More than 50% of adults with refractory or relapsed large B-cell lymphoma (LBCL) who were not deemed candidates for high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) had complete responses (CRs) following treatment with lisocabtagene maraleucel (Breyanzi).
In the phase 2 PILOT clinical trial, the overall response rate (ORR) with lisocabtagene maraleucel was 80% and the rate of CR was 54%, with a median follow-up of 12.3 months, reported Alison Sehgal, MD, Assistant Professor, Medicine, University of Pittsburgh Medical Center, Hillman Cancer Center, PA, and colleagues, in a poster presentation at the 2022 American Society of Clinical Oncology Annual Meeting. The responses in patients who achieved a CR were durable, with a median duration of response of 21.7 months.
“These results support liso-cel [lisocabtagene maraleucel] as a second-line treatment in patients with LBCL in whom HSCT is not intended,” the investigators stated.
For patients who are unable to have high-dose therapy or HSCT, there is no effective established standard of care and outcomes are historically poor, the investigators noted in laying out the rationale for the study.
The open-label, multicenter PILOT study enrolled a broad patient population of adults with refractory or relapsed LBCL after first-line treatment who were not considered candidates for HSCT based on age ≥70 years, Eastern Cooperative Oncology Group performance status of 2 and/or organ function, and comorbidities such as depressed left ventricular ejection fraction, a creatinine clearance <60 mL/min, or elevated levels of liver enzymes, regardless of time to relapse following first-line treatment.
A total of 74 patients underwent leukapheresis, 61 of whom received lisocabtagene maraleucel and were included in the safety and efficacy analysis. In all, 32 patients (52%) received bridging therapy before lymphodepletion and lisocabtagene maraleucel infusion. A total of 28 patients have discontinued the study, 20 of whom died. Treatment is ongoing in 26 patients. Of the patients treated with lisocabtagene maraleucel, 20 (33%) met ≥2 of the 6 protocol-specified criteria for ineligibility for transplant. Of the 61 patients who received lisocabtagene maraleucel, 20 were monitored in the outpatient setting.
The median patient age was 74 years. The LBCL histology was diffuse LBCL in 54%, transformed follicular lymphoma (FL) in 15%, high-grade B-cell lymphoma with LBCL histology in 30%, and grade 3B FL in 2%. In all, 54% of the patients had refractory LBCL, 21% relapsed after ≤12 months, and 25% relapsed after >12 months. Patients could receive multiple regimens as first-line treatment. First-line treatment for LBCL was R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) in 84% of patients, R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) in 16%, R-ICE (rituximab plus ifosfamide [Ifex], carboplatin, and etoposide), R-CHP (rituximab plus cyclophosphamide, doxorubicin, and prednisone), and/or other treatment in 13%, and 11% of the patients received radiotherapy. The best response to first-line therapy for LBCL was a CR in 46% of the patients and a partial response in 25%.
The median duration of response in the overall population at a median follow-up of 15.5 months was 12.1 months. The median progression-free survival (PFS) was 9 months (95% confidence interval [CI], 4.2-not reached [NR]), and the median overall survival has not been reached (95% CI, 17.3-NR).
The screening Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received lisocabtagene maraleucel was 2 in 56% of patients and 3 in 44%. The ORR by the HCT-CI total score was 79% for patients with an HCT-CI of <3 and 81% in those with an HCT-CI of ≥3, with CR rates of 17% and 16%, respectively. The median duration of response in these 2 groups was 11.2 months and not reached, respectively, and the median PFS was 7.4 months and not reached, respectively.
The safety profile of lisocabtagene maraleucel was manageable, with no new safety signals and low rates of severe cytokine release syndrome (CRS) or neurologic events, and no grade 4 or 5 CRS or neurologic events reported. Any-grade CRS occurred in 38% of patients, with grade 3 CRS reported in 1 (2%) patient.
In a separate analysis of patient-reported outcomes (PROs), patients who received lisocabtagene maraleucel and were evaluable for the PRO analysis (N = 56) showed significant improvements in fatigue and pain. Improvements in overall lymphoma symptoms were clinically meaningful after treatment; in an individual patient-level analysis, 70% of patients reported meaningful improvements in quality of life.
FDA Approval Update
Lisocabtagene maraleucel was approved by the FDA for the treatment of relapsed or refractory LBCL after nonresponse to first-line therapy on June 24, 2022. This approval was granted with priority review and received regenerative medicine advanced therapy, breakthrough therapy, and orphan drug designations.