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Low‐dose vs. high‐dose thalidomide for advanced multiple myeloma: a prospective trial from the Intergroupe Francophone du Myélome
Author(s) -
YakoubAgha Ibrahim,
Mary JeanYves,
Hulin Cyrille,
Doyen Chantal,
Marit Gérald,
Benboubker Lotfi,
Voillat Laurent,
Moreau Philippe,
Berthou Christian,
Stoppa AnneMarie,
Maloisel Frédéric,
Rodon Philippe,
Dib Mamoun,
Pegourie Brigitte,
Casassus Philippe,
Slama Borhane,
Damaj Ghandi,
Zerbib Robert,
Harousseau JeanLuc,
Mohty Mohamad,
Facon Thierry
Publication year - 2012
Publication title -
european journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.904
H-Index - 84
eISSN - 1600-0609
pISSN - 0902-4441
DOI - 10.1111/j.1600-0609.2011.01729.x
Subject(s) - thalidomide , medicine , tolerability , nausea , multiple myeloma , population , gastroenterology , clinical endpoint , dexamethasone , vomiting , prospective cohort study , somnolence , refractory (planetary science) , adverse effect , surgery , clinical trial , physics , environmental health , astrobiology
This multicentre prospective randomised trial compared the efficacy and safety of two doses of thalidomide in patients with relapsed or refractory myeloma. The study was designed to test the non‐inferior efficacy and to confirm the better tolerability of low‐dose thalidomide as compared to a higher dose. Four hundred patients were randomly assigned to receive either 100 or 400 mg/day of thalidomide. Dexamethasone treatment was added in both arms for patients with stable disease or treatment failure at 12 weeks. The primary endpoint was 1‐year overall survival (OS). Thalidomide 100 mg/day was better tolerated than 400 mg/day with less high‐grade somnolence, constipation, nausea/vomiting and peripheral neuropathy ( P < 0.001, P = 0.007, P = 0.03 and P = 0.007, respectively). In the per‐protocol population (PP), the estimated 1‐year OS rates were of 74.5% ( n = 149) and 67.3% ( n = 156) in the 400 and 100 groups, respectively. The upper limit of the difference between these rates was of 15.6% higher than the non‐inferiority acceptable limit of 12.75%, and the hypothesis of non‐inferiority of 100 could not be established ( P = 0.14). On the other hand, when intent‐to‐treat (ITT) population was analysed, the non‐inferiority was demonstrated because the 1‐year OS rates were of 72.8% ( n = 195) and 68.8% ( n = 205) in the same groups, leading to an upper limit of the difference of 11.49% lower than the non‐inferiority acceptable limit. In addition, in patients alive 12 weeks postrandomisation and those who received thalidomide plus dexamethasone, there were no significant differences in response rates, time to progression, progression‐free survival and OS between the two groups. Collectively, low‐dose thalidomide 100 mg/day has significant activity in advanced myeloma with an improved safety profile and can be a good salvage therapy in combination with dexamethasone.