Abstract
Comorbidities have been demonstrated to affect progression-free survival (PFS) and overall survival (OS), although their impact in multiple myeloma (MM) patients is as yet unsettled. We (1) assessed various comorbidities, (2) compared established comorbidity indices (CIs; Charlson comorbidity index (CCI), hematopoietic cell transplantation-specific comorbidity index (HCT-CI)), Kaplan Feinstein (KF) and Satariano index (SI) and (3) developed a MM-CI (Freiburger comorbidity index, FCI) in 127 MM patients. Univariate analysis determined moderate or severe pulmonary disease (hazard ratio (HR): 3.5, P<0.0001), renal impairment (via estimated glomerular filtration rate (eGFR); HR: 3.4, P=0.0018), decreased Karnofsky Performance Status (KPS, HR: 2.7, P=0.0004) and age (HR: 2, P=0.0114) as most important variables for diminished OS. Through multivariate analysis, the eGFR ⩽30 ml/min/1.73m2, impaired lung function and KPS ⩽70% were significant for decreased OS, with HRs of 2.9, 2.8 and 2.2, respectively. Combination of these risk factors within the FCI identified significantly different median OS rates of 118, 53 and 25 months with 0, 1 and 2 or 3 risk factors, respectively, (P<0.005). In light of our study, comorbidities are critical prognostic determinants for diminished PFS and OS. Moreover, comorbidity scores are important treatment decision tools and will be valuable to implement into future analyses and clinical trials in MM.
Highlights
Despite today’s novel therapeutic options,[1,2] multiple myeloma (MM) remains an incurable disease in the majority of patients with highly variable outcome, depending on various risk factors.[2,3] The classification of MM is based on Salmon and Durie (S&D) and International Staging System, including primarily disease-related risk
Apart from organ function,[14,18] comorbidity assessment in other diseases,[7,10,33,34,35] but not in MM, has been acknowledged as important. This has recently been stressed,[23] as there is a vastly enlarged arsenal of treatment options for MM patients today, so that comorbidity assessmentsFbeside disease-related risk factorsFmay immensely assist in the allocation of available therapies
Risk classifications in MM are based on diseaserelated factors, patient-related factors, such as impaired performance status or organ function, may influence outcome,[31,36] this being highly relevant as MM develops primarily in elderly patients
Summary
Despite today’s novel therapeutic options,[1,2] multiple myeloma (MM) remains an incurable disease in the majority of patients with highly variable outcome, depending on various risk factors.[2,3] The classification of MM is based on Salmon and Durie (S&D) and International Staging System, including primarily disease-related risk. Patient-related factors, like comorbidities and abnormal organ function, describing additional hazards on outcome, are not as yet integrated in prognostic models. Risk models are of importance, as myeloma patients are typically in their sixth to seventh decade of life and often fragile. Prior studies have shown that comorbidities have substantial impact on overall survival (OS), such as in patients with myelodysplastic syndromes,[5,6,7] acute
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