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Published on: July 15, 2015
Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment:
Meletios Dimopoulos1, Katja Weisel1, Niels W C J van de Donk1
1Meletios Dimopoulos, National and Kapodistrian University of Athens, Athens, Greece; Katja Weisel, University Hospital of Tuebingen, Tuebingen, Germany; Niels W.C.J. van de Donk, VU Universiteit Medical Center, Amsterdam; Pieter Sonneveld, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Karthik Ramasamy, Oxford University Hospital and NIHR BRC Blood Theme, Oxford; Matthew Streetly, Guy's and St Thomas' National Health Service Foundation Trust, London, United Kingdom; Barbara Gamberi, Arcispedale S. Maria Nuova, Reggio Emilia; Massimo Offidani, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona; Antonio Ardizzoia, Oncology Department, ASST Lecco, Lecco, Italy; Frank Bridoux, University Hospital and University of Poitiers, Poitiers, France; Javier de la Rubia, Hematology Service University Hospital Doctor Peset and Universidad Católica de Valencia "San Vicente Mártir," Valencia; Maria-Victoria Mateos, Instituto de Investigación Biomédica de Salamanca and University of Salamanca, Salamanca, Spain; Elisabeth Kueenburg, Shona Collins, Antonia Di Micco, Barbara Rosettani, and Pamela Bacon, Celgene International, Boudry, Switzerland; and Yan Li, Translational Development and Clinical Pharmacology, Celgene Corporation, Summit, NJ.
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 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); 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.
Insights
Pomalidomide plus low-dose dexamethasone effectively treats relapsed/refractory multiple myeloma in patients with renal impairment, including those on hemodialysis. The treatment demonstrated acceptable safety and efficacy across different stages of renal dysfunction.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Renal impairment (RI) significantly limits treatment options for patients with relapsed/refractory multiple myeloma (RRMM).
- Effective and safe therapeutic strategies are needed for RRMM patients with compromised kidney function.
Purpose of the Study:
- To prospectively evaluate the efficacy and safety of pomalidomide plus low-dose dexamethasone (LoDEX) in RRMM patients with moderate to severe RI.
- To assess outcomes in patients requiring hemodialysis.
Main Methods:
- A phase II trial (MM-013) enrolled 81 RRMM patients into three cohorts based on renal function: moderate RI, severe RI, and severe RI requiring hemodialysis.
- Patients received pomalidomide 4 mg/d (days 1-21) and LoDEX (20 or 40 mg weekly) in 28-day cycles.
- The primary endpoint was overall response rate (ORR).
Main Results:
- Overall response rates were 39.4% (moderate RI), 32.4% (severe RI), and 14.3% (hemodialysis).
- Disease control was achieved in 100%, 79.4%, and 78.6% of patients, respectively.
- Median overall survival varied from 16.4 months (moderate RI) to 5.2 months (hemodialysis). Grade 3/4 hematologic adverse events were more frequent in the hemodialysis cohort.
Conclusions:
- Pomalidomide plus LoDEX is an effective treatment for RRMM patients with moderate to severe renal impairment, including those on hemodialysis.
- The safety profile was acceptable across all renal impairment groups, with no new safety signals identified.
- Pomalidomide pharmacokinetics were consistent among the renal cohorts, supporting its use in this population.
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