In the Novel Agents Era, Is the International Staging System Still Has the Prognostic Value in Patients with Renal Impairment?

The International Staging System (ISS) is a robust prognostic tool for patients with symptomatic multiple myeloma (MM). In this study, we evaluated the prognostic value of ISS in patients with renal impairment who were treated with novel agents. We retrospectively analyzed 456 MM patients who were treated upfront with novel-agent containing regimen. The degree of renal failure was classified according to the National Foundation Kidney Disease Outcome Quality Initiative chronic kidney disease (CKD) classification. Renal impairment (RI) was defined as an eGFR< 60 mL/min/1.73m² (CKD3-5). Of the all patients, 207 (45.4%) patients had stage 3-5 CKD at initial diagnosis. The β2-microglobulin level were significantly negatively correlated with GFR (r = - 0.536, P < 0.001), and median β2-microglobulin level of patients with CKD 3-5 was 7,600 mg/L (range, 668-80,000 mg/L). Sixty-seven percent of patients with CKD3-5 had ISS-3, and 89.8% of patients with CKD 4-5 had ISS-3. Patients with CKD 3-5 had poor overall survival outcomes compared to CKD 1-2 in univariate and not in multivariate analysis. ISS was powerful prognostic tool in all patients (P=0.003), but ISS had no prognostic impact in patients with CKD 3-5 (P = 0.897). Furthermore, patients with ISS 3 showed favorable overall survival compared to patients with ISS 1 or 2 in CKD 3. By multivariate analysis, cytogenetic high risk (HR 2.232, 95% CI 1.319-3.777, P =0.003) and hypercalcemia ≥11.5 g/dl (HR 2.036, 95% CI 1.170-3.544, P=0.012) were significantly associated with overall survival. In conclusion, β2-microglobulin level increase in patients with RI, and most of patients with RI had ISS-3. In addition, the ISS had no prognostic value in patients with RI in the novel agent era. New prognostic tool including cytogenetic risk will be needed for patients with RI.