Researchers found that 60% of evaluated patients who received axicabtagene ciloleucel (axi-cel) for a large B-cell lymphoma experienced severe cytopenias during the study period, and significant cytopenias were particularly common among nonresponders to the therapy. The researchers described these and other findings in a report in the journal Leukemia & Lymphoma.

Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome are important adverse events that are often studied with chimeric antigen receptor T-cell (CAR-T) therapy. “However, cytopenias are common in practice, may result in dependency on supportive care, and can limit therapeutic options in patients who require further treatment after CAR-T therapy,” the researchers explained in their report.

The study evaluated patterns of patient and disease characteristics, as well as CAR-T-related toxicities, in patients who received axi-cel for diffuse B-cell lymphoma (DLBCL), primary mediastinal lymphoma (PMBCL), or transformed follicular lymphoma (tFL). Patients were treated with axi-cel at the Fred Hutchinson Cancer Research Center/University of Washington in Seattle, during a 2-year study period from February 2018 to February 2020.


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The primary study endpoint was severe cytopenia. This was defined by the presence of 1 or more of the following features between days 20 and 30 after axi-cel treatment: grade 3 or worse thrombocytopenia, grade 3 or worse neutropenia, or grade 3 or worse anemia; or a need for 2 or more doses of granulocyte colony-stimulating factor (G-CSF), 2 or more red blood cell (RBC) transfusions, or 2 or more platelet transfusions.

There were 53 patients included in the study, of whom 41 had DLBCL, 11 had tFL, and 1 had PMBCL. The patient population had a median age of 63 years. Most patients (72%) had primary refractory disease, and 28% had relapsed disease. After CAR-T therapy, 74% of patients had reached complete remission (CR) or partial remission (PR). The remaining 26% were considered nonresponders, having either progressive disease or stable disease.

Severe cytopenias were reported in 32 patients (60%) between days 20 and 30. These included 45% of the total study population having grade 3 or worse thrombocytopenia, 36% having grade 3 or worse neutropenia, 2% having grade 3 or worse anemia, 19% requiring G-CSF, 21% requiring RBC transfusion, and 28% requiring platelet transfusion. All nonresponders (100%) developed severe cytopenia, whereas 70% of responders — those with CR or PR — did (P =.01).

A multivariable model showed several independent factors significantly linked to development of severe cytopenia after axi-cel treatment. These included platelet transfusion in the 30 days prior to leukapheresis, the numbers of transfusions between leukapheresis and lymphodepletion of RBCs or platelets, prelymphodepletion lactate dehydrogenase level and absolute neutrophil count, and the number of dexamethasone treatments following CAR-T infusion.

“Our results highlight the importance of pre axi-cel cytopenias as well as post CAR-T corticosteroid use as predictors of post axi-cel cytopenias,” the researchers concluded in their report.

Reference

Panaite L, Wu QV, Voutsinas J, et al. Predictors of cytopenias after treatment with axicabtagene ciloleucel in patients with large B-cell lymphoma. Leuk Lymphoma. Published online July 9, 2022. doi:10.1080/10428194.2022.2095632