High versus attenuated dose dexamethasone has little effect on the speed or depth of response to induction therapy for myeloma

Introduction: High-dose corticosteroids in combination with novel anti-myeloma drugs produce high response rates but they are associated with increased adverse effects compared to regimens containing attenuated doses. In this retrospective study we compared the response rates of patients treated with high-dose dexamethasone (320mg/cycle) versus attenuated-dose dexamethasone (160mg/cycle) in combination with cyclophosphamide and immunomodulatory therapy. Methods: All patients with central laboratory serum free light chain (sFLC) and paraprotein results at presentation and the end of induction in Myeloma IX and all patients with complete results at presentation, end of cycle one and end of induction in Myeloma XI were included. The overall response rate (ORR) at the end of induction was calculated according to the IMWG Uniform Response Criteria. Paraprotein responses at the end of cycle one of induction chemotherapy was calculated in all patients with significant paraprotein levels ( 10g/L) and the end of cycle one sFLC response was calculated for all patients with significant sFLC levels (sFLC 100mg/l and a difference between the involved and uninvolved sFLC 100mg/L). Results: Complete sFLC and paraprotein results were available for 494 patients treated with CTD (320mg dexamethasone/cycle) or CTDa (160mg dexamethasone/cycle) in Myeloma IX and 1117 patients treated with RCD/CTD or RCDa/ CTDa in Myeloma XI at the end of induction. At the end of cycle one there was no difference in the sFLC reduction (78.3% compared to 80.9%, p1⁄40.71) between patients treated with RCD/CTD versus those treated with RCDa/CTDa. There was also no difference in the paraprotein reduction at the end of cycle one (55.2% versus 56.6%, p1⁄40.79), indicating there is no difference in speed of action between the regimes. At the end of induction there was a small increase in the ORR ( PR) in patients treated with CTD compared to those treated with CTDa in Myeloma IX (92.4% v. 85.3%, p1⁄40.01). However, in Myeloma XI there was no significant difference in ORR between patients treated with RCD/CTD versus those treated with RCDa/CTDa (93.7% v. 90.8, p1⁄40.08). Conclusions: High versus attenuated dose corticosteroid therapy has little effect on speed or overall response rate to induction chemotherapy. Combinations of novel agents plus attenuated-dose dexamethasone should be further evaluated to determine whether treatment-related toxicity can be reduced without loss of efficacy. 6. Multiple Myeloma Therapy Relapsed/Refractory Patients