Dr Michael Wang Outlines Progress With Chemo-Free Therapies to Treat MCL

To avoid the toxicities associated with use of chemotherapy, there has been progress in developing and utilizing chemotherapy-free therapies to treat mantle cell lymphoma, said Michael Wang, MD, professor in the Department of Lymphoma and Myeloma at MD Anderson.

Transcript

What were your findings of using ibrutinib as a frontline treatment in patients with MCL, and how might they change treatment decision making for these patients?

A perfect example of the toxicities of chemotherapy is the Hyper-CVAD [cyclophosphamide, vincristine, doxorubicin and dexamethasone] chemotherapy. Hyper-CVAD has been used for young patients newly diagnosed with mantle cell lymphoma. Hyper-CVAD, you have to be in the hospital for 7 days and every month for 8 cycles, therefore 8 months, and [approximately] 20% of patients after 15 years will develop another cancer. So, in order to cut down this therapy you cannot say, “Hey, Dr Wang, today I have ibrutinib and I don’t need hyper-CVAD,” that’s not science. Science and clinical medicine you cannot go from one extreme to the other extreme, you have to have a stepwise, gradual fashion.

So, WINDOW-1 clinical trial was designed, and it will be presented in a poster, we used ibrutinib chemo-free window—why’s it called a window, because before strictly heading to chemotherapy, we use rituximab-ibrutinib in the window period and we find out, after we get a complete remission, then we can use the chemotherapy with only 50% of the original dosage. The WINDOW-1 [clinical trial] utilized the chemo-free therapy upfront with ibrutinib and rituximab, in this case, the response rate is nearly 100%. The CR [complete remission] rate is between 92% to 94%, and you can see it in my poster and in my abstract. And my God, this is very powerful. And then, after patients are already in CR, we given them 4 cycles of chemo consolidation.

This is, so far, is very successful. I have presented these data many times. We think we made progress to cut down the chemotherapy by incorporating, in a rational way, the chemo-free therapy. And of course, you never want to stop—the WINDOW-2 trial, in addition to ibrutinib and rituximab, we added another chemo-free agent, called venetoclax, which is targeting BCL-2—very powerful. And with this we try to drive the overall response rate to 100%. And then, if the patient is low risk, there will be no chemotherapy needed. High-risk…blastoid, big tumors, and complex karyotype, 4 cycles. Low-risk none, intermediate[-risk] only 2 cycles. You can see from WINDOW-1 to WINDOW-2, gradually we are reducing chemo and try to further improve efficacy and decrease mortality from the toxicities. So, it’s a very exciting time for chemo-free therapy.