Revolutionizing Treatment for Patients With Relapsed/Refractory or Untreated MCL

Christopher Melani, MD, assistant research physician, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, discusses the unmet needs remaining in the mantle cell lymphoma (MCL) space.

Findings from phase 1 portion of the ViPOR study (NCT03223610) were presented during the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition. ViPOR is a novel combination targeted therapy regimen consisting of venetoclax (Venclexta), ibrutinib (Imbruvica), prednisone, and lenalidomide (Revlimid).

While findings of the phase 1b/2 ViPOR study appeared safe for use in patients with MCL and has demonstrated preliminary activity, most therapies have not been able to cure patients with MCL, leaving the field with a major unmet need.

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0:08 | MCL is still in general not curable with most therapies. We know that with high-dose chemotherapy we can get 3 or 4 years of remission. When you incorporate induction chemotherapy with autologous stem cell transplant, we're still able to get maybe out to 5 years or 6 years of remission. But again, there's still a continuous rate of relapse even after these intensive therapies.

0:40 | We know that patients who relapse and then go on BTK inhibitor and progress, the median progression-free survival is about 2.5 years, but I think 1 of the current unmet needs is these BTK patients who progress on BTK because again, retrospective studies have shown the median survival is very poor in patients who progress after BTK so what the most appropriate therapy is for those patients. In the ViPOR study, 44% of our patients were BTK had relapsed or refractory to BTK inhibitors. The fact that we're seeing CR rates, even in these patients who were exposed to prior BTK is pretty exciting.

1:32 | I think the BTK failures are certainly some areas in which we have to work on novel therapies. P53-mutated or deleted, patients often have very poor prognosis with standard chemotherapy, and then the blastoid mantle cell patients as well tend to have very aggressive disease and patients don't often respond well to chemotherapy. Whether some of this resistance of blastoid and p53-mutated mantle cells can be overcome from some of these newer novel combination therapy regimens, is still to be determined. We are assessing, we are sequencing our tumors and looking for those mutations to see if I may have overcome some of these negative prognostic markers.