Vemurafenib and obinutuzumab as frontline therapy for hairy cell leukemia Journal Article
| Authors: | Park, J. H.; Devlin, S.; Durham, B. H.; Winer, E. S.; Huntington, S.; von Keudell, G.; Vemuri, S.; Shukla, M.; Falco, V.; Cuello, B.; Gore, S.; Stone, R.; Abdel-Wahab, O.; Tallman, M. S. |
| Article Title: | Vemurafenib and obinutuzumab as frontline therapy for hairy cell leukemia |
| Abstract: | Background: Hairy cell leukemia (HCL) is characterized by the underlying genetic lesion of BRAFV600E and responsiveness to BRAF inhibitors. We assessed the safety and activity of the BRAF inhibitor vemurafenib combined with obinutuzumab in patients with previously untreated HCL. Methods: We conducted a single-arm, multicenter clinical study of vemurafenib plus obinutuzumab. Vemurafenib 960 mg twice daily was administered for four cycles, and obinutuzumab was administered in cycles 2 to 4. The primary end point was complete remission (CR). Secondary end points included assessment of safety, minimal residual disease (MRD), and BRAF allele burden according to digital droplet polymerase chain reaction (ddPCR). Results: Thirty patients were enrolled in the study, and 27 patients completed all four cycles of treatments and achieved CR (90%; 95% confidence interval [CI], 73 to 98). Three patients discontinued the study early because of adverse events and were not evaluable for response. Of the 27 patients who achieved CR, 26 patients (96%; 95% CI, 81 to 99) achieved MRD negativity. BRAFV600E allele was undetectable by ddPCR in all 21 evaluable patients. At a median follow-up of 34.9 months (95% CI, 29.6 to 36.9), no patient experienced disease relapse. The most common vemurafenib-related adverse events were rash and arthralgia. Febrile neutropenia occurred in two patients, and blood or platelet transfusions were required in two patients. Conclusions: Combined time-limited vemurafenib and obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. In this small study, acquired vemurafenib resistance or dose-limiting toxicity was not observed. Patients were not observed long enough to reveal secondary malignancies. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03410875.) |
| Keywords: | drug efficacy; prospective studies; polymerase chain reaction; alleles; confidence intervals; blood transfusion; clinical trials; descriptive statistics; antineoplastic agents, combined -- therapeutic use; antineoplastic agents, combined -- adverse effects; antibodies, monoclonal -- administration and dosage; antibodies, monoclonal -- adverse effects; antineoplastic agents, combined -- administration and dosage; antibodies, monoclonal -- therapeutic use; cancer patients; platelet transfusion; arthralgia -- chemically induced; human; protein kinase inhibitors -- administration and dosage; protein kinase inhibitors -- adverse effects; leukemia -- drug therapy; protein kinase inhibitors -- therapeutic use; exanthema -- chemically induced; febrile neutropenia -- chemically induced |
| Journal Title: | NEJM Evidence |
| Volume: | 2 |
| Issue: | 10 |
| ISSN: | 2766-5526 |
| Publisher: | Massachusetts Medical Society |
| Date Published: | 2023-10-01 |
| Language: | English |
| DOI: | 10.1056/EVIDoa2300074 |
| PROVIDER: | EBSCOhost |
| PROVIDER: | cinahl |
| PMCID: | PMC11110928 |
| PUBMED: | 38320179 |
| DOI/URL: | |
| Notes: | Accession Number: 172747589 -- Entry Date: 20231010 -- Revision Date: 20231010 -- Publication Type: Journal Article; clinical trial; research. -- Source: Cinahl |
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