Comparative efficacy of lisocabtagene maraleucel in the PILOT study versus second-line chemotherapy regimens in the real world

Abstract

This study assessed the comparative efficacy of lisocabtagene maraleucel (liso-cel) in the open-label, phase II PILOT study (clinicaltrials.gov NCT03483103) versus conventional second-line (2L) chemotherapy regimens in the real world administered to patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who were not intended for hematopoietic stem cell transplantation (HSCT). The liso-cel-treated cohort (N=61) was based on patients who received liso-cel in the PILOT study. The conventional chemotherapy cohort included patients who met PILOT eligibility criteria and received conventional 2L chemotherapy in the real-world clinical setting (N=273). After using the trimmed stabilized inverse probability of treatment weighting method to balance cohorts according to baseline characteristics, there were statistically significant differences in all tested measures of efficacy. Compared with real-world conventional chemotherapy regimens, liso-cel demonstrated higher overall response rates (79.6% with liso-cel vs. 50.5% with conventional chemotherapy; relative risk [RR]: 1.6; P<0.0001) and complete response rates (53.1% vs. 24.0%; RR: 2.2; P<0.0001), longer median duration of response (12.1 vs. 4.3 months; hazard ratio [HR: 0.40; P=0.0001), longer median event-free survival (7.0 vs. 2.8 months; HR: 0.43; P<0.0001), longer median progression-free survival (7.0 vs. 2.9 months; HR: 0.46; P<0.0001), and longer median overall survival (not reached vs. 12.6 months; HR: 0.58; P=0.0256). Results from analyses applying various additional statistical approaches consistently favored outcomes with liso-cel over real-world conventional chemotherapy regimens. These results reinforce the efficacy of liso-cel as 2L therapy for patients with R/R LBCL who are not intended for HSCT.

Figure 1.

Comparative adjusted efficacy outcomes in the lisocabtagene maraleucel–treated cohort versus the conventional chemotherapy cohort after application of PILOT eligibility criteria and balancing. (A) Event-free survival (EFS), (B) progression-free survival (PFS) and (C) overall survival (OS) adjusted by trimmed stabilized inverse probability of treatment weighting (IPTW) in the lisocabtagene maraleucel (liso-cel)–treated cohort versus the conventional chemotherapy cohort after balancing are shown. Multiple imputations were performed to create 30 datasets. Estimates were then obtained using Rubin’s rule to combine the individual estimates from each dataset. For the liso-cel–treated cohort, the weights = (1/propensity score) × the proportion of liso-cel patients. For the conventional chemotherapy cohort after balancing, the weights = (1/[1-propensity score]) × the proportion of patients with conventional chemotherapies. Stabilized IPTW were trimmed at the 5^th and 95^th percentiles. CI: confidence interval; HR: hazard ratio; NR: not reached.

Figure 2.

Comparative adjusted efficacy outcomes in the lisocabtagene maraleucel–leukapheresed cohort versus the conventional chemotherapy cohort after application of PILOT eligibility criteria and balancing. (A) Event-free survival (EFS), (B) progression-free survival (PFS) and (C) overall survival (OS) adjusted by trimmed stabilized inverse probability of treatment weighting (IPTW) in the lisocabtagene maraleucel (liso-cel)–leukapheresed cohort versus the conventional chemotherapy cohort after balancing are shown. Multiple imputations were performed to create 30 datasets. Estimates were then obtained using Rubin’s rule to combine the individual estimates from each dataset. For the liso-cel–treated cohort, the weights = (1/propensity score) × the proportion of liso-cel patients. For the conventional chemotherapy cohort after balancing, the weights = (1/[1-propensity score]) × the proportion of patients with conventional chemotherapies. Stabilized IPTW were trimmed at the 5^th and 95^th percentiles. CI: confidence interval; HR: hazard ratio; NR: not reached.

Figure 3.

First- and second-line treatment in the conventional chemotherapy cohorts before PILOT eligibility criteria. (A) Firstand (B) second-line treatments in all patients in the conventional chemotherapy cohort with relapsed/refractory large B-cell lymphoma after receiving therapy with an anthracycline and a CD20-targeted agent (N=601). *Collectively includes all treatments received by <1% of the total population.

Figure 4.

First- and second-line treatment in the conventional chemotherapy cohorts after application of PILOT eligibility criteria but before balancing. (A) First- and (B) second-line treatments in a subset of the conventional chemotherapy cohort who met the prespecified eligibility criteria of PILOT but before balancing to baseline characteristics with the lisocabtagene maraleucel– treated cohort (N=273). *Collectively includes all treatments received by <1% of the total population.