Background

CD19-targeted chimeric antigen receptor (CAR) therapy with lisocabtagene maraleucel (liso-cel) has demonstrated impressive efficacy with manageable toxicity in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) enrolled on the TRANSCEND (Abramson, Lancet, 2020) and TRANSFORM (Kamdar, Lancet, 2022) clinical trials. This led to the approval of liso-cel by the FDA for LBCL patients with R/R disease after 2 or more lines of prior therapy. We report outcomes of LBCL patients referred to our institution for liso-cel treatment in the non-trial setting.

Methods

We retrospectively analyzed the outcomes of consenting patients who arrived to the Bezos Family Immunotherapy Clinic at the Fred Hutchinson Cancer Center for planned treatment with liso-cel between January 2021 and May 2023 (intention-to-treat [ITT] group). Best response was determined within 3 months of CAR-T infusion by PET-CT imaging per Lugano 2014 criteria. Cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) were graded using ASTCT criteria. Vein-to-vein time was defined as the time from leukapheresis to CAR-T infusion.

Results

Of 51 ITT patients, 51 (100%) underwent leukapheresis, 49 (96%) received lymphodepletion (LD), and 47 (92%) received liso-cel. Seven of 47 infused patients (15%) received an out-of-specification product on an expanded access protocol. The median time from leukapheresis to liso-cel infusion was 34 days (interquartile range [IQR] 32-41). In the ITT group, the median patient age was 67 years (range 41-823), ECOG performance status was 1 (IQR 1.0-1.0), and hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was 2 (IQR 1.0-3.5). 28 of 51 ITT patients (55%) met eligibility criteria for the TRANSCEND trial. Reasons for ineligibility included: ECOG ≥2 (n=11), cardiac disease (n=7), significant central nervous system pathology (n=2), recent history of prior malignancy (n=2), and CKD (n=1). LBCL types included diffuse LBCL (DLBCL; 76%, n=39), transformed DLBCL from indolent histologies (tDLBCL; 18%, n=9), and high-grade B cell lymphoma (HGBCL; 5.9%, n=3). Bulky and extranodal disease were present in 13 (27%) and 28 patients (57%), respectively.

Liso-cel was administered in the outpatient setting in 41 (87%) infused patients, among whom 24 (59%) required admission. Among all infused patients, 40 (85%) required admission and the median total inpatient duration was 5 days (range 0 to 34). Four patients (8.5%) required ≥2 admissions. We observed CRS and ICANS after liso-cel infusion in 29 (63%; grade ≥3, 22%) and 15 patients (33%; grade ≥3, 30%), respectively, at median times of 4 (IQR 2-6) and 7 (IQR 2-17) days. Tocilizumab and steroids were administered to 14 (30%) and 18 (38%) patients, respectively.

Among patients evaluable for response (n=39), the best overall response (ORR) and complete response rates were 82% (ITT, 63%) and 56% (ITT, 43%), respectively. After a median follow-up of 11.3 months among infused patients, the 1-year duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were 57%, 47%, and 69%, respectively. In an exploratory univariate regression analysis, pre-LD LDH was associated with grade 3-4 ICANS (OR 12.0, 95% CI 2.18 to 128), OS (HR 33.7, 95% CI 1.46 to 780, p=.028), and PFS (HR 3.83, 95% CI 1.43 to 10.3, p=.008); and pre-LD ALC was associated with grade 3-4 CRS (OR 4.05, 95% CI 1.23 to 19.1, p=.037).

Conclusions

Our ITT analysis in an older patient population referred to our center for CD19 CAR-T therapy for R/R LBCL in the non-trial setting showed high rates of durable response after liso-cel with an acceptable safety profile.