Follow-Up Data Confirm Support for Use of Calquence in Patients with Relapsed/Refractory CLL, Expert Says

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“Final results from ASCEND confirm the findings of the interim analysis and support the favorable efficacy and safety of (Calquence) versus standard-of-care regimens in relapsed or refractory CLL,” said Dr. Paolo Ghia.

Follow-up data presented at the 2020 ASCO Virtual Scientific Program further support the use of Calquence (acalabrutinib) versus standard-of-care regimens in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to the lead author of the ASCEND trial.

“Overall, this data from ASCEND supports the use of (Calquence) in patients with relapsed (recurrent) or refractory (treatment-resistant) CLL, including those with high-risk genetic features,” said Dr. Paolo Ghia, director of the Strategic Research Program on CLL and the B-Cell Neoplasia Unit at Vita-Salute San Raffaele University in Italy, during a presentation of the results.

Ghia presented final results of the randomized, multi-center phase 3 trial, which assessed the safety and efficacy of single-agent Calquence (155 patients) versus Zydelig (idelalisib) given with Rituxan (rituximab) (119 patients) or Bendeka (bendamustine) given with Rituxan (36 patients) in relapsed/refractory CLL.

Calquence blocks the activity of Bruton’s tyrosine kinase, a protein that fuels the growth of CLL. Zydelig targets a different protein, PI3K, to fight cancer. Rituxan is a monoclonal antibody that targets the protein CD20, helping to kill cancer cells and activate the immune system against them. Bendeka is a chemotherapy. Standard-of-care treatments are those that are accepted as the best available and widely used.

“Bruton's tyrosine kinase inhibitors are preferred therapies in patients with relapsed or refractory CLL,” said Ghia. “Combination therapies such as (Rituxan) given in combination with (Zydelig) or (Bendeka) are also commonly used in these patients, but their associated toxicities can be treatment-limiting. (Calquence) … has demonstrated efficacy in both treatment-naive and relapsed or refractory CLL, including patients with high-risk features.”

Previous data from the ASCEND trial demonstrated that Calquence significantly improved progression-free survival (PFS), or the time from the start of treatment until disease worsened, compared with either standard-of-care combination after a median follow-up of 16.1 months.

This final analysis included an additional six months of follow-up.

After a median follow-up of 22 months, Calquence continued to show superior PFS rates, with an estimated 18-month PFS of 82% compared with 48% in the standard-of-care regimens. None of the treatment groups had yet reached a median overall survival rate.

The overall response rate, or the percentage of partial or complete responses to therapy, was similar in the Calquence (80%) and standard-of-care (84%) groups. The median duration of response was 18 months in the standard-of-care group and was not reached in the Calquence group.

Patients in the Zydelig with Rituxan group were most likely (56%) to discontinue treatment as a result of treatment-related side effects, compared with 17% in the Bendeka plus Rituxan arm and 16% in the Calquence arm. Despite the additional six months of follow-up, Ghia said, safety and efficacy data were similar to what was previously reported.

The most common side effects, regardless of severity, to occur in at least 20% of patients in the Calquence group included headache, diarrhea and upper respiratory infection. Neutropenia (17%), anemia (12%) and pneumonia (7%) were the most common serious or severe side effects to occur in the Calquence group.

Ghia did note that bleeding was more common in patients who received Calquence compared with the standard-of-care treatments. However, the incidence of major hemorrhages was low and similar among all treatment groups. Additionally, 65% of patients treated with either standard-of-care combination reported an infection compared with 63% of patients who received Calquence.

“Final results from ASCEND confirm the findings of the interim analysis and support the favorable efficacy and safety of (Calquence) versus standard-of-care regimens in relapsed or refractory CLL,” Ghia concluded.