Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma

Abstract

Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 -< 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 -< 60 mL/min (P<0.001) and 4.0 versus 2.0 months in the group with baseline creatinine clearance ≥ 60 mL/min (P<0.001). Median overall survival for pomalidomide + low-dose dexamethasone versus high-dose dexamethasone was 10.4 versus 4.9 months (P=0.030) and 15.5 versus 9.2 months (P=0.133), respectively. Improved renal function, defined as an increase in creatinine clearance from < 60 to ≥ 60 mL/min, was similar in pomalidomide + low-dose dexamethasone and high-dose dexamethasone patients (42% and 47%, respectively). Improvement in progression-free and overall survival in these patients was comparable with that in patients without renal impairment. There was no increase in discontinuations of therapy, dose modifications, and adverse events in patients with moderate renal impairment. Pomalidomide at a starting dose of 4 mg + low-dose dexamethasone is well tolerated in patients with refractory or relapsed and refractory multiple myeloma, and of comparable efficacy if moderate renal impairment is present. This trial was registered with clinicaltrials.gov identifier 01311687 and EudraCT identifier 2010-019820-30. Analysis of renal impairment in MM-

Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma

“… 11 , 12 , 13 The efficacy and tolerability of pomalidomide were maintained in all subgroups, including the elderly, 14 patients with high-risk cytogenetics 15 , 16 and those with moderate renal impairment. 17 , 18 …”

Adverse event management in patients with relapsed and refractory multiple myeloma taking pomalidomide plus low‐dose dexamethasone: A pooled analysis

“…Recently published analyzes of these trials demonstrated that pomalidomide plus low-dose dexamethasone is also safe and effective in patients with moderate renal impairment. 23,24 Here, we report a pooled analysis from these three clinical trials (MM-002, MM-003, and MM-010) that further examined the safety profile of pomalidomide plus low-dose dexamethasone-including the incidence and time to onset of the AEs of interest (hematologic AEs, infections, neuropathy, and thrombotic events)-in patients with RRMM and to assess AE management in this population.…”

“…Hematologic AEs and infections were the most common grade ≥ 3 AEs reported in these trials. Recently published analyzes of these trials demonstrated that pomalidomide plus low‐dose dexamethasone is also safe and effective in patients with moderate renal impairment …”

Paraprotein–Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy

“…There are few data on the reversal of renal impairment with these agents. However, a retrospective subgroup analysis of a phase 3 trial assessed renal recovery comparing pomalidomide with low-dose dexamethasone to high-dose dexamethasone in patients with MM refractory or relapsed after bortezomib and lenalidomide (36). Despite improved disease-free survival with the use of pomalidomide, in 149 patients with an eGFR of ,60 ml/min before treatment, there was no difference in the rate of renal recovery between the two groups (42% and 47%, respectively.…”