Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003) a randomised, open-label, phase 3 trial

SUMMARY: Pomalidomide (POMALYST®) is a novel, oral, immunomodulatory agent which is far more potent than Thalidomide (THALOMID®) and Lenalidomide (REVLIMID®). Only 2% of POMALYST® is excreted unchanged through the kidney whereas 80% of REVLIMID® is excreted unchanged via the kidneys. Therefore, POMALYST® may be a consideration for patients with renal insufficiency. Previously conducted phase II trials have shown POMALYST® to be active in Myeloma patients, refractory to REVLIMID® and Bortezomib (VELCADE®). In a multicenter, randomized, phase III trial, the efficacy and safety of POMALYST® given along with low-dose Dexamethasone (LoDEX) (n=302) was compared with high-dose Dexamethasone (HiDEX) (n=153) in Myeloma patients, who were refractory to both REVLIMID® and VELCADE®. The primary endpoint was Progression Free Survival (PFS). The Overall Survival (OS) was only evaluated if PFS was statistically significant. With a median follow up of 10 months, the PFS was significantly longer in the POMALYST® + LoDEX group compared to the HiDEX group (4 month vs 1.9 months; hazard ratio [HR]= 0.48; P <0 .0001). The median OS was significantly longer in the POMALYST® + LoDEX group compared to HiDEX group (12.7 months vs 8.1 months; HR=0.74; P=0.028). The authors concluded that POMALYST® along with low- dose Dexamethasone should be the new standard of care for patients who have Multiple Myeloma refractory to REVLIMID® and VELCADE®. Carfilzomib (KYPROLIS®), a new parenteral proteasome inhibitor is another option for patients with resistant and refractory Multiple Myeloma. San Miguel J, Weisel K, Moreau P, et al. Lancet Oncol 2013;14:1055-1066