Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results Journal Article
| Authors: | Advani, R. H.; Moskowitz, A. J.; Bartlett, N. L.; Vose, J. M.; Ramchandren, R.; Feldman, T. A.; LaCasce, A. S.; Christian, B. A.; Ansell, S. M.; Moskowitz, C. H.; Brown, L.; Zhang, C.; Taft, D.; Ansari, S.; Sacchi, M.; Ho, L.; Herrera, A. F. |
| Article Title: | Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results |
| Abstract: | This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167. © 2021 American Society of Hematology |
| Keywords: | adult; controlled study; aged; human cell; major clinical study; overall survival; prednisone; fatigue; neutropenia; cancer recurrence; salvage therapy; doxorubicin; drug efficacy; drug safety; cancer radiotherapy; flow cytometry; outcome assessment; positron emission tomography; follow up; t lymphocyte; biological marker; metabolism; carboplatin; dacarbazine; progression free survival; multiple cycle treatment; pharmacodynamics; gene expression; etoposide; nausea; interleukin 10; interleukin 4; cyclophosphamide; immunoglobulin; steroid; autologous stem cell transplantation; antineoplastic activity; ifosfamide; procarbazine; vinblastine; pneumonia; aspartate aminotransferase; vincristine sulfate; t lymphocyte receptor beta chain; cancer regression; regulatory t lymphocyte; immune response; neutrophil; multicenter study; prophylaxis; cancer size; stem cell mobilization; bleomycin; cd4 lymphocyte count; phase 1 clinical trial; gamma interferon inducible protein 10; immunosuppressive treatment; t lymphocyte subpopulation; t lymphocyte activation; interleukin 22; antihistaminic agent; electrocorticography; classical hodgkin lymphoma; interleukin 18; thymus and activation regulated chemokine; tumor microenvironment; apheresis; organizing pneumonia; corticosteroid therapy; brentuximab vedotin; nivolumab; infusion related reaction; human; male; female; article; rna sequencing; pembrolizumab; macrophage derived chemokine; plasma exchange; x-ray computed tomography; tumor necrosis factor receptor superfamily member 8; cd8 lymphocyte count |
| Journal Title: | Blood |
| Volume: | 138 |
| Issue: | 6 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2021-08-12 |
| Start Page: | 427 |
| End Page: | 438 |
| Language: | English |
| DOI: | 10.1182/blood.2020009178 |
| PUBMED: | 33827139 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2021 -- Source: Scopus |
