Findings from the phase 2 PILOT study reveal lisocabtagene maraleucel to provide benefit as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation.
Lisocabtagene maraleucel (JCAR017) shows potential as a second-line treatment in patients with large B-cell lymphoma who are not intended for haematopoietic stem-cell transplantation (HSCT), according to results from the phase 2 PILOT study (NCT03483103) published in the Lancet Oncology.1
Findings revealed that 49 patients had an overall response (80% [95% CI, 68-89]; P<0·0001) and 33 (54%) patients had a best overall response of complete response (CR; 41-67). Additionally, 8 patients had initial partial response (PR) converted to a CR.
“In the PILOT study, lisocabtagene maraleucel led to clinically significant and durable responses in a patient population with historically poor prognosis and no curative treatment options. Lisocabtagene maraleucel infusion resulted in high overall response [80%] and complete response [54%] rates, with durable responses in patients who had a complete response,” wrote the study authors. “Responses were observed across all prespecified subgroups, including in patients with high-risk features. No apparent differences in lisocabtagene maraleucel expansion and persistence were observed between second-line and third-line or later large B-cell lymphoma.”
This open-label, multicenter phase 2 study aims to evaluate both the efficacy and safety of lisocabtagene maraleucel in adult patients who have relapsed from or are refractory to a single-line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma. Patients also must be ineligible for HSCT.
The study was done at 18 clinical sites across the United States with patients who were aged 18 years or older with relapsed or refractory large B-cell lymphoma and PET-positive disease. Eligibility was open to patients who had received first-line therapy containing an anthracycline and a CD20-targeted agent, were not intended for HSCT, and met at least 1 prespecified transplantation not intended criterion.
Further enrollment criteria included histological confirmation of diagnosis at last relapse, an ECOG performance status of 0, 1, or 2, adequate vascular access for leukapheresis procedure. Subjects must also have agreed to use appropriate contraception and to not donate blood, organs, semen, and egg cells for usage in other individuals for over a 1 year following lymphodepleting chemotherapy.
Those enrolled will be treated with lisocabtagene maraleucel at a dose of 100×106 CAR T cells and will be followed for 2 years. Patients received lymphodepleting chemotherapy which consisted of intravenous (IV) fludarabine 30 mg/m2 and IV cyclophosphamide 300 mg/m2 daily for 3 days. This was followed by 2–7 days by 2 sequential lisocabtagene maraleucel infusions. Infusions consisted of equal target doses of CD8+ and CD4+ CAR T cells for a total target dose of 100 × 106 CAR T cells.
Primary end points of the trial was overall response rate (ORR) with secondary end points consisting of adverse events, laboratory abnormalities, antitumor activity, progression-free survival (PFS), event-free survival (EFS), duration of response (DOR), overall survival (OS), health-related quality of life, and assessment of health economics outcome research.
Seventy-four patients were enrolled and underwent leukapheresis between July 26, 2018, and Sept 24, 2021, 12 of whom did not receive CAR T cells. An additional 61 patients received lisocabtagene maraleucel, 1 of which has received non-conforming product.
The median age of those enrolled was 74 years (range, 70-78), 24 (39%) patients were women vs 37 (61%) men, and 54 (89%) patients were White. Additionally, 16 (26%) of 61 patients had an ECOG performance status of 2, 33 (54%) had refractory disease, 13 (21%) relapsed within 1 year of first-line therapy, and 15 patients (25%) relapsed after 12 months of first-line therapy. There were 32 (52%) of 61 patients who received bridging therapy, including 1 patient who received only radiotherapy. Five patients received more than 1 cycle of bridging therapy, and 2 received 3 to 4 cycles because of a delay in product manufacturing.
Patients with diffuse large B-cell lymphoma not otherwise specified made up 54% of patients (n = 33), high-grade B-cell lymphoma with diffuse large B-cell lymphoma histology made up 30% (n = 18) transformed follicular lymphoma made up 15% (n = 9), and grade 3B follicular lymphoma made up the rest (2%; n =1).
Of the 12 patients who underwent leukapheresis but did not receive lisocabtagene maraleucel infusion, 4 had disease progression, 3 of whom died, and 1 was admitted to hospice.
The median time from leukapheresis to product release was 24.0 days (range, 22.0-28.0). The median time from leukapheresis to lisocabtagene maraleucel infusion was 35.5 days (33.0-42.0). There were 20 patients receiving lisocabtagene maraleucel as outpatients and the median on-study follow-up time was 12.3 months (range 6.1-18.0) and 49 patients had an overall response.
Overall response and CR rates were observed across all subgroups. The PFS in all patients was 9.03 months (95% CI, 4.17-not reached) at a median follow-up of 13.0 months (range, 9.5-18.1). Then at a median follow-up of 16.4 months (range, 12.0-18.3), the median EFS in all patients was 7.23 months (95% CI, 3.22-22.60). The median follow-up of 17.6 months (range, 11.2-20.4) showed that the median OS in all patients was not reached (95% CI, 17.28-not reached), and the median DOR, which was assessed in the 49 patients who had a CR or PR, was 12.09 months (95% CI, 6.24-not reached) at a median follow-up of 15.5 months (range, 8.6-17.4).
Of the 33 patients who had a complete response, the median PFS was 22.60 months (95% CI, 12.98–not reached) and median OSl was also not reached (95% CI, not reached–not reached). The median DOR for the 33 patients who had CR was 21.65 months (95% CI 12.09–not reached).
In regard to safety, there were no treatment-related deaths and the safety profile of lisocabtagene maraleucel was consistent with previous studies. The most common grade 3 or worse treatment-emergent adverse events (TEAEs) were neutropenia in 29 patients (48%), leukopenia in 13 (21%), and thrombocytopenia in 12 (20%). Serious TEAEs deemed to be related to lisocabtagene maraleucel were observed in 13 (21%) patients. Two patients died due to TEAEs, 1 due to COVID-19 on day 62 after lisocabtagene maraleucel infusion and and 1 patient died due to COVID-19 pneumonia on day 42 after lisocabtagene maraleucel infusion.
Cytokine release syndrome occurred in 23 patients (38%), including 1 patient who had grade 3. Nineteen patients had neurological events (31%) 3 of whose were grade 3. No grade 4 events or deaths were observed in the study.