Patients with relapsed/refractory multiple myeloma with renal impairment who were treated with pomalidomide and low-dose dexamethasone had an overall response rate of up to 39%, according to findings of a phase II study published in the <em>Journal of Clinical Oncology.</em>
Meletios Dimopoulos, MD
Patients with relapsed/refractory multiple myeloma with renal impairment (RI) who were treated with pomalidomide (Pomalyst) and low-dose dexamethasone had an overall response rate (ORR) of up to 39%, according to findings of a phase II study published in theJournal of Clinical Oncology.
The phase II MM-013 study, a multicenter, open-label, noncomparative, study, was conducted at 18 sites across 8 countries in Europe. A total of 81 patients with relapsed/refractory multiple myeloma and RI were enrolled from February 2014 to July 2016.
Eligible adult patients had a documented diagnosis of multiple myeloma and measurable disease by M-protein or serum free light chain levels. Patients must have received at least 1 antimyeloma regimen, including lenalidomide (Revlimid), and documented progression per International Myeloma Working Group criteria during or after their last antimyeloma treatment. All patients were required to have impaired renal function with an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2according to the Modification of Diet in Renal Disease equation.
Investigators assigned patients to 1 of 3 renal cohorts: cohort A (moderate RI; eGFR 30 to <45 mL/min/1.73 m2; n = 33); cohort B (severe RI; eGFR < 30 mL/min/1.73 m2; n = 34); and cohort C: severe RI requiring hemodialysis (n = 14).
All patients received pomalidomide at 4 mg/day on days 1 to 21 of 28-day cycles. Patients aged ≤75 years received 40 mg of dexamethasone, and those over 75 years received 20 mg of dexamethasone on days 1, 8, 15, and 22. Thromboprophylaxis was mandatory for patients who did not require hemodialysis and used for patients on hemodialysis when appropriate and feasible.
The median age for the overall population was 72 years (range, 52-86). The majority of patients (81.5%) were aged 65 years or older and male (60.5%). Median time from multiple myeloma diagnosis to enrollment was 3.8 years (range, 0.5-19.4). Most patients had chronic (>1 month) renal insufficiency, with a median duration of renal insufficiency before study enrollment of 24.7 months in cohort A, 40.4 months in cohort B, and 9.4 months in cohort C.
Patients in cohort C had higher involved sFLC levels than did patients in cohorts A and B. Overall, patients received a median of 4 prior antimyeloma regimens. All patients had received prior lenalidomide treatment and 97.5% had received prior bortezomib (Velcade). Approximately 25% of patients underwent prior stem cell transplantation.
ORR was 39.4% with a median duration of response (DoR) of 14.7 months in cohort A compared with 32.4% and a median DoR of 4.6 months in cohort B, and 14.3% and a median DoR that was not reached in cohort C. More than half (51.5%) of patients in cohort A derived clinical benefit compared with 41.2% in cohort B, and 21.4% in cohort C.
Ten of the 14 patients in cohort C had their response assessed by M-protein (serum or urine) levels and 3 by sFLC levels. Among these patients, 57.1% had stable disease and 78.6% had disease control.
In patients who had a partial response or greater, median time to response was 0.99 months in cohort A, 0.95 months in cohort B, and 1.91 months in cohort C.
Prior therapy (odds ratio [OR], 3.25; 95% CI, 1.03-10.25;P= .0438) and time since diagnosis (OR, 3.65; 95% CI, 1.17-11.43;P= .0260) were identified as significant predictors of myeloma response in multivariable analysis.
With a median follow-up duration of 4.6 months, median progression-free survival was 6.5 months in cohort A compared with 4.2 months in cohort B and 2.4 months in cohort C. Median time to progression was 6.2 months overall, and 8.3 months, 5.5 months, and 4.0 months in cohorts A, B, and C, respectively. With a median follow-up duration of 8.6 months, median OS was 16.4 months, 11.8 months, and 5.2 months in cohorts A, B, and C, respectively.
“Results presented here add to the limited body of evidence of treatment options for patients with advanced stages of multiple myeloma and RI and will help healthcare providers make appropriate treatment choices for this patient population,” lead author Meletios Dimopoulos, MD, chair of clinical therapeutics at the University of Athens in Greece, and coinvestigators wrote.
As of the January 28, 2017, data cutoff, 13 patients were still on treatment7 in cohort A, 5 in cohort B, and 1 in cohort C. A total of 68 patients discontinued treatment, mostly because of progressive disease (39 patients; 48.1%).
A total of 23 patients (28.4%) died during treatment, which was defined as death on or after the date of first study drug dose and within 28 days of the last study drug dose. Myeloma progression was the most common cause of death, with plasma cell myeloma reported in 5 patients overall.
The most common grade 3/4 hematologic treatment-emergent adverse event (TEAE) across all 3 cohorts were neutropenia (53.1%), anemia (35.8%), and thrombocytopenia (27.2%). Infections, mainly pneumonia, were the most commonly reported grade 3/4 nonhematologic TEAEs26 (32.1%) overall, and 13 (39.4%), 9 (26.5%), and 4 (28.6%) in cohorts A, B, and C, respectively. Other grade 3 and 4 nonhematologic TEAEs included hypocalcemia, hyperkalemia, renal failure, pyrexia, fatigue, and peripheral edema.
A total of 51 patients (63.0%) presented with 1 or more serious TEAEs, including 18 (54.5%) in cohort A, 21 (61.8%) in cohort B, and 12 (85.7%) in cohort C. Three patients (3.7%) reported experiencing second primary malignancies, 1 each for squamous cell lung cancer, pancreatic cancer, and skin carcinoma.
Pomalidomide is approved by the FDA for use in combination with low-dose dexamethasone for the treatment of patients with relapsed/refractory multiple myeloma.
Dimopoulos M, Weisel K, van den Donk NWCJ, et a. Pomalidomide Plus low-dose dexamethasone in patients with relapsed/refractory multiple myeloma and renal impairment: results from a phase II trial [published online February 2, 2018].J Clin Oncol.doi: 10.1200/JCO.2017.76.1742.