Treatment with teclistamab in patients with relapsed or refractory multiple myeloma (R/R MM) who had been previously treated with an anti-B-cell maturation antigen (BCMA) treatment resulted in statistically significant and clinically meaningful responses to the antibody. The overall response rate (ORR) in the clinical trial was 52.5%, and 30.0% of patients achieved a complete response (CR) or better. The median duration of response (DOR) was 14.8 months. Results from cohort C of the phase I/II MajesTEC-1 trial were published in Blood.1
“Two-thirds of the patients were refractory to prior BCMA-targeted therapy, and still half of them responded in this trial,” said study author Cyrille Touzeau, MD, PhD, of the University Hospital of Nantes in France. “This response rate is superior to what has been observed with other bispecifics in a similar patient population.”
Teclistamab is a BCMA and CD3-directed bispecific antibody that is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with triple-class exposed R/R MM. Prior studies showed that patients with myeloma progressing on BCMA-targeted therapy can maintain BCMA expression and still respond to a different BCMA-targeted therapy.2,3 “Given the various modalities available to target BCMA, it is important to understand if serial targeting is a viable option for patients with myeloma,” Dr. Touzeau said.
Dr. Touzeau and his colleagues enrolled patients with R/R MM who had received a prior BCMA-targeted therapy, either a chimeric antigen receptor (CAR) T-cell therapy, an antibody-drug conjugate (ADC), or a bispecific antibody. Patients received subcutaneous teclistamab via a step-up dose, initially 0.06 mg/kg, followed by 0.3 mg/kg, and subsequently, the first treatment dose of 1.5 mg/kg once weekly, with the option to switch to every-two-week dosing if the patient achieved a CR or better for six or more months. To minimize the risk of cytokine release syndrome (CRS), patients were given premedication with dexamethasone, diphenhydramine, and acetaminophen and were hospitalized for observation during both step-up doses and the first full dose of teclistamab. The primary endpoint was the proportion of patients who achieved a partial response or better.
A total of 40 patients were enrolled in cohort C. The median age was 64 years (range = 32-82), and 62.5% of patients were male. All patients had previously received at least one BCMA-targeted therapy: 29 patients were previously treated with an ADC, 15 with a CAR T-cell therapy, and four patents had received both an ADC and CAR T-cell therapy targeted to BCMA. Patients received a median of six prior lines of therapy. Additionally, 85.0% (n=34) of the patients were triple-class refractory, and 67.5% (n=27) were refractory to a prior BCMA-targeted therapy.
The median follow-up was 28.0 months, and the median duration of teclistamab treatment was 6.0 months. Nine patients died on study, 21 discontinued treatment due to disease progression, three due to adverse events (AEs), two due to their physician’s decision, and one who refused further treatment.
Ten patients switched from weekly to biweekly dosing, including six patients who met the response-related criteria to switch to less frequent dosing. The four additional patients switched without meeting the protocol-defined criteria; of these, two switched to the less frequent dosing due to physician decision, and the other two switched because of neutropenia AEs.
The rate of a very good partial response was 47.5%. Response was similar in patients who had a prior BCMA-targeted ADC or CAR T-cell treatment, with an ORR of 55.2% and 53.3%, respectively. The ORR was similar across subgroups, including elderly patients and those who were renally impaired.
The median time to first response was 1.2 months, and median time to best response was 2.9 months. The 12-month event-free rate was 61.2%. The median progression-free survival was 4.5 months, and median OS was 15.5 months.
Among the 12 patients with a CR or better, the median DOR was 16.7 months. After a median follow-up of 26.3 months among the 21 responders, five patients (23.8%) maintained their response to teclistamab, and three were still on treatment at the time of cutoff.
“The safety profile, including the rate of cytopenias and infections, was comparable to that in patients who were anti-BCMA therapy naïve,” Dr. Touzeau said.
However, “the small dataset makes clinical interpretation regarding the optimum timing between BCMA-directed therapies challenging, and more research is needed,” he cautioned.
The most common hematologic AEs were neutropenia, anemia, lymphopenia, and thrombocytopenia. Of the 31 patients (77.5%) who had evidence of hypogammaglobulinemia, 16 (40.0%) received intravenous immunoglobulin treatment at any time during the study. The most common non-hematologic AEs were CRS (65.0%), constipation (37.5%), and diarrhea (37.5%). All CRS events were grade 1 or 2 and had a median duration of two days, and all resolved without ceasing teclistamab therapy. The most common neurotoxic event was headache (12.5%), and 11 patients experienced a treatment-emergent neurotoxicity.
“More data are needed to understand the mechanisms of response and resistance to teclistamab in BCMA-exposed patients, including patients exposed to BCMA bispecific antibodies,” Dr. Touzeau said.
Any conflicts of interest declared by the authors can be found in the original article.
References
- Touzeau C, Krishnan AY, Moreau P. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies [published online ahead of print, 2024 Aug. 20]. Blood. doi: 10.1182/blood.2023023616.
- Cohen AD, Garfall AL, Dogan A, et al. Serial treatment of relapsed/refractory multiple myeloma with different BCMA-targeting therapies. Blood Adv. 2019;3(16):2487-2490.
- Cohen AD, Mateos MV, Cohen YC, et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood. 2023;141(3):219-230.
