Teclistamab-cqyv Snags Accelerated Approval for Relapsed or Refractory Multiple Myeloma

Teclistamab-cqyv (Tecvayli) has received accelerated approval from the FDA for the indication of adult patients with relapsed or refractory multiple myeloma. To be eligible for treatment, these patients must have already undergone 4 prior 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). These data show that teclistamab elicited an objective response rate (ORR) of 61.8% (95% CI, 52.1%-70.9%) by independent review committee assessment and using 2016 International Myeloma Working Group 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 experienced stroke or seizure or had undergone allogeneic stem cell transplantation 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 75 years or older. Moreover, 56% of patients were male and 91% were White. Regarding disease stage at study entry, 50% had stage I disease, 38% had stage II disease, and 12% had stage III disease per the International Staging System criteria. 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). Furthermore, 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 number of prior lines of treatment received was 5 (range, 2-14). Notably, 76% of patients had triple-class refractory disease.

ORR served as a major efficacy outcome measure for the trial. Key secondary outcome 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 teclistamab, 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 teclistamab experienced serious adverse effects. Serious adverse reactions that occurred in more than 2% of patients included pneumonia (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 lymphocyte count, decreased neutrophil count, decreased white blood cell count, decreased hemoglobin level, and decreased platelet count.

References

1. FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma. FDA. October 25, 2022. Accessed October 25, 2022. https://bit.ly/3f3HffB
2. Tecvayli. Prescribing information. Janssen Biotech Inc; 2022. Accessed October 25, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf
3. A study of teclistamab 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