Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study

Abstract

We report final analysis results from the PILOT study of lisocabtagene maraleucel (liso-cel) for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Sixty-one adults with R/R LBCL who had received 1 previous line of therapy and met ≥1 hematopoietic stem cell transplantation (HSCT) not intended criterion. Overall response rate (primary end point) was 80%; 54% achieved complete response. After median on-study follow-up of 18.2 months, median duration of response was 23.3 months (95% confidence interval [CI], 6.2 to not reached [NR]). Median progression-free survival (PFS) was 9.0 months (95% CI, 4.2 to NR), median overall survival (OS) was NR (95% CI, 16.3 to NR), and 18-month PFS and OS rates were 43% (95% CI, 30-55) and 59% (95% CI, 45-70), respectively. In the treatment-emergent (TE) period (≤90 days after liso-cel administration), 79% had grade ≥3 adverse events (AEs), 38% had cytokine release syndrome (2% grade 3; no grade 4/5), 31% had neurological events (5% grade 3; no grade 4/5), and 7% had grade ≥3 infections. Of 57 patients in the post-TE period (≥91 days after liso-cel administration), 18% experienced grade ≥3 AEs; 1 patient had grade ≥3 infections. Thirty patients in the leukapheresis set (n = 74) died, mostly of disease progression (n = 24). In this population with high incidence of high-grade B-cell lymphoma, primary-refractory disease, advanced age, and comorbidities, liso-cel demonstrated durable efficacy and a favorable safety profile, consistent with previous reports. These results support liso-cel as second-line therapy for this underserved population of patients with R/R LBCL not intended for HSCT. This trial was registered at www.clinicaltrials.gov as #NCT03483103.

Graphical abstract

Figure 1.

Kaplan-Meier curves for DOR, PFS, EFS, and OS in the liso-cel–treated efficacy analysis set. (A) Duration of response; (B) progression-free survival; (C) event-free survival; (D) overall survival. Data on Kaplan-Meier curves are expressed as median (95% CI). Crosses denote censored patients. ∗Reverse Kaplan-Meier method was used to obtain median follow-up and its 95% CIs. †OS data include data from the long-term follow-up study. PD, progressive disease; PR, partial response; SD, stable disease.

Figure 1.

Kaplan-Meier curves for DOR, PFS, EFS, and OS in the liso-cel–treated efficacy analysis set. (A) Duration of response; (B) progression-free survival; (C) event-free survival; (D) overall survival. Data on Kaplan-Meier curves are expressed as median (95% CI). Crosses denote censored patients. ∗Reverse Kaplan-Meier method was used to obtain median follow-up and its 95% CIs. †OS data include data from the long-term follow-up study. PD, progressive disease; PR, partial response; SD, stable disease.

Figure 2.

ORR by prespecified subgroup (liso-cel–treated efficacy analysis set). ORR and 2-sided 95% Clopper-Pearson CIs are displayed.

Figure 3.

Liso-cel transgene persistence∗ (A) (cellular kinetic set) and incidence of B-cell aplasia† (B) (liso-cel–treated efficacy analysis set). ∗Number of patients with persistence of liso-cel in the blood/number of patients with an available sample at the specific time point. Persistence is defined as a transgene count greater than, or equal to, the lower limit of detection. Data obtained after the initiation of retreatment with liso-cel or after start of a new anticancer therapy are not included in the determination of persistence. †Number of patients with B-cell aplasia/number of patients with an available sample at the specific time point. B-cell aplasia is defined as <3% CD19⁺ B cells in peripheral blood lymphocytes; B-cell measurements taken after the initiation of retreatment or after another anticancer treatment are excluded. tx, treatment.