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
Author(s): ,
Lisa Pleyer
Affiliations:
3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology,Paracelsus Medical University,Salzburg,Austria;Salzburg Cancer Research Institute (SCRI),Salzburg,Austria;Cancer Cluster Salzburg (CCS),Salzburg,Austria
,
Michael Leisch
Affiliations:
3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology,Paracelsus Medical University,Salzburg,Austria;Salzburg Cancer Research Institute (SCRI),Salzburg,Austria
,
Alexandra Kouraklis
Affiliations:
Hematology Division, Dept. of Internal Medicine,University of Patras Medical School,Patras,Greece
,
Eric Padron
Affiliations:
Malignant Hematology,H. Lee Moffitt Cancer Center and Research Institute,Tampa,United States
,
Jaroslaw P. Maciejewski
Affiliations:
Dept. of Hematology and Medical Oncology,Taussig Cancer Institute, Cleveland Clinic,Cleveland,United States
,
Blanca Xicoy Cirici
Affiliations:
Institut Català d'Oncologia,Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute,Badalona,Spain
,
Jennifer Kaivers
Affiliations:
Department of Hematology, Oncology, and Clinical Immunology,Heinrich-Heine-University,Düsseldorf,Germany
,
Johanna Ungerstedt
Affiliations:
HERM, Dept. of Medicine, Huddinge, Karolinska Institute, and PO Hematology,Karolinska University Hospital,Stockholm,Sweden
,
Heibl Sonja
Affiliations:
Department of Internal Medicine IV,Klinikum Wels-Grieskirchen,Wels,Austria
,
Patiou Peristera
Affiliations:
Hematology Division, Dept. of Internal Medicine,University of Patras Medical School,Patras,Greece
,
Anthony Hunter
Affiliations:
Malignant Hematology,H. Lee Moffitt Cancer Center and Research Institute,Tampa,United States;University of South Florida Morsani School of Medicine,Tampa,United States
,
Elvira Mora
Affiliations:
Dept. of Hematology,Hospital Universitario y Politécnico La Fe,Valencia,Spain
,
Klaus Geissler
Affiliations:
Fifth Medical Dept.,Hospital Hietzing,Vienna,Austria
,
Maria Dimou
Affiliations:
Hematology Department, 1st Propedeutic Internal Medicine Clinic,Laikon General Hospital,Athens,Greece
,
Maria J. Jimenez Lorenzo
Affiliations:
Institut Català d'Oncologia,Hospital Germans Trias i Pujol, Josep Carreras Leukemia Research Institute,Badalona,Spain
,
David Kiesl
Affiliations:
2nd Medical Dept., University clinic for hematology and internal oncology,Kepler University Hospital,Linz,Austria
,
Athina-Nora Vyniou
Affiliations:
1st Dept. of Internal Medicine, Laikon General Hospital,University of Athens,Athens,Greece
,
Bhumika J. Patel
Affiliations:
Dept. of Hematology and Medical Oncology,Taussig Cancer Institute, Cleveland Clinic,Cleveland,United States
,
Arnan Montserrat
Affiliations:
Institut Català d'Oncologia-Hospital Duran y Reynals,Hospitalet de Llobregat,Barcelona,Spain
,
Peter Valent
Affiliations:
Department of Internal Medicine I, Division of Hematology and Hemostaseology,Medical University of Vienna,Vienna,Austria;Ludwig Boltzmann Institute for Hematology and Oncology,Vienna,Austria
,
Roubakis Christoforos
Affiliations:
Dept. of Hematology,G.GENNIMATAS General Hospital,Athens,Greece
,
Teresa Bernal
Affiliations:
Hospital Universitario Central Asturias,Oviedo,Spain
,
Athanasios Galanopoulos
Affiliations:
Dept. of Hematology,G.GENNIMATAS General Hospital,Athens,Greece
,
Manisa Calabuig Munoz
Affiliations:
Hospital Clinico Universitario de Valencia,Valencia,Spain
,
Nicolas Bonadies
Affiliations:
Dept. of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital,University of Bern,Bern,Switzerland
,
Antonio Almeida
Affiliations:
Hospital da Luz,Lisbon,Portugal;Centro de Investigação Interdisciplinar em Saúde, Universidade Católica Portuguesa de Lisboa,Lisbon,Portugal
,
Jaroslav Cermak
Affiliations:
Institute of Hematology and Blood Transfusion,Prague,Czech Republic
,
Andrés Jerez
Affiliations:
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación,Universidad de Murcia, IMIB,Murcia,Spain
,
Julia Montoro
Affiliations:
Dept. of Hematology,University Hospital Vall d'Hebron, University Autònoma of Barcelona,Barcelona,Spain
,
Albert Cortés
Affiliations:
Hematology Dept.,Hospital de la Santa Creu i Sant Pau,Barcelona,Spain
,
Alejandro Avendaño Pita
Affiliations:
Hospital Universitario de Salamanca,Salamanca,Spain
,
Bernardo Lopez Andrade
Affiliations:
Hematology Dept. Hospital Universitario Son Espases,Palma Mallorca,Spain
,
Eva Hellstroem-Lindberg
Affiliations:
HERM, Dept. of Medicine, Huddinge, Karolinska Institute, and PO Hematology,Karolinska University Hospital,Stockholm,Sweden
,
Ulrich Germing
Affiliations:
Department of Hematology, Oncology, and Clinical Immunology,Heinrich-Heine-University,Düsseldorf,Germany
,
Mikkael Sekeres
Affiliations:
Dept. of Hematology and Medical Oncology,Taussig Cancer Institute, Cleveland Clinic,Cleveland,United States
,
Alan List
Affiliations:
Malignant Hematology,H. Lee Moffitt Cancer Center and Research Institute,Tampa,United States
,
Argiris Symeonidis
Affiliations:
Hematology Division, Dept. of Internal Medicine,University of Patras Medical School,Patras,Greece
,
Guillermo F. Sanz
Affiliations:
Dept. of Hematology,Hospital Universitario y Politécnico La Fe,Valencia,Spain;CIBERONC, Instituto Carlos III,Madrid,Spain
Richard Greil
Affiliations:
3rd Medical Dept. with Hematology, Medical Oncology, Rheumatology and Infectiology,Paracelsus Medical University,Salzburg,Austria;Salzburg Cancer Research Institute (SCRI),Salzburg,Austria;Cancer Cluster Salzburg (CCS),Salzburg,Austria
EHA Library. Pleyer L. Jun 15, 2019; 267423; S840
Lisa Pleyer
Lisa Pleyer
Contributions
×
Abstract

Abstract: S840

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 12:15 - 12:30

Location: Elicium 1

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).

Aims

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

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).

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.

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Chronic myelomonocytic leukemia, Outcome, Survival, Treatment

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