Examining 48 patients at day 30 after infusion of CAR-T therapy, grade 3 to grade 4 neutropenia, anemia, and thrombocytopenia were observed in 54%, 17%, and 50% of patients, respectively. By day 90, looking at 36 patients, those figures had declined to 8.3%, 11%, and 13.8% respectively. Those findings recently appeared in the journal Biology of Blood and Marrow Transplantation.2
The results are broadly consistent, yet slightly higher, than those recorded in the ZUMA-1 study with axicabtagene ciloleucel, where 11% of 108 patients with refractory large B-cell lymphoma experienced grade 3 to grade 4 neutropenia, 3% experienced anemia, and 7% experienced thrombocytopenia, Dr Ibrahim noted.3 She added that her results, which included patients with lymphoma and myeloma, were slightly higher.
Overall, in the study by Dr Ibrahim and her coauthor, prolonged cytopenias were observed in 50% of patients beyond day 30. By day 90, the majority of patients had shown improvements, with a small proportion of patients experiencing cytopenias until the end of the study (day 180).
There is limited research investigating why cytopenias occur. One hypothesis is that the release of cytokines by CAR-T cells, and the use of lymphodepleting therapies, could be contributing factors. Some have also suggested that myelodysplastic syndrome and certain CHIP mutations may play a role in some patients, Dr Ibrahim explained.4
Interestingly, the MSKCC study found a statistically significant correlation between the recovery of hemoglobin, platelet, and neutrophil counts; and higher-grade cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and inflammatory markers.
To Dr Ibrahim, it made sense that post–CAR-T inflammatory responses could influence hematological recovery in some patients, because “inflammation can cause bone marrow suppression,” which could impede the production of new blood cells, she explained.
The MSKCC study also noted a correlation between the number of prior therapies and the appearance of certain cytopenias. For instance, absolute neutrophil count was associated with prior hematopoietic stem cell transplantation and 3 or more prior lines of therapy. In addition, lack of hemoglobin recovery at 1 month was associated with lymphodepletion using high-dose cyclophosphamide. The authors also noted a correlation between complete count recovery at 3 months and the type of CAR-T construct utilized, an association that “can be influenced by underlying diagnosis, as specific CAR constructs were used for specific diagnosis,” they noted.
To Drs Ibrahim and Osman, the 2 studies underscore the need to understand patients’ risk for infections after the receipt of CAR-T — and how long they should receive antimicrobial prophylaxis and support in the form of growth factors. The pair hopes to answer such questions in future research.
“Over time, it will be important to know whether … for those patients who get cytopenias … does it correlate with increased risk of infection? Does it correlate with response to the therapy or not?” Dr Osman said. “Only over time will we know the answers to all those questions.”
- Jain T, Knezevic A, Pennisi M, et al. Hematopoietic recovery following chimeric antigen receptor T cell (CAR T) therapy in hematological malignancies. Presentation at: the 2020 Transplantation and Cellular Therapy Meetings of ASCT and CIBMTR; February 19-23, 2020; Orlando, FL. Abstract 84.
- Locke FL, Ghobadi A, Jacobson CA, et al. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019;20(1):31-42.
- Ibrahim U, Osman K. Cytopenias following CAR-T therapy – a single center experience. Biol Blood Marrow Transplant. 2020;26(3):S260.
- Logue JM, Krivenko GS, Larson V, et al. Cytopenia following axicabtagene ciloleucel (axi-cel) for refractory large B-cell lymphoma (LBCL). J Clin Oncol. 2019;37(15_suppl). doi: 10.1200/JCO.2019.37.15_suppl.e14019