Open AccessPF377 ACALABRUTINIB WITH OBINUTUZUMAB IN TREATMENT‐NAIVE AND RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA: 3‐YEAR FOLLOW‐UP
Author(s) -
Woyach J.A.,
Rogers K.,
Bhat S.,
Blachly J.,
Jianfar M.,
Frigault M.M.,
Hamdy A.,
Izumi R.,
Munugalavadla V.,
Quah C.,
Wang M.H.,
Byrd J.C.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000559720.03914.f5
Subject(s) - medicine , obinutuzumab , adverse effect , gastroenterology , rash , refractory (planetary science) , nausea , chronic lymphocytic leukemia , leukemia , physics , astrobiology
Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor. Aims: This Phase 1b/2 trial evaluated acalabrutinib with the CD20 antibody obinutuzumab in patients with treatment‐naive or relapsed/refractory chronic lymphocytic leukemia (CLL). Methods: Patients with treatment‐naive or relapsed/refractory (≥1 prior therapy) CLL were eligible. In 28‐day cycles, acalabrutinib was given orally at 100 mg twice daily or 200 mg once daily (n = 15; all switched to 100 mg twice daily) until progressive disease; obinutuzumab was given in standard fashion for 6 cycles starting with Cycle 2. The primary endpoints were overall response rate (ORR) and safety. Minimal residual disease (MRD) was assessed using flow cytometry (sensitivity 10 –4 ). Results: Nineteen treatment‐naive and 26 relapsed/refractory patients were treated. The median age of all patients was 61 years (range, 42 to 76). Patient characteristics, disposition, efficacy and MRD are in the Table . Common adverse events (any grade) were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%), and dizziness (47%). Common Grade 3/4 adverse events were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight and cellulitis (9% each). There were 2 (4%) Grade 3 bleeding events (hematuria, muscle hemorrhage) and 1 (2%) Grade 3 atrial fibrillation event. Summary/Conclusion: Acalabrutinib plus obinutuzumab was well tolerated and yielded high response rates that were durable and deepened over time in treatment‐naive and relapsed/refractory patients with CLL.