Trial Results Demonstrate Long-Term Efficacy and Tolerability of Acalabrutinib for CLL

Both the phase 2 ACE-CL-001 trial and the pivotal phase 3 ASCEND trial showed the long-term efficacy and tolerability of acalabrutinib in patients with chronic lymphocytic leukemia.

Results from both the phase 2 ACE-CL-001 trial and the pivotal phase 3 ASCEND trial demonstrated the long-term efficacy and tolerability of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL), according to AstraZeneca, the developer of the agent.

The results were presented during the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress, held from June 11-14, 2020.

“These long-term data reaffirm that (acalabrutinib) delivers a durable response with a favorable safety profile for chronic lymphocytic leukemia patients,” José Baselga, executive vice president of Oncology R&D, said in a press release. “Patients with chronic lymphocytic leukemia are typically 70 years or older with comorbidities and often require treatment over a long time, making the sustained safety and efficacy profile highly relevant to their quality of life.”

In the single-arm ACE-CL-001 trial, previously untreated patients with CLL were randomized to either 100 mg of acalabrutinib twice daily (n = 62) or 200 mg once daily (n = 37). Of note, on May 1, 2015, patients receiving the 200 mg dosing regimen were switched to the 100 mg regimen.

Overall, 86% of patients with CLL who were treated with acalabrutinib as a first-line monotherapy remained on treatment at a median follow up of more than 4 years. The trial showed an overall response rate (ORR) of 97%, with 7% having a complete response (CR) and 90% a partial response (PR).

Moreover, a 100% ORR was observed in subgroups of patients with high-risk disease characteristics, including patients with unmutated IGHV (n = 57), 17p deletion (n = 9), TP53 mutation (n = 9), and complex karyotype (n = 12); a reduction in lymph node disease was noted in all patients tested (n = 97).

The safety findings of ACE-CL-001 reported no new long-term issues. Six patients discontinued treatment due to adverse events (AEs) and 3 discontinued for progressive disease (PD). However, incidence of AEs generally diminished with time on the trial.

The most common AEs (≥40%) of any grade in the trial were diarrhea (52%), headache (45%), upper respiratory tract infection (44%), arthralgia (42%), and contusion (42%). All-grade and grade ≥3 events of clinical interest included infection (84% and 15%, respectively), bleeding events (66% and 3%), hypertension (22% and 11%), leukopenia (9% and 9%), and thrombocytopenia (3% and 1%). Further, atrial fibrillation of all grades occurred in 5% of patients, with grade ≥3 occurring in 2%. Second primary malignancies excluding non-melanoma skin of all grades occurred in 11% of patients. Serious adverse events (SAEs) were reported in 38% of patients. SAEs reported in more than 2 patients included pneumonia (n = 4) and sepsis (n = 3).

In the global, randomized, multicenter, open-label phase 3 ASCEND trial, patients with relapsed or refractory CLL were given either 100 mg twice daily of acalabrutinib (n = 155) or the investigator’s choice of rituximab (Rituxan) combined with idelalisib (Zydelig) or bedamustine (Treanda; n = 155). In the final analysis of the trial, approximately 82% of patients with relapsed or refractory CLL who were treated with acalabrutinib were alive and free from disease progression at 18 months compared with 48% of those who were given rituximab combined with idelalisib or bendamustine. Previously, the trial met the primary end point of Independent Review Committee-assessed progression-free survival at the interim analysis.

In total, 16% of patients on acalabrutinb, 56% of patients on idelalisib, and 17% of patients on bendamustine discontinued treatment due to AEs. Common which AEs occurred in more than 15% of patients of any grade in the acalabrutinib arm of the trial included headache (22%), neutropenia (21%), diarrhea (20%), upper respiratory tract infection (20%), cough (16%), and anemia (16%). Events of clinical interest for acalabrutinib versus controls included atrial fibrillation (all grade, 6% and 3%, respectively), major hemorrhage (all grade, 3% in both arms), infections (grade ≥3, 20% and 25%, respectively), and SPM excluding non-melanoma skin cancer (all grade, 5% and 2%, respectively). SAEs of any grade occurred in 33% of patients receiving acalabrutinib, 56% of those receiving idelalisib, and 26% of those receiving bendamustine.

“These data demonstrate no new safety concerns for acalabrutinib, confirming its ability to safely provide meaningful, long-term clinical benefit for patients with treatment-naive and relapsed or refractory disease,” Richard R. Furman, director of the CLL Research Center at Weill Cornell Medicine, explained in the release. “The safety profile of acalabrutinib makes treatment to progression an important and plausible option for patients.”

Importantly, results from the phase 2 ACE-CL-001 trial informed the development of the pivotal phase 3 ELEVATE TN trial, which, combined with the findings of the phase 3 ASCEND trial, formed the basis for the US approval of acalabrutinib for the treatment of patients with CLL or small lymphocytic lymphoma (SLL).


Calquence showed long-term efficacy and tolerability for patients with chronic lymphocytic leukaemia in two trials [news release]. Published June 12, 2020. Accessed June 15, 2020.

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