CRS Tool Predicts Risk Events in Patients With R/R NHL Receiving Glofitamab

Results of an ongoing phase 1/2 trial evaluating glofitamab influenced a predictive model to be developed to identify risk factors of grade ≥ 2 cytokine release syndrome (CRS) in patients with relapsed or refractory (R/R) non-Hodgkin’s lymphoma (NHL).

“CRS is a potentially life-threatening toxicity caused by immune activation. CRS can be triggered non-specifically by T-cell engaging therapies. Risk factors for CRS are expected to be disease-specific, and prediction of an individual patient’s CRS risk is not currently possible,” explained Krishna Komanduri, MD, Division of Transplantation and Cellular Therapy, Sylvester Comprehensive Cancer Center, University of Miami, Florida, and co-authors.

Researchers said while CRS is observed with glofitamab, a T-cell engaging bispecific antibody targeting CD20 and CD3, cases mostly happen at grade 1 or 2 severity with the vast majority of first CRS events occurring during the first cycle of therapy.

The model was designed to enable risk stratification after the first glofitamab dose with future implications to improve CRS management and monitoring of low-risk patients. 

The primary outcome was defined as grade ≥ 2 CRS in the week after the first glofitamab dose and included 65 events. The researchers evaluated the association between the dose, putative risk factors (including demographics, medical history, disease characteristic variables, baseline laboratory values), and the occurrence of CRS.

“To predict the occurrence of grade ≥ 2 CRS after the first glofitamab dose, a multivariable model was developed to include glofitamab first dose and a combined risk score (CRSRS), which is the weighted sum of binarized risk factor values at baseline,” continued Dr Komanduri and co-researchers.

Findings showed that the predictive ability was tested in a validation data set where the incidence of grade ≥ 2 CRS was 14%. A low-risk group (CRSRS < 5.0) was shown to be 60% of the test cohort, with patients in this group having a 5% chance of experiencing a grade ≥ 2 CRS.

Further, the researchers reported the induction of cytokines, including IL-6 and TNFα, were observed upon treatment with glofitamab, and peak magnitude of cytokine induction was associated with CRS incidence and severity. Cytokine induction was evident by end of glofitamab infusion and peak levels of TNFα were observed by mid-infusion.

“The CRSRS alone or in combination with cytokine induction represents a tool to predict the occurrence of grade ≥ 2 CRS after the first glofitamab dose to enable stratification of patients according to risk of CRS with possible future implications for the intensity of monitoring for those at low risk,” concluded Dr Komanduri, et al.—Alexa Stoia

Komanduri K, Belousov A, Byrtek M, et al. Development of a Predictive Model for Cytokine Release Syndrome to Inform Risk Stratification and CRS Management Following Immunotherapy. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 1459.