Safety of treatment with pomalidomide and low-dose dexamethasone in patients with Relapsed or Refractory Multiple Myeloma with renal impairment

Interim results of an ongoing study assessing the safety and efficacy of the combination of pomalidomide and low dose dexamethasone (LoDEX) in patients with relapsed, refractory multiple myeloma (RRMM) suffering from renal impairment were presented at ASH 2015. The preliminary findings of this trial indicate that the safety profile of pomalidomide plus LoDEX in patients with renal impairment, including patients on dialysis, is consistent with what was seen in the pivotal trials with this combination. As such, this study suggests that pomalidomide, at the approved starting dose of 4 mg, can be safely administered together with LoDEX to (RRMM) patients with renal impairment (RI).

RI is common in patients with myeloma. Studies indicate that RI occurs in approximately 20-30% of newly diagnosed MM patients and it was shown to be associated with a poor prognosis. Data from 2 pivotal trials (MM-002 and MM-003) suggested comparable efficacy and tolerability of pomalidomide and LoDEX in patients with or without moderate RI. This is not surprising, as pomalidomide is extensively metabolized, with less than 5% of the drug being eliminated through the kidney. However, the trial looking into RI excluded patients with severe RI. To address the concerns on pomalidomide + LoDEX use in these patients, the MM-013 study was set up. MM-013 is a European multicenter, open-label, phase II study designed to assess the efficacy, safety, and pharmacokinetics of pomalidomide in combination with LoDEX in RRMM patients with moderate or severe RI, including those on dialysis. The presentation at ASH focused only on the safety and pharmacokinetic data.

The ongoing trial is set up to include 80 patients with RRMM across 3 cohorts: cohort A includes patients with moderate RI (estimated glomerular filtration rate [eGFR] ≥30 to

At the time of the presented analysis, 16 patients were included in cohort A, 21 in cohort B, and 10 in cohort C (47 patients in total). The median age of patients in the study was 71 years, 62% of the patients was male and the median baseline eGFR level was 24.8 mL/min/1.73m2 (range from 5.0 to 45.1 mL/min/1.73m2). The median duration of the renal insufficiency was 24.7 months. At the time of the analysis, treatment was still ongoing in 25 patients (11 in cohort A, 13 in cohort B, and 1 in cohort C). The main reason for treatment discontinuation was disease progression (N=15), while in 7 patients the treatment was stopped due to an adverse event. In total, 9 deaths were reported during the treatment period. In only 5 patients the pomalidomide dose had to be reduced due to a treatment-emergent adverse event (1 in cohort A, 3 in cohort B, and 1 in cohort C).

The most frequently observed grade 3/4 hematological toxicities were neutropenia (53%, respectively 50%, 52% and 60% in cohorts A, B, and C), anemia (30%, respectively 6%, 33% and 60% in cohorts A, B, and C) and thrombocytopenia (28%, respectively 31%, 19% and 40% in cohorts A, B, and C). The most common non-hematological grade 3/4 treatment-emergent adverse events were pneumonia (6%, 2 cases in cohort A, 1 case in cohort B) and hypocalcemia (6%, 1 case in cohort A, 2 cases in cohort B). Grade 3/4 infections were reported in 10 patients in total (21%). Peripheral neuropathy was seen in 4 patients, but this was always mild and only one case seemed treatment-related. There were no thromboembolic events in the study so far. From a pharmacological point of view, the pomalidomide exposure and the plasma concentration of pomalidomide appeared to be similar in the 3 study cohorts.

In summary, these data suggest that the combination of pomalidomide and LoDEX can be safely administered in patients with RI, including patients on dialysis. The efficacy data of this study will be reported in future presentations.

Reference

Ramasamy K, Dimopoulos M, van de Donk N, et al. Safety of Treatment (Tx) with Pomalidomide (POM) and Low-Dose Dexamethasone (LoDEX) in Patients (Pts) with Relapsed or Refractory Multiple Myeloma (RRMM) and Renal Impairment (RI), Including Those on Dialysis. Presented at ASH 2015; Abstract #374.