Dr Phillips on the Treatment Landscape for Patients With MCL

Tycel Phillips, MD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses the treatment landscape for patients with mantle cell lymphoma (MCL), highlighting key discussions from the 2024 OncLive® Bridging the Gaps in Hematologic Malignancies meeting.

Phillips begins by saying that his talk centered on non-chemotherapy induction regimens for patients with MCL, which essentially refers to induction regimens devoid of cytotoxic agents. During the presentation, recent and historical trials that evaluated chemotherapy options for patients with MCL were explored, he states. The discussion commenced with the phase 2 WINDOW-1 trial (NCT02427620), which represented an initial investigation into non-cytotoxic chemotherapy induction regimens, he elucidates. This trial examined the efficacy of ibrutinib (Imbruvica) and rituximab (Rituxan) administered for 12 cycles, followed by consolidation therapy with rituximab plus hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone, allowing patients to receive up to 8 cycles of chemotherapy depending on their initial treatment response to ibrutinib plus rituximab, he reports.

Subsequently, the phase 2 WINDOW-2 trial (NCT03710772) emerged as a completely non-cytotoxic chemotherapy regimen, incorporating ibrutinib, venetoclax (Venclexta), and rituximab, he expands. Additional trials explored combinations such as obinatuzumab (Gazya) with ibrutinib or venetoclax. Notably, the phase 2 BOVen trial (NCT03824483), for which findings were presented at the 2023 ASH Annual Meeting, investigated zanubrutinib (Brukinsa), obinatuzumab, and venetoclax in patients with P53-mutated MCL, he notes. Moreover, the Cornell group presented a study on acalabrutinib (Calquence), lenalidomide (Revlimid), and rituximab at ASH.

However, it's crucial to note that many of these trials have been relatively small, involving single institutions or enrolling a limited number of patients, typically ranging from 20 to 90 individuals, Phillips continues. Consequently, the MCL space is lacking large, randomized trials commonly conducted in Europe, where the standard of care is compared with experimental arms, he reports. Thus, in the United States, there remains a need for further evaluation to determine the placement of these novel non-cytotoxic regimens, he notes. Nonetheless, progress is being made, and it is anticipated that these advancements may eventually render autologous stem cell transplantation obsolete in the management of MCL, possibly within the next year or so, as treatment approaches continue to be refined, he concludes.