Effect of delayed cell infusion in patients with large B-cell lymphoma treated with chimeric antigen receptor T-cell therapy
Andrew P. Jallouk,
Naishu Kui,
Ryan Sun,
Jason R. Westin,
Raphael E. Steiner,
Ranjit Nair,
Loretta J. Nastoupil,
Luis E. Fayad,
Ajlan Al Zaki,
Misha Hawkins,
Sherry Adkins,
Mansoor Noorani,
Kaberi Das,
Jared Henderson,
Elizabeth J. Shpall,
Partow Kebriaei,
Jeremy Ramdial,
Christopher R. Flowers,
Sattva S. Neelapu,
Sairah Ahmed,
Paolo Strati
Affiliations
Andrew P. Jallouk
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN
Naishu Kui
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
Ryan Sun
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
Jason R. Westin
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Raphael E. Steiner
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Ranjit Nair
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Loretta J. Nastoupil
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Luis E. Fayad
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Ajlan Al Zaki
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Misha Hawkins
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Sherry Adkins
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Mansoor Noorani
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Kaberi Das
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
Jared Henderson
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Elizabeth J. Shpall
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Partow Kebriaei
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Jeremy Ramdial
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Christopher R. Flowers
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Sattva S. Neelapu
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Sairah Ahmed
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
Paolo Strati
Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
Complications occurring after lymphodepleting chemotherapy (LDC) may delay chimeric antigen receptor (CAR) T-cell infusion. The effect of these delays on clinical outcomes is unclear. We performed a retrospective analysis of 240 patients with relapsed/refractory large B-cell lymphoma treated with standard-of-care axicabtagene ciloleucel (axi-cel) and identified 40 patients (16.7%) who had delay in axi-cel infusion. Of these, 85% had delay due to infection. At time of LDC initiation, patients with delayed infusion had lower absolute neutrophil count (P=0.006), lower platelets (P=0.004), lower hemoglobin (P5 days (4.6 vs. 8.2 months; P=0.036), but not 1 day (5.7 vs. 8.2 months; P=0.238). Following propensity score matching, patients with delayed infusion continued to have shorter median PFS (3.5 vs. 6.0 months; P=0.015). Levels of pro-inflammatory cytokines on day of infusion were significantly higher in patients with delayed infusion. Together, these findings suggest that delays in CAR T-cell administration after initiation of LDC are associated with inferior outcomes. Further studies are needed to guide strategies to improve efficacy in such patients.
