Impact of baseline characteristics on efficacy and safety after bortezomib-based induction and maintenance in newly diagnosed multiple myeloma (MM) patients ineligible for transplant in the phase IIIb UPFRONT study.

Abstract

8072 Background: The multicenter, phase IIIb UPFRONT study compares the efficacy and safety of 3 bortezomib (Vc)-based induction regimens, VcD (Vc–dexamethasone), VcTD (Vc–thalidomide–dexamethasone) and VcMP (Vc–melphalan–prednisone), followed by weekly Vc maintenance, in newly diagnosed MM patients ineligible for HDT–SCT. Methods: Patients were randomized (1:1:1) to receive 8 three-week cycles of induction followed by 5 five-week cycles of maintenance. Efficacy and safety data were analyzed by patient and disease baseline characteristics including age, gender, Charlson comorbidity index (CCI) and ISS stage after 300 patients (100 patients per arm) had the opportunity to complete all 13 cycles. Data were pooled across all three treatment arms. Response was assessed using IMWG criteria. AEs were graded by NCI-CTCAE v3.0. Results: Rates of ≥VGPR were higher in patients age <75 years (p=0.034). Patients with a CCI of 0 showed a trend to better ≥VGPR (p=0.078). A multivariate analysis showed similar results. There was no significant difference in ≥VGPR by gender, race, or ISS stage. Grade ≥3 AE rates appeared lower in patients <75 years, and PN rates (all grade) tended to be lower in males and in white patients. There were no apparent trends in the rates of grade ≥3 AEs or PN (all grade) by CCI or ISS stage. Previous reports from this study have shown that ≥VGPR rates were similar by treatment arm, but that rates of grade ≥3 AEs and PN were higher in the VcTD arm (Niesvizky, ASH 2010). Conclusions: The results of this subgroup analysis show that patients <75 years had higher rates of ≥VGPR and lower rates of grade ≥3 AEs in the UPFRONT study. These results suggest that Vc-containing regimens are active across various patient subgroups including gender, race, co-morbidity status, and ISS stage. Baseline characteristic N ≥VGPR (%) P value* <75 years 157 48 0.034 ≥75 years 100 35 Male 137 40 0.292 Female 120 47 White 192 43 0.789 Nonwhite 65 45 CCI 0 146 48 0.078 CCI ≥1 111 37 ISS 1 62 45 0.238 ISS 2 111 40 ISS 3 72 51 * Univariate chi-square p value.