On October 25, 2022, the bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager teclistamab-cqyv was granted accelerated approval for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.1
Because of the risk of cytokine-release syndrome and neurologic toxicity, teclistamab is available only through a restricted program called the TECVAYLI Risk Evaluation and Mitigation Strategy (REMS).
Supporting Efficacy Data
Approval was supported by findings in the multicohort, multicenter MajesTEC-1 trial (ClinicalTrials.gov identifier NCT03145181, NCT04557098). A total of 110 patients in the efficacy population with no prior BCMA-targeted therapy received step-up doses of 0.06 and 0.3 mg/kg, followed by 1.5 mg/kg subcutaneously (SC) once weekly until disease progression or unacceptable toxicity.
OF NOTE
Teclistamab has a boxed warning for life-threatening or fatal cytokine-release syndrome and neurologic toxicity.
A partial response or better on independent review committee assessment was achieved in 68 patients (61.8%, 95% confidence interval [CI] = 52.1%–70.9%), with a complete response or better in 31 (28.2%). With a median follow-up of 7.4 months among responders, the median response duration was not estimable, with 90.6% and 66.5% of responses ongoing at 6 and 9 months, respectively.
How It Is Used
The recommended teclistamab dose is 0.06 mg/kg via SC injection on day 1, 0.3 mg/kg on day 4, and 1.5 mg/kg on day 7, followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.
No dose reduction is recommended. Product labeling provides instructions on the management of cytokine-release syndrome and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS).
Safety Profile
Among 165 patients who received teclistamab in MajesTEC-1, the most common adverse events of any grade were pyrexia (76%), cytokine-release syndrome (72%), musculoskeletal pain (44%), injection-site reaction (37%), fatigue (33%), upper respiratory tract infection (26%), nausea (25%), headache (25%), pneumonia (24%), and diarrhea (21%). The most common grade 3 or 4 adverse events included hypertension (4.8%) and musculoskeletal pain (4.2%). Neurologic toxicity of any grade occurred in 57% and ICANS, in 6%. Grade 3 cytokine-release syndrome occurred in 0.6% and grade 3 or 4 neurologic toxicity, in 2.4%. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (84%), neutrophils (56%), and white blood cell counts (41%).
KEY POINTS
- Teclistamab was granted accelerated approval for treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy.
- The recommended teclistamab dose is 0.06 mg/kg via SC injection on day 1, 0.3 mg/kg on day 4, and 1.5 mg/kg on day 7, followed by 1.5 mg/kg once weekly until disease progression or unacceptable toxicity.
Serious adverse events occurred in 54% of patients, most commonly pneumonia (15%), cytokine-release syndrome (8%), sepsis (6%), general physical health deterioration (6%), and COVID-19 (6%). Discontinuation because of adverse events occurred in 1.2% of patients, with causes including pneumonia and hypercalcemia. Fatal adverse events occurred in 5% of patients, including COVID-19 (1.8%), pneumonia (1.8%), septic shock (0.6%), acute renal failure (0.6%), and hemoperitoneum (0.6%).
Teclistamab has a boxed warning for life-threatening or fatal cytokine-release syndrome and neurologic toxicity, including ICANS. Teclistamab also has warnings/precautions for hepatotoxicity, infections, neutropenia, hypersensitivity and other administration reactions, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving teclistamab.
REFERENCE
1. Tecvayli (teclistamab-cqyv) injection, for subcutaneous use, prescribing information, Janssen Pharmaceutical Companies, October 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf. Accessed November 16, 2022.
