At the 2022 ASCO Annual Meeting, the primary analysis of the phase 2 PILOT study showed the durability and feasibility of lisocabtagene maraleucel as second-line therapy in certain patients with large B-cell lymphoma.
Second-line therapy with lisocabtagene maraleucel (liso-cel) led to durable responses in patients with relapsed or refractory large B-cell lymphoma who were not intended to undergo hematopoietic stem cell transplantation (HCST), according to a primary analysis of the phase 2 PILOT study (NCT03483103).1
The primary end point of the study was overall response rate (ORR) in the efficacy analysis set of all 61 patients treated with liso-cel, and 80% of patients achieved an objective response (95% CI, 68.2%-89.4%, P < .0001). Among 27 patients with a hematopoietic cell transplantation specific comorbidity index (HCT-CI) score of 3 or more, the ORR was 81% (95% CI, 61.9%-93.7%), and patients with an HCT-CI score less than 3 had an ORR of 79% (95% CI, 62.1%-91.3%).
These data from the open-label, multicenter, phase 2 PILOT study looked at 61 patients with relapsed/refractory large B-cell lymphoma treated with liso-cel as a second-line treatment. The primary analysis of these data showing liso-cel’s durability was presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting by Alison Sehgal, MD, from the University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, Pennsylvania.
The complete response (CR) rate observed in the overall population was 54% (95% CI, 40.8%-66.9%), which was achieved after a median follow-up of 12.3 months (range, 1.2-26.5). Researchers also determined that the CRs were durable with a median duration of response (DOR) of 21.7 months (95% CI, 12.1-not reached [NR]).
Moreover, median progression-free survival (PFS) in the entire efficacy analysis group was 9 months (95% CI, 4.2-NR) after a median follow-up of 13 months (range, 12-18.1), while median OS was NR (95% CI, 17.3-NR) after a median follow-up of 17.6 months (range, 12.4-18.6).
Median PFS was not reached in the group of patients with an HCT-CI score of 3 or greater but was 7.4 months (95% CI, 2.9-13) in the patient group with an HCT-CI score lower than 3. This was also observed when measuring event-free survival (EFS) with patients with a score lower then 3 having a longer EFS at 7.4 months (95% CI, 2.9-13) versus 7.2 months (95% CI, 3-NR) in those with a score of 3 or higher. Median OS was NR in both groups.
The researchers noted that there were no significant differences among the efficacy or safety outcomes depending on the patients’ HCT-CI score. However, slight differences were seen among the numerous subgroups of patients observed in the study, but none that altered the overall results.
When analyzing CR rates by subgroup, investigators found that 56.3% of patients 70 years of age of older achieved a CR (95% CI, 41.2%-70.5%) compared with 46.2% (95% CI, 19.2%-74.9%) of patients younger than 70. Moreover, 80% (95% CI, 51.9%-95.7%) of patients who had a disease relapse greater than 12 months after treatment achieved a CR with second-line liso-cel. In comparison, 45.7% (95% CI, 30.9-61%) of patients who were refectory or relapsed at 12 months or less had a CR, and ultimately 67.9% (95% CI, 47.6%-84.1%) of all patients with relapsed large B-cell lymphoma had a CR on liso-cel versus 42.4% (25.5%-60.8%) of refractory patients.
Liso-cel is an autologous CD19-directed, defined composition, 4-1BB chimeric antigen receptor (CAR) T-cell treatment that is administered at equal target doses of CD8 and CD4 CAR T cells.
The objective of the PILOT study was to evaluate the efficacy and safety of liso-cel in patients with relapsed or refractory large B-cell lymphoma not intended for HSCT after 1 prior line of therapy, as there is no effective established standard-of-care treatment for this patient population in the second line of treatment. Patients eligible for the trial had to have 1 prior line of treatment that included anthracycline and a CD20-targeted agent, an ECOG performance score of 2, and adequate organ function. Moreover, eligible patients had to have diffusing capacity of the lungs for carbon monoxide at 60% or less, left ventricular ejection fraction less than 50%, a creatine clearance less than 60 mL/min (calculated using Cockcroft-Gault), and/or alanine aminotransferase or aspartate aminotransferase greater than double the upper limit of normal as reasons for not undergoing HSCT.
At the start of the trial, 74 patients underwent leukapheresis but 12 did not receive CAR T cells, 5 patients died, 4 no longer met the trial eligibility criteria, 1 had rapid clinical progression and was admitted to hospice, 1 had PET-negative after bridging therapy, and 1 was taken off due to investigator decision. Sixty-two patients received lymphodepleting chemotherapy and CAR T cells, but 1 received a non-conforming product leading to 61 patients being given liso-cel as part of the safety and efficacy analysis sets. Liso-cel was given at 100 x 106 CAR-T cell for 2 to 7 days after fludarabine/cyclophosphamide lymphodepletion at 30 mg/m2 and 300 mg/m2, respectively.
The median age range of the 61 patients observed was 74 years of age (range, 53-84) with 61% (n = 37) of patients identifying as male. Eighty-nine percent of patients were White (54) with 2 Asian patients, 1 Black patient, and 4 patients who did not identify their race. Histology of the patients showed that most had diffuse large B-cell lymphoma (DLBCL) not otherwise specified followed by patients with high-grade B-cell lymphoma with a DLBCL histology (33 vs 18 patients, respectively). Moreover, 43% of patients had a germinal center B-cell (GCB) cell of origin if they had DLBCL and 30% had activated B-cell–like DLBCL.
When looking at the safety profile of liso-cel in this study, researchers saw it was consistent with previous reports and no new or increased safety profiles were reported. The most common grade 3 or greater treatment-emergent adverse events (AEs) were neutropenia (48%), leukopenia (21%), thrombocytopenia (20%), and anemia (11%). Grade 3 or greater infections were reported in 4 patients, with 2 having grade 5 COVID-19–related treatment-emergent AEs.
Cytokine release syndrome (CRS) or neurotoxicity incidence was low with no grade 4 or 5 events and was managed with tocilizumab and/or corticosteroids in 26% and 13%, respectively. Overall, 23 patients had CRS of any grade with 11 patients having grade 1 CRS and 11 having grade 2 CRS. Nineteen patients had neurotoxicity of any grade, with 11 patients experiencing grade 1 neurotoxicity, 5 having grade 2 neurotoxicity, and 3 patients had grade 3 neurotoxicity.
The median time to resolution for patients experiencing neurotoxicity was 6 days (range, 1-89) compared with a median onset of 4 days (range, 1-12) for patients that experienced CRS and a median of 4 days (range, 1-12) to resolution.
A total of 20 patients were monitored as outpatients compared with 41 monitored as inpatients with 50 patients of the 61 patients observed admitted 72 hours or less after infusion on or before day 4 of the study. In the outpatient group less than half were hospitalized and only 1 patient was admitted to the ICU.
Sehgal A, Hoda D, Riedell P, et al. Lisocabtagene maraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study. J Clin Oncol. 2022;40(suppl 16):7062. doi:10.1200/JCO.2022.40.16_suppl.7062