Ten-Day Decitabine with Venetoclax Versus Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia: A Propensity Score Matched Analysis

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.30-33
• Main Authors: Maiti, Abhishek, DiNardo, Courtney D., Kadia, Tapan M., Jabbour, Elias, Rausch, Caitlin R., Daver, Naval, Borthakur, Gautam, Pemmaraju, Naveen, Short, Nicholas J., Yilmaz, Musa, Alvarado, Yesid, Montalbano, Kathryn S, Wade, Allison, Maduike, Rita, Guerrero, Julio A, Vaughan, Kenneth, Bivins, Carol A., Pierce, Sherry A., Ravandi, Farhad, Kantarjian, Hagop M., Konopleva, Marina
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-138375

Background: Patients (pt) with relapsed or refractory (R/R) acute myeloid leukemia (AML) have poor outcomes. Pts without actionable mutations (e.g. FLT3, IDH1/2) do not have standard approved treatments, and outcomes with available salvage therapies are poor (Roboz et al. J Clin Oncol. 2014). While venetoclax with azacitidine is now the standard for older or unfit pts with newly diagnosed AML, it is unknown how venetoclax-based lower intensity regimens compare to intensive chemotherapy (IC) for salvage therapy in adult pts with AML. Methods: We compared outcomes of adult pts (>18 yrs) with R/R AML treated on a prospective phase 2 trial of 10-day decitabine and venetoclax (DEC10-VEN) with a historical cohort of patients treated with intensive chemotherapy (IC) using a propensity score matched analysis (PSMA). Pts treated with DEC10-VEN received decitabine 20 mg/m2 daily for 10 days with daily venetoclax for induction followed by decitabine for 5 days with venetoclax for consolidation (NCT03404193); prior exposure to venetoclax was exclusion criteria. Patients in the IC cohort received either CLIA, CIA, or FIA without venetoclax on 2 prospective clinical 1b/2 trials (NCT02115295, NCT01289457). CLIA regimen included cladribine 5 mg/m2 IV on days (D) 1-5, ara-C 1-2 g/m2 IV on D1-5 and idarubicin 10 mg/m2 IV on D1-3. CIA and FIA included idarubicin 10 mg/m2 IV daily on D1-3, ara-C 1 g/m2 IV daily on D1-5, and clofarabine 15 mg/m2 IV daily on D1-5 or fludarabine 30 mg/m2 IV on D1-5, respectively. PSM with nearest neighbor method was used to select the IC comparison group using a 1:1 matching with caliper control of 0.3. Propensity scores were calculated from baseline characteristics including age, ECOG performance status, European LeukemiaNet risk group and number of prior lines of therapies received. SPSS 24, R Essentials for SPSS 24, R 3.2, and PSMATCHING3.03 package were used to conduct the PSM. Chi-square, Student’s t, and log-rank were used to compare categorical, continuous, and time-to-event variables, respectively. Results: 54 out of 55 pts treated with DEC10-VEN were best matched to 54 out of 197 pts treated with IC. The standardized mean differences of variables selected for PSM before and after matching was low, ranging from -0.067 to 0.042 suggesting significant reduction of bias between the two intervention groups. Pts in DEC10-VEN cohort were treated between January 2018 and December 2019 while pts in IC cohort received treatment between February 2