Introduction:
Risk stratification of patients with light chain (AL) amyloidosis at diagnosis is invaluable. Currently, the Mayo 2012 staging system is mainly used to risk-stratify patients. We evaluated the role of increased mean corpuscular volume (MCV) at diagnosis in predicting survival.
Methods:
We conducted a retrospective study of patients with newly diagnosed AL amyloidosis seen at Mayo Clinic, Rochester between January 2006 through December 2015. The diagnosis of AL was confirmed with biopsy and the determination of organ involvement was according to consensus criteria. Staging was done according to the Mayo 2012 staging system and patients with stage III/IV were considered to have advanced stage disease. Patient and disease factors were compared for categorical and continuous variables using the χ2 and the Wilcoxon signed rank tests, respectively. Overall survival (OS) was defined as the time from diagnosis to death of any cause. Survival analysis was done using the Kaplan-Meier method.
Results:
A total of 1064 patients were identified and were divided into two groups: those with an MCV ≥ 96 fl (Elevated MCV, n=180) and those with an MCV <96 fl (Low MCV, n=884). The median age at diagnosis for the whole cohort was 64, with an interquartile range (IQR) of 57-71. Overall, 222 (23%) had Mayo 2012 stage 1, 199 (21%) had stage 2, 239 (25%) had stage 3, and 290 (31%) had stage 4 disease. Patients with an elevated MCV were more likely to be more than 65 years old compared to patients with a low MCV (61% vs. 44%, p<0.0001). They were also likely to have an advanced Mayo 2012 stage (68% vs. 53%, P=0.0008).
The median OS was significantly lower in patients with an elevated MCV compared to patients with a low MCV (median PFS 13 months vs. 41 month, respectively, P<0.0001)(Figure 1). On a univariable analysis, predictors of OS were advanced Mayo 2012 stage (RR 3.26, P<0.001) and MCV ≥ 96 (RR 1.6, P<0.0001). On the multivariable analysis, both variables remained predictors of OS [advanced Mayo 2012 stage (RR 3.19, P<0.001) and MCV ≥ 96 (RR 1.3, P=0.016)].
Conclusion:
The median OS was shorter by 28 months in newly diagnosed AL amyloidosis patients with an MCV ≥ 96 compared to patients with an MCV<96. An elevated MCV was predictive of shorter survival, independent of the Mayo Stage. This variable is easily available, measured in all newly diagnosed patients, and provides valuable prognostic information for the treating physician.
Dispenzieri:Intellia: Consultancy; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Alnylam: Research Funding; Celgene: Research Funding; Akcea: Consultancy. Lacy:Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Kapoor:Sanofi: Consultancy, Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Glaxo Smith Kline: Research Funding. Gertz:i3Health: Other: Development of educational programs and materials; Alnylam: Consultancy; Celgene: Consultancy; Appellis: Consultancy; Teva: Speakers Bureau; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Ionis/Akcea: Consultancy; Prothena Biosciences Inc: Consultancy; Janssen: Consultancy; International Waldenstrom Foundation: Research Funding; Proclara: Membership on an entity's Board of Directors or advisory committees; Johnson and Johnson: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; DAVA oncology: Speakers Bureau. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.
