Dr Phillips on Unmet Needs in Patients With Relapsed/Refractory MCL

Tycel Phillips, MD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses unmet needs for patients with relapsed/refractory mantle cell lymphoma (MCL), highlighting the need for more effective treatment options for this patient population.

Phillips begins by stating that the patients who have high-risk MCL are the ones with the most unmet needs. Even trials such as the single-arm phase 2 WINDOW-1 (NCT02427620) and WINDOW-2 (NCT03710772) trials lack comprehensive data, Phillips explains. Notably, the WINDOW-1 trial evaluated ibrutinib (Imbruvica) plus rituximab (Rituxan) and hyper-CVAD consolidation therapy in newly diagnosed young patients with MCL, and the WINDOW-2 trial investigated ibrutinib plus rituximab followed by venetoclax (Venclexta) and hyper-CVAD consolidation therapy in the same newly diagnosed patient population.

The phase 2 BOVen trial (NCT03824483)—investigating zanubrutinib (Brukinsa), obinutuzumab (Gazyva), and venetoclax—focused specifically on high-risk patients with MCL, and a phase 2 trial (NCT03863184) assessed acalabrutinib (Calquence), lenalidomide (Revlimid), and rituximab in patients with untreated disease, Phillips continues. Furthermore, despite the introduction of novel regimens, high-risk patients seem to exhibit poor responses, he elucidates, adding that the BOVen trial is still ongoing, leaving uncertainties about its eventual outcome. Phillips shares that he is hopeful BOVen will yield positive results. However, many trials have shown worse outcomes with novel therapies in patients with TP53mutations compared with those without, he notes.

A similar trend in clinical outcomes is being observed in patients with blastoid and pleomorphic variants, Phillips expands. These patients generally do not fare as well as most patients with MCL, he states, noting that high-risk patients constitute approximately 20% to 25% of those undergoing initial therapy. However, high-risk patients represent the majority in the relapsed/refractory setting because they experience quicker relapses, necessitating rapid treatment changes, and are likely to succumb to their disease sooner than those with lower-risk disease, Phillips reports. Since the most effective and durable responses often occur during initial treatment for incurable cancers, failing to achieve responses to early lines of therapy sets patients on a challenging treatment course, he concludes.