ASH: Zanubrutinib Demonstrates Long-Term Efficacy in Patients With Waldenström Macroglobulinemia

In an interview with Pharmacy Times® at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, Shirley D'Sa, MD, professor of hematology at University College Hospital in London, United Kingdom, highlights the sustained efficacy and tolerability of zanubrutinib (Brukinsa; BeiGene) in the long-term extension of the ASPEN trial. The data, being presented on Sunday, December 8 at ASH, showcases the durable response and favorable safety profile of zanubrutinib in patients with Waldenström macroglobulinemia (WM), even in patients with MYD88 mutation. D'Sa explains how pharmacists can counsel patients on the treatment benefits of zanubrutinib for a shorter-duration.

Pharmacy Times: Could you elaborate on the clinical significance of these findings for both patients with Waldenström macroglobulinemia (WM) and the health care providers that treat them?

Shirley D’Sa: Bruton tyrosine kinase inhibitors (BTKis) have become a standard of care for Waldenström macroglobulinemia (WM). The ASPEN study compared head-to-head ibrutinib versus zanubrutinib, and the study showed that the results of using zanubrutinib were trending to superiority, but more importantly, the tolerability of the drug was good and maintained even through to the long-term extension study, and that is spanning quite a few years. That is very reassuring, because this is a long-term, continuous therapy in its current form. I think that is important, both for health care providers who counsel patients about having these treatments, as well as good news for patients themselves.

Pharmacy Times: How has the long-term use of zanubrutinib impacted the quality of life of patients with WM? Can you discuss any specific patient-reported outcomes that have been assessed in the ASPEN study?

D’Sa: The results of ASPEN, which showed that the tolerability of zanubrutinib was superior to that of ibrutinib, has continued to show effects in the long-term extension study. That does markedly impact on the quality of life for patients. We must bear in mind that these medications are taken continuously, without interruption, unless there is a specific need for interruption. Effectiveness of a drug is, of course, very important, but when you take it continuously, that is also of crucial importance for patients, because that is what determines how long they can have a good dose of the treatment. That, in turn, impacts on how effective the treatment is in that particular patient. The quality of life questionnaires used were the EORTCQLQC30, and the EQ5D5L, and in both cases, there was great improvement in quality of life using these measures in the zanubrutinib arm versus the ibrutinib arm. This continued and remained stable with zanubrutinib through to the long-term extension study, and these findings were statistically significant.

Pharmacy Times: The ASPEN study included patients with both MYD88-mutated and MYD88-wild type WM. Can you discuss the efficacy and safety of zanubrutinib in these specific patient subgroups?

D’Sa: Many patients with WM do have MYD88 mutation, but those that do not, and they were tested in the cohort 2, and all received zanubrutinib, are a concern in the treatment of these patients, because traditionally, ibrutinib has been found to be less effective in that cohort. The good news was that we did see that there were good response rates in cohort 2, which is the wild type MYD88 patients. This persisted in the long-term extension study, so durable responses are possible and seem to continue over a long period of time. This really bodes well and is promising for both MYD88-mutated and unmutated patients.

Pharmacy Times: Are there unique advantages of zanubrutinib that have been observed in the ASPEN study compared with alternative treatments? Could these be leveraged to better patient care?

D’Sa: The advantages of zanubrutinib, I think, come from 2 sources. One is that there appears to be an inherent improvement in effectiveness and efficacy. But if we think about what makes a drug effective in a disease, it is a combination of that inherent effectiveness, but also what sort of dose you can get into the patient. That is the other strength of Zanubrutinib; it is a well-tolerated drug, and therefore dose reductions are less likely to happen. The other main factor of importance with zanubrutinib is in the wild type group. This is a high-risk group, and it is very reassuring to see that zanubrutinib can achieve responses in this group. There were also improvements seen compared to ibrutinib in those with CXCR4 mutations and P53 mutations, although in ASPEN, the methods used were earlier in their development, whereas in the long-term extension study, methodologies improved. Overall numbers of those 2 subgroups were relatively small. These are promising findings, but further study is needed to confirm them.

Pharmacy Times: What should pharmacists and treatment providers educate themselves on regarding these results to counsel patients with Waldenström macroglobulinemia (WM)?

D’Sa: Pharmacists and health care providers, when talking to patients about zanubrutinib, clearly need to explain that in the current use in WM, it is a long-term continuous therapy. However, studies have shown, particularly ASPEN and the long-term extension study, that over a long period of time, a good proportion of patients tolerate this drug well. People need not be inherently concerned that they will be taking a drug for a long time. Some of the adverse events of special interest, particularly atrial fibrillation and diarrhea, have been better based on ASPEN and the long-term extension study. These are aspects that can be mentioned to patients when counseling them. Clearly, there's no absence of side effects, but when there is promise for fewer side effects, even over a long period of follow up, I think this is a very promising thing to tell patients.