Real-World (RW) Outcomes of Lisocabtagene Maraleucel (liso-cel) As Second-Line (2L) Therapy in Patients (pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL): First Results from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry
Authors: Bobillo Maria Silvina Odstrcil , Kambhampati Swetha , Lee Dasom , Hunter Bradley D. , Egini Ogechukwu , Patel Krish , Reagan Patrick M. , Bernasconi David , Kim Soyoung , Santiago Parrilla Charimar , Krimmel Tracy , Liu Fei Fei , Roy Debasmita , Ahmed Sairah , Crombie Jennifer L. , Dahiya Saurabh , Hamadani Mehdi , Lee Catherine J. , Pasquini Marcelo C. , Shadman Mazyar , Herrera Alex F. , Frigault Matthew 
Published: December 2024

Background: The increasing use of CAR T cell therapies in the 2L setting underscores the need to evaluate outcomes in the context of standard of care (SOC), including in pts ineligible for clinical trials. Liso-cel demonstrated significant efficacy in the TRANSFORM (NCT03575351) and PILOT (NCT03483103) studies in pts with R/R LBCL in the 2L setting, regardless of pts' transplantation eligibility. Here, we report on the effectiveness and safety of liso-cel as SOC based on CIBMTR data collected as part of a postmarketing study for 2L R/R LBCL.
Methods: This observational study included pts in the United States who received commercial liso-cel as 2L therapy between 06/2022 and 05/2024 and had ≥ 1 postinfusion safety and response assessment reported in the CIBMTR Registry. Outcomes evaluated included ORR, CR rate, duration of response (DOR), PFS, OS, AEs of special interest (AESI), and nonrelapse mortality (NRM; defined as death before disease progression/relapse). Univariable Logistic Regression was used to assess association between increasing age and early effectiveness outcomes.
Results: At data cutoff (05/07/2024), in 128 eligible pts, median age was 73 y (range, 24-85; ≥ 70 y, 55%; ≥ 75 y, 43%) and 57% were male. Most pts (80%) had DLBCL (germinal center B cell type, 50 pts; activated B-cell type, 39 pts; not otherwise specified, 13 pts), 14% had high-grade B-cell lymphoma, and 6% had other histologies. At the time of infusion, 91% of pts had active disease, 62% had primary refractory disease, and 54.5% (60/110) had extranodal involvement, including 4.5% (5/110) with CNS involvement. In 107 pts with ECOG PS data, 5% had ECOG 2 and none had ECOG 3 or 4. At least 1 comorbidity was reported in 62/105 (59%) pts with available data, with cardiac (24%), pulmonary (13%), and obesity (14%) being the most common (&gt; 10%); 45% (55/123) of pts had elevated LDH at infusion, and ≥ 65% (84 pts) would have been TRANSFORM ineligible mainly due to age and/or comorbidities. Of 121 pts with available data on prior therapies, 91% had received R-CHOP (single regimen, 59%; with other chemotherapy regimens, 41%), and 18% and 21% received intrathecal and radiation therapies, respectively. Most pts (73% [86/118]) received bridging therapy.
At a median (range) follow-up of 6.2 mo (0.3-13.8), ORR and CR rate (95% CI) in the overall cohort were 84% (77-90) and 68% (59-76), respectively. TRANSFORM-ineligible pts (n = 83) had ORR of 82% (72-90) and CR rate of 65% (54-75), while those who might have been eligible (n = 44) had ORR of 89% (75-96) and CR rate of 73% (57-85). Median DOR, PFS, and OS were not reached.
Early-response analysis of the population stratified by age showed that pts &lt; 70 y (n = 57) had ORR and CR rate (95% CI) of 88% (76-95) and 79% (66-89), respectively; pts ≥ 70 y (n = 71) had ORR and CR rate (95% CI) of 81% (70-90) and 59% (46-70). Further, younger age was associated with significantly higher CR rates (P &lt; 0.05). Additional subgroup analyses, such as stratification by PILOT criteria, and multivariable analyses will be included in the presentation.
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in 45% (grade 1, 37 pts; grade 2, 17 pts; 1 pt each with grade 3, 4, and 5) and 20% (grade 3, 7 pts; none with grades 4 or 5) of pts, respectively. Other reported AESIs were prolonged cytopenia (grade ≥ 4 at Day 30; 9% [11/124]), clinically significant infections (28%), second primary malignancies (2%; none of hematologic origin), and 6 cases of grade 3/4 organ toxicity; no tumor lysis syndrome was reported. The 6-mo cumulative incidence of NRM was 2.7% (95% CI, 0.7-7.1) and that of relapse/progression or death due to primary disease was 40.4% (95% CI, 31.0-49.7). There were 3 deaths ≤ 30 d of infusion; 2 were due to progression of primary disease (including 1 pt with grade 5 CRS noted as a contributing cause) and 1 due to cardiac failure.
Conclusions: Liso-cel continued to demonstrate consistently deep responses in this broad, albeit older, RW pt cohort with 2L R/R LBCL, with early responses being stronger in pts aged &lt; 70 y and those who might have been eligible for TRANSFORM. The safety profile remained predictable; most pts did not experience, or had low-grade CRS, ICANS, prolonged cytopenia, or infections. While longer follow-up in a larger cohort is needed, these results provide additional compelling evidence supporting the use of liso-cel as 2L SOC treatment for pts, young and old alike, with R/R LBCL.