Calquence, Brukinsa Outperform Imbruvica in CLL/SLL Treatment

Both Calquence (acalabrutinib) and Brukinsa (zanubrutinib) outperformed Imbruvica (ibrutinib) for the frontline treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to research presented at the 2024 European Hematology Association (EHA) Annual Congress.

One outcome the researchers measured was time patients lived before stopping therapy or death (time to discontinuation or death; TTD). At a median follow-up of 20.5 months (range 0.4 to 46) in the Imbruvica group, the median TTD was 13.7 months. At a median follow-up of 14.2 months (range, 0.1 to 46) in the Calquence group, the median TTD was 19.2 months. Finally, the Brukinsa group had a median follow-up of six months (range, 1.1 to 26.6), and the median TTD was 19.3 months.

The median times to next treatment or death (TTNT) were 30.2 months in the Imbruvica arm, 35.8 months in the Calquence arm and not reached in the Brukinsa arm. Researchers could not calculate an average TTNT in the Brukinsa group because not enough patients experienced death or a new treatment to calculate an average time to one of those events. In the overall population (2,815 patients), the median TTD and TTNT were 16.2 months and 32.3 months respectively.

“This study demonstrated better real-world safety and [efficacy] outcomes for [Calquence] and [Brukinsa] versus [Imbruvica] [in patients with CLL/SLL],” Dr. Jing-Zhou Hou, a clinical hematological oncologist at the UPMC Hillman Cancer Center in Pittsburgh, and coauthors wrote in a poster presentation of the findings. “The proportions of patients continuing treatment and the median TTNT was longer for patients who received [Brukinsa]. Additional research is needed to explain and validate observed differences favoring [Brukinsa] over [Calquence].”

To conduct their study, investigators collected data across 55 practices and over 1,600 providers in the community oncology setting. The analysis included adult patients with CLL/SLL who initiated treatment with a BTK inhibitor from Jan. 1, 2020, to Jul. 31, 2023, with follow-up through Oct. 31, 2023. Eligible patients had at least five CLL/SLL visits or more CLL/SLL visits than non-CLL/SLL visits, and all patients had at least two evaluation and management visits.

The study outcomes were cardiovascular (heart-related) side effects, TTNT and TTD.

At the start of the trial, patient characteristics were well balanced between the Imbruvica, Calquence and Brukinsa groups; the median age was 71 years (range, 35 to 90), 72 years (range, 36 to 90) and 72 years (range, 33 to 90), respectively. Most patients in each group were male (63.6 versus 63.0% versus 60.6%), White (60.6% versus 63.4% versus 62.6%), and had an ECOG performances status of 1 or less, indicating that they could perform all their daily tasks independently (62.0% versus 61.3% versus 66.0%). Prior heart-related health conditions were reported in 16.6%, 15.7% and 10.3% of patients, respectively.

Heart Complications from BTK Inhibitors

Additional findings from the analysis demonstrated that patients in the Imbruvica (1,134 patients), Calquence (903 patients) and Brukinsa (176 patients) arms with at least three months of follow-up experienced cardiovascular side effects in the first line setting at rates of 8.7%, 5.9% and 7.4%, respectively. Among patients in the Imbruvica (972 patients), Calquence (753 patients) and Brukinsa (96 patients) groups with at least six months of follow-up, significantly more patients who received Imbruvica experienced cardiovascular side effects. These rates were 12.1%, 7.6% and 7.3%, respectively. Patients who received Imbruvica (790 patients), Calquence (573 patients) and Brukinsa (47 patients) with at least nine months of follow-up experienced a cardiovascular side effect at rates of 14.6%, 9.4% and 8.5%, respectively.

Calquence, Brukinsa and Imbruvica are all a type of drug called Bruton tyrosine kinase (BTK) inhibitors. While they have proven to be effective in treating CLL/SLL, they are associated with heart complications, such as atrial fibrillation (rapid, irregular heartbeat) ventricular arrhythmias (abnormal heartbeats originating in the lower chambers of the heart), heart failure and high blood pressure, according to the American Society of Hematology.

MORE: CLL: Supportive Care and Managing Adverse Effects With BTK Inhibitor

Probability of Switching Treatment

The researchers noted that “the median TTD in [the] first-line was shorter for [Imbruvica] than [Calquence] or [Brukinsa]. The associated probability of continuing treatment and not having new treatment were higher with [Brukinsa] versus [Imbruvica] or [Calquence] at month six.”

The probability of continuing the same treatment at different time points for each of the therapies was as follows:

• Six months: 64.8% for Imbruvica; 64.8% for Calquence; and 81.6% for Brukinsa
• 12 months: 53.3%; 57.7%; and 64.1%, respectively
• 18 months: 46.2%; 51.2%; and 51%, respectively
• 24 months: 40.9%; 46.9%; and 42.5%, respectively
• 30 months: 36.5% and 43.9% for Imbruvica and Calquence, respectively
• 36 months: 32% and 37%, respectively
• 42 months: 29.8% and 37%, respectively

A total of 55.8%, 45.5% and 22.2% of patients in the Imbruvica, Calquence and Brukinsa groups discontinued treatment or died, the researchers found.

Among patients who received frontline Imbruvica, 12.7% discontinued therapy and switched to a second-generation BTK inhibitor.

The probability of not receiving another treatment at certain time points was:

• At six months: 75.4% for Imbruvica; 71.3% for Calquence; and 85.3% for Brukinsa
• At 12 months: 67.3%; 66.3%; and 75%
• At 18 months: 60.5%; 60.3%; and 63.3%
• At 24 months: 54.9%; 56.1%; and 57%
• At 30 months: 50%; 53.9%, for Imbruvica and Calquence, respectively
• At 36 months:45.8%; 49.2%, respectively
• At 42 months: 39.9%; 49.2%, respectively

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