Treatment with chimeric antigen receptor (CAR) T-cell therapy achieves favorable responses and survival in patients with relapsed or refractory large B-cell lymphoma (LBCL) in both the second-line (2L) and third-line or later setting (3L+), according to a study presented at the 66th American Society of Hematology Annual Meeting & Exposition.
Using the Cell Therapy Consortium registry, the researchers identified 155 adult patients treated with axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel). Fifty-three (34%) patients received CAR-T in 2L, including 74% who received axi-cel and 26% who received liso-cel. A total of 102 (66%) patients received CAR-T in 3L+, including 48% who received axi-cel, 24% who received tisa-cel, and 28% who received liso-cel. Lymphodepleting chemotherapy regimens consisted of fludarabine and cyclophosphamide (76%) or bendamustine (23%).
The researchers noted that baseline characteristics differed between the two cohorts. These include disease status at the time of referral (51% refractory in 2L vs 35% in 3L+; P<.01) and CAR-T product received (74% axi-cel in 2L vs 48% in 3L+; P<.01).
A majority of patients (68%) experienced cytokine release syndrome (CRS), with grade 3-4 CRS occurring in 6% of patients. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 35% of patients, including 15% with grade 3-4 ICANS. Fifty deaths were attributed to lymphoma, and 15 deaths were attributed to infection (4%), other malignancies (2%), and other causes (3%). The rate of CRS or ICANS and causes of death did not differ between the 2L and 3L+ cohorts.
The median follow-up was 11.1 months. Thirty days after infusion, the objective response rate (ORR) was 80% and the complete response (CR) rate was 54% among 137 evaluable patients. Ninety days after infusion, the ORR was 70% and the CR rate was 57% among 122 evaluable patients. The response rates did not differ between the 2L and 3L+ cohorts.
The nine-month progression-free survival (PFS) was 48% (95% CI, 41-57) for all patients, 56% (95% CI, 44-71) for the 2L cohort, and 45% (95% CI, 36-56) for the 3L+ cohort. (P=.18). The nine-month overall survival (OS) was 64% (95% CI, 57-72) for all patients, 75% (95% CI, 63-88) for the 2L cohort, and 59% (95% CI, 50-69) for the 3L+ cohort (P=.11). The mine-month nonrelapse mortality rate for all patients was 9% (95% CI, 4-13), with no difference between the 2L and 3L+ cohorts.
In a multivariable analysis, factors associated with PFS were elevated lactate dehydrogenase (LDH) before lymphodepleting chemotherapy (hazard ratio [HR], 3.6; P<.01) and Eastern Cooperative Oncology Group (ECOG) performance status (0, 1, ≥2) (HR, 1.8; P=.01). Factors associated with OS were elevated LDH before lymphodepleting chemotherapy (HR, 2.7; P<.01), discrete number of lines of prior therapy (HR, 1.3; P<.01), and ECOG performance status (0,1, ≥2) (HR, 1.9; P=.02).
“While our analysis is limited by short follow-up and limited subgroup cohort size, our data suggest similar outcomes for early [relapsed or refractory] LBCL [patients] treated with CAR-T in 2L versus 3L+,” the researchers concluded. “Selection of more fit [patients] and efforts to reduce disease burden prior to infusion may improve survival outcomes for early [relapsed or refractory] LBCL [patients] treated with CAR-T regardless of line of therapy.”
Reference
Rojek AE, Ahmed N, Gomez Llobell M, et al. CAR T cell therapy in early relapsed/refractory large B-cell lymphoma: real world analysis from the cell therapy consortium. Abstract #4503. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.