Lead Researcher Highlights Latest Acalabrutinib MCL Data

Michael Wang, MD

Responses, progression-free and overall survival (OS) with single-agent acalabrutinib (Calquence) remained consistent during long-term follow-up, confirming efficacy in patients with relapsed/refractory mantle cell lymphoma (MCL), according to data presented at the 2018 ASH Annual Meeting.

“Acalabrutinib has been used as a standard-of-care regimen since the FDA approval,” said lead study author Michael Wang, MD. “Longer follow-up data in terms of efficacy and tolerability, specifically with these molecular minimal residual disease responses, are critical. This will make the drug even more popular.”

In the study, 124 patients with MCL received oral acalabrutinib at 100 mg twice daily. The median age of patients was 68 years, and most were male (80%). The median time since diagnosis was 46.3 months and 93% of patients had an ECOG performance status of 0 or 1. The median number of prior treatments was 2 (range, 1-5), which included stem cell transplant for 18% of patients.

The initial data, which showed a complete response (CR) rate of 40% and a partial response rate of 41%, led to the FDA’s October 2017 approval of acalabrutinib as a treatment for adult patients with MCL following at least 1 prior line of therapy.

At a median follow-up of 26.3 months, the investigator-assessed overall response rate (ORR) with acalabrutinib was 81% and proved consistent across subgroups based on tumor bulk. The median duration of response to the BTK inhibitor was 26 months, and the median progression-free survival was 20.0 months. Median OS was not yet reached, but the estimated 2-year OS rate was 72% (95% CI, 64%-80%).

The most frequent adverse events (AEs) were primarily grade 1/2 and included headache (38%), diarrhea (36%), fatigue (28%), cough (22%) and myalgia (21%). Grade 3/4 AEs (≥5%) included anemia (10%), neutropenia (10%) and pneumonia (6%). There were 13 patients (10%) with 16 cardiac events, including 4 grade 3/4 AEs (3%) in 1 patient each (acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, and coronary artery disease).

The second-generation BTK inhibitor has not been compared head-to-head with first-generation inhibitor ibrutinib (Imbruvica).

OncLive: Please provide an overview of this study.

What were the long-term data?

In an interview with OncLive during the 2018 ASH Annual Meeting, Wang, a professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center, discussed the promise of single-agent acalabrutinib in the treatment of patients with relapsed/refractory MCL.Wang: At this meeting, I presented data pertaining to the use of single-agent acalabrutinib in patients with relapsed/refractory MCL. This was the pivotal trial [that led to] the FDA approval, and the initial data were published in Lancet Oncology. At the time of the initial reporting, follow-up was only 15 months. At this meeting, we presented a longer follow-up of over 26 months.I would like to say the results were very good. The efficacy actually improved with the CR improving to 43%; the ORR remained the same. Long-term toxicity data were even more favorable because all categories of AEs, such as bleeding and rash, decreased over time. Acalabrutinib is a very well-tolerated agent, especially in the longer-term.

What are the next steps for acalabrutinib?

Is there anything you would like to add?

In addition to the efficacy and toxicity data, we presented brand-new data on minimal residual disease (MRD). Out of 29 patients, many achieved a CR in terms of MRD. This further demonstrated that single-agent acalabrutinib, with a very favorable toxicity profile, is very effective; it can also drive a CR into a molecular CR, based on MRD.The next steps [is the ECHO study, which] we are accruing very rapidly on; this is a massive international clinical trial with over 100 centers. We are [evaluating the use of] bendamustine and rituximab (Rituxan) plus acalabrutinib versus placebo. It is an ongoing phase III clinical trial in previously untreated elderly patients. This is a frontline trial that we hope will change the way that patients with MCL are treated worldwide.As an academic hematologic oncologist [who has been working in the space] for over 2 decades, I have witnessed the therapy for hematologic malignancies expand from just toxic chemotherapy to targeted therapy. We are now rapidly getting into the peak of cellular immunotherapy. We are seeing a lot of data on chimeric antigen receptor T cells, which is very exciting. By the 2019 ASH Annual Meeting, we will see a much greater precision medicine approach. MRD is becoming a more important endpoint in trials, which is also exciting. We need to prepare for the genomic medicine era.

Wang M, Rule S, Zinzani PL, et al. Long-term follow-up of acalabrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma. In: Proceedings from the 2018 ASH Annual Meeting; December 1-4, 2018; San Diego, California. Abstract 2876. ash.confex.com/ash/2018/webprogram/Paper110327.html.