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Alexey Danilov, MD, PhD, discussed how chemotherapy-free regimens have influenced treatment decision-making for patients with mantle cell lymphoma.
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“Chemotherapy-free regimens have begun to shift the treatment paradigm in patients with MCL.”
Alexey Danilov, MD, PhD, the Marianne and Gerhard Pinkus Professor of Early Clinical Therapeutics, medical director of the Early Phase Therapeutics Program for the Systems Clinical Trials Office, co-director of the Toni Stephenson Lymphoma Center, and a professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, discussed how the emergence of chemotherapy-free regimens have influenced treatment decision-making for patients with mantle cell lymphoma (MCL).
Notably, Danilov provided insights to OncLive® following the publication of a manuscript detailing treatment developments and unmet needs across the MCL, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia treatment paradigms.
The emergence of chemotherapy-free regimens has begun to alter the therapeutic landscape for patients with MCL, Danilov began. Historically, chemoimmunotherapy has constituted the mainstay of initial treatment, frequently followed by consolidation with autologous stem cell transplantation (ASCT) in eligible patients, he explained. However, recent data from studies like the phase 3 TRIANGLE trial (NCT02858258), as well as other cooperative group and early-phase studies, has introduced regimens that exclude traditional chemotherapy, demonstrating promising efficacy and raising questions about the continued necessity of ASCT in frontline management, he stated.
Currently, comparative data between chemotherapy-free regimens and conventional chemoimmunotherapy remain limited, Danilov reported. For example, the phase 3 ENRICH trial (ISRCTN11038174) showed potential advantages of ibrutinib (Brukinsa)–based regimens over standard chemoimmunotherapy. However, it is important to note that the comparator in this trial included rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), which is no longer widely regarded as the standard of care in frontline MCL, he said. When ibrutinib-based therapy was compared with bendamustine plus rituximab—now a more commonly used regimen in clinical practice—the observed differences in efficacy were less pronounced, he noted.
Ongoing and upcoming studies are investigating chemotherapy-free approaches in patients with previously untreated MCL, including both randomized phase 3 trials and smaller phase 2 studies, according to Danilov. Despite the continued widespread use of chemoimmunotherapy in clinical settings, there is a growing adoption of BTK inhibitor–based regimens, especially in patients with high-risk MCL subtypes, such as those harboring TP53 mutations, who tend to respond poorly to conventional chemotherapy, he emphasized.
Pirtobrutinib (Jaypirca), a noncovalent BTK inhibitor, is now included in the National Comprehensive Cancer Network guidelines for select patients with MCL, reflecting its increasing integration into clinical practice, Danilov explained. Nevertheless, BTK inhibitors alone do not provide a definitive treatment solution for patients with biologically aggressive MCL, he said. This highlights the need for innovative therapeutic strategies, such as the incorporation of immunotherapeutic agents like bispecific antibodies, in the frontline setting to optimize treatment outcomes in this challenging disease, he concluded.
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