@article{3109418,
    title = "Phase II study of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide for sub-optimal response as second-line treatment for patients with multiple myeloma",
    author = "Dimopoulos, M.A. and Beksac, M. and Benboubker, L. and Roddie, H. and Allietta, N. and Broer, E. and Couturier, C. and Mazier, M.-A. and Angermund, R. and Facon, T.",
    journal = "Haematologica-the hematology journal",
    year = "2013",
    volume = "98",
    number = "8",
    pages = "1264-1272",
    doi = "10.3324/haematol.2013.084376",
    keywords = "bortezomib;  cyclophosphamide;  dexamethasone;  doxorubicin;  lenalidomide;  melphalan;  prednisolone;  prednisone;  thalidomide;  vincristine, adult;  aged;  anemia;  article;  constipation;  controlled study;  drug efficacy;  drug safety;  drug withdrawal;  female;  follow up;  glomerulus filtration rate;  human;  kidney function;  major clinical study;  male;  multiple cycle treatment;  multiple myeloma;  neuralgia;  neutropenia;  parallel design;  peripheral neuropathy;  phase 2 clinical trial;  pneumonia;  polyneuropathy;  randomized controlled trial;  sensory neuropathy;  thrombocytopenia, Adult;  Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Boronic Acids;  Cyclophosphamide;  Dexamethasone;  Female;  Humans;  Kaplan-Meier Estimate;  Male;  Middle Aged;  Multiple Myeloma;  Prospective Studies;  Pyrazines;  Thalidomide;  Treatment Outcome",
    abstract = "This phase II study is the first prospective evaluation of bortezomib-dexamethasone as second-line therapy for relapsed/refractory multiple myeloma. A total of 163 patients were enrolled to receive four cycles of bortezomibdexamethasone. Patients were investigator-assessed for response at cycle 5 Day 1, then treated as follows: responding patients received another four cycles of bortezomib-dexamethasone, while patients with stable disease were subsequently randomized to sequential treatment with a further four cycles of bortezomib-dexamethasone alone or with added cyclophosphamide or lenalidomide. The primary end point was response to sequential therapy; however, this could not be evaluated because investigator-assessed response rates to bortezomib-dexamethasone after four cycles were high, and an insufficient number of patients were randomized to sequential treatment per protocol. Among all 163 patients, validated best confirmed response rate was 66%, including 37% complete/very good partial responses; median response duration was 9.7 months. After a median follow up of 16.9 months, median time to progression and progression-free survival were 9.5 and 8.6 months, respectively; estimated 1-year overall survival was 81%. Median glomerular filtration rate improved from baseline during treatment. Among 58 patients with baseline glomerular filtration rate below 50 mL/min, 24 had renal responses. Grade 3/4 adverse events included: thrombocytopenia (17%), anemia (10%), constipation (6%), peripheral sensory neuropathy (5%), and polyneuropathy (5%). Overall, 57% of neuropathy events improved/resolved; median time to improvement was 2.1 months. These findings suggest bortezomib-dexamethasone represents an active, feasible second-line treatment option for patients with relapsed/refractory myeloma.. © 2013 Ferrata Storti Foundation."
}