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Brentuximab vedotin, nivolumab combination appears active for Hodgkin lymphoma
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ATLANTA — A combination of brentuximab vedotin with nivolumab appeared tolerable and safe among patients with relapsed or refractory Hodgkin lymphoma, according to results from a phase 1/phase 2 clinical trial presented at the ASH Annual Meeting and Exposition.
An unmet clinical need remains for relapsed or refractory Hodgkin Lymphoma, despite medical advances.
Alex F. Herrera, MD, assistant professor in the department of hematology and hematopoietic cell transplantation at City of Hope, and colleagues evaluated whether brentuximab vedotin (Adcetris, Seattle Genetics) in combination with nivolumab (Opdivo, Bristol-Myers Squibb) induced durable responses among patients with Hodgkin lymphoma who relapsed or were refractory to frontline chemotherapy.
Researchers thought targeted killing of CD30-expressing Reed-Sternberg cells with brentuximab vedotin, in combination with restoration of immune response with nivolumab, would improve the complete response rate and durability of responses following autologous hematopoietic stem cell transplant.
Sixty-one patients (median age 36 years; 52% women) received 1.8 mg/kg brentuximab vedotin on day 1 and 3 mg/kg of nivolumab on day 8 in the first 21-day cycle. In cycles 2 to 4, patients received brentuximab vedotin and nivolumab on day 1.
Forty-five percent of patients had primary refractory disease and 31% relapsed within 1 year of frontline therapy. No patients had received prior salvage therapy, brentuximab vedotin or immuno-oncology therapy, or allogeneic or autologous stem cell transplant. Patients could undergo autologous HSCT after cycle 4 assessment.
Fifty-eight patients completed treatment and four discontinued treatment due to an adverse event (n = 1), investigator decision (n = 1) or patient decision (n = 2). Sixty patients had efficacy data available for evaluation.
Median follow-up was 5.7 months (range, 1-17) from first dose of brentuximab vedotin.
Researchers reported an objective response rate of 85%, including a 62% complete response rate. Five patients achieved stable disease and four progressed on treatment.
At the time of analysis, 39 patients initiated autologous HSCT, and researchers had collected a median 5.1 x 106 CD34-positive cells/kg (range, 3-60). Median follow-up postautologous HSCT was 3 months (range, 0-12).
Forty-one percent of patients experienced infusion-related reactions. Excluding these events, 84% of patients experienced potential immune-related adverse events, including five patients (8%) who received systemic steroids for grade 4 pneumonitis, grade 4 pneumonitis and colitis, grade 2 pneumonitis, grade 3 diarrhea and colitis, and grade 3 aspartate aminotransferase elevation.
Researchers used peripheral blood immunophenotyping, serum cytokine/chemokine analyses, T-cell receptor sequencing and intracellular cytokine staining to evaluate the combination regimen’s impact on the immune system.
After the first dose of brentuximab vedotin, researchers observed an elevation in proinflammatory cytokines and chemokines and concurrent reduction in serum thymus and activation-regulated chemokine levels, which were maintained after addition of and treatment with nivolumab.
Researchers also observed a reduction in T-cell regulators and other T-cell subsets after first dose of brentuximab vedotin and an elevation in T-cell subsets after combined treatment.
Various patients had effector memory CD8-positive T-cells with increased intracellular IL-2 and tumor necrosis factor alpha after interaction with control peptide pools MHC class 1 and 2 compared with baseline, which may have indicated high activation of the immune system following combination treatment.
The concept of trying to shy away from chemotherapy as salvage therapy is impressive, according to Andre Goy, MD, MS, director of John Theurer Cancer Center, and chief of the division of lymphoma at Hackensack Meridian Health in New Jersey.
“For decades, Hodgkin lymphoma has had the same treatment. We haven’t had anything really new,” Goy told HemOnc Today. “The idea [here] is to try and see if we can combine novel agents in the relapsed and refractory setting to maybe replace chemotherapy as salvage treatment. The results are impressive, despite a small cohort of patients.” – by Melinda Stevens
Reference:
Herrera AF, et al. Abstract 649. Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta.
Disclosures: Herrera reports consultant roles with Bristol-Myers Squibb, Genentech, Merck and Pharmacyclics; and research funding from Seattle Genetics. Goy reports consultant/advisory or board of directors roles with and honoraria or research funding from Acerta Pharma, Celgene, Genentech, Pharmacyclics/Johnson & Johnson, Seattle Genetics and Takeda. Please see the abstract for all other authors’ relevant financial disclosures.