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.

Related Videos
Daniel G. Stover, MD, suggests that stromal tumor infiltrating lymphocytes may serve as a biomarker of immune activation and can potentially help optimize therapy with microtubule-targeting agents for patients with metastatic breast cancer.
Sara M. Tolaney, MD, MPH, discusses how, compared with antibody-drug conjugates, chemotherapy produces low response rates and disease control in the treatment of those with hormone receptor–positive, HER2-negative metastatic breast cancer.
Hope Rugo, MD, speaks to the importance of identifying patients with aromatase inhibitor–resistant, hormone receptor–positive, HER2-negative advanced breast cancer who are undergoing treatment with capivasertib/fulvestrant who may be at a high risk of developing diabetes or hyperglycemia.
Sara M. Tolaney, MD, MPH, describes the benefit of sacituzumab govitecan for patients with HER2-low metastatic breast cancer seen in the final overall survival analysis of the phase 3 TROPiCS-02 study.
An expert from Vanderbilt University Medical Center says that patients with relapsed/refractory multiple myeloma may be able to live a normal life following response to salvage treatment with bispecific monoclonal antibodies.
A recovery tracker and other digital tools may be useful in helping to manage patient symptoms following debulking surgery for gynecologic cancer, according to an expert from Memorial Sloan Kettering Cancer Center.
Common symptoms following debulking surgery for gynecologic cancer appear to include pain, diarrhea, and nausea, according to an expert from Memorial Sloan Kettering Cancer Center.
Patients who use a recovery tracker tool appear to experience lower hospital readmission rates following gynecologic cancer debulking surgery compared with those who did not.
Medical oncologists and gynecologic oncologists alike have a shared responsibility to help treat symptoms of neuropathy in patients undergoing chemotherapy for gynecologic cancer, according to an expert from Duke University Medical Center.
Future research assessing cryocompression for those with gynecologic cancers will make use of different products to make the intervention easier and more accessible for patients.