Cytogenetics and long-term survival of patients with refractory or relapsed and refractory multiple myeloma treated with pomalidomide and low-dose dexamethasone
Meletios A Dimopoulos 1 , Katja C Weisel 2 , Kevin W Song 3 , Michel Delforge 4 , Lionel Karlin 5 , Hartmut Goldschmidt 6 , Philippe Moreau 7 , Anne Banos 8 , Albert Oriol 9 , Laurent Garderet 10 , Michele Cavo 11 , Valentina Ivanova 12 , Adrian Alegre 13 , Joaquin Martinez-Lopez 14 , Christine Chen 15 , Andrew Spencer 16 , Stefan Knop 17 , Nizar J Bahlis 18 , Christoph Renner 19 , Xin Yu 20 , Kevin Hong 20 , Lars Sternas 20 , Christian Jacques 20 , Mohamed H Zaki 20 , Jesus F San Miguel 21
Patients with refractory or relapsed and refractory multiple myeloma who no longer receive benefit from novel agents have limited treatment options and short expected survival. del(17p) and t(4;14) are correlated with shortened survival.
The phase 3 MM-003 trial demonstrated significant progression-free and overall survival benefits from treatment with pomalidomide plus low-dose dexamethasone compared to high-dose dexamethasone among patients in whom bortezomib and lenalidomide treatment had failed.
At an updated median follow-up of 15.4 months, the progression-free survival was 4.0 versus 1.9 months (HR, 0.50; P<0.001), and median overall survival was 13.1 versus 8.1 months (HR, 0.72; P=0.009). Pomalidomide plus low-dose dexamethasone, compared with high-dose dexamethasone, improved progression-free survival in patients with del(17p) (4.6 versus 1.1 months; HR, 0.34; P <0.001), t(4;14) (2.8 versus 1.9 months; HR, 0.49; P=0.028), and in standard-risk patients (4.2 versus 2.3 months; HR, 0.55; P<0.001).
Although the majority of patients treated with high-dose dexamethasone took pomalidomide after discontinuation, the overall survival of patients treated with pomalidomide plus low-dose dexamethasone or high-dose dexamethasone was 12.6 versus 7.7 months (HR, 0.45; P=0.008) in patients with del(17p), 7.5 versus 4.9 months (HR, 1.12; P=0.761) in those with t(4;14), and 14.0 versus 9.0 months (HR, 0.85; P=0.380) in standard-risk subjects.
The overall response rate was higher in patients treated with pomalidomide plus low-dose dexamethasone than in those treated with high-dose dexamethasone both among standard-risk patients (35.2% versus 9.7%) and those with del(17p) (31.8% versus 4.3%), whereas it was similar in patients with t(4;14) (15.9% versus 13.3%).
The safety of pomalidomide plus low-dose dexamethasone was consistent with initial reports. In conclusion, pomalidomide plus low-dose dexamethasone is efficacious in patients with relapsed/refractory multiple myeloma and del(17p) and/or t(4;14).
CITA DEL ARTÍCULO Haematologica. 2015 Oct;100(10):1327-33.