Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure

Abstract

This analysis assessed the efficacy and safety of lenalidomide ؉ dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomideexposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide ؉ dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo ؉ dexamethasone despite prior thalidomide exposure. Among lenalidomide ؉ dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P ‫؍‬ .04), with longer median TTP (P ‫؍‬ .04) and PFS (P ‫؍‬ .02). Likewise for dexamethasone alone-treated patients (P ‫؍‬ .03 for ORR, P ‫؍‬ .03 for TTP, P ‫؍‬ .06 for PFS). Prior thalidomide did not affect survival in lenalidomide ؉ dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomideexposed patients had similar toxicities. Lenalidomide ؉ dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo ؉ dexamethasone, independent of prior thalidomide exposure. Lenalidomide ؉ dexamethasone was superior to placebo ؉ dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo ؉ dexamethasone; similar benefits compared with placebo ؉ dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials. gov under NCT00056160 and NCT00424047.

Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone

“…Wang et al 14 reported that efficacy of lenalidomide and dexamethasone was superior to dexamethasone alone in patients with relapsed or refractory MM treated with lenalidomide and dexamethasone regardless of prior thalidomide exposure. The efficacy results were more favorable for patients without than with prior thalidomide treatment; however, this was also observed for patients treated with dexamethasone alone and probably reflects the fact that patients with prior thalidomide exposure were more heavily pretreated (median 3 vs 2 prior therapies).…”

Treatment of patients with relapsed/refractory multiple myeloma with lenalidomide and dexamethasone with or without bortezomib: prospective evaluation of the impact of cytogenetic abnormalities and of previous therapies

“…Indeed, our results in thalidomide-resistant patients are similar to that of thalidomideresistant patients treated in phase 2 or 3 trials. The median PFS of thalidomide refractory patients in MM009 and MM010 trials was 7 months (95% CI: 4.9-16.9), 26 the median PFS for thalidomide refractory patients in the report by Avet-Loiseau et al 27 was 5.7 months, whereas the median time to progression in immunomodulatory drug refractory patients in the MMY-3001 study was 6 months for patients treated with bortezomib and pegylated liposomal doxorubicin and 5.5 months for those treated with bortezomib alone. 28 It is also interesting that the addition of bortezomib to RD could not overcome the major detrimental effect of previous thalidomide resistance.…”

Management of older adults with multiple myeloma

“…60 Patients previously treated with a thalidomide-containing regimen benefit from treatment with lenalidomide, although efficacy and survival may be lower. 61 Because of the lack of neurotoxicity, lenalidomide is suggested in case of concomitant peripheral neuropathy. 60 The second generation proteasome inhibitor carfilzomib has shown a remarkable activity in relapsed/refractory MM patients, with a low rate of hematological AEs and the absence of neurotoxicity.…”