The results from the STRATUS trial ( MM-010 ), a single-arm phase IIIb study of Pomalidomide ( Imnovid, Pomalyst ) plus low-dose Dexamethasone in patients with relapsed and refractory multiple myeloma were presented at the 56th American Society of Hematology annual meeting.
In the study, 599 patients with refractory, or relapsed and refractory, disease who had previously failed Lenalidomide and Bortezomib had been enrolled at the time of the data cutoff.
The primary endpoint was safety, and key secondary endpoints included Pomalidomide exposure, overall response rate ( ORR; greater than or equal to partial response ), duration of response ( DOR ), progression-free survival ( PFS ), overall survival ( OS ), and cytogenetic analyses.
Patients had a median five prior therapies. All patients received thromboprophylaxis with low-dose Acetylsalicylic acid ( Aspirin ), low-molecular-weight Heparin ( LMWH ), or equivalent.
The most frequent grade 3-4 adverse events were hematologic, including neutropenia ( 42% ), neutropenic fever ( 5% ), anemia ( 29% ), and thrombocytopenia ( 22% ); grade 3-4 non-hematological toxicities included pneumonia ( 11% ), fatigue ( 5% ), and hypercalcemia ( 4% ).
Grade 3/4 deep vein thrombosis was low ( 1% ) with prophylaxis, and peripheral neuropathy was 1%.
Dose reductions of either Pomalidomide or low dose Dexamethasone due to adverse reactions were required in 18% of patients; 9% of discontinuations were due to adverse reactions 9%.
At a median follow-up of 6.8 months with a median four cycles received, the median progression-free survival and overall survival were 4.2 months and 11.9 months, respectively.
The ORR was 35%, with 8% of patients achieving at least a very good partial response ( VGPR ).
The median DOR was 6.8 months.
In patients refractory to prior Lenalidomide ( n=572 ) or Lenalidomide and Bortezomib ( n=473 ), similar progression-free survival ( 4.2 months and 4.1 months ), overall survival ( 12 months for each ), and ORR ( 34% and 35% ) were achieved.
In addition, a sub-group analysis was conducted to determine the impact of the therapy on patients with moderate renal impairment. Of the 604 patients enrolled in the study, 215 had moderate renal impairment ( creatinine clearance [ CrCl ] greater than 45 mL/min but less than 60 mL/min ).
ORR was generally similar between patient groups receiving Pomalidomide plus low-dose Dexamethasone ( 37% with moderate renal impairment versus 33% without moderate renal impairment ) despite differences in renal function.
The median DOR was 6 months versus 7.9 months, respectively.
Progression-free survival ( was slightly extended in patients without moderate renal impairment, but did not meet statistical significance ( 3.7 versus 4.6 months, p=0.1142 ).
The most common grade 3-4 nonhematologic adverse reactions were infections ( 29% vs. 30% ) and pneumonia ( 12% vs. 11% ).
Twelve percent of patients with moderate renal impairment and 7% of patients without moderate renal impairment discontinued Pomalidomide due to adverse effects.
Pomalidomide starting dose was 4 mg daily for days 1-21 of 28-day cycle. Dexamethasone was given at 40mg/day ( 20 mg for more than 75 years ) on days 1, 8, 15, 22.
Dose intensity was comparable in both groups ( 94% and 93% ). No dose adjustment was required for renal impairment. ( Xagena )
Source: Celgene, 2014