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Tisagenlecleucel Gives Rise to an Immunogenic Response, but it Does not Affect Activity in ALL
Immunogenic responses to the murine single-chain variable fragment domain contained in tisagenlecleucel did not affect the chimeric antigen receptor (CAR) T therapy’s activity in young patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and adult patients with R/R diffuse large B-cell lymphoma (DLBCL).
“Similar to other biologics, CAR-T cell therapies can cause an immune response that may be more likely with murine-derived components, and that may affect efficacy or result in adverse events,” wrote Karen Mueller, Novartis Institutes for BioMedical Research, East Hanover, NJ, and co-authors.
Researchers examined the effects of humoral and cellular immune responses to tisagenlecleucel on clinical outcomes using 2 assays. Humoral responses were determined by flow cytometric measurement of anti-murine CAR19 (mCAR19) antibodies in serum, while cellular responses were determined using T-cell production of interferon-g in response to 2 different pools of mCAR19 peptides.
Data were pooled from 143 patients in the ELIANA and ENSIGN trials in R/R B-ALL, and 115 patients in the JULIET trial in R/R DLBCL.
Previous therapy with murine or humanized monoclonal antibodies was infrequent (10%) in patients with B-ALL (11 in ELIANA; 3 in ENSIGN). However, almost all of the patients in JULIET (98%) received prior rituximab, and 14% received it within a month of the tisagenlecleucel infusion.
Researchers found that post-treatment anti-mCAR19 antibodies were higher than baseline in 42% R/R B-ALL and 9% of R/R DLBCL patients, that did not affect tisagenlecleucel cellular kinetics, including maximum concentration and persistence, clinical response (comprising day-28 response, duration of response [DOR], and event-free survival [EFS]), or safety.
