Dr Kahl on the Potential for Frontline BTK Inhibitors in Mantle Cell Lymphoma

Brad S. Kahl, MD, a professor in the Department of Medicine, Oncology Division, at Washington University School of Medicine in St. Louis, discusses the potential for BTK inhibitors to shift the frontline treatment setting in mantle cell lymphoma (MCL).

The covalent BTK inhibitors zanubrutinib (Brukinsa) and acalabrutinib (Calquence) are currently approved by the FDA for the treatment of patients with MCL who have received at least 1 prior line of therapy. Ibrutinib (Imbruvica) was previously approved in the same setting; however, this indication was voluntarily withdrawn in the United States in April 2023. Although BTK inhibitors have become a staple in the treatment of patients with relapsed/refractory MCL, emerging data could help shift these agents to the frontline setting, according to Kahl.

Data from the phase 3 TRIANGLE trial (NCT02858258) could help facilitate this shift, Kahl says. Findings presented at the 2022 ASH Annual Meeting showed that the addition of ibrutinib to induction chemotherapy with autologous stem cell transplant (ASCT) or without transplant plus subsequent ibrutinib maintenance improved outcomes compared with chemotherapy followed by ASCT and observation in patients with MCL. Although mature data for the study have yet to read out, the National Comprehensive Cancer Network (NCCN) guidelines list the ibrutinib-based regimen as a preferred option in the frontline setting for younger patients with MCL, according to Kahl. He notes that insurance approval is needed to utilize this regimen since regulatory approval is still awaited.

Kahl also adds that there is not a compendium listing in the NCCN guidelines for the use of this regimen in older patients with MCL, noting that the best strategy for these patients is to save the use of a BTK inhibitor for the second line.

In the coming years, Kahl expects BTK inhibitors to make the official shift to the frontline setting, with trials such as TRIANGLE and the phase 3 MANGROVE study (NCT04002297) potentially supporting the change. Pirtobrutinib (Jaypirca), which was approved by the FDA in January 2023 for the treatment of adult patients with relapsed/refractory MCL following at least 2 lines of systemic therapy, including a BTK inhibitor, could then potentially become an option in the second-line setting if covalent BTK inhibitors become a standard in the frontline, Kahl concludes.