Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma

Abstract

Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant. Glomerular filtration rate was graded in four renal classes (RCs), RC1–RC4 (RC1 ⩾90 ml/min/1.73 m2, RC2 60–89 ml/min/1.73 m2, RC3 30–59 ml/min/1.73 m2 and RC4 <30 ml/min/1.73 m2). RC1–3 had comparable clinical outcomes while RC4 was deleterious, even after improvement to better RC after transplant. Among the 85% of patients with gene expression profiling defined low-risk MM, Cox regression modeling of baseline and pre-transplant features, which also took into consideration RC improvement and MM complete response (CR), identified the presence of metaphase cytogenetic abnormalities and baseline RC4 as independent variables linked to inferior TTP post-transplant, while MM CR reduced the risk of progression and TTP by more than 60%. Failure to improve clinical outcomes despite RI improvement suggested MM-related causes. Although distinguishing RC4 from RC<4, 46 gene probes bore no apparent relationship to MM biology or survival.

Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma

“…For example, while irradiation is effective in combating tumor burden (24), it degrades the bone matrix (20) and damages the spectra of cellular constituents which govern bone remodeling (26). Chemotherapy diminishes tumor burden but, amongst other side effects, can be associated with renal toxicity and pancytopenia (25, 27). Extensive radiation and/or chemotherapy may necessitate BM transplantation, increasing likelihood of secondary side effects (i.e., graft-vs.-host disease, acute myelodysplastic leukemia, or myelodysplastic syndrome) (28, 29).…”

A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end‐stage renal disease requiring haemodialysis

“…Depending on the threshold applied to define RI, up to half of patients with MM develop this condition (Clark et al , 1999; Tosi et al , 2015). MM‐associated RI presents distinct therapeutic challenges and, in its severe forms, is predictive of a poorer prognosis (Gonsalves et al , 2015; Khan et al , 2015; Laing et al , 2015). Previous studies suggest that the currently available PIs, bortezomib and carfilzomib, are effective and well tolerated in MM patients with varying degrees of RI (San Miguel et al , 2008; Chanan‐Khan et al , 2012; Badros et al , 2013).…”

Spectrum of Cerebrovascular Disease in Patients with Multiple Myeloma Undergoing Chemotherapy—Results of a Case Control Study

“…Additionally the kidney and the brain share similar susceptibilities to hemodynamic derangements [42]. Also noteworthy, patients with MM who developed renal insufficiency had worse clinical outcomes despite improvement in their renal function or lack of significant difference in their baseline renal functions between various treatment protocols [43]. Thus increased risk of stroke, recurrent stroke, and mortality in our cohort could partly be due to renal disease, which may or might not have resulted from myeloma.…”