Ibrutinib, lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma: Phase I trial results

• Published in: Hematological oncology Vol. 40; no. 4; pp. 695 - 703
• Main Authors: Ailawadhi, Sikander, Parrondo, Ricardo D., Moustafa, Muhamad Alhaj, LaPlant, Betsy R., Alegria, Victoria, Chapin, Dustin, Roy, Vivek, Sher, Taimur, Paulus, Aneel, Chanan‐Khan, Asher A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2022
• Subjects: Anemia; Design standards; Dexamethasone; Enzyme inhibitors; ibrutinib; Immunotherapy; Kinases; Leukopenia; Lymphopenia; Multiple myeloma; Neutropenia; Patients; Protein-tyrosine kinase; small molecule inhibitors; Steroids; Targeted cancer therapy; Thrombocytopenia; Toxicity; Tyrosine; ibrutinib; small molecule inhibitors; multiple myeloma
• ISSN: 0278-0232; 1099-1069
• DOI: 10.1002/hon.3012

Therapeutic strategies that target novel pathways are urgently needed for patients with relapsed/refractory multiple myeloma (RRMM). Ibrutinib is an oral covalent inhibitor of Bruton tyrosine kinase, which is overexpressed in MM cells. This phase 1 dose‐escalation study examined various doses of ibrutinib in combination with standard doses of lenalidomide (25 mg) and dexamethasone (40 mg) using a standard 3 + 3 design in RRMM patients. The primary objective was to determine the maximum tolerated dose (MTD) of ibrutinib in combination with lenalidomide and dexamethasone. Patients (n = 15) had received a median of 4 prior regimens, 53% were triple‐class exposed, 33% were penta‐exposed, and 54% were lenalidomide‐refractory. The MTD of ibrutinib was 840 mg (n = 6) and only 1 dose‐limiting toxicity; a grade 3 rash possibly related to ibrutinib was noted. The most common ≥ grade 3 adverse events were rash in 2 (13%), lymphopenia in 2 (13%), leukopenia, neutropenia, thrombocytopenia, and anemia all occurring in 3 (20%) patients each. One patient achieved a partial response for an overall response rate of 7%. The clinical benefit rate was 80%. The median time to progression was 3.8 months. Ibrutinib, lenalidomide and dexamethasone appears to be a safe and well‐tolerated regimen with reasonable efficacy in heavily pretreated RRMM patients.