Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma.

=This pilot study (NCT03168438) assessed the safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy targeting NY-ESO-1/LAGE-1a positive myeloma cells, alone or in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma (RRMM). Eligible patients expressed NY-ESO-1 and/or LAGE-1a and were positive for either HLA-A*02:01, *02:05, or *02:06. Patients received lete-cel single infusion alone (Arm 1) or with pembrolizumab (200 mg IV 3 weeks post lete-cel and every 3 weeks; Arm 2). The primary endpoint was safety/tolerability. One hundred and twenty-seven patients were screened, and 6 patients (3 per arm) were enrolled. Three patients received lete-cel alone or with pembrolizumab. All patients exhibited grade 3/4 cytopenias, which resolved or improved to grade 1. One patient (Arm 1) had grade 3/4 lete-cel-related adverse events (AEs); 2 patients (Arm 2) had grade 3/4 AEs related to lete-cel and lymphodepletion. Three patients with grade 1/2 cytokine release syndrome (CRS) exhibited elevated post lete-cel IL-6 levels compared with those without CRS. Pooled overall response rate was 50% (95% CI: 11.8-88.2%) including 1 patient each with confirmed CR, VGPR and PR and progression-free survival ranged from 1.3-5.2 months. Responders (Arm 1: n = 1; Arm 2: n = 2) had a time to response of 3 weeks, duration of response of 2.1 months. Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM.