Outcomes of Consecutive Patients With Newly Diagnosed Myeloma Requiring Dialysis: Dialysis Independence is Associated with Rapid Myeloma Response and Predicts for Longer Survival

Renal failure (RF) commonly complicates symptomatic myeloma and may be severe enough to require extrarenal hemodialysis (HD). Immediate effective anti-myeloma therapy and vigorous supportive care are required to improve renal function. High cutoff HD to rapidly reduce the load of nephrotoxic light chains may offer some additional benefit in selected patients treated with bortezomib-based therapies (Cook M et al EHA 2016, Bridoux F et al ASH 2016). Outside clinical trials, there are limited data on the contemporary management and outcomes of NDMM patients requiring HD. Between 1995 and 2016, 50 patients (6.2% of 796 consecutive NDMM), who were treated in the Department of Clinical Therapeutics, presented with severe RF requiring HD, at the time of diagnosis. All patients received HD with regular filters. Median age was 69 years (37-88), 68% were >65 years; 92% had Hgb<10 gr/dl, 24% had hypeprcalcemia, 48% had elevated LDH, all had elevated β2-microglobulin (median 21.7 mg/L, range 6-60), and all were ISS stage 3. High risk cytogenetics (N=40) were present in 38%; per R-ISS, 75% were R-ISS-3 and 25% R-ISS-2. Median Bence Jones proteinuria (in patients who retained urine flow) was 2.2 gr/24h (range 0.1-8.8) and median level of involved free light chain (iFLC) was 9080 mg/l (range 119-201000 mg/l). Treatment was bortezomib-based in 41 (82%): 22% received bortezomib+dexamethasone (VD), 42% VD+cyclophosphamide (VCD), 16% VD+thalidomide (VTD), 2% VD+doxorubicin (PAD); 9(18%) patients received non-bortezomib containing regimens. Twenty five (50%) patients became HD independent at a median of 158 days from start of therapy (range 4-336); age ≤65 years was associated with higher probability (75% vs 38%) and shorter time to dialysis independence (51 vs 336 days) (p=0.027). Bortezomib-based triplets vs VD alone were associated with higher probability of HD independence (57% vs 27%; p=0.06). Median survival is 29 months; early mortality (<2 months from start of therapy) was 16%, mostly due to infectious complications. On intent to treat, 64% of the patients achieved ≥PR (CR:6%, VGPR: 32%, PR: 26%). At landmark analysis, patients who with ≥PR within the first 2 months had higher HD independence rates (68% vs 27%, p=0.004). At landmark analysis, discontinuation of HD was associated with a significant improvement in survival (median OS 63 vs 22 months for patients who remained on HD, p=0.002) and was similar to that of the rest of MM patients (57 months). High dose therapy (HDT) followed by ASCT was performed in five patients while on dialysis; 4/5 became dialysis independent approximately one month after HDT. In conclusion, about 6% of NDMM present severe RF requiring HD but half of them can become HD independent and this chance increases with bortezomib-based triplet therapy, without the use of special filters, and independence from HD is associated with a significant improvement in prognosis.