Calquence, a next-generation BTK inhibitor, significantly prolonged survival compared with standard of care, along with no new side effects at three years in chronic lymphocytic leukemia. These findings also pertained to some patients with high-risk genetic features.
Patients with relapsed/refractory chronic lymphocytic leukemia who were treated with Calquence (acalabrutinib) obtained a survival benefit out to three years compared with standard of care, recent study findings demonstrated.
Long-term follow-up from the ASCEND study, which was presented by Dr. Wojciech Jurczak, head of the department of hematology at Maria Skłodowska – Curie National Research Institute of Oncology in Kraków, Poland, at the 2021 ASH Annual Meeting & Exposition, also demonstrated that Calquence was well tolerated with no new safety findings.
“Overall, these data support the use of (Calquence) in patients with relapsed refractory chronic lymphocytic leukemia including those with high-risk features,” Jurczak said during the presentation.
Jurczak explained that Calquence “is the next-generation, highly selective covalent BTK inhibitor approved for treatment of chronic lymphocytic leukemia.”
In the study, 310 patients (median age, 67 years) with relapsed/refractory chronic lymphocytic leukemia were assigned either Calquence (155 patients) or the investigator’s choice of standard of care: Zydelig (idelalisib) with Rituxan (rituximab; 119 patients) or bendamustine plus Rituxan (36 patients).
Jurczak also referenced the primary findings of the ASCEND study.
“In the primary analysis of the ASCEND study, (Calquence) demonstrated superior progression-free survival and a favorable safety profile compared to investigators’ choice,” he explained. “Primary analysis was done at the median follow up of 16 months. Here, we present the data at three years.”
Both groups received treatment until unacceptable toxicity or disease progression. Researchers assessed overall survival (the time when a patient with cancer is still alive), progression-free survival (the time when a patient lives with cancer without worsening), safety and overall response rate (the percentage of patients with a partial or complete response to a treatment) during a median follow-up of 36 months for the Calquence group and 35.2 months for those treated with Zydelig/Rituxan or bendamustine/Rituxan.
During follow-up, patients treated with Calquence monotherapy had significantly prolonged progression-free survival compared with those treated with Zydelig/Rituxan or bendamustine/Rituxan (median, not reached versus 16.8 months). In particular, not reaching a median progression-free survival means that researchers could not calculate this because more than half of patients were alive. More patients in the Calquence group achieved 36-month progression-free survival compared with the investigator-selected treatments (63% versus 21%). When assessed separately, similar benefits regarding progression-free survival were observed when Calquence was compared with Zydelig/Rituxan (median, 16.2 months) and with bendamustine/Rituxan (median, 18.6 months).
A progression-free survival benefit was also observed in high-risk subgroups. Patients with the del(17p) mutation treated with Calquence did not reach the median progression-free survival compared with 13.8 months in those treated with either Zydelig/Rituxan or bendamustine/Rituxan. This benefit persisted for 36-month progression-free survival (66% versus 5%, respectively).
Patients with unmutated IGHV did not achieve the median progression-free survival with Calquence compared with 16.1 months in those treated with Zydelig/Rituxan or bendamustine/Rituxan. Progression-free survival at 36 months was 61% in the Calquence group versus 17% in the Zydelig/Rituxan or bendamustine/Rituxan group.
Both groups did not reach the median overall survival. At 36 months, overall survival was 80% in patients assigned Calquence versus 73% in those assigned Zydelig/Rituxan or bendamustine/Rituxan.
“It should be noted that nearly 50% of the patients in the investigators’ choice arm have crossed over to the (Calquence) arm, which may limit the ability to detect differences in overall survival by this study,” Jurczak explained during the presentation.
The overall response rate was 83% in the Calquence group and 85% in the Zydelig/Rituxan or bendamustine/Rituxan group. When the overall response rate included partial response with lymphocytosis (an increase in peripheral blood lymphocytes, which can help fight off disease), rates were 92% and 88%, respectively.
The most common side effects of any severity, occurring in at least 20% of patients treated with Calquence, included neutropenia (lower levels of a white blood cell called neutrophils, which can increase the risk for infection; 23%), headache (23%), upper respiratory tract infection (20%) and diarrhea (21%). Common side effects in patients treated with Zydelig/Rituxan included neutropenia (47%) and diarrhea (53%). In those treated with bendamustine/Rituxan, common side effects comprised of fatigue (23%), neutropenia (34%), nausea (20%) and infusion-related reaction (23%).
Researchers observed serious side effects in 38% of patients in the Calquence group, 63% of those in the Zydelig/Rituxan group and 26% of patients in the bendamustine/Rituxan group. Serious side effects that occurred in at least 5% of patients in any treatment arm were fever, pneumonia and diarrhea. Drug discontinuation from side effects occurred in 21% of patients assigned Calquence, 65% assigned Zydelig/Rituxan and 17% assigned bendamustine/Rituxan.
Several events of clinical interest occurred such as high blood pressure, irregular and rapid heart rhythm, severe or worse infections, major hemorrhage and primary malignancies excluding nonmelanoma skin cancer.
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