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IMPACT OF 1ST LINE TREATMENT ON OVERALL SURVIVAL IN 1.633 PATIENTS WITH CHRONIC MYELOMONOCYTIC LEUKEMIA - A MULTINATIONAL COLLABORATIVE EFFORT COORDINATED BY THE AGMT STUDY GROUP

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Pleyer, L.1, 2, 3; Leisch, M.1, 2; Kouraklis, A.4; Padron, E.5; Maciejewski, J. P.6; Cirici, Xicoy B.7; Kaivers, J.8; Ungerstedt, J.9; Sonja, H.10; Peristera, P.4; Hunter, A.5, 11; Mora, E.12; Geissler, K.13; Dimou, M.14; Lorenzo, Jimenez M.J.7; Kiesl, D.15; Vyniou, A.-N.16; Patel, B. J.6; Montserrat, A.17; Valent, P.18, 19; Christoforos, R.20; Bernal, T.21; Galanopoulos, A.20; Munoz, Calabuig M.22; Bonadies, N.23; Almeida, A.24, 25; Cermak, J.26; Jerez, A.27; Montoro, J.28; Cortés, A.29; Pita, Avendaño A.30; Andrade, Lopez B.31; Hellstroem-Lindberg, E.9; Germing, U.8; Sekeres, M.6; List, A.5; Symeonidis, A.4; Sanz, G. F.12, 32; Greil, R.1, 2, 3

doi: 10.1097/01.HS9.0000561640.50111.49
Simultaneous Sessions II: Improvements in MDS treatment
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13rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology, Paracelsus Medical University

2Salzburg Cancer Research Institute (SCRI)

3Cancer Cluster Salzburg (CCS), Salzburg, Austria

4Hematology Division, Dept. of Internal Medicine, University of Patras Medical School, Patras, Greece

5Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa

6Dept. of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, United States

7Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute, Badalona, Spain

8Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany

9HERM, Dept. of Medicine, Huddinge, Karolinska Institute, and PO Hematology, Karolinska University Hospital, Stockholm, Sweden

10Department of Internal Medicine IV, Klinikum Wels-Grieskirchen, Wels, Austria

11University of South Florida Morsani School of Medicine, Tampa, United States

12Dept. of Hematology, Hospital Universitario y Politécnico La Fe, Valencia, Spain

13Fifth Medical Dept., Hospital Hietzing, Vienna, Austria

14Hematology Department, 1st Propedeutic Internal Medicine Clinic, Laikon General Hospital, Athens, Greece

152nd Medical Dept., University clinic for hematology and internal oncology, Kepler University Hospital, Linz, Austria

161st Dept. of Internal Medicine, Laikon General Hospital, University of Athens, Athens, Greece

17Institut Català d'Oncologia-Hospital Duran y Reynals, Hospitalet de Llobregat, Barcelona, Spain

18Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna

19Ludwig Boltzmann Institute for Hematology and Oncology, Vienna, Austria

20Dept. of Hematology, G.GENNIMATAS General Hospital, Athens, Greece

21Hospital Universitario Central Asturias, Oviedo

22Hospital Clinico Universitario de Valencia, Valencia, Spain

23Dept. of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

24Hospital da Luz

25Centro de Investigação Interdisciplinar em Saúde, Universidade Católica Portuguesa de Lisboa, Lisbon, Portugal

26Institute of Hematology and Blood Transfusion, Prague, Czech Republic

27Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB, Murcia

28Dept. of Hematology, University Hospital Vall d'Hebron, University Autònoma of Barcelona

29Hematology Dept., Hospital de la Santa Creu i Sant Pau, Barcelona

30Hospital Universitario de Salamanca, Salamanca

31Hematology Dept. Hospital Universitario Son Espases, Palma Mallorca

32CIBERONC, Instituto Carlos III, Madrid, Spain

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Background:

