Treatment of multiple myeloma with thalidomide, dexamethasone, and zoledronate in an inner-city population with high prevalence of HIV/AIDS

B80

This single-arm, open-label trial evaluated the efficacy and safety of low-dose thalidomide in combination with dexamethasone and zoledronate (TDZ) for the treatment of multiple myeloma (MM) in a largely African-Caribbean inner-city population with high prevalence of HIV/AIDS. TDZ is non-myelotoxic and compatible with HAART, and thus appropriate for HIV+ patients with MM. Methods: 45 consecutive patients with newly diagnosed MM were enrolled. TDZ was given for 24 months or until progression, and consisted of: thalidomide, 100 mg daily; dexamethasone, 10-40 mg for 4 days/week for 3 weeks each month for 6 months, then reduced to 4 days each month; zoledronate, 4 mg IV monthly; and ASA, 81 mg daily. Response was stratified by reduction of M protein levels: > 75% (very good partial response [VPR]), > 50-75% (partial response [PR]), or 25-50% (minor response [MR]). Kaplan-Meier survival analyses provided estimates of longitudinal survival. Differences between HIV+ and HIV- patients were assessed by the log-rank test or the Fisher Exact Test with mid-P correction for small samples. Results: 8 of 45 enrollees were HIV seropositive, 7 of whom had AIDS and were on HAART. 38 (27F/11M; median age = 60.4 years) were evaluable, including all 8 HIV patients. Patients with HIV were younger (Mann-Whitney U test, P < .001; median HIV+ = 47.4 y, HIV- = 62.3 y). HIV+ patients had marginally higher β₂-microglobulin levels (P = .076). Overall response rate was 84%. 6/8 vs. 18/31 (HIV+ vs. HIV-) achieved PR or better (P = .220). Among responders, HIV+ patients tended to respond more quickly than HIV- (median: 2.4 months vs. 3.6 months; P = .100). Median survival time for all patients was 33.7 months. Cumulative survival at 30 and 60 months was 51.8% and 38.0%, respectively, which compares favorably to NCI SEER data (5-year relative survival rate for 1996-2003: 35.1% for black men; 31.7% for black women). Survival analysis did not show a significant difference between HIV+ and HIV- patients: P = .297 at 30 months, P = .154 at 60 months, both by the log-rank test. Creatinine clearance was not adversely affected by monthly treatment with zoledronate (P > .2 for both). Despite prophylactic ASA, thromboembolism occurred in 6 patients (16%), all of whom were successfully treated with full anticoagulation. Other toxicities ≥ Grade 2, were not observed. Skeletal events occurred in 8% of patients; osteonecrosis of the jaw was not encountered. Conclusion: Thalidomide administered at half the standard dose in combination with zoledronate and dexamethasone provides safe, efficacious long-term treatment of MM in HIV and HIV+ patients. The modest frequency of toxicity and skeletal events under TDZ improves quality of life as well as survival. The high incidence of HIV in our study cohort suggests a pathogenetic role in MM.