Key points
Nivolumab monotherapy following CAR-T therapy failure in multiple myeloma or non-Hodgkin lymphoma rarely leads to clinical responses
However, for a minority of patients with myeloma, nivolumab leads to remarkably durable responses likely driven by endogenous T cells
We conducted a single-center open-label phase 2 trial (clinicaltrials.gov ID: NCT04205409) of the PD-1 inhibitor nivolumab for patients with multiple myeloma (MM) or non-Hodgkin lymphoma (NHL) following failure of last-line chimeric antigen receptor T-cell (CAR-T) therapy. The primary endpoint was overall response rate (ORR). Among 20 enrolled patients (11 MM, 9 NHL), the ORR was 15%: 18% for MM (n = 2) and 11% for NHL (n = 1). The durations of responses in the two responding MM patients were 18.9 and 18.3 months; in NHL, the single response lasted 1.6 months. In the 17 non-responders, progressive disease occurred at a median of 0.9 months (range: 0.2-1.8 months) following nivolumab initiation. Cytokine release syndrome did not occur. Three immune-related adverse events (all Grade 1-2) occurred, including two in a responding patient with MM who developed Grade 2 thyroiditis and Grade 1 rash (8 and 12 months respectively) after nivolumab initiation. Circulating CAR T cells were detectable in 6 patients (30%) at nivolumab initiation, including in one responder. However, these CAR T cells demonstrated an exhausted phenotype and generally did not expand despite high PD-1 expression at baseline. Conversely, endogenous T-cell activation occurred in all patients regardless of clinical response. Although our study did not meet its primary endpoint, responses to nivolumab monotherapy following CAR-T failure appeared remarkably durable in a minority of patients with MM. These responses may have been driven by endogenous T-cell activation. Better understanding of why these responses occur may help improve immunotherapies for hematologic malignancies.
Author notes
These authors contributed equally.
Data sharing statement: Available from the corresponding author upon reasonable request.
