MDS (Myelodysplastic syndromes)/ MPN (Myeloproliferative neoplasms) Prognosis and treatment November 4th 2011, Paris Reinhard STAUDER MD, MSc, Associate Professor Department of Internal Medicine V (Hematology & Oncology) Medical University Innsbruck, Austria reinhard.stauder@i‐med.ac.at
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Total Score: 0...low; 1‐2...intermediate; ≥ 3...high risk Sorror et al.; Blood, 2005
Sorror Score of Co‐morbidity
AUCZ
FR
GE
GR
ND
RO
SPSW
UK
0.5
11.
52
2.5
33.
54
Mea
n S
orro
r Sco
re
Mean Score 2.4, median 2, range (0 to 11)(0...low risk; 1-2...intermediate risk; ≥ 3...high risk) EU-MDS Registry
Comorbidity as Prognostic Variable in MDS
ScoreOverall survival (OS)
Event‐free survival (ES)
AML‐freeSurvival(AFS)
HCT‐CIUnivariat P<0.05 P<0.05 n.s.
Multivariat P<0.05 P<0.05 n.s.W. Sperr et al., Ann. Oncology, 2009
Comorbidities arean independentprognostic factorfor OS and EFS in univariate and in multivariate analyses.
Comparative Evaluation of the HCT‐CI and CCI in a Core Data Set of 419 Patients of the Austrian MDS Platform.
Impact of comorbidities in MDS
1708 SEER MDS patients ≥65 yrscm significant in uni‐ and multivariateMost relevant myocardial infarction and COPD
Wang R. et al., Leuk. Research 2009
ACE‐27 MDACC* MDS Score (n=600, retrospective )
Comorbidities %Survival median(months)
None 23 32
Mild 42 17
Moderate 21 15
Severe 14 10
ComorbiditySignificance
for OS
Cardiovascular .0001
Malignancy .0001
Renal .02
Gastrointestinal .05
Endocrine .07
Multivariate model
Parameter Score
Age 2
Comorbiditiesmildmoderatesevere
13
IPSSInt‐2High
23
*MDACC (MD Anderson Cancer Center) Garcia‐Manero et al., # 605; ASH 2010 & JCO 2011
No correlation with leukemia transformation
Hematological malignancies in elderly ‐ Items
Demographic analyses & description of “real life” (in registries) beyond euphemistic situation in clinical studies.
Use appropriate statistical methods.
Individualize treatment based on age‐adjusted life expectancy, geriatric assessment & patients´ expectations (biological age).
Develop recommendations & guidelines for elderly. Address renal, cardiac and cognitive impairment and neuropathy.
Perform clinical studies in elderly & in non‐fit.
Propagate the fair treatment for all elderly cancer patients!
ESA(Lenalidomid1)
Treatment options in senior low‐risk MDS (IPSS Low‐grade und Intermediate I)
Symptomatic anaemia, granulopenia, thrombopenia
ESA ± G‐CSF (RARS)
CyA (ATG)
Valproic‐acid
Del(5q)
Supportive therapy including transfusions& iron‐chelation
EPO < 500 U/l and/or low
transfusion need 2
EPO ≥ 500 U/land/or high
transfusion need 2
Hypoplastic MDS
HLA‐DR15 3
1 MDS approval so far only by FDA; EMEA approval is pending. Thalidomid?2 Based on predictive model (Nordic score)3 Response more frequent in younger patients, in hypoplastic MDS and in HLADR‐15. 4 5‐Azacytidine EMEA approval for high‐risk MDS & CMML. Might be effective in low risk MDS even in granulopenia and thrombopenia. Is analysed in clinical studies. Has replaced LDARA‐C & LD Melphalan.ATG, anti‐thymocyte globulin; CMML, Chronic myelomonocytic leukemia; ESA, erythropoiesis‐stimulating agent; CyA, Cyclosporin‐A
(5‐Azacytidine4)(Lenalidomid1)
Stauder & Wolf, ESMO Handbook of Cancer in the Senior Patient, 2010
No
Donor
RIC‐HSCT2AML‐like induction/consolidation
or 5‐Azacytidine
Intensive therapy 1
Yes
5‐Azacytidine3or Clinical study
or BSC4
No Donor
1 Depending on age, performance status, comorbidities, feasability, karyotype and patient preference. 2 Upper age limits applied are 50‐55yrs for myeloablative HSCT (hamatopoietic stem‐cell transplantation ) and 65‐70yrs for RIC‐HSCT (reduced intensity conditioning HSCT)3 5‐Azacytidine represents the treatment of choice in elderly patients who are not eligible for intensive therapieslike AML‐induction or HSCT. AZA is effective even in unfavourable karyotype like monosomy 7 or complex aberrations. 4 BSC (best supportive care).
Stauder & Wolf, ESMO Handbook of Cancer in the Senior Patient, 2010
Treatment options in senior high‐risk MDS (IPSS Intermediate II und High grade)
Hematological malignancies in elderly ‐ Items
Demographic analyses & description of “real life” (in registries) beyond euphemistic situation in clinical studies.
Use appropriate statistical methods.
Individualize treatment based on age‐adjusted life expectancy, geriatric assessment & patients´ expectations (biological age).
Develop recommendations & guidelines for elderly. Address renal, cardiac and cognitive impairment and neuropathy.
Perform clinical studies in elderly & in non‐fit.
Propagate the fair treatment for all elderly cancer patients!
Azacitidine (Vidaza)Phase III, AZA‐001
Fenaux et al., Lancet Oncol, 2009
Hematological malignancies in elderly ‐ Items
Demographic analyses & description of “real life” (in registries) beyond euphemistic situation in clinical studies.
Use appropriate statistical methods.
Individualize treatment based on age‐adjusted life expectancy, geriatric assessment & patients´ expectations (biological age).
Develop recommendations & guidelines for elderly. Address renal, cardiac and cognitive impairment and neuropathy.
Perform clinical studies in elderly & in non‐fit.
Propagate the fair treatment for all elderly cancer patients!