Predictors and management of relapse to Axicabtagene Ciloleucel in patients with aggressive B-cell lymphoma

Jose Vicente Forero-Forero, Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA
Paula A. Lengerke-Diaz, Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA
Eider Moreno-Cortes, Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA
Megan Melody, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL, USA
Zaid Abdel Rahman, Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA
Allison C. Rosenthal, Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USA
Mohamed A. Kharfan-Dabaja, Division of Hematology-Oncology and Blood and Marrow Transplantation and Cellular Therapy Program, Mayo Clinic, Jacksonville, FL, USA
Januario E. Castro, Department of Internal Medicine, Division Hematology-Oncology, Mayo Clinic, Phoenix, AZ, USAFollow

Abstract

Objective/background: Despite the success of chimeric antigen receptor (CAR) T-cell therapy in patients with aggressive non-Hodgkin lymphoma (aNHL), some patients still fail treatment, and their prognosis is dismal. Methods: We performed a retrospective study of aNHL patients treated with axicabtagene ciloleucel (axi-cel) at two Mayo Clinic centers between 2018 and 2020. We evaluated predictive factors, toxicities, and responses to salvage regimens after CAR T-cell therapy. Results: Thirty-four patients received axi-cel with a median length of hospitalization of 14 days. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 91% and 41% of patients, respectively. Furthermore, 71% of patients responded to therapy, with 53% achieving a complete response (CR). The CRS grade and absolute lymphocyte count at leukapheresis (ALCLeuk) correlated with CR and overall survival (OS), respectively. After a median follow-up of 6.8 months (interquartile range [IQR]

4.6–14.9), 15 patients (44%) showed progressive disease (PD). Most patients (60%) progressed during the first 3 months and had persistent CD19 tumor expression. Elevated C-reactive protein at baseline increased the risk of PD, whereas elevated ferritin increased PD and mortality risk. Twelve patients received salvage therapy, but only three responded. Median OS of relapsed/refractory patients to axi-cel was 3 months (IQR 1.3–5.1). Conclusion: The grade of CRS and ALCLeuk correlated with better outcomes to axi-cel therapy. In addition, elevated inflammatory markers at baseline were associated with PD and shorter survival. Relapses after treatment frequently occur within months after axi-cel infusion; they confer a poor prognosis and create an urgent need for novel and effective treatment options in this patient population.

Recommended Citation

Forero-Forero, Jose Vicente; Lengerke-Diaz, Paula A.; Moreno-Cortes, Eider; Melody, Megan; Rahman, Zaid Abdel; Rosenthal, Allison C.; Kharfan-Dabaja, Mohamed A.; and Castro, Januario E. (2023) "Predictors and management of relapse to Axicabtagene Ciloleucel in patients with aggressive B-cell lymphoma," Hematology/Oncology and Stem Cell Therapy: Vol. 16 : Iss. 2 , Article 6.
Available at: https://doi.org/10.1016/j.hemonc.2021.09.001