Transcript: Michael Wang, MD: Recent approvals include 3 BTK [Bruton tyrosine kinase] inhibitors. The first BTK inhibitor, ibrutinib, was approved in November 2013. The second, acalabrutinib, was approved in October 2017, and most recently they have the FDA-approved third irreversible inhibitor, zanubrutinib.

With this, it is dramatically changing the landscape of a mantle cell lymphoma relapsed/refractory beyond the first cycle from chemotherapy to chemotherapy-free therapies. So, it’s a big change. While we are welcoming more changes in the future, the most recent one, zanubrutinib, indicates that we are probably using more chemotherapy-free therapies to treat a very difficult-to-treat lymphoma, relapsed mantle cell lymphoma.

The academic doctors will really learn about the new approvals first. Then the community doctors, who are very busy and are mainly focused on treating solid tumors and liquid tumors, which is very complicated in the community. Let’s say lymphoma has more than 60 to 90 subtypes. It’s very difficult for a community doctor to keep up with all the literature. I think there is a delayed response from the community, and also in the community some doctors would pay attention to new data a little more than the others, so there’s a heterogeneous population. Eventually everybody will learn how to use it from their own CME [continuing medical education] activities and different functions. What’s important is they will also learn from their interaction with the academic institutions.

For example, I work with community doctors all over the United States, and I frequently send the patients home with a treatment plan. The treatment plan often reflects the most recent CAR [chimeric antigen receptor] T-cell therapy for relapsed mantle cell lymphoma. And the doctors—I give them my cellphone, my email. They always contact me, and I will influence their practice for the next case…very effectively.

For young patients with newly diagnosed mantle cell lymphoma, we relied very heavily on chemotherapy in the past. The Nordic regimen is 6 cycles of induction chemotherapy followed by the highest chemotherapy you can give to a human being, the autologous stem cell transplantation. The Nordic regimen is chemotherapy heavy. But it induces the risk of survival rate in young patients with mantle cell lymphoma over 12 years. This is very significant. Similarly, the hyper—CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone] therapy is a very tough 6 to 8 cycles of intensive chemotherapy. It keeps the patient in the hospital for a week for each cycle, and the response—the overall survival with that trial on the hyper–CVAD—is 13.4 years.

We know that chemotherapy could save patients and put their survival beyond 10 years. Those patients are still in the community treated with chemotherapy. However, with an academic institution like The University of Texas MD Anderson Cancer Center, my colleagues and I have designed the WINDOW-1 trial, which takes advantage of a chemotherapy-free therapy, rituximab-ibrutinib, and caps the chemotherapy, hyper-CVAD, to 50%.

Then on the success of the WINDOW-1 trial, we are gradually using chemotherapies to replace chemotherapies, which we think are very toxic to the patients. With the WINDOW-2 trial, we’re using ibrutinib-rituximab-venetoclax to further reduce to no chemotherapy in the low-risk cohort—to take the high-risk cohort of 4 cycles and moderate it to 2 cycles. Systemically, we are progressively replacing chemotherapy with chemotherapy-free therapy. But until all the follow-up proves that these approaches are effective, a lot of patients are still being treated with chemotherapy.

Transcript Edited for Clarity