Combination Vemurafenib, Obinutuzumab Yields High Rate of Complete Remission In Untreated Hairy Cell Leukemia

By Jeff Craven, MD /alert Contributor
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Patients with hairy cell leukemia (HCL) had a complete response rate of 100% and 96% had undetectable minimal residual disease (MRD) at median 16.7 months of follow-up after receiving vemurafenib and obinutuzumab combination therapy, according to recent research from the 63rd ASH Annual Meeting and Exposition.

The combination of vemurafenib and obinutuzumab “is a promising chemotherapy-free targeted therapeutic approach for HCL,” Jae H. Park, MD, of the Leukemia Service, Department of Medicine at Memorial Sloan Kettering Cancer Center in New York, and colleagues wrote in their study abstract.

In a phase 2 trial, investigators from Memorial Sloan Kettering Cancer Center enrolled 30 patients (median 54 years old; 90% male) with treatment-naïve HCL with an absolute neutrophil count < 1,000/μl, hemoglobin < 10.0g/dL, or a platelet count of < 100,000/μl between March 2018 and February 2021. After a lead-in cycle of vemurafenib (960 mg twice per day for 28 days) patients received between 2 months and 4 months of treatment with intravenous obinutuzumab (1,000mg days 1, 8, and 15 on month 2, day 1 on months 3-4) and vemurafenib. The investigators measured with bone marrow biopsy and performed CT scans at 4 months. Complete response (CR) was the primary outcome, with secondary outcomes of safety, undetectable MRD, and BRAF allele burden. At baseline, 16 of 28 patients who received a CT scan had splenomegaly, and 3 patients discontinued treatment during the study due to verrucous hyperplasia, pneumonia, and rash.

Overall, 27 patients completed treatment and were available for analysis. At 4 months, CR was 96%, with 1 patient (4%) demonstrating a partial response; CR was achieved by all patients at 10 months without further treatment, the investigators said.

Park and colleagues evaluated MRD in 26 of 27 patients who achieved CR, and found undetectable MRD in 96% of patients. Prior to receiving obinutuzumab, treatment with vemurafenib alone at 1 month led to recovery of absolute neutrophil count to > 1,000/μl in 74% of patients, hemoglobin to > 10.0g/dL in 93% of patients, and a platelet count to 100,000/μl in 89% of patients. CD4 counts at 5 months through 8 months and at 12 months were > 200 cells/μl.

When receiving vemurafenib, patients experienced rash (61%), arthralgia (46%), fatigue (29%), alopecia (25%), and pruritis (21%). Grade 1 fever was experienced by 14% of patients overall. Regarding infusion reactions, there were 2 patients who experienced grade 2 reactions during the first infusion but completed their intended doses without further reactions, 5 patients who experienced a dose reduction for vemurafenib, and 12 patients who had their dose of vemurafenib interrupted because of a rash, arthralgia, or other adverse event. 

“While we have not observed any relapse to date, a longer follow-up is needed to assess durability of remission compared to purine nucleoside-treated cohorts,” the researchers concluded.