Ibrutinib Improves Time to Next Therapy Vs Acalabrutinib in Real-world Analysis of Patients With CLL


The use of frontline ibrutinib was associated with a longer time to next treatment compared with acalabrutinib in patients with chronic lymphocytic leukemia.

The use of frontline ibrutinib (Imbruvica) was associated with a longer time to next treatment compared with acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL), according to findings from a real-world study presented at the ASH 2022 Annual Meeting.

In an evaluation of data from 1083 patients with CLL, a total of 7.5% of patients in the acalabrutinib arm (n = 373) initiated next or additional treatment, compared to 5.9% in the ibrutinib arm (n = 710), making those on acalabrutinib 89% more likely to start additional therapy, when adjusting for baseline characteristics (HR, 1.89; 95% CI, 1.12-3.13; P = 0.016). The researchers found similar results when censoring for anti-CD20 add-ons throughout any time of treatment (HR, 1.82; 95% CI, 1.08-3.03; P=0.025).

“We are unlikely to get a prospective comparison of ibrutinib and acalabrutinib in the frontline setting,” said study author Ryan Jacobs, MD, hematologist-oncologist at Atrium Health Levine Cancer Institute said in a presentation of the data. “With that in mind, we [utilized] our real-world data and leveraging it to look at what we would deem as a real-world marker of [progression-free survival], which is time to next treatment, and look and see if there were any differences between these two groups.”

The researchers analyzed data between November 21, 2018 (the day the Food and Drug Administration approved acalabrutinib for CLL) and April 30, 2022. If patients had a concomitant use of another antineoplastic agent within the first 28 days post-index, their data was excluded.

Most patient characteristics were balanced between the two arms; mean age was 71.5 and 72.4 years in the ibrutinib and acalabrutinib arms, respectively; 38.5% and 38.3% were female; mean baseline Quan-CCI score was 3.1 and 3.0 in the ibrutinib and acalabrutinib arms, respectively.

The ibrutinib arm had a higher percentage of patients with chronic pulmonary disease (13.6% vs 8.8%), peripheral vascular disease (7.8% vs 4.1%) and hypertension (41.4% vs 20.1%). Baseline corticosteroids use was lower in the ibrutinib arm (14.5%) than in the acalabrutinib arm (20.1%), as was antiplatelet use (7.0% vs 3.5%).

The average time to next treatment was 6.8 months in the ibrutinib cohort and 4.6 months in the acalabrutinib arm. Of note, in both groups, the most common next treatment was venetoclax (Venclexta).

Jacobs emphasized that time to next treatment could be a “meaningful measure” of disease.

“Unfortunately, prospective trials don't always report time to next treatment, but for indolent lymphomas like CLL and follicular lymphoma, for example, where we might have disease progression that doesn't meet clinical progression and doesn't actually immediately lead to initiation of therapy, time to next treatment could be considered a potentially even more meaningful clinical endpoint for the CLL patient. And we feel like it's a good metric to look at with our real-world data,” he said.

Further research in this space is warranted, Jacobs said, noting that he’d be interested in seeing longer follow-up and a larger sample size (especially looking at those treated with first line acalabrutinib) comparing these two BTK inhibitors.

“Of course, this data generates a lot of questions. We have questions too, [such as] what might have potentially lead to these differences that we observed,” he said.


  1. Jacobs R, Lu X, Emond B, et. al. Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-Line Treatment with Ibrutinib Versus Acalabrutinib. Blood. 2022;140(suppl 1):1931-1933. doi:10.1182/blood-2022-163387.
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