Program: Oral and Poster Abstracts
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster I
Patients and Methods Patients were identified through the MDS Clinical Research Consortium and were included if they had a WHO diagnosis of MDS, MDS/myeloproliferative neoplasm (MPN), therapy related MDS (t-MDS), or AML (20-30% myeloblasts) and had any karyotypic abnormality involving chromosome 3. Data analyzed included baseline demographics, disease characteristics, IPSS/IPSS-R scores, treatment and outcome. Responses to HMA therapy were evaluated using International Working Group (IWG) 2006 criteria. Kaplan-Meier estimates were used for overall survival.
Results A total of 413 patients were identified with a median age at diagnosis of 67 years. WHO classification was as follows: 9% RA/RARS, 12% RCMD, 26% RAEB-1, 31% RAEB-2, 2% MDS/MPN, 7% MDS Unclassified, 13% AML; 34% had t-MDS. Overall, 97% of patients were higher risk by IPSS-R (i.e., intermediate to very high risk) with a median blast % in bone marrow of 8%. Distribution of cytogenetic abnormalities were inv(3) (10%), del(3q) (12%), t(3q) (18%), monosomy 3 (22%), 3p abnormalities (22%), and other chromosome 3 changes (17%). Median OS for the cohort was 12.0 months (95% C.I. 10.8 to 13.9 months) and 31% of patients without AML transformed to AML. IPSS-R was predictive of median OS across subgroups (P < 0.00001). The specific cytogenetic abnormality was predictive for survival (P < 0.00001) with median OS for t(3q) 19 months, inv(3) 13 months, del(3q) 13 months, 3p 10 months, monosomy 3 9 months, and other 3 abnormalities 11 months. There was no survival difference between patients with translocations of 3q21 versus 3q26 (median OS 18 months versus 18.6 months, P = 0.96). Patients with an isolated chromosome 3 abnormality had significantly improved OS (25.1 months versus 10.9 months (P < 0.00001). Complex karyotype (>/= 3 abnormalities) was observed in 74% of patients and was associated with decreased OS (11 months versus 21 months, P < 0.00001). Of patients who received HMA therapy (48%), the overall response rate was 46% (17% hematological improvement (HI), 7% PR, 20% CR, 2% marrow CR (CRm) with stable disease in 23%). Median OS with and without HMA was 15.5 months versus 8.4 months (p=0.038). In int-2/high risk patients by IPSS, HMA treated patient had a median OS of 14.0 months versus 7.6 months for patients not treated with HMAs (P = 0.005) with no benefit for HMAs in lower-risk patients (median OS 24.5 months with HMA versus 38.7 months without; P =0.41). Cox regression modeling with HMA therapy, IPSS and clinical site confirmed the HMA OS benefit in higher-risk patients (HR 0.69; 95% CI 0.53-0.89; P = 0.005), but showed decreased OS in lower-risk patients (HR 2.0; 95% CI 1.03-3.92; P = 0.04). Allogeneic transplantation was performed in 18% (n=75) of patients, with median OS of 18 months versus 10 months in non-transplanted patients (P < 0.00001).
Conclusion In this large cohort of patients with MDS and oligoblastic AML associated with chromosome 3 abnormalities, survival was heterogeneous but overall poor, with isolated chromosome 3 abnormality and t(3q) patients having a more favorable OS than patients with other chromosome 3 anomalies. MDS patients with 3p changes have poor outcomes. Although some patients with chromosome 3 respond to HMA therapy, the overall survival remains poor and novel approaches are needed.
Disclosures: Sekeres: TetraLogic: Membership on an entity’s Board of Directors or advisory committees ; Celgene Corporation: Membership on an entity’s Board of Directors or advisory committees ; Amgen: Membership on an entity’s Board of Directors or advisory committees . Steensma: Amgen: Consultancy ; Celgene: Consultancy ; Incyte: Consultancy ; Onconova: Consultancy . Lancet: Boehringer-Ingelheim: Consultancy ; Kalo-Bios: Consultancy ; Pfizer: Consultancy ; Seattle Genetics: Consultancy ; Celgene: Consultancy , Research Funding ; Amgen: Consultancy . List: Celgene Corporation: Honoraria , Research Funding . Komrokji: Incyte: Consultancy ; Pharmacylics: Speakers Bureau ; Celgene: Consultancy , Research Funding ; Novartis: Research Funding , Speakers Bureau .
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