Multicenter phase 2 trial of thalidomide in relapsed/refractory multiple myeloma: adverse prognostic impact of advanced age

Abstract

Relapsed or refractory multiple myeloma has a poor outlook. Some patients respond to thalidomide; however, criteria for predicting response have not been conclusively identified. We initiated a prospective multicenter phase 2 trial in patients with relapsed/ refractory myeloma using thalidomide up to the maximum dose, 800 mg/d. Interferon-␣-2B (1.5-3.0 ؋ 10 6 U, subcutaneously, 3 times per week) was added at week 12 if disease was responsive or stable. Patients intolerant of interferon continued thalidomide alone. Thalidomide with or without interferon was continued until disease progression. Objectives were to determine toxicity, response rate (RR), progression-free survival (PFS), and overall survival (OS) and to elucidate relevant prognostic factors. We enrolled 75 patients, with median age 64 years (range, 36-83 years). Median individual maximum-tolerated dose of thalidomide was 600 mg/d; 41% reached 800 mg/d. Overall RR was 28%, and 55% stable disease (SD). The only predictor for response was age 65 years or younger (38% versus 17%; P ‫؍‬ .043). At 18 months median followup, the actuarial median PFS and OS were 5.5 and 14.6 months, respectively. Multivariate analysis for OS demonstrated age exceeding 65 years (median, 9.2 months versus longer than 26 months; P ‫؍‬ .011), raised serum lactate dehydrogenase (P ‫؍‬ .002), and raised serum creatinine (P ‫؍‬ .007) predicted inferior outcomes. Nineteen patients received interferon. Ten discontinued owing to toxicity. Four of 12 patients who received interferon for longer than 4 weeks were converted from SD to partial response. Our findings confirm substantial activity of thalidomide in relapsed/refractory myeloma. Interferon may improve response in selected patients, but is often not tolerated.

First-line thalidomide–dexamethasone therapy in preparation for autologous stem cell transplantation in young patients (<61 years) with symptomatic multiple myeloma

“…19 Response rates of about 30% reported by Singhal et al 8 were confirmed by others groups. 9,[20][21][22][23] Addition of dexamethasone to thalidomide in patients who failed to benefit from prior therapy, including both thalidomide and dexamethasone given as single agents, further increased responses, up to an overall response rate of 50-55%. 10,11 These data suggested a synergy between thalidomide and dexamethasone and prompted several groups to explore this combination also in patients with previously untreated MM.…”

“…Number of days to ANC4500/ml 11 (9-16) PLTC420 000/ml 14 (10-22) PLTC450 000/ml 17 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) PLT transfusions (no.) 3 (0-16) RBC transfusions (no.)…”

An evaluation of factors predicting long-term response to thalidomide in 234 patients with relapsed or resistant multiple myeloma

“…A multivariate analysis of the OS of relapsed or refractory MM patients demonstrated that advanced age (exceeding 65 years) raised the serum level of LDH and also the concentration of creatinine predicted inferior outcomes (Mileshkin et al, 2003). Since an antiangiogenic effect is postulated as one of the most important mechanisms of THAL action pretreatment, angiogenesis was evaluated as a predictor of response.…”

Second auto-SCT for treatment of relapsed multiple myeloma

“…On the other hand, novel agents such as thalidomide, lenalidomide or bortezomib are associated with a higher risk of grade III or IV toxicities such as neuropathy, myelosuppression and thrombosis. [22][23][24][25] Hence, providers and patients may prefer the transient toxicity associated with auto-SCT2 in place of the continuous toxicities of novel agents. There is no evidence that the efficacy of future novel agent salvage Second SCT for myeloma WI Gonsalves et al therapies may be compromised by the prior sequence of salvage transplantation therapy.…”