Bone Marrow Research Study Agents San Miguel et al. (VISTA) [31] Chanan-Khan et al. [33] oBt+hevraargieetnytsof Dialysis dependence mandatory Renal Inclusion criteria VMP versus MP No renal exclusions Kastritis et al. [34] Morabito et al. [35] Ludwig et al. [36] Ludwig et al. [37] VAD Tosi et al. [38] T + other VAD (or similar), M + sCr >2 mg/dL hdD or D alone mandatory at Group B: hdD + enrolment T +/ B VD ++ DothoerrVag+ents No renal exclusions V, V + D or V, D + A GFR <20 mls/min mandatory at enrolment GFR <50 mls/min mandatory at enrolment sCr >130 μmol/l mandatory at enrolment Dimopoulos et al. [39] R + D No renal exclusions Dimopoulos et al. [40] R + D versus D sCr <2.5 mg/dL Dimopoulos et al. [40] R + D No renal exclusions 5 Renal outcomes Reversal = GFR >60 at end from <50 at start VMP group = 44% reversal MP group = 34% sCr <2 g/dL deﬁned as renal reversal, 83% met this defn median TTR = 1.9 mo 80% of those previously dialysed came oﬀ dialysis Reversal = normalisation of CrCl, occurred in 41% with no diﬀerences across treatment subgroups 22% of those previously dialysed came oﬀ dialysis Median sCr fell from 9.05 to 2.1 mg/dL (0.8–2.4) No deﬁned criteria for renal recovery, median GFR increased to 48.4 ml/min (6.7–135.5 mls/min), improvement in GFR correlated with tumour response Yes, Improvement deﬁned as sCr <130 μmol/l, 12/15 responding pts had renal recovery Recovery deﬁned as either CrCl, 50 to >60 or movement from one subgroup to another, 42% of those with renal impairment had some improvement Improvement deﬁned as movement from one subgroup to a better one, 72% of those who received R+D had some improvement, data for D alone not quoted 26.6% had some change from one renal subgroup to another, 12.5% had deterioration of renal function Table 1: Renal characteristics of chemotherapy trials where both baseline renal characteristics and outcomes are reported. V: bortezomib, D: dexamethasone, M: Melphalan, P: prednisolone, A: doxorubicin, hD: high dose, T: Thalidomide, BMT: bone marrow transplant, R: Lenalidomide, CrCl: creatinine clearance (mls/min), Bx: biopsy, sCr: serum creatinine, CR: complete response, MR: minimal response, TTR: time to response, GFR: glomerular ﬁltration rate. Klein et al. reported a retrospective analysis of patients with relapsed/refractory MM and renal impairment; the cohort included patients who were dialysis dependent [32]. After treatment with Lenalidomide and dexamethasone they report an improvement in renal function in 26%; patients whose renal function stabilised or improved had a higher frequency of PR than those whose renal function deteriorated [41]. All but 1 dialysis dependent, No clear defnof renal reversal Median sCr = 6.8 mg/dL 4 had “improved” renal function (1 pt (3.1–12.8)? before starting never started dialysis, 2 came oﬀ dialysis dialysis after a CR and 1 oﬀ dialysis after a MR) No renal Bx Baseline renal characteristics CrCl < 30 = 6% (B), 5% (control) CrCl 30–60 = 28% (B), 50% (control) CrCl >60 = 46 (B), 46% (control) sCr >4 mg/dL = 44% sCr 2–4 mg/dL = 56% 24% dialysis dependent No renal Bx CrCl 51–80 = 10.3% CrCl 30–50 = 19.7% CrCl <30 = 70% 12% dialysis dependent Mean sCr 9.05 mg/ml (5.2–12) 63% dialysis dependent No renal Bx Median GFR 20.5 mls/min (3.7–49.9 mls/min) 6 renal Bx (2 showed amyloid so patients excluded) Initial sCr for all listed, Median = 155 μmol/l Range 131–998 μmol/l 24 had baseline CrCl, 50 (13–49), 2% dialysis dependent at baseline CrCl >60 = 71% CrCl 30–60 = 24% CrCl <30 = 5% CrCl >80 = 56% CrCl 50–80 = 23.9% CrCl 30–50 = 12.6% CrCl <30 = 7.2% 3% dialysis dependent