Primary Analysis of PILOT Revealed Durable Responses with Liso-cel in the 2L Treatment of R/R LBCL

Patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after first-line (1L) treatment who are unable to undergo high-dose chemotherapy and hematopoietic stem-cell transplantation (SCT) have no established standard of care, and outcomes are historically poor. The PILOT study (NCT03483103) evaluated lisocabtagene maraleucel (liso-cel), an autologous, CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, as second-line (2L) treatment in patients with R/R LBCL not intended for SCT.1 Results from the primary analysis were first presented at the 2022 American Society of Clinical Oncology Annual Meeting and have since been published in Lancet Oncology.1,2

Eligible patients for PILOT were adults with R/R LBCL after 1L treatment who were not deemed candidates for SCT by their investigator and met ≥1 frailty criteria: age ≥70 years, Eastern Cooperative Oncology Group performance status (ECOG PS) of 2, DLCO ≤60%, LVEF <50%, CrCl <60 mL/min, and/or ALT/AST >2 × ULN. Patients with secondary central nervous system lymphoma were allowed. Patients received lymphodepletion with FluCy followed 2 to 7 days later by liso-cel at a target dose of 100 × 106 CAR-T cells, with bridging therapy allowed. Cytokine release syndrome (CRS) was graded per Lee 2014 criteria, and neurological events (NEs) per National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. The primary end point was overall response rate (ORR) per independent review committee (IRC) according to Lugano 2014 criteria. Main secondary end points were adverse events (AEs) and laboratory abnormalities, complete response (CR) rate per IRC, duration of response (DOR), progression-free survival (PFS), event-free survival (EFS), and overall survival (OS).

Of 74 patients who underwent leukapheresis, 61 received liso-cel. Common reasons for the pre-infusion dropout included death and loss of eligibility (5 each). For patients treated with liso-cel, median age was 74 years (range, 53-84; 79% ≥70 years) and 31% met ≥2 of the 6 protocol-specified frailty criteria. ECOG PS of 2 was recorded in 26% of patients, and 44% had hematopoietic cell transplantation–specific comorbidity index score of ≥3. After 1L treatment, 54% of patients had refractory disease, 21% relapsed within ≤12 months (mo), and 25% relapsed after 12 mo. Median on-study follow-up was 12.3 mo (range, 1.2-26.5). In the overall population of 61 patients receiving liso-cel, ORR and CR rates were 80% and 54%, respectively; patients achieving CR had durable responses, with a median (m)DOR of 21.7 mo. In the overall patient population, mDOR and mPFS were 12.1 mo and 9.0 mo, respectively; mEFS was 7.2 mo, and mOS was not reached. Most frequently observed grade ≥3 treatment-emergent AEs (TEAEs) were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Grade 3 CRS was seen in 1 patient (2%), with no grade 4 or 5 CRS observed. Grade 3 NEs were seen in 3 patients (5%), with no grade 4 or 5 NEs observed. Any-grade CRS and NEs occurred in 38% and 31% of patients, respectively. For the treatment of CRS, 10% of patients received tocilizumab and 16% received tocilizumab plus corticosteroids. For the treatment of NEs, 13% of patients received corticosteroids. Grade ≥3 infections were reported in 4 patients (7%), with 2 grade 5 COVID-19–related TEAEs.

In conclusion, in the PILOT study, liso-cel as 2L treatment in patients with LBCL for whom SCT was not intended demonstrated substantial and durable overall and complete responses, with no new safety concerns raised.1

References

  1. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy for relapsed or refractory large B-cell lymphoma in patients not intended for hematopoietic stem cell transplantation: primary analysis from the phase 2 PILOT study. J Clin Oncol. 2022;40:16. Abstract 7062.
  2. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022;23:1066-1077.

Related Items

Conference Correspondent Coverage is Brought to You by the Publishers of:
Oncology Practice Management
The Oncology Nurse–APN/PA

Learn more about our family of publications.

View Our Publications