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
Mené sur 61 patients atteints d'un lymphome à grandes cellules B réfractaire ou récidivant et non éligibles à une greffe de cellules souches hématopoïétiques (âge médian : 74 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale, et la toxicité du lisocabtagène maraleucel (une immunothérapie à base de lymphocytes CAR-T ciblant CD19) en traitement de seconde ligne
Background : Patients with relapsed or refractory large B-cell lymphoma after first-line treatment who are not intended for haematopoietic stem-cell transplantation (HSCT) have poor outcomes and limited treatment options. We assessed the antitumour activity and safety of lisocabtagene maraleucel, an autologous, CD19-directed chimeric antigen receptor(CAR) T-cell product, as second-line treatment in adults with relapsed or refractory large B-cell lymphoma not intended for HSCT. Methods : PILOT, an open-label, phase 2 trial done at 18 clinical sites in the USA, included adults aged 18 years or older who had relapsed or refractory large B-cell lymphomaand PET-positive disease, had received first-line therapy containing an anthracyclineand a CD20-targeted agent, were not intended for HSCT by their physician, and metat least one prespecified transplantation not intended criterion. Patients receivedlymphodepleting chemotherapy (intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 days) followed 2–7 days later by two sequential lisocabtagene maraleucelinfusions (equal target doses of CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 106 CAR+ T cells). The primary endpoint was the overall response rate and was assessed inall patients who received lisocabtagene maraleucel and had confirmed PET-positivedisease before lisocabtagene maraleucel administration based on an independent reviewcommittee according to the Lugano 2014 criteria. Safety was assessed in all patientswho received lisocabtagene maraleucel. Patient follow-up is ongoing. This study isregistered with ClinicalTrials.gov, NCT03483103. Findings : Between July 26, 2018, and Sept 24, 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets); median age was 74 years (IQR 70–78), 24 (39%) patients were women versus 37 (61%) men, and 54 (89%) patients were White. 16 (26%) of 61 patients hadan Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractorydisease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsedafter 12 months of first-line therapy. Median on-study follow-up was 12·3 months (IQR6·1–18·0). 49 (80% [95% CI 68–89]; p<0·0001) patients had an overall response. Themost common grade 3 or worse treatment-emergent adverse events were neutropenia (29[48%] patients), leukopenia (13 [21%]), and thrombocytopenia (12 [20%]). Lisocabtagenemaraleucel-related serious treatment-emergent adverse events were reported in 13 (21%)patients. There were no treatment-related deaths. Cytokine release syndrome occurredin 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 inthree) patients, with no grade 4 events or deaths. Interpretation : These results support lisocabtagene maraleucel as a potential second-line treatmentin patients with large B-cell lymphoma for whom HSCT is not intended.