P1130: Acalabrutinib in Treatment-naive or Relapsed/refractory Waldenström Macroglobulinemia: 5-year Follow-up of a Phase 2, Single-arm Study
Year: 2022
Type: conference-abstract
Study design: Clinical Trial
Abstract: Background: Bruton tyrosine kinase (BTK) inhibitors are effective in the treatment of Waldenström macroglobulinemia (WM). Acalabrutinib is a highly selective, potent, covalent BTK inhibitor that demonstrated less toxicity and improved tolerability in a head-to-head trial versus ibrutinib in chronic lymphocytic leukemia. Aims: The aim of this trial was to determine the efficacy and safety of acalabrutinib in patients with treatment-naive (TN) or relapsed/refractory (R/R) WM. Interim results at 25 months (mo) of median follow-up have been previously reported. At a 5-year median follow-up, we report the final results of this trial. Methods: In this single-arm, multicenter, phase 2 trial, after informed consent was obtained, patients with TN or R/R WM received 100 mg oral acalabrutinib twice daily (or 200 mg acalabrutinib once daily, later switched to 100 mg twice daily). The primary endpoint was investigator-assessed overall response rate (ORR). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Efficacy parameters were based on the modified 3rd International Workshop on Waldenström Macroglobulinemia (IWWM) criteria (Kimby 2006). Mutation data were available for a minority of patients and therefore are not reported. Results: Of 106 patients treated with acalabrutinib, 14 were TN and 92 were R/R; median age was 69 years (range 39–90); 94% had ECOG PS ≤1; median serum IgM was 3615 mg/dL (range 291–9740). Patients with R/R disease had a median of 2 prior therapies (range 1–7). ORR was 93% (95% CI: 66, 100) in the TN cohort and 95% (88, 98) in the R/R cohort; major response rates (≥partial response) were 79% (49, 95) and 82% (72, 89), respectively. Median DOR was not estimable (NE) (12, NE) in the TN cohort and 65 mo (55, NE) in the R/R cohort; the estimated 66-mo DOR was 90% (TN; 47, 99) and 45% (R/R; 27, 61). At a 63.7-mo median follow-up, median PFS rate was NE (TN; 19, NE) and 68 mo (R/R; 53, NE); estimated 66-mo PFS rate was 84% (TN; 48, 96) and 52% (R/R; 39, 63). Median OS rate was NE for the TN and R/R cohorts; estimated 66-mo OS rate was 91% (TN; 51, 99) and 71% (R/R; 60, 80). Of the patients who remained on treatment, 7 (50%) were in the TN cohort and 43 (47%) were in the R/R cohort. The main reasons for discontinuing acalabrutinib were adverse events (AEs) (4 [29%] patients in the TN cohort, 15 [16%] patients in the R/R cohort) and progressive disease (PD) (1 [7%] patient in the TN cohort, 20 [22%] patients in the R/R cohort). The most common AEs and selected events of clinical interest are listed in the Table. There were 12 grade 5 AEs (11 and 1 patients in the R/R and TN cohorts, respectively); 1 (intracranial hematoma [R/R]) was considered treatment-related. Image:Summary/Conclusion: Acalabrutinib is a highly effective treatment that achieved durable responses with a favorable safety profile in patients with TN or R/R WM.
Source: HemaSphere
Institutions: St James's University Hospital, Royal Bournemouth Hospital, AstraZeneca (Canada), University of Plymouth, University College London, The University of Texas MD Anderson Cancer Center, University Hospital Southampton NHS Foundation Trust, University of Southampton, Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam, Istituto di Ematologia di Bologna, University of Bologna, Royal Marsden Hospital, Churchill Hospital, Utrecht University, University Medical Center Utrecht, National and Kapodistrian University of Athens, Georgetown University Medical Center, Georgetown Lombardi Comprehensive Cancer Center, University of Leicester, AstraZeneca (United States), NewYork–Presbyterian Hospital
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,480
OpenAlex ID: W4283333285