Introduction: Renal impairment (RI) is a common complication of multiple myeloma (MM) that causes significant morbidity and mortality. Approximately 20%-30% of patients (pts) at diagnosis and more than 50% of pts with advanced disease present RI. Moreover, pts with Acute Kidney Injury (AKI) are more likely to suffer advanced mortality and have worse prognosis. Thus, reverting renal dysfunction is critical for the management of these pts. However, there is little information on the renal evolution of pts with relapsed refractory MM (RRMM) receiving treatment with novel agents in clinical practice.
Aims: This is an observational, prospective, multicenter study aimed to evaluate the renal response to the administered therapy in pts with RRMM and moderate (clearance [CrCl] 30-50 mL/min) or severe (CrCl<30 mL/min) RI. We present results focused on the subgroup of pts with severe RI from an intermediate analysis 15 mos) after completion of the inclusion period (cut-off: May 8, 2017).
Methods: Renal and MM responses were evaluated according to International Myeloma Working Group criteria. eGFR by the Cockroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas were compared to analyse renal response. Descriptive statistics have been used for response rates and Kaplan Meier estimates for Progression-Free Survival (PFS) and overall survival (OS).
Results: A total of 327 pts were recruited and 99 pts with severe RI at study entry were included in the current analysis (mean ± SD age 75 ± 10 years, 49% male, 58% in first relapse). Main comorbidities were arterial hypertension (59%) and diabetes (27%). At diagnosis, 46% of pts had ISS stage III. Median time (range) from MM diagnosis was 2.5 (0.2-10.4) years. Main MM types were Ig G (50%), Bence Jones (20%), and Ig A (13%); 13% of pts with severe RI presented with high risk cytogenetic abnormalities. Main anti-myeloma therapies were: lenalidomide (LEN; 37%), bortezomib (BORT; 31%), and other treatments (OT; 32%: different chemotherapy regimens, 20%; and other non-chemotherapy treatments, 12%).The mean baseline eGFRs according to CG, MDRD and CKD-EPI formulas were 20.0/19.9/19.1 (± 7.5/9.4/9.0) mL/min,with a strong correlation between them (coefficients: CG/MDRD = 0.91; CG/CKD-EPI = 0.93; MDRD/CKD-EPI = 0.99). Using RIFLE classification, the proportion of pts with AKI during the MM treatment was 51.5%. Overall, 26.3% (95% CI, 16.7%-33.8%) of patients had a renal response (2.1% renal complete response [renalCR], 2.1% renal partial response [renalPR], and 22.1% renal minor response [renalMR]) according to the CG formula while responses measured by the MDRD formula, were 24.0% (3.1% renalCR, 2.1% renalPR, and 18.8% renalMR). Median time to best renal response was 1.7mos (range, 0.5-8.9 mos). After adjusting by demographic and clinical characteristics (52 evaluable pts), ISS stage III was statistically significantly associated with poor renal response. There were no significant differences in GFR improvement between pts according to the administered treatment (P = 0.306). The overall MM efficacy response rate (≥ PR) was 35.4%. The overall response rates were 48.4% and 38.9% for pts receiving BORT and LEN, respectively whereas only 11.5% of pts receiving OT achieved at least PR. PFS was 14.9 mos with LEN-based, 6.5 mos with BORT-based, and 2.6mos with OT (P=0.0003). OS was 24.6mos with LEN-based, 14.6 mos with BORT-based, and 4.6mos with OT (P < 0.0001).
Conclusions: This observational study shows that LEN- and BORT-based treatments are the regimens most commonly used in the clinical practice in RRMM pts with severe RI. These therapies can improve RI in approximately 26% of pts, with no differences between treatments. Despite this, there are still many pts who develop AKI during the course of treatment.
Morales: Alexion: Other: Personal fees; Celgene: Other: Personal fees. de la Rubia: Amgen: Other: Honoraria; Janssen: Other: Honoraria; Celgene: Other: Honoraria.
Asterisk with author names denotes non-ASH members.