ASH 2017 | Acalabrutinib monotherapy shows durable remission results with R/R and high-risk disease in early- to mid-stage CLL trial 

On Sunday 10 December 2017 during an oral abstract session at the 59^th Annual meeting American Society of Hematology (ASH), John C. Byrd of The Ohio State University Comprehensive Cancer Center in Columbus, Ohio, on behalf of his colleagues, presented results of the phase I/II ACE-CL-001 Study in relapsed/refractory chronic lymphocytic leukemia (CLL).

This abstract (#498), “Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Updated Results from the Phase 1/2 ACE-CL-001 Study,” was presented during Oral Session: 642. “CLL: Therapy, excluding Transplantation: Targeting MRD Negative CLL with Combinations of Novel Agents and Chemoimmunotherapy Regimens, New Treatments”, this summary is based on the latest data presented during the session as covered by the LH, which may supersede data included in the pre-published ASH abstract.

Highlight

• Treatment with acalabrutinib continues to be associated with high response rates and durable remissions in patients with R/R CLL/SLL, including those with high-risk disease

Treatment

• Patients with confirmed CLL/small lymphocytic lymphoma (SLL) were eligible if they had relapsed after or were refractory to ≥1 prior treatment
  • Eligible patients were ≥18 years of age with an ECOG performance status (PS) ≤2
• Oral acalabrutinib was administered in 28-day cycles at 100-400 mg QD or 100-200 mg BID in the dose-escalation phase of the study and 100 mg BID or 200 mg QD (later switched to 100 mg BID) in the expansion phase
  • All patients were treated until progressive disease (PD) or unacceptable toxicity
• Primary endpoint was safety, secondary endpoints included investigator-assessed overall response rate (ORR)

Efficacy

• ORR (complete response [CR] + partial response [PR]) was 85% and ORR including PR with lymphocytosis (PRL) was 93%
  • 2% of patients achieved CR
  • ORRs were consistent across high-risk subgroups of del(17)(p13.1) (23/27 [85%]), del(11) (q22.3) (18/21 [86%]) and unmutated IGHV (71/81 [88%])
• Median DOR was not reached; 18-month DOR rate was 85% (95% CI, 72%-92%)
  • Patients with del(11)(q22.3) or del(17)(p13.1), the median DOR was not reached, and the 18-month DOR rates were 100% and 71%, respectively
• Median PFS was also not reached, and the 18-month PFS rate was 88% (95% CI, 81%-93%)
  • Median PFS was also not reached in patients with del(11)(q22.3) or del(17)(p13.1), and the 18-month PFS rates were 100% and 78%, respectively.

Safety

• Most common adverse events (AEs; ≥20%) of any grade were headache (46%), diarrhea (43%), upper respiratory tract infection (28%), fatigue (27%), nausea (27%), arthralgia and pyrexia (each 23%), contusion (22%) and petechiae and weight increased (each 21%)
• Grade 3/4 AEs (≥5% of patients) were infrequent and were neutropenia (11%) and pneumonia (10%)
• Other AEs of interest (any grade/grade ≥3) included hypertension (11%/3%) and atrial fibrillation (3%/2%)
  • no Grade ≥3 bleeding events occurred
• Most patients (81%) remain on treatment; the primary reasons for treatment discontinuation were AEs (8%), PD (6%), and death (2%)
• Most common AEs leading to discontinuation were pneumonia (n=3), anemia, neutropenia and thrombocytopenia (n=2 each) 

Acalabrutinib continues to demonstrate high response rates and durable remissions in patients with R/R CLL/SLL, including those with high-risk disease. It’s also encouraging to note that the reported AEs indicated a tolerable safety profile. It will be worth following the progress of acalabrutinib in larger sets of patients with R/R CLL in two ongoing Phase 3 studies, ACE-CL-006 (NCT02477696) and ACE-CL-309 (NCT02970318).