Dr. Suzanne Trudel, Princess Margaret Cancer Centre, discusses the results of a tocilizumab (TCZ) pretreatment arm of the ongoing Phase I study of cevostamab (an FcRH5xCD3 TDB) to see if a single dose of TCZ prior to cevostamab reduces the incidence of cytokine release syndrome.

Background:

Blockade of the IL-6 receptor cytokine with monoclonal antibodies like tocilizumab (TCZ) is crucial in managing both CAR-T and T-cell dependent bispecific monoclonal antibody (TDB) induced cytokine release syndrome (CRS). Studies show that inhibiting IL-6, IL-1, or TNF-α signaling before TDB administration can prevent CRS without affecting anti-tumor activity. To confirm this in clinical trials, a TCZ pretreatment arm was added to the ongoing Phase I study (NCT03275103) of cevostamab (an FcRH5xCD3 TDB) to see if a single dose of TCZ prior to cevostamab reduces the incidence of CRS.

Conclusions:

Clinical data from the GO39775 study shows for the first time that TCZ pretreatment can significantly reduce the risk of developing TDB-induced CRS without an apparent impact on anti-myeloma activity. The data support additional investigation of the use of anti-cytokine pretreatment with the goal of substantially reducing the frequency and potentially the severity of CRS.

Authors:

Suzanne Trudel, MD Nizar J. Bahlis, MD, Andrew Spencer, Rayan Kaedbey, MD, Paula Rodriguez Otero, MD, Simon J Harrison, MD, Chihunt Wong, Grant R. Goodman, MD, Rin Nakamura, Voleak Choeurng, James Cooper and Maria-Victoria Mateos, MD

ASH Abstract #567: https://ash.confex.com/ash/2022/webprogram/Paper159381.html (https://ash.confex.com/ash/2022/webprogram/Paper159381.html)