Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed/refractory multiple myeloma.
Thomas G Martin, Maria Victoria Mateos, Ajay Nooka, Arnob Banerjee, Rachel Kobos, Lixia Pei, Ming Qi, Raluca Verona, Margaret Doyle, Jennifer Smit, Weili Sun, Danielle Trancucci, Clarissa Uhlar, Niels W C J van de Donk, Cesar Rodriguez
Author Information
Thomas G Martin: University of California, San Francisco, San Francisco, California, USA. ORCID
Maria Victoria Mateos: University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain.
Ajay Nooka: Winship Cancer Institute, Emory University, Atlanta, Georgia, USA. ORCID
Arnob Banerjee: Janssen Research and Development, Spring House, Pennsylvania, USA.
Rachel Kobos: Janssen Research and Development, Raritan, New Jersey, USA.
Lixia Pei: Janssen Research and Development, Raritan, New Jersey, USA.
Ming Qi: Janssen Research and Development, Spring House, Pennsylvania, USA.
Raluca Verona: Janssen Research and Development, Spring House, Pennsylvania, USA.
Margaret Doyle: Janssen Sciences, Dublin, Ireland.
Jennifer Smit: Janssen Research and Development, Spring House, Pennsylvania, USA.
Weili Sun: Janssen Research and Development, Los Angeles, California, USA.
Danielle Trancucci: Janssen Research and Development, Raritan, New Jersey, USA.
Clarissa Uhlar: Janssen Research and Development, Spring House, Pennsylvania, USA.
Niels W C J van de Donk: Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Cesar Rodriguez: Icahn School of Medicine at Mount Sinai, New York, New York, USA.
BACKGROUND: Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, demonstrated an overall response rate of 63.0% in 165 heavily pretreated patients with relapsed or refractory multiple myeloma in the phase 1/2 MajesTEC-1 study. cytokine release syndrome (CRS), a known manifestation of T-cell redirection, was observed in 119 of 165 patients (72.1%). METHODS: patients received once-weekly Teclistamab 1.5 mg/kg subcutaneously after two step-up doses (0.06 and 0.3 mg/kg). CRS was graded according to American Society for Transplantation and Cellular Therapy criteria and managed according to the study protocol, including use of tocilizumab and/or steroids. RESULTS: Most cases of CRS occurred during the step-up dosing schedule of Teclistamab and were grade 1 (50.3% of patients) or grade 2 (21.2% of patients); a single case of grade 3 CRS was reported in a patient with concurrent grade 3 pneumonia. All CRS cases resolved and none led to treatment discontinuation. Overall, 33.3% of patients had >1 CRS event; CRS recurrence was reduced when tocilizumab was administered for the first CRS event compared with when it was not (20.0% vs. 62.2%, respectively). Baseline characteristics such as tumor burden and cytokine levels did not appear to predict CRS incidence or severity. CONCLUSIONS: Findings of this study support the need for preemptive planning and prompt management of CRS in patients treated with T-cell-engaging bispecific antibodies. Intervention with tocilizumab for CRS appears to decrease the likelihood of patients experiencing subsequent CRS events without compromising response to Teclistamab. PLAIN LANGUAGE SUMMARY: cytokine release syndrome (CRS), observed in 72.1% of patients treated with Teclistamab in the MajesTEC-1 study, was mostly grade 1 or 2 and manageable, without requiring treatment discontinuation. Most CRS occurred during the step-up schedule, requiring vigilance during treatment initiation. Ensure fever is resolved and patients have no signs of infection before initiating the Teclistamab step-up schedule or administering the next Teclistamab dose, to avoid exacerbating CRS. tocilizumab reduced the risk of subsequent CRS in patients receiving it for their first CRS event (20.0% vs. 62.2% in those not receiving it), without affecting response to Teclistamab. No baseline characteristics, including tumor burden or cytokine levels, appeared to clearly predict for CRS occurrence or severity.
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