Randomized trial of 10 days of decitabine ± bortezomib in untreated older patients with AML: CALGB 11002 (Alliance)

Abstract

Novel treatment strategies are needed for older patients with acute myeloid leukemia (AML). This randomized phase 2 trial compared the efficacy and safety of 20 mg/m2 of IV decitabine on days 1 to 10 alone (arm A) with those of 1.3 mg/m2 of subcutaneous bortezomib (arm B) on days 1, 4, 8, and 11 for up to 4 10-day cycles followed by monthly 5-day cycles. Previously untreated AML patients age ≥60 years (excluding those with FLT3 mutations and favorable-risk cytogenetics) without restrictions in performance status (PS) or organ function were eligible. Median age was 72.4 years (range, 60.5-92.3 years); 31 patients (19%) had baseline PS ≥2, 35 (22%) had an antecedent hematological disorder, 58 had (39%) adverse cytogenetics, and 7 (5%) and 23 (14%) had abnormal cardiac or renal function. There were no statistically significant differences in overall survival (OS) or responses between the 2 treatment arms. The overall response rate (complete remission + complete remission with incomplete blood count recovery) was 39% (n = 64), with median OS of 9.3 months. Nineteen responders (31%) underwent allogeneic stem cell transplantation. The most common adverse event was febrile neutropenia, and there were no unexpected toxicities. Adding bortezomib to decitabine did not improve outcomes, but responses were better than those in previous trials using 5-day decitabine cycles. This trial was registered at www.clinicaltrials.gov as #NCT01420926.

Conflict of interest statement

Conflict-of-interest disclosure: G.J.R. has consulted for AbbVie, Actinium, Amphivena, Argenx, Array BioPharma, Astex, Astellas, Bayer, Celgene, Celltrion, CTI BioPharma, Daiichi Sankyo, Eisai, Janssen, Jazz, MedImmune, MEI Pharma, Novartis, Orsenix, Otsuka, Pfizer, Roche/Genentech, Sunesis, Sandoz, and Takeda and received compensation. E.C.A. is currently employed by and has equity ownership in Agios. L.G. is currently employed by Eli Lilly and Company and has ownership interests in Foundation Medicine and Tango Therapeutics. The remaining authors declare no competing financial interests.

© 2018 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

CONSORT diagram.

Figure 2.

Kaplan-Meier estimate of OS by treatment arm. Arm A, decitabine; arm B, decitabine + bortezomib.

Figure 3.

Oncoprint of mutations found in all treated patients. Each column corresponds to an individual patient, and each row corresponds to a specific mutation, the frequency of which is indicated as a percentage on the left of the figure and as a bar graph on the right. The bar plot on the right indicates the number of mutated patients. The bar plot at the top indicates the number of mutations in each patient.