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 m(2), RC2 60-89 ml/min/1.73 m(2), RC3 30-59 ml/min/1.73 m(2) and RC4 <30 ml/min/1.73 m(2)). 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.

Figure 1

Clinical outcomes with Total Therapy protocols (TT2, TT3) according to baseline eGFR class (RC1-4). (a) Overall survival; (b) progression-free survival.

Figure 2

Overall and progression-free survival by Total Therapy protocol (TT2–Thal, TT2+Thal, TT3a and TT3b combined) for RC1-3 and RC4 baseline classes. (a) Overall survival for RC1–3; (b) overall survival for RC4; (c) progression-free survival for RC1-3; and (d) progression-free survival for RC4.

Figure 3

Time to progression in GEP70-defined low-risk myeloma according to RC. (a) By individual RC quartiles; (b) RC4 versus RC1-3.

Figure 4

Overall survival, progression-free survival and time to progression in GEP70-defined low-risk myeloma according to baseline and transplant RCs. (a) Overall survival is superior with RC1–3 at both time points; (b) progression-free survival is superior with RC1–3 at both time points; (c) time to progression most shallow with RC1–3 at both time points.