Long-term treatment of newly-diagnosed multiple myeloma with low-dose thalidomide, dexamethasone and zoledronate (TDZ)

Abstract

6697 Background: The efficacy and safety of long-term use of TDZ in newly-diagnosed multiple myeloma (MM) is unknown and subject of this phase II trial. Zoledronate mitigates bone resorption and inhibits tumor growth and angiogenesis, and was expected to boost the therapeutic effect of thal/dex. Methods: Of 34 consecutive enrollees, 29 (20F/9M) were evaluable. Mean age was 61 (43–82), 8 patients had stage 2, 20 had stage 3 MM, 4 were HIV+ women on HAART. Patients received thalidomide 100 mg QD, dexamethasone 10–40 mg PO on Days 1–4, 9–12, and 17–20 monthly for 6 months, then on 4 days/month; and zoledronate 4 mg IV monthly, until progression. Response was stratified according to reduction of M-protein levels as: >50% (partial response, PR), >90% (very good PR, VGPR), 25–50% (minor response, MR). The cumulative probability of response (CPR) (±standard error) was estimated by Kaplan-Meier approach. Results: Mean duration of treatment with TDZ was 12 months. So far 13 patients have been followed for 12–24 months. Age-adjusted one-year survival is 74.4% and is identical to SEER data (73.7%). No deaths occurred after 10 months, whereas cumulative survival for the SEER population dropped to 60.1% at two years. All HIV+ patients remain in remission. Average time to response was 5.9 months, with 42% of patients responding within 4 months. PR occurred in 62%, including 28% VGPR with a CPR of 73% (±20.6) within 10 months. MR was observed in 28%. Maintenance of PR and VGPR over 1 year was achieved in 67%. The CPR of at least a minor response by 10 months was 100%. 1 patient progressed and 3 relapsed. Also, 1 patient died of secondary malignancy, and another of myocardial infarction. Thromboembolism occurred in 6 cases, prompting addition of aspirin 81 mg/day to the protocol. Other toxicities were not observed. Conclusions: The non-myelotoxic combination regimen TDZ is effective in the long-term management of new MM, including HIV+ patients on HAART. There may be a synergistic effect between thal/dex and zoledronate, allowing for lower doses of thalidomide than those used in earlier protocols. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Novartis