New York, NY — Notwithstanding the therapeutic breakthroughs in CAR T-cell therapy for cancer treatment, recent research highlights concerning complications that can sometimes be lethal. This advanced form of immunotherapy, commonly utilized in combatting lymphoma and multiple myeloma, has shown remarkable efficacy, yet a segment of patients succumb not to their cancer, but to treatment-related complications, predominantly infections.
The Memorial Sloan Kettering Cancer Center conducted a systematic review and meta-analysis recently that identified from a large dataset involving 18 clinical trials and 28 real-world studies that approximately 6.8% of patients experienced nonrelapse mortality (NRM) due to collateral effects of CAR T-cell therapy. Dr. Kai Rejeski, the study’s lead author, stated, “It is invariably distressing when a treatment designed to save lives inadvertently results in death.”
In reviewing data of 7,604 patients, researchers found that slightly more than half of the nonrelapse deaths were attributed to infections. Infections led the list of causes at 50.9%, with other malignancies, and cardiovascular or respiratory conditions also contributing to the mortality rate.
These numbers highlight the primary challenge treatment specialists face with immunotherapies such as CAR-T: managing the delicate balance of fighting cancer while safeguarding against severe immunosuppression that can lead to deadly infections. Rejeski pointed out that while significant strides have been made in managing certain CAR T-cell therapy complications such as immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), infections remain a critical area needing more focus and improved management strategies.
Adding to this discourse, Dr. Michael Jain from the Moffitt Cancer Center in Tampa, Florida, underscored that despite these risks, the bulk of fatalities still occur due to the cancer itself, rather than the treatment. Jain emphasized the importance of continued research in this area to refine and develop methods to reduce these risks, potentially including the use of prophylactic antibiotics, increased immune supplementation, or more tailored treatment regimens based on individual immune reconstitution profiles.
Jain also remarked on the need for greater attention to the secondary effects of cancer treatments generally: “Almost every cancer therapy, especially those targeting the immune system, raises the risk for infections.”
Dr. Rejeski further noted that the specific CAR T-cell products, axicabtagene ciloleucel and ciltacabtagene autoleucel, were independently associated with higher rates of NRM, suggesting that certain treatments might pose more risk than others. This could influence treatment choices, especially for older patients or those with multiple health issues.
In response to these findings, Rejeski has advocated for a more detailed presentation of infectious complications in medical forums and literature, stressing the need for comprehensive data that delineate infection types, timing, and treatment specifics.
These conversations and analyses are not only pivotal in optimizing patient outcomes but also play a crucial role in guiding future research directions and policy making in oncology. As the field of CAR T-cell therapy progresses, understanding and mitigating the risks associated with this potent treatment are paramount. The balance between cancer eradication and the prevention of therapy-related complications remains a top priority for oncologists worldwide.