Safety of Pomalidomide/Low-Dose Dexamethasone Treatment in Renally Impaired Patients with Relapsed or Refractory Multiple Myeloma
Renal impairment (RI) is associated with poor prognosis, and occurs in about one-third of newly diagnosed patients with multiple myeloma (MM).1 Pomalidomide is a third-generation immunomodulatory drug approved for the treatment of patients with relapsed/refractory MM (RRMM), and has been reported to show comparable efficacy and tolerability in patients with or without moderate RI in the pivotal MM-002 and MM-003 trials.2,3 Since the pivotal trials did not enroll patients with severe renal impairment, including those on dialysis, the ongoing phase 2 MM-013 trial was specifically designed to assess the efficacy, safety, and pharmacokinetics of pomalidomide (4 mg) plus low-dose dexamethasone (LoDEX) in RRMM patients with moderate or severe RI; Ramasamy and colleagues reported on the safety and tolerability data from this trial.4
The MM-013 trial has a planned enrollment of 80 patients with MM-related RI who had received ?1 prior therapies (including lenalidomide) across 3 cohorts: cohort A (moderate RI, estimated glomerular filtration rate [eGFR] ?30 to <45 mL/min/1.73 m2; n = 33), cohort B (severe RI without dialysis, eGFR <30 mL/min/1.73 m2; n = 33), and cohort C (severe RI requiring dialysis; n = 14). At the time of this analysis, 47 patients had been enrolled; of these, 16 were assigned to cohort A, 21 to cohort B, and 10 to cohort C. The median age of the patient cohort was 71 years, the median number of prior therapy was 4, and the median duration of renal insufficiency was 24.7 months. Of the 47 patients, 22 discontinued treatment. Treatment discontinuation was due to progressive disease (PD) in 15 patients, adverse events (AEs) in 7 patients, and death in 9 patients (8 of these were deemed not related to study treatment). Pomalidomide dose reductions due to treatment-related adverse events (TEAEs) were only reported in 5 patients. Grade 3/4 AEs included neutropenia (53%), anemia (30%), thrombocytopenia (28%), and leukopenia (13%). Febrile neutropenia was reported in 1 patient; granulocyte-macrophage colony-stimulating factor was used in 47% of patients. The incidence of grade 3/4 TEAEs was slightly higher in patients with severe RI, which was attributed to disease biology. Non-hematologic toxicities were less common, and included pneumonia, hypocalcemia, pyrexia, peripheral edema, and fatigue. Infections occurred in 10 patients, and peripheral neuropathy was reported in 4 patients (all grade 1/2). Pomalidomide exposure and plasma concentration was found to be similar in all 3 cohorts. These data indicate that pomalidomide at a starting dose of 4 mg in combination with LoDEX can be administered to patients in all stages of RI; the authors recommend dose modifications and interruptions to manage hematologic toxicities.
- Knudsen LM, et al. Eur J Haematol. 2000;65:175-181.
- Siegel DS, et al. ASH 2012. Abstract 4072.
- Weisel KC, et al. ASCO 2013. Abstract 8527.
- Ramasamy K, et al. ASH 2015. Abstract 374.