Chronic myelomonocytic leukemia (CMML) is a rare myeloid stem cell disorder, defined by the presence of absolute monocytosis (≥1.0x109/μl), with dysplastic (MD) and proliferative (MP) features (Orazi A, IARC Press Lyon 2017, pp82-86). The only curative treatment option is allogeneic stem cell transplantation (allo-SCT), from which most patients are excluded (Symeonidis A, BJH 2015, pp239-246). Other options including hypomethylating agents (HMA), are not curative. Only one matched-pair analyses (Pleyer L, Leuk Res 2014, pp475-843) and one randomized clinical trial exclusively recruiting CMML patients (Wattel E, Blood 1996, pp2480-2487) have been published, with another one being underway (NCT02214407). We do not currently know whether active treatments provide overall survival (OS) benefit compared to best supportive care (BSC).

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Aims:

To evaluate the impact of 1stline and cumulative treatment on OS.

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Methods:

Data was collected from 7 European study groups and 2 US MDS Centers of Excellence. Data from 1633 patients was received; 67 patients were excluded (missing data); data cut-off 10.02.19; ML and LP performed data cleaning. Assign Data Management and Statistics GmbH performed statistical analyses with SAS 9.3.

Results: Median age (range) was 73 (18-104) years, male (68%), splenomegaly (25%), B-symptoms (17%), elevated serum LDH (55%), ECOG PS 0-1 (49%), t-CMML (7%), MP-CMML (49%), transfusion dependent (TD) (33%), IPSS cytogenetic good risk (57%), CMML-0 (39%), CMML-1 (29%), CMML-2 (19%); 33% were diagnosed in the pre-HMA era; 71% had died at data cut-off. In total, 42, 32, 16 and 10% of patients received 0, 1, 2, or ≥3 treatment lines, respectively; 24, 23, 6, 5 and <1% received hydroxyurea (HU), HMA, low-dose AraC (LDAC)/ImiDs/other drugs, intensive chemotherapy (IC) or allo-SCT as 1st line treatment, respectively.

Patients receiving BSC only had significantly less adverse risk factors, as compared to patients receiving treatment: Splenomegaly (8 vs 38%, p < 0.001), B-symptoms (4 vs 27%, p < 0.001), elevated LDH (30 vs 70%, p < 0.001), MP-CMML (31 vs 56%, p < 0.001), ECOG PS 32 (11 vs 16%, p = 0.008), RBC-TD (12 vs 45%, p < 0.001), PLT-TD (3 vs 12%, p < 0.001), poor IPSS cytogenetic risk (4 vs 9%, p < 0.001), trisomy 8 (0 vs 11%, p < 0.001), complex karyotype 0 vs 5%, p < 0.001), CMML-2 (14 vs 22%, p < 0.001).

Median OS [95% CI] was 27.9 [25.6, 26.9] months as of initial diagnosis for the total cohort, and 18.9 [17.1, 20.8] months for all patients with 1stline treatment, respectively. The impact of 1st line treatment, number of treatment lines, FAB subtype and initial diagnosis timepoint on OS are summarized in Fig1. Median OS [95% CI] for patients receiving BSC only was 29.3 [24.7, 34.5] months, and median OS from diagnosis (treatment start) was 24.1 (17.6), 32.2 (21.1), 31.8 (26.5), 19.1 (11.5) and 42.0 (38.2) months for patients receiving HU, HMA, others, IC or Allo-SCT as 1st line treatment, respectively. Patients with MP-CMML had significantly worse OS as compared to MD-CMML (median OS 18.7 vs 37.0 (p < 0.001) and 16.1 vs 24.5 months (p < 0.001) from diagnosis and treatment start, respectively). Patients diagnosed after approval of HMA had significantly longer OS from diagnosis as compared to those diagnosed in the pre-HMA era (29.9 vs 24.5 months, p < 0.001).

Figure

Figure

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Summary/Conclusion:

Allo-SCT as 1st line treatment remains the most effective treatment approach. Patients treated with HU or IC 1st line seem to fare worst. Multiple therapy lines are not indicative of poor outcome but may help maintain OS. Biologic selection may play a role.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.