Acalabrutinib May Be A Safer Alternative to Ibrutinib in CLL

Lori A. Lesie, MD

The treatment landscape of chronic lymphocytic leukemia (CLL) was expanded with the FDA’s approval of acalabrutinib (Calquence), a BTK inhibitor, in November 2019. Ibrutinib (Imbruvica), another BTK inhibitor, has already been approved in this setting, and the FDA expanded the indication in April 2020 for the frontline treatment of all adult patients with CLL.

While ibrutinib is associated with promising outcomes in patients with CLL, the toxicity profile can be a challenge among patients. This provides a role in the treatment landscape for acalabrutinib in patients who are unable to tolerate ibrutinib as the agent has a different toxicity profile. However, data from clinical trials demonstrating these outcomes does not cover the real-world population that are treated in the community setting.

In a real-world analysis presented at the 2019 American Society of Hematology Annual Meeting, outcomes of real-world patients with CLL treated with acalabrutinib were reviewed to determine the benefit in a more realistic patient population. Overall, investigators noted that the discontinuation rate of acalabrutinib in patients who could not tolerate ibrutinib was low, which suggests the agent is a well-tolerated alternative to ibrutinib for patients who are likely to benefit from BTK inhibition but cannot tolerate the toxicities associated with ibrutinib.

In an interview with Targeted Oncology, Lori A. Leslie, MD, lymphoma attending, John Theurer Cancer Center, discussed the importance of analyzing treatment outcomes in real-world patients with CLL compared with only reviewing data from clinical trials that do not represent all patients seen in the community setting.

TARGETED ONCOLOGY: Could you discuss the rationale for the retrospective analysis of real-world patients with CLL treated with acalabrutinib?

Leslie: There has been an explosion of new agents entering our treatment options of CLL. Acalabrutinib is a BTK inhibitor that has recently been approved for use in the frontline as well as for relapsed/refractory CLL. The difference between the previously available BTK inhibitor ibrutinib is that it potentially has a different toxicity profile. The goal of doing this real-world outcome study was to look at patients treated in the real world rather than in a clinical trial, who received acalabrutinib. We found that the rate of discontinuation of acalabrutinib for those who did not tolerate ibrutinib was low, suggesting this is a well-tolerated alternative for patients who would benefit from BTK inhibition but cannot tolerate ibrutinib for whatever side effect.

I think the importance of real-world data is becoming more and more transparent as we have these agents rapidly entering our treatment landscape. Doing a specific study comparatively takes time to mature, especially in CLL, so by looking at large cohorts of patients treated, it helps us answer questions such as sequencing, AEs, and rates of infection. It also helps us determine which patients benefit from a certain sequence versus another and additionally, the cost of therapy, which is becoming more important as we use combination therapy, whether it is a targeted therapy as monotherapy or combination.

TARGETED ONCOLOGY: What are the differences in the patient populations of clinical trials versus real-world?

Leslie: Patients in the real-world are a little more variable than what we see in clinical trials. Patients on trials typically are fit and have fewer comorbidities compared to your average CLL patient. By the time patients are diagnosed, they are commonly in their 60s or 70s, and by then they have time to accumulate some comorbidities. The real-world data is helpful because that’s more of what the general oncologist sees in their day to day practice. It’s not the academic setting with a preferred patient who can travel several hours to be on clinical trials; it’s the person who pops across the street and needs a medication to take care of their CLL.

TARGETED ONCOLOGY: What would you say are the implications of these data?

Leslie: We have a large collaborative group of patients looking at outcomes of treatment with targeted agents in CLL. I think there are several registries available trying to answer these questions in real-time because figuring out how to sequence and combine all of these agents in patients depending on their clinical or molecular risk factors is very challenging to do and takes a lot of time. Making sure we are bringing the most effective and least toxic affordable treatment to patients is our biggest issue in CLL right now because thankfully we have a lot of choices to select from.