"A BRAF New World": Vemurafenib in classic HCL
We held our inaugural HCLF Family Support roundtable in March as part of our new series of online community roundtables. One topic discussed is vemurafenib, a BRAF inhibitor that shows promise in treating classic HCL with the BRAF mutation.
While most people with classic HCL have the BRAF mutation, those with the HCL variant do not. So, vemurafenib and other BRAF inhibitors don't work in HCL variant.
In a paper on vemurafenib monotherapy published in late 2022, Dr. Jae Park and co-authors from multiple HCL Centers of Excellence concluded that vemurafenib is "a highly effective option, regardless of the dosage or duration of therapy, in patients with relapsed or refractory HCL. Vemurafenib retreatment can achieve high response rates, and acquired resistance is rare."
That said, the authors note that remission durations were shorter with each subsequent relapse, and a combination with anti-CD20 antibodies such as rituximab or obinutuzumab can shorten the duration of vemurafenib treatment and prolong remission durations.
Their findings can be found here. >>
During the roundtable, much discussion focused on whether vemurafenib could replace cladribine or pentostatin as frontline treatments. In a commentary accompanying the 2022 article from Dr. Park, Dr. Claire Dearden from the Royal Marsden Hospital wrote convincingly that non-chemotherapy options, such as vemurafenib, could become the preferred choice for patients with classic HCL. She noted that, especially in a post-COVID world, treatment that is not immunosuppressive is critically essential.
While trials are underway, Dr. Dearden stated that there are unanswered questions due to HCL's uniqueness. "More patients with HCL have received a BRAF inhibitor in the frontline setting," she wrote. "The big question is whether BRAF inhibitors can come close to delivering the exceptionally long remissions seen after frontline purine analogs (PA), an unlikely possibility, given the relatively short remission (12-18 months)."
This illuminating commentary titled "A BRAF New World for Hairy Cell Leukemia" can be read here. >>
Dr. Enrico Tiacci from the University of Perugia and his colleagues published a paper in 2021, looking at vemurafenib and rituximab. Assembling two multicenter studies with 54 refractory or relapsed HCL patients from Italy and the United States, Dr. Tiacci noted that 91% of the patients had an overall response and 35% had a complete response. Yet, hairy cells remained, leading to potential relapse. The addition of rituximab resulted in a "short and safe treatment that was capable of rapidly inducing a deep and durable complete response in the majority of patients with refractory or relapsed HCL. Compared with historical data on vemurafenib alone, adding rituximab to vemurafenib led to more than double the percentage of patients with a complete response."
Dr. Tiacci's study is linked here. >>
With the generous support of patients with HCL and their families, the HCLF is funding two clinical trials involving vemurafenib: one that will open at Memorial Sloan Kettering (MSK) later this year and another currently open in Italy. We have decades of data on cladribine, so we need more long-term data for vemurafenib and other BRAF inhibitors so that they are readily available as the first choice in treatment.
Clinical trials are critical to increase options for patients.
The next Family Support roundtable will be on May 16, and registration is now open on our website. We have other upcoming community roundtable meetings, including an HCLF Women's Group meeting in June. These meetings provide valuable insights and support for patients and caregivers navigating HCL.
We can't thank you enough for your continued participation and support! Your engagement is essential in driving progress in HCL research and patient care.