PILOT Trial Supports Lisocabtagene Maraleucel as Second-Line Therapy for Relapsed/Refractory LBCL

Lisocabtagene maraleucel shows promise a potential second-line treatment in patients with large B-cell lymphoma (LBCL) who are not intended for hematopoietic stem-cell transplantation (HSCT), according to a phase 2 trial published in the Lancet Oncology.

“Patients with relapsed or refractory [LBCL] after first-line treatment who are not intended for [HSCT] have poor outcomes and limited treatment options,” wrote Alison Sehgal, MD, University of Pittsburgh Medical Center Hillman Cancer Center, PA, and colleagues. “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 [LBCL] not intended for HSCT.”

The open-label, phase 2 PILOT trial was conducted across 18 clinical sites in the United States. Patients were aged 18 years or older, had confirmed relapsed/refractory LBCL and PET-positive disease, had received first-line therapy containing an anthracycline and a CD20-targeted agent, and were not intended for HSCT by their physician. Patients received lymphodepleting chemotherapy (intravenous fludarabine 30 mg/m² and intravenous cyclophosphamide 300 mg/m² daily for 3 days) followed 2 to 7 days later by 2 sequential lisocabtagene maraleucel infusions (equal target doses of CD8⁺ and CD4⁺ CAR⁺ T cells for a total target dose of 100 × 10⁶ CAR⁺ T cells).

The primary end point in this trial was overall response rate (ORR) evaluated in all patients who received lisocabtagene maraleucel and those who had confirmed PET-positive disease before lisocabtagene maraleucel administration. ORR was determined by independent review committee according to the Lugano 2014 criteria. Safety was assessed in all patients who received lisocabtagene maraleucel, and patient follow-up is ongoing.

Between July 26, 2018, and Sept 24, 2021, which was the data cutoff for the trial’s primary analysis, 74 patients underwent leukapheresis and 61 received lisocabtagene maraleucel (efficacy and safety sets), and the median age was 74 years (interquartile range of 70 to 78). Overall, 16 (26%) of the 61 patients had an Eastern Cooperative Oncology Group performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 (25%) relapsed after 12 months of first-line therapy.

The median on-study follow-up was 12.3 months (interquartile rage [IQR[, 6.1 to 18). A total of 49 (80%; 95% confidence interval, 68 to 89]; P <0.0001) patients had an overall response.

The most common grade 3 or worse treatment-emergent adverse events were neutropenia in 29 (48%) patients, leukopenia in 13 (21%), and thrombocytopenia in 12 (20%). Lisocabtagene maraleucel-related serious treatment-emergent adverse events were reported in 13 (21%) patients. There were no treatment-related deaths. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in 3) patients.

“These results support lisocabtagene maraleucel as a potential second-line treatment in patients with [LBCL] for whom HSCT is not intended,” Sehgal and co-authors concluded.

Source:

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(8):1066-1077. doi:10.1016/S1470-2045(22)00339-4