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EHA 2019: ASCEND Trial Compares Acalabrutinib vs Investigator’s Choice in Relapsed or Refractory CLL

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Key Points

  • Acalabrutinib significantly prolonged IRC-assessed progression-free survival vs rituximab/idelalisib or rituximab/bendamustine (median = not reached vs 16.5 months).
  • 23% of patients randomly assigned to rituximab/idelalisib or rituximab/bendamustine crossed over to receive subsequent treatment with acalabrutinib.
  • Common all-grade adverse events with acalabrutinib were headache (22%), neutropenia (19%), diarrhea (18%), anemia (15%), and cough (15%); discontinuation due to adverse events occurred in 11% of patients treated with acalabrutinib.

The randomized, global, multicenter, open-label phase III ASCEND trial evaluated the efficacy and safety of acalabrutinib vs investigator’s choice of rituximab/idelalisib or rituximab/bendamustine in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Ghia et al presented the results at the 24th Annual Congress of the European Hematology Association (EHA; Abstract LB2606).

ASCEND Methods

A total of 310 eligible patients were randomly assigned 1:1 to receive 100 mg of acalabrutinib twice daily until disease progression vs rituximab/idelalisib (150 mg of idelalisib 150 mg twice daily in combination with up to 8 intravenous [IV] infusions of rituximab [375 or 500 mg/m2]) or rituximab/bendamustine (70 mg/m2 IV bendamustine on day 1 and 2 of each cycle combined with rituximab [375 or 500 mg/mIV] on day 1 of each 28-day cycle for up to six cycles). Patients were stratified by del(17p) status, ECOG status, and prior lines of therapy.

Median age was 67 years; 16% had del(17p); 27% had del(11q); 42% had Rai stage III/IV CLL. The median number of prior therapies was 1 (range = 1–8) for acalabrutinib and 2 (range = 1–10) for rituximab/idelalisib or rituximab/bendamustine; patients had received prior purine analogs (69%), alkylating agents (85%), and anti-CD20 antibodies (80%). 

The primary endpoint was progression-free survival assessed by independent review committee (IRC). Patients with confirmed disease progression on rituximab/idelalisib or rituximab/bendamustine could cross over to receive acalabrutinib.

Findings

At a median follow-up of 16.1 months, acalabrutinib significantly prolonged IRC-assessed progression-free survival vs rituximab/idelalisib or rituximab/bendamustine (median = not reached vs 16.5 months; hazard ratio [HR] = 0.31, 95% confidence interval [CI] = 0.20–0.49; P < .0001). This represented a 69% reduction in risk of progression or death. Progression-free survival was improved with acalabrutinib across subgroups including del(17p), TP53 mutation, and Rai stage.

IRC-assessed overall response rate was not significantly different with acalabrutinib vs rituximab/idelalisib or rituximab/bendamustine (81% vs 75%). Twelve-month overall survival rates were 94% and 91% for acalabrutinib and rituximab/idelalisib or rituximab/bendamustine, respectively. Twenty-three percent of patients randomly assigned to rituximab/idelalisib or rituximab/bendamustine crossed over to receive subsequent treatment with acalabrutinib.

Safety

Common all-grade adverse events with acalabrutinib were headache (22%), neutropenia (19%), diarrhea (18%), anemia (15%), and cough (15%); with rituximab/idelalisib, diarrhea (47%), neutropenia (45%), pyrexia (18%) and cough (15%); and with rituximab/bendamustine, neutropenia (34%), infusion-related reaction (23%), fatigue (23%), nausea (20%), and pyrexia (17%). Grade ≥ 3 adverse events reported with acalabrutinib were neutropenia (16%), anemia (12%), and pneumonia (5%); with rituximab/idelalisib, neutropenia (40%) and diarrhea (24%); and with rituximab/bendamustine, neutropenia (31%), anemia (9%), and constipation (6%).

Treatment discontinuation due to adverse events occurred in 11% of patients receiving acalabrutinib.

The authors concluded, “Acalabrutinib monotherapy significantly improved progression-free survival with a more tolerable safety profile compared with rituximab/idelalisib or rituximab/bendamustine in patients with relapsed or refractory CLL.”

Disclosure: For full disclosures of the study authors, visit library.ehaweb.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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