Nivolumab following CAR-T failure in multiple myeloma and non-Hodgkin lymphoma: results of a phase 2 study
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: We conducted a single-center open-label phase 2 trial of the programmed cell death protein 1 (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 end point was overall response rate (ORR). Among 20 enrolled patients (11 with MM, 9 with NHL), the ORR was 15%, whereas it was 18% for MM (n = 2) and 11% for NHL (n = 1). The durations of response in the 2 responding patients with MM were 18.9 and 18.3 months; in NHL, the single response lasted 1.6 months. In the 17 nonresponders, progressive disease occurred at a median of 0.9 months (range, 0.2-1.8) following nivolumab initiation. Cytokine release syndrome did not occur. Three immune-related adverse events (all grade 1-2) occurred, including 2 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-Ts were detectable in 6 patients (30%) at nivolumab initiation, including in 1 responder. However, these CAR-Ts 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 end point, 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. This trial was registered at www.clinicaltrials.gov as #NCT04205409.
Authors: Rahul Banerjee, Sylvain Simon, Jenna M. Voutsinas, Qian Vicky Wu, Daria Gausman, Joshua Dizon, Ethan Xie, Cecilia C. S. Yeung, Minggang Lin, Ryan C. Lynch, Chaitra S. Ujjani, Brian G. Till, Mary L. Kwok, Sarah S. Lee, Rebecca Silbermann, Eva Medvedova, Peter Wilcox, Jorge Ramos, Mazyar Shadman, Jordan Gauthier, Cameron J. Turtle, Damian J. Green, Ajay K. Gopal, Stanley R. Riddell, Andrew J. Cowan
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,000
Funder: Bristol-Myers Squibb
OpenAlex ID: W4416410833