Addition of Relatlimab to Nivolumab in B-Cell Malignancy: Efficacy Significantly Varies by Disease Subset

The RELATIVITY-022 multicenter, open-label, phase 1/2a study was an evaluation of the anti–LAG-3 antibody relatlimab in management of relapsed or refractory B-cell malignancies. This study included an assessment of combination of relatlimab with the anti–PD-1 monoclonal antibody nivolumab in this setting, findings of which were published in Blood Advances.

“Nivolumab plus relatlimab demonstrated evidence of antitumor activity only in a subset of immune checkpoint-naive patients with HL [Hodgkin lymphoma], but it remains unclear whether the addition of LAG-3 inhibition enhances activity over PD-1 inhibitor alone,” wrote study first author Ajay K. Gopal, MD, of Fred Hutchinson Cancer Center, Seattle, Washington, and colleagues.

RELATIVITY-022 enrolled adult patients with B-cell malignancies that were refractory to at least one prior standard intervention. The relatlimab plus nivolumab arm of the study only included patients with HL or diffuse large B-cell lymphoma (DLBCL), who received this combination as relatlimab 160 mg and nivolumab 240 mg every 2 weeks.

The specific subset of patients in whom the relatlimab plus nivolumab combination showed encouraging antitumor activity consisted of 21 patients with relapsed or refractory HL naive to treatment with a PD-1 or PD-L1 inhibitor. They had an objective response rate (ORR) of 62%, complete response (CR) rate of 19%, partial response (PR) rate of 43%, median progression-free survival (PFS) of 19 months, and median duration of objective response (DOR) of 14 months.

In comparison, the combination’s efficacy was found to be diminished in the subset of 20 patients with HL that had progressed or relapsed despite treatment with a PD-1 or PD-L1 inhibitor; these patients had an ORR of 15%, CR rate of 0%, PR rate of 15%, median PFS of 6 months, and median DOR of 6.4 months. The combination’s efficacy was further reduced in the subset of 15 patients with DLBCL; these patients had an ORR of 7%, CR rate of 0%, PR rate of 7%, and median PFS of 2 months.

“Although the results do not provide robust support for a clinical benefit from the addition of relatlimab to PD-1 blockade, the study’s limitations (such as a small sample size, lack of a comparator group, and nonrandomized design) make comparing efficacy challenging,” Dr. Gopal and colleagues cautioned.

The investigators found the combination to be safe, tolerable, and manageable overall. No unexpected safety signals occurred and there were no patient deaths associated with the study treatment.