Citations

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. Thalidomide-exposed 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 thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + 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.

Purpose The combination of oral weekly cyclophosphamide and alternate day prednisone is a convenient regimen for relapsed/refractory multiple myeloma (MM), and we sought to improve its efficacy by adding bortezomib, a proteasome inhibitor with proven antimyeloma activity. Patients and Methods We conducted a phase I-II trial evaluating six dose levels to define the maximum tolerated dose (MTD) of this combination in relapsed/refractory MM. An additional 10 patients were evaluated at the highest dose level reached. Results Thirty-seven patients were treated on this study. The MTD was not defined. Both of the highest dose levels of bortezomib tested (1.3 mg/m 2 on days 1, 4, 8, and 11 and 1.5 mg/m 2 on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m 2 per week and prednisone. At these dose levels, the overall response rate was 95% (complete responses [CR] plus partial response plus minimal response), with CR observed in more than 50% of patients. The weekly bortezomib regimen resulted in fewer instances of grade 3 thrombocytopenia and grade 1 to 2 peripheral neuropathy; the 1-year progression-free and overall survival probabilities with this dose level were 83% (95% CI, 73% to 96%) and 100%, respectively. Conclusion Weekly bortezomib 1.5 mg/m 2 plus oral cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory patients with MM. Further evaluation of this promising regimen is warranted both in relapsed and newly diagnosed disease.