http://www.curetoday.com/articles/what-patients-with-cllsll-should-know-about-the-fdas-approval-of-calquence
What Patients With CLL/SLL Should Know About the FDA's Approval of Calquence

Kristie L. Kahl

The Food and Drug Administration’s approval of Calquence (acalabrutinib) for adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) offers yet another tool in the toolbox in treating this patient population, according to Dr. John C. Byrd.   This approval was done collaboratively by health authorities from three countries (Canada, Australia, and the United States), making this widely available for use in CLL.

“(The FDA’s approval) places another active drug in the combinations of therapy in the in the repertoire in development for physicians,” Byrd – D. Warren Brown Chair of Leukemia Research; Distinguished University Professor of Medicine Medicinal Chemistry, and Veterinary Biosciences; and senior advisor for cancer experimental therapeutics at The Ohio State University Comprehensive Cancer Center – said in an interview with CURE.

The approval, which was granted under the FDA’s Real-Time Oncology Review and newly established Project Orbis programs, was based on positive results from the interim analyses of two phase 3 clinical trials: the ELEVATE-TN trial in patients with previously untreated CLL and the ASCEND trial in patients with relapsed or refractory CLL.

In the randomized, multicenter, open-label, phase 3 ELEVATE-TN trial, the researchers evaluated the safety and efficacy of Calquence alone or in combination with Gazyva (obinutuzumab) compared with chlorambucil plus Gazyva in 535 treatment-naïve patients with CLL.

Median progression-free survival (time from treatment to disease progression) was 22.6 months in the control arm, but was not yet reached in both of the Calquence treatment arms. The objective response rate (complete and partial responses to treatment) was 79% in the control arm, compared with 94% in the Calquence combination arm and 86% in the monotherapy arm. Median overall survival was not yet reached in any of the three arms at a median follow-up of 28.3 months.

In the international, multicenter, open-label, phase 3 ASCEND trial, 310 previously treated patients with CLL were randomized to receive either single-agent Calquence or rituximab (Rituxan) plus idelalisib (Zydelig) or bendamustine.

At a median follow-up of 16.1 months, the median progression-free survival with Calquene was not reached, compared with 16.5 months in the control arms. At 12 months, 88% of patients on Calquence showed no disease progression compared with 68% in the control arm.

Common side effects included anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea and musculoskeletal pain.

Of note, tolerability of treatments for CLL/SLL have been an issue with the current treatment landscape. Therefore, the favorable tolerability and safety profile associated with Calquence is important.

“Having less side effects for a chronic therapy is very important when you get into adverse events such as hypertension where you know there are not only effects that are irritating but also affect our cardiovascular system and the risk of other bad things happening,” said Byrd.

With this, it is an exciting time with such advancements for the treatment of this disease. “We’re in a great place in CLL now that we have several targeted therapies that are approved. All of these options are good options for our patients. This just puts another nail in the coffin for treatment with chemotherapy,” Byrd said, noting that he does not recommend patients consider chemotherapy as a treatment option.

“The era of getting chemotherapy for this disease is virtually done,” Byrd said. “Essentially, I would say for almost all patients, chemotherapy should not be a consideration. There's only one very small subset, the IGBH-mutated patients…but for the majority of patients, those who have high-risk disease, doing chemotherapy plus immunotherapy is not a good option. Targeted therapies offer an alternative approach that is better than chemotherapy.”

To conclude, he added that new studies are even evaluating the approach of time-limited therapy, where patients would receive therapy for a set period of time, and if they experience remission, stop treatment, versus receiving continuous BTK inhibitor therapy. 

Read CURE’s original coverage of the FDA’s approval of Calquence for patients with CLL/SLL.
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