As reported in The Lancet Oncology by Sehgal et al, the phase II PILOT trial showed that the autologous, CD19-directed chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel produced a high response rate in the second-line treatment of patients with relapsed or refractory large B-cell lymphoma who were not intended to receive hematopoietic stem cell transplantation (HSCT).
The study supported the June 2022 approval of lisocabtagene maraleucel (along with the TRANSFORM trial) for patients with refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy who are not eligible for HSCT due to comorbidities or age.
PILOT Details
The multicenter PILOT study enrolled patients who had received first-line therapy containing an anthracycline and a CD20-targeted agent; who were not intended for HSCT by their physician; and who met at least one prespecified criterion for transplantation not intended. Between July 2018 and September 2021 (data cutoff for the primary analysis), 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety population). Patients received lymphodepleting chemotherapy with fludarabine/cyclophosphamide followed 2 to 7 days later by two sequential lisocabtagene maraleucel infusions consisting of 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 overall response rate on independent review committee assessment according to Lugano 2014 criteria.
Responses
KEY POINTS
- Lisocabtagene maraleucel produced responses in 80% of patients.
- Complete response was achieved in 54%.
Median on-study follow-up was 12.3 months (interquartile range [IQR] = 6.1–18.0 months). Response was observed in 49 (80%, 95% confidence interval [CI] = 68%–89%) of 61 patients (P < .0001 vs null hypothesis of 50%), with complete response seen in 33 patients (54%, 95% CI = 41%–67%). At median follow-up of 15.5 months (IQR = 8.6–17.4 months), median duration of response was 12.09 months (95% CI = 6.24 months–not reached) among all responders and 21.65 months (95% CI = 12.09 months–not reached) among those with complete response.
Median progression-free survival was 9.03 months (95% CI = 4.17 months–not reached) among all patients and 22.60 months (95% CI = 12.98 months–not reached) among patients with complete response.
Adverse Events
The most common grade ≥ 3 adverse events were neutropenia (48%), leukopenia (21%), and thrombocytopenia (20%); grade ≥ 3 prolonged cytopenias occurred in 30% of patients. Treatment-related serious adverse events occurred in 21% of patients. Cytokine-release syndrome of any grade occurred in 23 patients (38%; grade 3 in 1 patient) and neurologic adverse events of any grade occurred in 19 (31%; grade 3 in 3 patients). Adverse events led to death in two patients; both deaths were due to COVID-19, with one considered related to treatment.
The investigators concluded, “These results support lisocabtagene maraleucel as a potential second-line treatment in patients with large B-cell lymphoma for whom HSCT is not intended.”
Alison Sehgal, MD, of the University of Pittsburgh Medical Center, Hillman Cancer Center, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Juno Therapeutics, a Bristol Myers Squibb company. For full disclosures of the study authors, visit thelancet.com.
