Results of the randomized phase IIB ADMIRE trial of FCR with or without mitoxantrone in previously untreated CLL

• Published in: Leukemia 2017-10, Vol.31 (10), p.2085-2093
• Main Authors: Munir, T, Howard, D R, McParland, L, Pocock, C, Rawstron, A C, Hockaday, A, Varghese, A, Hamblin, M, Bloor, A, Pettitt, A, Fegan, C, Blundell, J, Gribben, J G, Phillips, D, Hillmen, P
• Format: Article
• Language: English
• Subjects: 631/67/1990/283/1895; 692/308/2779/109/1941; 692/308/2779/777; 692/699/67/1059/99; 692/700/565/1436/1437; Adult; Aged; Analysis; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Cancer; Cancer Research; Chemotherapy; Chronic lymphocytic leukemia; Clinical trials; Colony-stimulating factor; Confidence intervals; Critical Care Medicine; Cyclophosphamide; Cyclophosphamide - administration & dosage; Disease-Free Survival; Diseases; Drug therapy; Female; Fludarabine; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - therapeutic use; Hematology; Humans; Intensive; Internal Medicine; Intravenous administration; Kaplan-Meier Estimate; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukocytes (granulocytic); Lymphatic leukemia; Lymphocytic leukemia; Male; Medicine; Medicine & Public Health; Methods; Middle Aged; Minimal residual disease; Mitoxantrone; Mitoxantrone - administration & dosage; Monoclonal antibodies; Neoplasm, Residual; Neutropenia; Neutropenia - drug therapy; Neutropenia - prevention & control; Oncology; original-article; Patient outcomes; Patients; Pharmaceutical industry; Product development; Prophylaxis; Public relations executives; Randomization; Remission; Remission Induction; Rituximab; Rituximab - administration & dosage; Survival; Survival Rate; Targeted cancer therapy; Toxicity; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Workshops (Educational programs)
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2017.65

ADMIRE was a multicenter, randomized-controlled, open, phase IIB superiority trial in previously untreated chronic lymphocytic leukemia. Conventional front-line therapy in fit patients is fludarabine, cyclophosphamide and rituximab (FCR). Initial evidence from non-randomized phase II trials suggested that the addition of mitoxantrone to FCR (FCM-R) improved remission rates. Two hundred and fifteen patients were recruited to assess the primary end point of complete remission (CR) rates according to International Workshop on Chronic Lymphocytic Leukemia criteria. Secondary end points were progression-free survival (PFS), overall survival (OS), overall response rate, minimal residual disease (MRD) negativity and safety. At final analysis, CR rates were 69.8 FCR vs 69.3% FCM-R (adjusted odds ratio (OR): 0.97; 95% confidence interval (CI): (0.53–1.79), P =0.932). MRD-negativity rates were 59.3 FCR vs 50.5% FCM-R (adjusted OR: 0.70; 95% CI: (0.39–1.26), P =0.231). During treatment, 60.0% ( n =129) of participants received granulocyte colony-stimulating factor as secondary prophylaxis for neutropenia, a lower proportion on FCR compared with FCM-R (56.1 vs 63.9%). The toxicity of both regimens was acceptable. There are no significant differences between the treatment groups for PFS and OS. The trial demonstrated that the addition of mitoxantrone to FCR did not increase the depth of response. Oral FCR was well tolerated and resulted in impressive responses in terms of CR rates and MRD negativity compared with historical series with intravenous chemotherapy.