Nivolumab plus relatlimab for patients with relapsed or progressed B-cell malignancies in RELATIVITY-022.

Abstract: Despite high response rates, anti-programmed death 1 (anti-PD-1) monotherapy eventually fails in most patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and is ineffective in most other B-cell malignancies. The lymphocyte activation gene 3 (LAG-3) cell-surface receptor represents another immune checkpoint that can be targeted to induce remissions in these diseases; dual inhibition of PD-1 and LAG-3 is approved in advanced melanoma. We performed a multicenter phase 1/2a open-label study of the anti-LAG-3 antibody relatlimab (RELATIVITY-022) administered as monotherapy or in combination with nivolumab in patients with R/R B-cell malignancies. We treated 106 patients and no dose-limiting toxicities were observed during escalation. The recommended phase 2 dose was relatlimab 240 mg as monotherapy or nivolumab 240 mg plus relatlimab 160 mg, administered every 2 weeks. No unexpected safety signals were observed compared with anti-PD-1 monotherapy. In the HL expansion cohorts, objective response rate (ORR) was 62% and complete response rate (CRR) was 19% in anti-PD-1/anti-programmed death ligand 1 (anti-PD-[L]1)-naive patients (n = 21), with a median progression-free survival (PFS) of 19 months; ORR was 15% and CRR 0%, with median PFS of 6 months in anti-PD-(L)1-progressed patients (n = 20). In diffuse large B-cell lymphoma, ORR was 7% with no CRs (n = 15), and median PFS was 2 months. Nivolumab plus relatlimab appeared to be safe and tolerable. Responses in patients with anti-PD-(L)1-naive HL was encouraging, although the contribution of relatlimab to overall efficacy of the combination needs to be further evaluated. This trial was registered at www.ClinicalTrials.gov as #NCT02061761.