Treatment with Calquence resulted in fewer toxicities, including atrial fibrillation, flutter and hypertension, in patients with previously treated chronic lymphocytic leukemia, compared with Imbruvica treatment, according to findings from the analysis of a phase 3 trial.
The use of Calquence (acalabrutinib) was associated with fewer cardiovascular-related toxicities as well as a lower overall toxicity burden among patients with chronic lymphocytic leukemia (CLL), compared with Imbruvica (ibrutinib), according to recent findings.
The study authors conducted an analysis of data from the phase 3 ELEVATE-RR trial which had previously shown that treatment with the Bruton’s tyrosine kinase (BTK) inhibitor Calquence resulted in progression-free survival outcomes that were noninferior to those that occurred with Imbruvica — another BTK inhibitor — in patients with previously treated CLL.
This analysis, the results of which were presented at the recent 2021 American Society of Hematology (ASH) Annual Meeting, was conducted to further assess the occurrence of BTK inhibitor-associated side effects as well as the toxicity profiles of Calquence and Imbruvica.
Measuring progression-free survival (or the time during and after treatment when the patient lives without disease progression) was the main goal of the trial. Other goals included observing the incidence of atrial fibrillation (AFib)/flutter of any severity, as well as serious or severe infections and overall survival.
“Event-based analyses demonstrated a higher BTK inhibitor–related toxicity burden with ibrutinib in this head-to-head trial,” John F. Seymour, from the Peter MacCallum Centre and the Royal Melbourne Hospital in Melbourne, Australia, said in his presentation. “Exposure-adjusted assessments of AFib/flutter, hypertension, and bleeding events demonstrated a lower cardiovascular-related toxicity burden with acalabrutinib compared to ibrutinib. Cumulative incidences of hypertension and AFib/flutter were also lower with acalabrutinib in patients without a prior history of these events.”
After a median follow-up of 41 months, investigators assessed events of clinical interest in 268 patients receiving Calquence and 265 patients receiving Imbruvica. Of these events, the occurrence of AFib/flutter, hypertension and bleeding of any severity were statistically higher with Imbruvica. Exposure-adjusted incidence and exposure-adjusted time with these events were about 1.5 to 4.1 times higher with Imbruvica.
Other common BTK–related side effects noted for being significantly higher with Imbruvica in this analysis were any-severity diarrhea (46% vs 35%), joint pain (23% vs 16%), back pain (13% vs 8%), muscle spasms (13% vs 6%), and shortness of breath (12% vs 4%). Incidence of any-severity contusion and urinary tract infection (UTI) were also higher in those who received Imbruvica. Besides UTI, exposure-adjusted incidence and exposure-adjusted time with events were about 1.4 to 13.1 times higher with Imbruvica.
The only side effects with statistically higher incidence with Calquence were any-severity headache and cough, which occurred at rates of 35% and 29%, respectively, versus 20% and 21% with Imbruvica.
Investigators observed a longer median time to onset of any-severity AFib/flutter with Calquence versus Imbruvica, at 28.8 months and 16 months, respectively. Hypertension of any severity had a similar median time to onset for both therapies. Concomitant medication use for AFib/flutter or hypertension for all patients was less common in those administered Calquence.
The cumulative incidence of AFib/flutter and hypertension of any severity were consistently lower with Calquence up to 36 months, according to Seymour. Additionally, incidence of these two side effects was lower in patient subgroups regardless of the number of prior therapies, age, and having no prior history of AFib/flutter and hypertension. For patients with no prior history of AFib/flutter or hypertension, there was a lower cumulative incidence in patients receiving Calquence compared with Imbruvica.
There was, however, a similar time to onset for Calquence and Imbruvica in terms of inducing bleeding events of any severity. But incidence was lower for the Calquence group regardless of age and in patients with 1 to 3 prior lines of therapy. Few patients in either treatment group required dose modification due to bleeding events. Also, fewer patients given Calquence used concomitant medication for bleeding events than patients given Imbruvica. Moreover, the cumulative incidence of bleeding of any severity over 36 months was lower in those treated with Calquence.
At the data cutoff, 43% of patients on the ELEVATE-RR trial were still receiving treatment.
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