New York, NY — A recent comprehensive study sheds new light on the side effects related to CAR T-cell therapy, a cutting-edge treatment for lymphoma and multiple myeloma, highlighting that a significant concern is infections leading to nonrelapse mortality (NRM). The research led by Dr. Kai Rejeski of Memorial Sloan Kettering Cancer Center involved a detailed examination of NRM in patients treated with this innovative therapy.
Dr. Rejeski’s team analyzed data from 18 clinical trials and 28 real-world studies, accounting for a total of 7,604 patients. They discovered that approximately 6.8% of the patients experienced NRM, translating to about one in every 15 patients. Notably, infections were the primary cause of these deaths, responsible for more than half of the cases.
The study underscored the gravity of NRM, characterized by nonrelapse causes such as infections, other malignancies, and cardiovascular or respiratory events. Among these, infections presented the most significant risk, often overshadowing other severe complications like immune effector cell-associated neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), and hemophagocytic lymphohistiocytosis (HLA). These findings suggest that the management of infections remains a crucial challenge in the post-treatment phase.
Mantle cell lymphoma patients were found to have the highest NRM rate at 10.6%, with multiple myeloma and large B-cell lymphoma following closely. This variability across different diseases prompts a need for tailored approaches in managing and monitoring patients undergoing CAR T-cell therapy.
Dr. Rejeski and his colleagues are advocating for a greater focus on understanding and managing infectious complications following CAR T-cell administration. “Current discussions often center around CRS and ICANS management,” Dr. Rejeski noted, “However, our findings demand that equal attention be given to cytopenias and subsequent infection risks.”
Supporting this perspective, Dr. Michael Jain of Moffitt Cancer Center in Tampa, Florida, emphasized the lesser-known risks of infections associated with cancer treatments, especially those targeting the immune system. He remarked on the general vulnerability of cancer patients to infections due to the immunosuppressive nature of many treatments.
According to the study, strategies to combat these infection risks might include the prophylactic use of antibiotics, enhanced immune system monitoring, and possibly the integration of preventative strategies into patient management plans.
While the potential for relapse remains the primary cause of mortality post-CAR T-cell therapy, this study highlights the crucial aspect of NRM — particularly infections — that warrants more detailed investigation and responsive clinical strategies.
Furthermore, interventions to improve immune system reconstitution post-therapy were discussed as essential for reducing NRM. These interventions could offer a lifeline to those with severely compromised immune responses following treatment.
The study also noted a variability in NRM rates among different CAR T-cell products, with specific therapies for large B-cell lymphoma and multiple myeloma showing higher NRM. This finding suggests that product-specific risks should be considered when selecting suitable treatment options for patients, particularly those who are older or have multiple comorbidities.
As the medical community continues to harness the power of CAR T-cell therapy, the insights from Dr. Rejeski’s research provide critical guidance on improving patient outcomes and navigating the complex landscape of immunotherapy.