Real-World Analysis Explores Current Role of Acalabrutinib in MCL

Kellie Ryan, MPH

Kellie Ryan, MPH

Bruton’s tyrosine kinase (BTK) inhibitors are an important treatment option for patients with mantle cell lymphoma (MCL). These therapies include ibrutinib (Imbruvica), a first-in-class BTK inhibitor, and acalabrutinib (Calquence), which are both FDA approved for the treatment of MCL, among others that are under investigation.

Acalabrutinib has demonstrated promising responses and safety in patients with relapsed/refractory MCL. However, investigators recently sought to discover how physicians are using acalabrutinib in the real-world setting. Data from an analysis of the long-term follow-up of acalabrutinib in patients with both MCL and chronic lymphocytic leukemia (CLL) were presented at the 2019 American Society of Hematology (ASH) Meeting.

According to these findings, a third of patients with MCL received therapy with ibrutinib before being treated with acalabrutinib. In addition, 60% of patients in both the MCL and CLL cohorts were at highriskof atrial fibrillation. These data suggest to investigators how physicians are using this agent now, relative to their patients’ background and clinical characteristics, as well as demographics.

In an interview withTargeted Oncology, Kellie Ryan, MPH, director of Health Economics and Outcomes Research at AstraZeneca, discussed the data on how physicians are currently using acalabrutinib as treatment of patients with MCL in the real-world setting. She highlighted where she sees this research evolving in time.

TARGETED ONCOLOGY:What was the rationale for this analysis?

Ryan:For us, we wanted to understand how physicians were viewing our product and who they were deciding to use acalabrutinib in. It is interesting to see where they see the product fitting.

TARGETED ONCOLOGY:What did you find?

Ryan:Interestingly, we saw that a third of the MCL patients and two-thirds of the CLL patients had received prior ibrutinib treatment before receiving acalabrutinib. That was interesting to us. Additionally, of note, we found that 60% of the patients in both the CLL and the MCL cohorts were determined to be at high risk of atrial fibrillation. Again, this is interesting in terms of what physicians are thinking about relative to their background, clinical and demographic characteristics.

TARGETED ONCOLOGY:How do you plan to move forward with these findings?

Ryan:One of the things we looked at was just the duration of follow-up we have in these patients. We know this is of key interest in terms of the long-term real-world outcomes of the patients. We saw that only 40% of the patients had at least 6 months of follow-up. What we will be doing is continuing to check in in terms of the maturity of the data. We need to see about 12 months of follow-up before we look at outcomes, so for us, it will be just monitoring that length of follow-up to see if we can go ahead and look at both safety and efficacy outcomes.

TARGETED ONCOLOGY:Is there anything else that was particularly interesting that came out of this analysis?

Ryan:We are interested in having that more matured data with longer-term outcomes. Other things that were interesting to us were in terms of that comorbidity profile and understanding how that changes over time. What we have seen with other treatments is as physicians become more comfortable, their treatment patterns shift in terms of for whom they prescribe that. I think that will be interesting to see overtimehow that changes for our product.

TARGETED ONCOLOGY:As physicians gain more comfort with acalabrutinib, do you think we might see more use with this agent?

Ryan:It is hard to say. It is going to come down to the clinician to determine, based on the data, who they think are the right patients are for which drugs. I think there is a lot of data coming out right now with the BCL2 therapies and the BTK inhibitors, so we will have to wait to see what the data shows and where the clinicians think it is most appropriate to use each treatment.

TARGETED ONCOLOGY:With these novel agents, what is the advantage over using first-generation therapies?

Ryan:That is unclear right now. The real-world data will show us that; right now, we know we have a potentially more selective target, but in terms of what impact that has on patients, we have to wait and see data show us.

TARGETED ONCOLOGY:What do you think these data provide or add to the treatment landscape of MCL?

Ryan:What we see here internally is what other physicians are doing in terms of how they are using acalabrutinib. I think both our studies and other investigators are looking at for clinicians to see when they are thinking of who to use this product in and where it’s being used. The purpose is to give them that information on what other physicians are doing.

TARGETED ONCOLOGY:How does this impact physicians in the community setting?

Ryan: