Calquence (acalabrutinib) may be a safe and effective treatment option for patients with relapsed or refractory chronic lymphocytic leukemia, according to the updated phase 2 results of an ongoing study.
Given the milder side effects associated with its use, Calquence (acalabrutinib) could be a safe and effective treatment option for patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to the updated phase 2 results of an ongoing study.
While it has been transformative in the care of this patient population, Imbruvica (ibrutinib), another BTK inhibitor like Calquence, is also associated with adverse events (AEs) such as diarrhea, rash, atrial fibrillation, bleeding and more.
That’s why researchers set out to examine the use of Calquence in this trial, results of which were recently reported on in Blood, the journal of the American Society of Hematology. The latest report includes updated results on an expanded cohort of patients from the initial phase 2 study as well as long-term follow-up of the first cohort of patients.
The phase 1/2 multicenter study involved 135 patients enrolled between January 2014 and November 2015, all with relapsed/refractory CLL or SLL. The median age of all participants was 66 years, and the median number of prior therapies was two. Of the total, 134 patients received more than one dose of Calquence.
In the dose-escalation portion of the study, a smaller cohort of patients initially received Calquence at varied doses: nine patients at 100 mg, eight patients at 250 mg, six patients at 400 mg once daily and six patients at 200 mg twice daily. In phase 2, after additional patients were enrolled, 65 participants received 100 mg twice daily while 33 received 200 mg once daily.
Patients received Calquence for a median of 41 months, and 26% received treatment for more than 4 years. More than 56% of patients (75) remained on treatment at data cutoff, while 59 of patients (44%) discontinued treatment, mainly due to disease progression (21%) or AEs (11%). Seventeen patients died (13%), with 10 of those deaths being attributed to AEs and the other seven due to disease progression.
All patients reported more than one AE, the majority of which were mild or moderate. The most common AE was diarrhea (52%) and headache (51%). Grade 3 or higher AEs occurred in 89 patients, and 10 patients experienced grade 5 AEs.
The overall response rate (ORR) was 94%, which included six patients who saw complete response, 112 who achieved partial response and eight who achieved partial response with lymphocytosis, which is a condition where the white blood cell count of an individual is higher than normal. Nine patients relapsed, and BTK mutation was detected in six of those nine patients (67%).
The researchers noted that at the time of publication, the median duration of response and progression-free survival (PFS) had not been reached. However, they estimated the 45-month PFS rate to be at 62%.
In conclusion, the authors explain that these efficacy results confirm the results found earlier in the study by doubling the number of patients involved. In terms of safety, the authors noted that Calquence was a more selective BTK inhibitor than Imbruvica, meaning that patients experienced fewer AEs when taking it, regardless of how long they were on this treatment.
“As BTK inhibition requires chronic dosing until progression, the importance of long-term tolerability cannot be overstated, especially when treating a disease that occurs in the elderly, such as CLL,” the authors wrote.
“This updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation in previously untreated and treated patients with CLL/SLL,” they conclude in the study.