FDA Approves Teclistamab-cqyv for Relapsed or Refractory Multiple Myeloma

FDA

The FDA has granted accelerated approval to teclistamab-cqyv (Tecvayli) for adult patients with relapsed or refractory multiple myeloma who have received at least 4 previous lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (iMID), and an anti-CD38 monoclonal antibody.¹

The regulatory decision is supported by data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098), which showed that teclistimab elicited an objective response rate of 61.8% (95% CI, 52.1%-70.9%) by independent review committee assessment and utilizing International Myeloma Working Group 2016 criteria.

Moreover, at a median follow-up of 7.4 months in responders, the estimated duration of response rate (DOR) at 6 months with the agent was 90.6% (95% CI, 80.3%-95.7%); at 9 months, this rate was 66.5% (95% CI, 38.8%-83.9%). The median DOR was not estimable (NE; 95% CI, 9.0-NE).

MajesTEC-1

The single-arm, open-label, multicenter trial enrolled patients who had received at least 3 prior treatments, including a PI, an iMID, and an anti-CD38 monoclonal antibody.² Those who had stroke or seizure, or who had undergone an allogeneic stem cell transplantion within the past 6 months, were excluded. Other exclusion criteria included having an ECOG performance status of 2 or higher, known active central nervous system involvement or signs of meningeal involvement of the disease, or active or documented history of autoimmune disease.

Study participants received step-up doses of teclistamab at 0.06 mg/kg and 0.3 mg/kg followed by 1.5-mg/kg doses of the agent administered subcutaneously once weekly thereafter. Treatment was administered until progressive disease or intolerable toxicity.

The median age in the efficacy population (n = 110) was 66 years (range, 33-82), with 16% of patients aged 75 years or older. Moreover, 56% of patients were male and 91% were White. Regarding disease stage at study entry, per the International Staging System criteria, 50% had stage I disease, 38% had stage II disease, and 12% had stage III disease. Twenty-five percent of participants had high-risk cytogenetics in the form of the presence of del(17p), t(4;14), and t(14;16). Further, 17% of patients had extramedullary plasmacytomas. Notably, those who previously received BCMA-targeted therapy were excluded from the efficacy analysis.

Patients were heavily pretreated, with 78% of patients having received at least 4 prior lines of therapy. The median nuymber of prior lines of treatment received was 5 (range, 2-14). Notably, 76% of patients were triple-class refractory.

ORR served as a major efficacy outcome measure for the trial. Key secondary outcomes measures comprised DOR, very good partial response (VGPR) or better rate, complete response (CR) or better rate, stringent CR rate, time to response, progression-free survival, and overall survival, among others.³

Additional data showed that of those who responded to treatment, the CR or better rate was 28.2%, the VGPR rate was 29.1%, and the PR rate was 4.5%. The median time to first response was 1.2 months (range, 0.2-5.5).

Among the 165 patients who received teclistimab, 47% were exposed to the drug for at least 6 months; 7% were exposed for at least 1 year. In the safety population, the median age was 64 years (range, 33-84); 58% of patients were male and 81% were White.

Fifty-four percent of patients who received teclistimab experienced serious adverse effects. Serious adverse reactions that occurred in more than 2% of patients included penumonia (15%), cytokine release syndrome (CRS; 8%), sepsis (6%), general physical health deterioration (6%), COVID-19 (6%), acute kidney injury (4.8%), pyrexia (4.8%), musculoskeletal pain (2.4%), and encephalopathy (2.4%).

Five percent of patients experienced fatal adverse reactions, which were due to COVID-19 in 1.8% of patients, pneumonia in 1.8%, septic shock in 0.6%, acute renal failure in 0.6%, and hemoperitoneum in 0.6%.

Only 1.2% of patients experienced toxicities that required permanent discontinuation of teclistamab. These patients experienced pneumonia and hypercalcemia. Seventy-three percent of patients required dose interruptions.

The toxicities that were most frequently experienced with the agent included pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common grade 3 or 4 laboratory abnormalities included decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.

References

1. FDA approves teclistimab-cqyv for relapsed or refractory multiple myeloma. News release. FDA. October 25, 2022. Accessed October 25, 2022. https://bit.ly/3f3HffB
2. Tecvayli. Prescribing information; 2022. Janssen Biotech, Inc. Accessed October 25, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf
3. A study of teclistimab, in participants with relapsed or refractory multiple myeloma (MajesTEC-1). Clinicaltrials.gov. Updated October 6, 2022. Accessed October 25, 2022. https://clinicaltrials.gov/ct2/show/NCT04557098