Researchers Identify Potential Risk Factors of Uncommon Thrombotic Events Following CAR T-Cell Treatment

Although rare, patients should be monitored for thrombotic events while receiving chimeric antigen receptor (CAR) T-cell therapy, explain researchers of a new study published in International Journal of Molecular Sciences.

The study, wrote the researchers, offers insight into emerging and uncommon complications following CAR T-cell therapy. To date, little has been explored in the association between thrombotic risk and CAR T-cell treatments.

“The toxicity profile of CAR T-cell therapy is rapidly evolving as the number of treated patients continues to increase, novel products become FDA vapproved, and clinical trials with new targets and indications open,” described the researchers. “A better understanding of the risks of CAR T-cell therapy may help clinical management.”

Seven percent of the 140 patient participants developed a thrombosis complication across CAR T-cell indications, including relapsed or refractory B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma, and multiple myeloma (MM).

Notably, thrombotic events occurred in 9.7% of patients with B-cell lymphomas and just 2.9% of patients with MM. Eight events occurred among patients with DLBCL and 1 occurred among a patient with FL; these patients received treatment with axicabtagene ciloleucel. For the event that occurred among a patient with MM, treatment was with ciltacabtagene autoleucel.

Time to primary thrombotic event happened an average of 63 days following infusion, but this ranged significantly: from 3 to 346 days post treatment. The researchers flagged that the patient who experienced a thrombotic event at 346 days was potentially an outlier. They also noted that thrombotic events that occurred within 30 days post infusion may have been a different etiology than those that occurred without close hospital monitoring.

Analyses of potential risk factors suggested that risk factors for thrombosis following CAR T-cell therapy contrasted traditional risk factors.

Assessment of coagulation parameters and cytokine release syndrome (CRS)/immune effector cell–associated neurotoxicity syndrome (ICANS) showed that D-dimer peak levels may be suggestive of thrombosis risk for these patients; a D-dimer peak elevation of 3 times the upper limit of normal was found to be most associated with a thrombotic event. Having ICANS was also significantly associated with having a thrombotic event. Other coagulation parameters, such as prothrombin time, activated partial thromboplastin time, fibrinogen, platelet nadir, ferritin peak differences, and presence of CRS showed no significant associations.

There were no statistically significant associations found based on age, sex, diagnosis, body mass index, prior history of bleeding, venous thromboembolism or preexisting cardiovascular condition, or anticoagulation therapy prior to infusion.

Thrombotic events included 9 venous complications—deep venous thromboses (DVT), pulmonary embolisms, and cerebral vein sinus thrombosis—and 1 arterial complication of non-ST elevation myocardial infarction (NSTEMI).

“Interestingly, we report a coronary artery thrombosis with NSTEMI in a DLBCL patient treated with CAR T-cell therapy,” wrote the researchers. “This patient had a previous medical history of coronary artery disease and myocardial infarction with a prior right leg DVT 5 months before CAR T-cell infusion. Chest pain and elevated troponin were present without significant EKG changes 3 days after CAR T-cell infusion. Percutaneous coronary intervention was performed to successfully resolve the thrombosis. No thrombosis recurrence was noted on patients who underwent anticoagulation treatment.”

Reference

Schorr C, Forindez J, Espinoza-Gutarra M, Mehta R, Grover N, Perna F. Thrombotic events are unusual toxicities of chimeric antigen receptor T-cell therapies. Int J Mol Sci. Published online May 6, 2023. doi:10.3390/ijms24098349