The FDA has granted accelerated approval to teclistamab-cqyv (Tecvayli®, Janssen Biotech) for adult patients with relapsed/refractory multiple myeloma previously treated with four or more lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistimab is the first bispecific B-cell maturation antigen (BCMA)–directed CD3 T-cell engager.
"Standard treatment of multiple myeloma includes the administration of immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies. However, available therapies for patients who have had disease progression after receiving these agents are limited, and outcomes are generally poor," wrote Philippe Moreau, MD, Head of the Hematology Department at the University Hospital of Nantes, France, and colleagues, in their abstract of the MajesTEC-1 trial (NCT03145181, NCT04557098) on which the approval was based. "Teclistamab is a bispecific antibody that targets both CD3 expressed on the surface of T cells and BCMA expressed on the surface of myeloma cells, thus mediating T-cell activation and subsequent lysis of BCMA-expressing myeloma cells."
The efficacy population of MajesTEC-1, a single-arm, multi-cohort, open-label, multicenter phase 1/2 study, enrolled 110 patients with relapsed/refractory multiple myeloma who had received three or more prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and who had not previously received BCMA-targeted therapy were also included. Patients received 1.5 mg/kg of teclistamab once weekly via subcutaneous injection, after receiving step-up doses of 0.06 mg and 0.3 mg/kg. The primary end point was overall response rate.
Teclistamab produced an overall response rate of 61.8% according to International Myeloma Working Group (IMWG) 2016 criteria. At a median follow-up of 7.4 months among responders, teclistamab produced an estimated response duration rate of 90.6% at 6 months and 66.5% at 9 months.
Among 165 patients in the safety population, adverse events occurring in at least 20% of patients included pyrexia, cytokine release syndrome (CRS), musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. Grade 3/4 laboratory abnormalities occurring in at least 20% of patients included decreased lymphocytes, neutrophils, white blood cells, hemoglobin, and platelets.
The prescribing information for teclistamab includes a boxed warning for life-threating or fatal CRS, neurologic toxicity, immune effector cell–associated neurotoxicity (ICANS). In patients who received the recommended dose of teclistamab, CRS was experienced by 72% of patients, neurologic toxicity by 57%, and ICANS by 6%. Grade 3 CRS was experienced by 0.6% of patients, and grade 3 or 4 neurological toxicity by 2.4%. Due to these risks, teclistamab is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.
"In this phase 1/2 study, teclistamab had substantial clinical activity that compares favorably with that of existing therapies for patients with heavily pretreated relapsed or refractory multiple myeloma," concluded Dr. Moreau and colleagues. "The high rate of deep and durable responses in this population indicates the potential for teclistamab to provide substantial clinical benefit to a broader population of patients."
The recommended dose of teclistamab is 0.06 mg/kg by subcutaneous injection of Day 1, 0.3 mg/kg on Day 4, and 1.5 mg/kg on Day 7, followed by a once-weekly dose of 1.5 mg/kg until disease progression or unacceptable toxicity.
For More Information
Moreau P, Garfall AL, van de Donk NWCJ, et al (2022). Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med, 387:495-505. DOI:10.1056/NEJMoa2203478
Clinicaltrials.gov (2022). Dose escalation study of teclistamab, a humanized BCMA*CD3 bispecific antibody, in participants with relapsed or refractory multiple myeloma (MajesTEC-1). NLM identifier: NCT03145181.
Clinicaltrials.gov (2022). A study of teclistamab, in participants with relapsed or refractory multiple myeloma (MajesTEC-1). NLM identifier: NCT04557098.
Tecvayli® (teclistamab-cqyv) prescribing information (2022). Janssen Biotech. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf
US Food & Drug Administration (2022). FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma
Image credit: KGH. Licensed under CC BY-SA 3.0
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