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Nivolumab regimen ‘highly active’ in relapsed/refractory primary mediastinal large B-cell lymphoma
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Nivolumab in combination with brentuximab vedotin appeared safe and induced high antitumor activity among patients with relapsed or refractory primary mediastinal B-cell lymphoma, according to results of the phase 2 CheckMate 436 trial published in Journal of Clinical Oncology.
“Primary mediastinal B-cell lymphoma (PMBL) is a rare but aggressive lymphoma of thymic B-cell origin, accounting for 2% to 4% of non-Hodgkin lymphomas and up to 10% of diffuse large B-cell lymphomas,” Pier Luigi Zinzani, MD, PhD, associate professor of hematology at Institute of Hematology Seràgnoli at University of Bologna in Italy, and colleagues wrote. “No standard of care for relapsed or refractory PMBL has been established; it is often treated similarly to other forms of DLBCL. New therapeutic strategies are urgently needed for patients with [this disease].”
Phase 1 of CheckMate 436 established 240 mg IV nivolumab (Opdivo, Bristol-Myers Squibb), an anti-programmed death-1 (PD-1) immune checkpoint inhibitor, and 1.8 mg/kg IV brentuximab vedotin (Adcetris, Seattle Genetics), an CD30-targeted antibody-drug conjugate, as the recommended dose for the phase 2 expansion cohorts.
In phase 2 of the open-label, multicenter trial, Zinzani and colleagues administered this dose to 30 patients with relapsed or refractory PMBL (median age, 35.5 years; range, 19-83; 57% women; 87% white) every 3 weeks until disease progression or unacceptable toxicity.
Investigator-assessed objective response rate served as the primary endpoint.
Median follow-up was 11.1 months.
Results showed an ORR of 73% (95% CI, 54-88), with a 38% complete remission rate per investigator assessment, and an ORR of 70% (95% CI, 51-85) with a 43% complete metabolic response rate per blinded independent central review. First objective response occurred at a median 1.3 months (range, 1.3-1.6) and complete response at a median 3.2 months (range, 2.5-5.6).
Eleven patients who responded subsequently underwent allogeneic (n = 6) or autologous (n = 5) hematopoietic stem cell transplantation.
Researchers observed a 6-month PFS rate of 63.5% (95% CI, 42.5-78.6) and a 6-month OS rate of 86.3% (95% CI, 67.5-94.6).
Median duration of response, median PFS and median OS had not been reached.
Most patients (n = 25) experienced treatment-related adverse events, with nine experiencing grade 3 or grade 4 neutropenia. Other adverse events included peripheral neuropathy, thrombocytopenia, rash, peripheral sensory neuropathy and hyperthyroidism.
“The efficacy results of nivolumab plus brentuximab vedotin combination therapy showed substantial clinical benefits in this population of patients with highly refractory disease,” Zinzani and colleagues wrote. “[This combination] may be synergistic and is highly active in patients with relapsed or refractory PMBL, serving as a potential bridge to other consolidative therapies of curative intent.” – by John DeRosier
Disclosures: Zinzani reports consultant/advisory or speakers’ bureau roles with Bristol-Myers Squibb, Celgene, Celltrion, EUSA Pharma, Gilead Sciences, Immune Design, Janssen-Cilag, Kyowa Hakko Kirin, Merck, Portola Pharmaceuticals, Roche, Sandoz, Servier and Verastem. Please see the study for all other authors’ relevant financial disclosures.
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