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Leo I. Gordon, MD, FACP
Leo I. Gordon, MD, FACP
Posted: Tuesday, March 29, 2022
Theodore W. Laetsch, MD, of Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, and colleagues examined the humoral and cellular immune responses to tisagenlecleucel—an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy—in patients with diffuse large B-cell lymphoma (DLBCL) and B-cell acute lymphoblastic leukemia (ALL). Published in Blood Advances, these results suggest that the presence of anti-mCAR19 antibodies or T-cell responses may not alter the activity of tisagenlecleucel in these patients.
“Data from clinical trials of tisagenlecleucel in patients with relapsed/refractory B-cell acute lymphoblastic leukemia and…DLBCL demonstrated that the presence of preexisting anti-mCAR19 antibodies or the development of posttreatment anti-mCAR19 antibodies did not affect tisagenlecleucel cellular kinetics, efficacy, or safety,” the investigators concluded. “Studies examining CAR T-cell therapy immunogenicity have been limited to date; therefore, it will be important to harmonize guidance for evaluating immunogenicity across CAR T-cell therapies.”
From the ELIANA, ENSIGN, and JULIET trials, data on 115 adults with relapsed or refractory DLBCL and 143 pediatric patients with relapsed or refractory B-cell ALL were collected. Humoral responses were determined by flow cytometry of anti-mCAR19 antibodies in serum, and cellular responses were identified using T-cell production of interferon-γ in response to two different mCAR19 peptide pools.
Baseline anti-mCAR19 antibodies were found in 94% of patients with DLBCL and 81% of those with ALL, and most patients had consistently low CD4-positive and CD8-positive T-cell responses to mCAR19 peptides over time. In 42% and 9% of patients with ALL and DLBCL, respectively, post-treatment anti-mCAR19 antibodies appeared to be higher than the patient-specific baseline.
Tisagenlecleucel cellular kinetics, such as maximum concentration and persistence, safety, and clinical response, did not appear to be influenced by pre- and post-treatment anti-mCAR19 antibodies in either population. Of note, overall response rates at day 28 were similar among all participants, and the duration of response and overall survival were generally unaffected by anti-mCAR19 antibodies.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
