A phase II study of ibrutinib in combination with ixazomib in patients with Waldenström macroglobulinaemia

• Published in: British journal of haematology Vol. 204; no. 5; pp. 1825 - 1829
• Main Authors: Parrondo, Ricardo D., Dutta, Navnita, LaPlant, Betsy R., Elliott, Jamie, Fernandez, Andre, Zimmerman, Ashley, Cicco, Gina, Han, Bing, Heslop, Keisha, Chapin, Dustin, Sher, Taimur, Roy, Vivek, Rasheed, Ahsan, Das, Saurav, Chanan‐Khan, Asher A., Paulus, Aneel, Ailawadhi, Sikander
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2024
• Subjects: Adenine - analogs & derivatives; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Boron Compounds - administration & dosage; Boron Compounds - adverse effects; Boron Compounds - therapeutic use; Bruton's tyrosine kinase; c-Met protein; clinical trials; Female; Glycine - administration & dosage; Glycine - adverse effects; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; Male; Middle Aged; non Hodgkin's lymphoma; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - therapeutic use; Proteasomes; Pyrazoles - administration & dosage; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Pyrimidines - administration & dosage; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Toxicity; Treatment Outcome; Waldenstrom Macroglobulinemia - drug therapy; Waldenstrom's macroglobulinaemia; non Hodgkin's lymphoma; clinical trials; Waldenstrom's macroglobulinaemia
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/bjh.19320

Summary This phase II study evaluated time‐limited (24 cycles) treatment with ibrutinib and ixazomib in newly diagnosed (NDWM; n = 9) and relapsed/refractory (RRWM; n = 12) Waldenström macroglobulinaemia (WM). The overall response rate (ORR) was 76.2% (n = 16) in 21 evaluable patients with no patient achieving a complete response (CR). The median duration of treatment was 15.6 months, and after a median follow‐up time of 25.7 months, the median progression‐free survival (PFS) was 22.9 months. While the primary end‐point was not met (CR rate at any time) and 28.5% discontinued treatment due to toxicity, ibrutinib plus ixazomib led to a clinically meaningful ORR and PFS. Combined Bruton's tyrosine kinase (BTK) and proteasome inhibition merits further evaluation in WM.