Teclistamab Induces Durable Responses in Phase 1/2 MajesTEC-1 Trial in R/R Multiple Myeloma

Results from the phase 1/2 MajesTEC-1 trial highlighted sustained responses when teclistamab was used to treat patients with relapsed/refractory multiple myeloma who are triple refractory.

Patients with relapsed/refractory multiple myeloma who are triple refractory experienced long-lasting responses when treated with teclistamab, according to data from the phase 1/2 MajesTEC-1 trial (NCT03145181; NCT04557098) published in the New England Journal of Medicine.

The overall response rate (ORR) was 63.0% (95% CI, 55.2%-70.4%) and 39.4% of patients had a complete response (CR) or better. Patients had a median time to first response of 1.2 months, and the median time to best response was 3.8 months. The minimal residual disease–negativity rate for those who had a CR or better was 46%. The median follow-up was 14.1 months. Moreover, median duration of response was 18.4 months (95% CI, 14.9-not estimable), and median progression-free survival was 11.3 months (95% CI, 8.8-17.1).

A total of 165 patients enrolled and received 1.5 mg/kg of teclistamab. Overall, 42.4% of patients were continuing with treatment as of March 2022; patients had a median treatment duration of 8.5 months. Teclistamab treatment was given to 59.4% of patients for a minimum of 6 months and 47.9% were treated for at least 9 months. Patient characteristics were similar between the phase 1 and 2 studies.

Adverse effects (AEs) occurred in all patients, with 94.5% having grade 3/4 toxicities. During cycle 21, 1 patient had a dose reduction because of neutropenia, and 63.0% of patients skipped a dose of treatment due to toxicities. Discontinuation of teclistamab occurred in 2 patients because of AEs. The most common AEs were neutropenia (70.9%), anemia (52.1%), and thrombocytopenia (40.0%). Of those with neutropenia (n = 117), 91 patients were treated with granulocyte colony-stimulating factor therapy.

Infections occurred in 76.4% of patients, 44.8% of which were grade 3 or 4. A total of 123 patients experienced hypogammaglobulinemia, 65 of whom received intravenous immunoglobulin. Injection-site reactions were reported in 36.4% of patients, all of which were low grade.

Cytokine release syndrome (CRS) occurred in 72.1% of patients, with 3.6% having CRS during cycle 2 or later. The majority of CRS events were grade 1 or 2 and fully resolved with the exception of 1 grade 3 event that occurred in a patient with concurrent pneumonia; the event resolved within 2 days. The median onset to CRS was 2 days with a duration of 2 days. Supportive measures for CRS were given in 66.7% of patients and included tocilizumab (Actemra) treatment in 36.4%, low-flow oxygen in 12.7%, and glucocorticoids in 8.5%.

Neurotoxic effects were reported in 24 patients, most of which were low-grade grade with the exception of 1 grade 4 seizure in a patient with bacterial meningitis during cycle 7. Headache was described as the most frequent neurotoxicity and was related to teclistamab in 8.5% of patients. Nine events of immune effector cell–associated neurotoxicity occurred with 7 being concurrent with CRS; all events resolved without discontinuation or dose reduction. Within these patients, 4 received supportive treatment, such as tocilizumab (n = 3), dexamethasone (n = 3), levetiracetam (n = 2), and gabapentin (n = 1).


Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387(6):495-505. doi:10.1056/NEJMoa2203478