Pomalidomide/Dexamethasone Effective in R/R Myeloma With Renal Insufficiency

February 28, 2018

Nearly 80% of R/R myeloma patients with severe renal impairment requiring hemodialysis achieved disease control with this treatment combination.

The combination of pomalidomide plus low-dose dexamethasone showed efficacy with high rates of disease control in relapsed or refractory multiple myeloma patients with severe renal impairment, according to the results of a phase II study.

About 20% to 30% of patients diagnosed with myeloma will present with renal impairment, and more patients will develop it over time. Renal impairment is associated with poor prognosis and short survival duration, with a median overall survival of less than 2 years.

Pomalidomide plus low-dose dexamethasone administered in combination has shown efficacy in patients with relapsed or refractory myeloma who have normal kidney function or moderate renal impairment. Additionally, pomalidomide is mostly metabolized through the liver. Therefore, in this study, Meletios Dimopoulos, MD, of the National and Kapodistrian University of Athens School of Medicine, Greece, and colleagues wanted to test this combination regimen in patients with moderate or severe renal impairment.

The study include 81 patients enrolled in three cohorts. Cohort A comprised patients with moderate renal impairment, cohort B included patients with severe renal impairment, and cohort C consisted of patients with severe renal impairment requiring hemodialysis. Patients were assigned to pomalidomide at a dosage of 4 mg per day on days 1 to 21 and low-dose dexamethasone at 20 or 40 mg once per week in 28-day cycles. The results of the study were published in the Journal of Clinical Oncology.

The overall response rates for cohorts A, B, and C were 39.4%, 32.4%, and 14.3%, respectively. Patients in cohort A had a median duration of response longer than 1 year (14.7 months); the median duration of response in cohort B was 4.6 months and in cohort C was not estimable. Disease control was achieved in 100%, 79.4%, and 78.6% of patients in cohorts A, B, and C, respectively.

“Of note, 78.6% of patients in cohort C achieved disease control, despite receiving a short duration of treatment-median of three cycles-and having advanced disease,” the researchers wrote.

With a median follow-up of 4.6 months, the median progression-free survival was 6.5 months, 4.2 months, and 2.4 months for cohorts A, B, and C, respectively. With a median follow-up of 8.6 months, the median overall survival was 16.4 months for cohort A, 11.8 months for cohort B, and 5.2 months for cohort C.

“Complete renal responses were observed only in cohort A (18.2%), whereas patients in cohort B experienced partial (5.9%) and minimal (29.4%) renal responses, which suggests that the normalization of renal function during treatment with pomalidomide plus low-dose dexamethasone is more likely to occur in patients with moderate renal impairment,” the researchers wrote.

No patients in cohort C were able to become hemodialysis-independent.