Earlier Calquence Leads to Improved Survival Outcomes in CLL

Patients with chronic lymphocytic leukemia (CLL) who received Calquence (acalabrutinib) during earlier lines of treatment experienced better survival outcomes than patients who received Calquence after other treatments, according to a presentation at the 2024 European Hematology Association (EHA) Congress.

Specifically, overall survival (OS; time patients live until death of any cause), progression-free survival (PFS; time patients live until disease worsening) and time to next treatment (TTNT) were better in patients who received Calquence earlier.

A combined analysis of the phase 3 ELEVATE-TN, ELEVATE-RR and ASCEND trials demonstrated these benefits with earlier Calquence in the overall patient population and for patients with deletion 17p, which is a genetic aberration associated with poorer prognosis.

Calquence is a Bruton tyrosine kinase (BTK) inhibitor that works by blocking the activity of the BTK enzyme, which helps develop and mature B cells. BTK inhibitors may help prevent the growth of cancer cells, according to the National Cancer Institute.

“In the overall population, those with no prior lines of therapy had improved outcomes versus those with one prior line of therapy,” Dr. Paolo Ghia said in his presentation of the pooled analysis at the EHA Congress. “Those with one prior line of therapy also had consistently improved outcome versus those with two or more prior lines of therapy in the overall population, as well as those with the [deletion 17p].”

Researchers from this presentation evaluated the impact of the number of prior lines of therapy for Calquence in treatment naïve (patients who have not received any treatment) or relapsed or refractory CLL, which was previously unknown.

Data from the Calquence monotherapy groups of the phase 3 trials were also reviewed.

The ELEVATE-TN trial had a data cut-off of March 3, 2023; a median follow-up of 74.5 months; and 179 patients who received zero prior lines of therapy. The ELEVATE-RR had a data cut-off of Sept. 15, 2020; median follow-up of 40.9 months; 132 patients who received one prior lines of therapy and 135 patients with two or more prior lines of therapies. The ASCEND trial had a data cut-off of Sept. 3, 2021; median follow-up of 46.5 months; 82 patients who received one prior lines of therapy and 73 patients with two or more prior lines.

The outcomes for the analysis included OS, PFS and TTNT, comparing zero versus one prior lines of therapy and one versus two or more prior lines of therapy.

In total, 601 patients were treated with Calquence monotherapy (Calquence alone): 179 with zero prior lines of therapy, 214 with one prior line of therapy and 208 with two or more prior lines of therapy. The number of patients with high-risk features and stage 4 disease was higher in the groups of pretreated patients.

In the overall population, patients with zero prior lines of therapy had a 45% lower risk of death than those with one prior line of therapy; 92% versus 85% of patients were alive at 36 months, respectively.

There was 56% lower risk of disease progression or death and 52% lower risk of initiating subsequent therapy for patients with zero prior lines of therapy versus one prior line. At 36 months, 84% of patients with zero prior lines of therapy were progression free and had not initiated subsequent therapy versus 73% and 75% with one prior line of therapy, respectively.

There was a 46% lower risk of death in patients with one prior line of therapy than in those with two or more prior treatments. At 36 months, 85% of the patients who received one prior line of therapy were alive versus 76% of patients who received two or more therapies.

The risk of disease progression or death was 39% lower in patients with one prior line compared two or more prior lines of therapy, and 73% of patients were progression free versus 58% at 36 months. In patients with one prior line, there was a 33% lower risk of initiating subsequent therapy, and 75% had not initiated subsequent therapy compared with 64% at 36 months.

Increased risk of death in the overall population was associated with prior lines of therapy, TP53 mutation, ECOG performance status of 2 or more (which indicates that patients cannot independently perform their daily tasks), disease stage 3 or more, 65 years of age or more and being male.

Regarding patients with deletion 17p with zero versus one prior line of therapy, there were not enough patients to calculate outcome differences. Researchers reviewed the OS, PFS and TTNT in patients with deletion 17p who had one and two or more prior lines of therapy.

“Findings were consistent in patients with deletion 17p, where patients with one prior line of therapy had a significantly lower risk of disease progression or death and initiating subsequent therapy compared with those with two or more prior lines of therapy,” Ghia explained.

At 36 months, 81% versus 65% of patients were alive; 74% versus 45% of patients were progression free; and 72% versus 56% of patients had not initiated subsequent therapy of those who received one prior lines of therapy versus two or more, respectively.

The discontinuation of Calquence monotherapy was most commonly due to side effects in 17.9%, 13.1% and 22.6% in the zero, one and two or more prior lines of therapy groups, respectively, and disease progression was seen in 14.0%, 23.4% and 31.7%, respectively.

“In conclusion, improved OS, PFS and TTNT were consistently observed when [Calquence] was initiated in earlier versus later [lines of therapy],” Ghia said.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.