Faster Time to Next Therapy Observed with Acalabrutinib Vs Ibrutinib in CLL


The average time to next treatment among patients with chronic lymphocytic leukemia occurred faster in those treated with acalabrutinib vs ibrutinib.

Patients treated with frontline acalabrutinib (Calquence) were more likely to require treatment intensification or a change in therapies sooner vs patients treated with ibrutinib (Imbruvica) for chronic lymphocytic leukemia (CLL), according to real-world study findings presented during the 2022 American Society of Hematology (ASH) Annual Meeting.

“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 from 1,083 patients with CLL undergoing frontline treatment for their disease — 710 with ibrutinib and 373 with acalabrutinib — between Nov. 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%).

A total of 7.5% of patients in the acalabrutinib arm initiated next or additional treatment, compared to 5.9% in the ibrutinib arm, 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).

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.


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. Presented at the 2022 American Society of Hematology Annual Meeting; December 10-13; New Orleans, LA. Abstract 797.

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