Expert Emphasizes Importance of Acalabrutinib Approval in MCL

Michael Wang, MD,

The treatment of patients with mantle cell lymphoma (MCL) has undergone immense progress in the past year, says Michael Wang, MD. One of the biggest developments was the recent FDA approval of acalabrutinib (Calquence) for patients with relapsed disease.

The single-arm phase II ACE-LY-004 study of acalabrutinib was the basis for the approval of the oral BTK inhibitor, as it demonstrated compelling efficacy and a tolerable safety profile. At the time of analysis, the median duration of response had not been reached.

Wang, who is the lead ACE-LY-004 study author, reported that 72% of patients were still responding at 12 months (95% CI, 62%-80%), and the progression-free survival (PFS) at 12 months was 67% (95% CI, 58%-75%). Additionally, the overall survival (OS) rate was 87% (95% CI, 79%-92%), and both the median PFS and OS had not been reached at the time of the analysis.

At a median follow-up of 15.2 months, 56% of the 124 enrolled patients remained on the study. The investigator-assessed overall response rate was 81%, with 40% of patients achieving a complete response (CR).

“Chemo-free therapy is replacing chemotherapy—not only with better efficacy, but with a better toxicity profile,” said Wang.

OncLive: Could you discuss the Lymphoma Moonshot Program?

In an interview with OncLive during the ASH 2017 Annual Meeting, Wang, professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discussed the impact of acalabrutinib on patients with MCL, ongoing progress in the field, and The University of Texas MD Anderson Cancer Center’s Lymphoma Moonshot Program.Wang: B-cell lymphoma is a very common disease affecting many Americans. In the United States, about 0.7 million people live with lymphoma, and B-cell lymphoma accounts for the majority of lymphoma, and it has many subtypes. I am the co-leader of the Lymphoma Moonshot Program at The University of Texas MD Anderson Cancer Center, and the mission of this program is to double the cure rate of B-cell lymphoma from 30% to 60% within 5 to 10 years. We are already 3 years into this program and we are making tremendous progress. The subtypes of B-cell lymphoma include large cell lymphoma, follicular lymphoma, marginal zone lymphoma, and MCL.

Let’s take the MCL program, for example. MCL is a rare disease in the community, but a lot of progress has been made. For example, at the 2017 ASH Annual Meeting, I had the honor to present an international clinical trial with 40 hospitals across 10 countries from 3 continents. A total of 124 patients were treated with acalabrutinib and, based on this clinical trial, the FDA approved acalabrutinib in MCL.

This means a lot to our patients. Imagine, in the past, being able to achieve this kind of efficacy. We have to give the patient chemotherapy, 5 drugs all together in the hospital, hair is gone, [they have] nausea, vomiting, low blood count, infections, transfusions. But now in this era of biological therapy, acalabrutinib is just a pill. The patient can take it at home, they don't need to come into the hospital, they do not need a central line catheter, and their lymphoma goes away 81% of the time.

Can you provide some insight on acalabrutinib?

What are the next steps with this agent?

The era of biological therapy is here, and chemo-free therapy is replacing chemotherapy. I am so excited, and this means so much to our patents—their quality of life, their survival, and their hope. Our generation is the luckiest generation in history, as we have more technology and knowledge—but we also have a duty to properly utilize this technology and these scientific advances to get the best benefit for our patients. My "American dream" is to contribute to the cure of MCL.Acalabrutinib is a small-molecule drug that is taken orally twice a day, the side effects are minor, and it does not affect daily life much. The side effects include minor headaches, minor bruising, minor diarrhea, and fatigue, but the efficacy is powerful. There is an 81% response rate by Lugano Criteria, a 40% CR rate, and 94% of patients on this clinical trial had a dramatic reduction of their lymphoma masses. Do not underestimate chemo-free therapy—it is powerful. Combination therapy is almost always better than single-agent therapy. We would like to explore combinations with acalabrutinib in clinical trials so that we can get even better efficacy and survival.

In your mission to cure MCL, what are some challenges ahead?

What should community oncologists know about acalabrutinib now that it is commercially available?

There is an international phase III study of rituximab (Rituxan) plus or minus acalabrutinib versus placebo. Many more combinations will come in time. We must advance the science to understand the disease even better, and develop great medicines, such as ibrutinib (Imbruvica), acalabrutinib, bortezomib (Velcade), and lenalidomide (Revlimid). After a while, however, the patient will, inevitably, develop resistance. Therefore, our number 1 enemy is resistance and the only way to overcome it is through science and technology. For community oncologists and hematologists, remember the name acalabrutinib, and know it is FDA-approved for relapsed MCL—that is all they need to know.

Wang M, Rule S, Zinzani PL, et al. Efficacy and safety of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma in the phase 2 ACE-LY-004 study. In: Proceedings from the 59th ASH Annual Meeting and Exposition; December 9-12, 2017; Atlanta, Georgia. Abstract 155.