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Identifying responders to melphalan and dexamethasone for newly diagnosed multiple myeloma patients

Background: MY7 clinical trial compared dexamethasone plus melphalan (MD) vs. prednisone plus melphalan (MP) in multiple myeloma treatment and found no statistically significant difference in overall survival (OS) between the two groups. But, patients reacted to treatment differently. We aimed to identify patients who might have benefited from dexamethasone, and characterize them by their baseline demographic and clinical factors.
Methods: First, the prognostic model for OS was developed on the MP arm. The estimated coefficients and baseline hazard were applied to the MD arm to derive martingale residuals (MR). Classification and regression tree analysis was done to identify independent predictive factors for OS and MR was used as response variable. All covariates in categorical shape were used as independent variables to develop the predictive model in MD arm. MP arm was divided accordingly. Subgroups with negative mean MR (survived > expected) were candidates for positive responders while those with positive mean MR (survived < expected) were candidates of negative responders. Mean MR in each subgroup and p values from comparison of OS (log rank test stratified by subgroups) were used to combine the appropriate subgroups as the positive responders or negative responders.
Results: A total of 97 patients (42%) in MD arm were identified as positive responders and their OS (median of 44.5 months) was significantly longer than that (median of 33 months) in the corresponding subgroups in MP arm (HR = 0.56, 95% CI 0.4-0.8; p = 0.0014). All positive responders had three common baseline characteristics: aged ≤75 years, calcium concentration ≤2.6 mmol/L and Durie-Salmon stages 2 or 3. Among patients with ECOG performance status<2 those with either HGB≥100 mg/dl or HGB<100 mg/dl and WBC≥4,000 and <4 lytic bone lesions were categorized as positive responders. Also, among the patients with ECOG performance status≥2, males with >3 lytic bone lesions were positive responders. Negative responders (HR = 1.56, 95% confidence interval 1.1 – 2.2; p = 0.006) included patients aged >75 or aged ≤75 with calcium concentration >2.6 mmol/L or aged ≤75 with calcium concentration ≤2.6 mmol/L but had Durie-Salmon stage 1.
Conclusions: Evaluation of the hypotheses validity warrants further studies. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2008-07-21 13:46:53.748

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/1330
Date22 July 2008
CreatorsEsmaeili, Abbas
ContributorsQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish, English
Detected LanguageEnglish
TypeThesis
Format1795692 bytes, application/pdf
RightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
RelationCanadian theses

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