Lisocabtagene Maraleucel (liso-cel) As Second-Line Therapy for R/R Large B-Cell Lymphoma in Patients Not Intended for Hematopoietic Stem Cell Transplantation (HSCT): Final Analysis of the Phase 2 PILOT Study

Background We report final analysis results from the PILOT study (NCT0348303) after a median follow-up of 18.2 mo (range, 1.2–32.8). Methods Eligible adults with R/R large B-cell lymphoma (LBCL) who received 1 prior line of therapy with an anthracycline and CD20-targeted agent, were not intended for HSCT, and met ≥ 1 transplant not–intended criterion by investigator (age ≥ 70 years, ECOG PS of 2, diffusing capacity of the lung for carbon monoxide ≤ 60%, LVEF < 50%, CrCl < 60 mL/min, or ALT/AST > 2 × ULN) were enrolled. Patients (pts) received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m² and intravenous cyclophosphamide 300 mg/m² daily for 3 days) followed by liso-cel infusion 2–7 days later. The primary endpoint was ORR by independent review committee (IRC) per Lugano 2014 criteria; secondary endpoints included safety; CR rate, duration of response (DOR), and PFS by IRC; and OS. Results Of 61 pts included in the liso-cel–treated analysis set, median age was 74 years (range, 53–84 years; ≥ 75 years, 46%), 26% had ECOG PS of 2, 25% had CrCl < 60 mL/min, 54% had diffuse LBCL not otherwise specified, 30% had high-grade lymphoma with diffuse LBCL histology (HGBCL), 33% had double-/triple-hit disease, and 54% had refractory disease. ORR was 80.3%, with 54.1% achieving CR (Table). Responses were durable, with a median DOR of 23.3 mo (95% CI, 6.2–not reached [NR]; median follow-up, 23.1 mo); median DOR for those with CR was NR (95% CI, 21.65–NR) vs 2.1 mo (95% CI, 1.4–3.3) for those with PR. Median PFS was 9.0 mo (95% CI, 4.2–NR) and median OS was NR (95% CI, 16.3–NR).Twenty-four pts died, mostly of disease progression (n = 20). In the treatment-emergent (TE) period (≤ 90 days after liso-cel administration), 96.7% had TEAEs (grade ≥ 3, 78.7%), 37.7% had cytokine release syndrome (grade 3, 1.6%; no grade 4–5), 31.1% had neurological events (grade 3, 4.9%; no grade 4–5), 8.2% had hypogammaglobulinemia, and 6.6% had grade ≥ 3 infections. Of 57 pts included in the post-TE period (starting from 91 days after liso-cel administration), 50.9% experienced AEs (grade ≥ 3, 17.5%; Table); the most common grade ≥ 3 AEs were anemia and thrombocytopenia. In the post-TE period, 1 pt had hypogammaglobulinemia and 1 had grade ≥ 3 infections (bacteremia and sepsis). Overall, 2 pts had second primary malignancies (squamous cell carcinoma of skin and malignant external ear neoplasm [n = 1] and myelodysplastic syndrome [n = 1]). Conclusions This final analysis of PILOT demonstrated a high CR rate and durable CRs with liso-cel treatment in pts with R/R LBCL for whom HSCT was not intended. Despite the high incidence of HGBCL, primary refractory disease, advanced age, and comorbidities, the safety profile was consistent with previous reports, with no new or increased safety signals. Results continue to support liso-cel as second-line therapy for this underserved population of pts with R/R LBCL.