Impact of renal impairment on bortezomib-based treatment outcome in patients with plasma cell disorders
Olga V. Pirogova, Elena E. Davidova, Valentina V. Porunova, Olga V. Kudyasheva, Elena I. Darskaya, Mariya S. Khrabrova, Boris V. Afanasyev, Alexey V. Smirnov
R. M. Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Chair of Hematology, Transfusiology and Transplantology, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russian Federation
Summary
Introduction
About 50% of newly diagnosed multiple myeloma (MM) patients have renal impairment (RI), 20% have acute kidney injury (AKI), and ~1–5% need hemodialysis at diagnosis. We evaluated the RI prevalence and its impact upon survival of patients with plasma cell disorders (PCD) treated at our center.Patients and methods
We analyzed 258 consecutive patients with PCD treated in the I. Pavlov First St. Petersburg State Medical University since 2008 to 2017. 97 patients with systemic AL-amyloidosis were excluded. 71 patients with renal impairment were identified (RI-group): 62 (87.3%) with MM and 9 (12.7%) with monoclonal gammopathy of renal significance. All patients received bortezomib-based chemotherapy, but the response data was available only for 51 (81.7%) of the RI-group patients. Myeloma response and progression were accessed using International Myeloma Working Group definitions. The Kidney Disease Improving Global Outcomes (KDIGO) guideline was used to asses RI and AKI. Complete renal response (CRR) was defined by proteinuria levels of 0.5 g/24 h or less, with albuminemia levels of 30 g/L and no more than 10% decrease in glomerular filtration rate (eGFR, estimated by MDRD formula) from baseline value. Partial RR (PRR) was defined by posttreatment proteinuria between 0.5 and 2.5 g/24 h, or by 50% or more reduction from baseline value, with albuminemia levels of 25 g/L or more and no more than a 10% decrease in eGFR from baseline value. 40 patients (56.3%) underwent renal biopsy.Results
Median follow-up was 621 day (93-3124). Median eGFR in RI-group at initial diagnosis was 23.03 (0.03-77.9) mL/ min/1.73 m2, median proteinuria was 6 g/day (0.15 – 33.95). In RI-group 23 patients (32.3%) had AKI greater than stage 1, 51 patients (57.7%) had severe RI (eGFR <30 ml/min/ 1.73 m2), 14 (19.7%) patients needed of dialysis. Renal lesions included cast nephropathy (n=9, 22.5%), light chain deposition disease (n=9, 22.5%), C3 – glomerulopathy (n=3, 7.5%), light chain amyloidosis (n=13, 32.5%), tubulointerstitial nephritis (n=3, 7.5%), membranoproliferative glomerulonephritis (n=1, 2.5%). One patient presented with focal segmental glomerulosclerosis. After first-line therapy, 33% achieved complete hematological response, 20.5%, very good partial response, 35.9%, partial response. Median time to RR was 87 days (10 to 570). Complete RR, partial RR and no RR were estimated in 26.6%, 46.6%, 26.8% of RI-group patients, respectively. Median eGFR in RI-group after the first-line therapy significantly increased to 36 (11.28 – 88.9) mL/min/1.73 m2 (p=0.001), median proteinuria significantly decreased to 0.64 (0-26.4) g/day (p=0.00007). In presence of AKI, including dialysis-dependent conditions, RR did not influence overall survival (OS) and progression-free survival (PFS) in RI group (p>0.05). Moreover, there were no statistically differences in overall survival and progression-free survival between RI-group and RI-free patients (n=90; p>0.05).Conclusion
In our study, patients with plasma cells disorders frequently had detectable renal impairment, but it did not significantly influence overall and progression-free survival.Keywords
Plasma cell disorders, chemotherapy, bortezomib, renal function, survival.