Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial

Abstract

Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed.

Single‐agent daratumumab in patients with relapsed and refractory multiple myeloma requiring dialysis: results of a Spanish retrospective, multicentre study

“…However, there are very few studies focused on the treatment of MM patients who progress to end stage renal disease and require dialysis (Chanan‐Khan et al , ; de la Rubia et al , ). Recently, results from a phase II clinical trial with pomalidomide and dexamethasone in patients with RI have been reported, with a PFS of 2·4 months in the cohort of patients requiring dialysis (Dimopoulos et al , ). Daratumumab data in patients with end‐stage RI requiring dialysis are based only on isolated case reports (Rocchi et al , ) and, to the best of our knowledge, our study is the first one to analyse the safety and efficacy of single‐agent daratumumab in patients with end‐stage renal disease.…”

NCCN Guidelines Insights: Multiple Myeloma, Version 1.2020

“…Although prospective data to define optimal dosing are often lacking, pomalidomide has been studied in patients with relapsed myeloma in 3 different categories of renal insufficiency (eGFR 30-40 mL/min/1.73 m 2 , eGFR ,30 mL/min/1.73 m 2 , and those requiring dialysis), and full-dose pomalidomide of 4 mg/d was found to be safe in all 3 groups. 51 High-dose chemotherapy and autologous stem cell transplantation can be safely performed in patients with renal insufficiency, including those on dialysis. Conditioning with reduced-dose melphalan has outcomes comparable to standard-dose melphalan and should be considered in those who are otherwise eligible for the procedure.…”

Tolerability and safety of real‑world use of pomalidomide in patients with relapsed/refractory multiple myeloma

“…LEN requires dose modification according to renal function. However, POM is indicated and is efficacious and safe even in patients with severe renal impairment (21). Maciocia et al (13) reported no significant difference in response, survival, or tolerability by renal function.…”