Effects of the Therapeutic Armamentarium on Survival and Time to Next Treatment in CMML Subtypes: An International Analysis of 950 Cases Coordinated By the AGMT Study Group

• Published in: Blood 2019-11, Vol.134 (Supplement_1), p.844-844
• Main Authors: Pleyer, Lisa, Leisch, Michael, Kourakli, Alexandra, Padron, Eric, Maciejewski, Jaroslaw P., Xicoy, Blanca, Kaivers, Jennifer, Ungerstedt, Johanna, Heibl, Sonja, Patiou, Peristera, Hunter, Anthony M., Mora, Elvira, Geissler, Klaus, Dimou, Maria, Jimenez, María-José, Kiesl, David, Viniou, Nora-Athina, Patel, Bhumika J., Arnan Sangerman, Montserrat, Valent, Peter, Roubakis, Christoforos, Bernal del Castillo, Teresa, Galanopoulos, Athanasios, Calabuig, Marisa, Bonadies, Nicolas, Medina de Almeida, Antonio, Cermak, Jaroslav, Jerez, Andres, Montoro, Julia, Cortés, Albert, Avendaño Pita, Alejandro, López Andrade, Bernardo, Hellstrom Lindberg, Eva, Germing, Ulrich, Sekeres, Mikkael A., List, Alan F., Symeonidis, Argiris, Sanz, Guillermo F., Greil, Richard
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2019-123941

▪ Background Chronic myelomonocytic leukemia (CMML) is an ultrarare stem cell disorder defined by the presence of monocytosis (≥1.0 G/l, ≥10%). Depending on white blood cell (WBC) count, CMML can be divided into a myelodysplastic (MD) (WBC ≤13 G/l) and a myeloproliferative (MP) variant (WBC >13 G/l). Although hypomethylating agents (HMA) have been shown to prolong overall survival (OS) in MDS patients (pts) in prospective, randomized phase III trials, only 6-14 MD-CMML pts were included, and MP-CMML pts were excluded [Silverman 2002; Kantarjian 2006; Fenaux 2009]. EMA approval of azacitidine (AZA) in CMML is thus based on limited experience and restricted to MD-CMML with 10-29% bone marrow blasts (BMB), whereas decitabine (DAC) is not approved for treatment (trt) of CMML in the EU. Smaller analyses and single-arm trials of HMA in CMML exist [Wijermans 2008; Ades 2013; Pleyer 2014; Zeidan 2017; Duchmann 2018; Santini 2018; Coston 2019; Diamantopoulos 2019], but it is still unclear whether HMA provide a benefit in CMML (subgroups) compared with other trts. Aim Evaluate the impact of HMA and hydroxyurea (HU) trt on OS and time to next trt (TTNT). Methods Data were collected from 7 European study groups and 2 US MDS Centers of Excellence; database lock 27.05.19; Assign Data Management and Biostatistics GmbH performed statistical analyses with SAS® 9.3. Of 1657 CMML pts, only those who received trt (n=950), with documented WBC and BMB at 1st line, were included in these analyses (n=845, cohort 1). Pts were stratified according to the EMA approved AZA indication, and inclusion/exclusion criteria of the GFM-DAC-CMML trial assessing DAC +/- HU vs HU (NCT02214407) (diagnosis of CMML, no prior trt [except supportive care, erythropoietin or ≤6 weeks HU], WBC ≥13 G/l and ≥2 of the following: BMB ≥5%, clonal cytogenetic abnormality [other than -Y], hemoglobin 16 G/l, platelet count 2 excluded) (n=486; cohort 2). Results In cohort 1, pts receiving HMA 1st line (n=375) had longer OS (19.8 vs 16.3 months [mo], P=0.0102) and TTNT (13.2 vs 6.7 mo, P=0.0001) than pts treated with non-HMA 1st line (n=470). Survival benefit was longer when comparing pts who received HMA (any time) (AZA [n=442], DAC [n=37], both [n=27]) with those that never received HMA (never HMA; n=339) (23.0 vs 13.0 mo, P