued treatment as a result. During treatment, 2.4% of patients received more than 1 dose of tocilizumab (Actemra) to help treat a CRS event. The time to onset was 2 days, and the median duration was 2 days.

No patients required dose reduction from neurotoxicity. The most common neurotoxicity was headache (n = 14), and all events were grade 1/2. Immune effector cell therapy neurotoxicity syndrome was grade 1/2, and 7 of 9 events coincided with cytokine release syndrome, all of which resolved. The time to onset was 2.5 days and the median duration was 3.0 days.


1. Janssen submits biologics license application to US FDA seeking approval of teclistamab for the treatment of patients with relapsed or refractory multiple myeloma. News Release. Janssen Pharmaceutical Inc. December 29, 2021. Accessed January 3, 2022.

2. Moreau P, Usmani S, Garfall A, et al. Updated results from the MajesTEC-1: phase 1/2 study of teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in relapsed/refractory multiple myeloma. Presented at the 2021 American Society of Hematology; December 11-14, 2021; Virtual. Accessed January 3, 2021. Abstract 896.

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