Thalidomide in the management of multiple myeloma.
ABSTRACT A phase II trial of thalidomide in refractory multiple myeloma was initiated using a dose schedule that escalated from 200 mg/d to 800 mg/d. More than two thirds of patients had cytogenetic abnormalities and more than half had received at least two cycles of high-dose therapy. A paraprotein reduction of at least 25% was noted in 37% of patients and 14% had either a complete remission (CR) or a near CR. No treatment-related mortality was observed. With a median follow-up of almost 2 years, the 2-year event-free survival (EFS) and overall survival (OS) estimates were 15% and 60%, respectively. A reduction of paraprotein levels by greater than 50% was associated with a significant reduction in bone marrow plasmacytosis and beta(2)-microglobulin levels (beta2M), and greater recovery of hemoglobin and IgM levels compared to patients whose paraprotein was reduced by a lesser degree. Responses occurred more frequently among patients with a lower plasma cell labeling index (PCLI) and normal cytogenetics. Comparing response and survival by thalidomide dose for low- and high-risk groups revealed a thalidomide dose-response effect in the high-risk group of patients. The virtual absence of myelosuppressive toxicity, except in heavily pretreated patients with compromised bone marrow function, suggests that thalidomide is an ideal agent to be used in combination with cytotoxic agents and dexamethasone. Several trials are currently underway at the Arkansas Myeloma and Transplantation Research Center to determine the clinical benefit of adding thalidomide to post-transplant salvage therapy and in the upfront management of patients.
SourceAvailable from: Josep M CasanovaPiel 01/2003; 18(8):446–458. DOI:10.1016/S0213-9251(03)72753-1
Article: Traitement du myélome multiple[Show abstract] [Hide abstract]
ABSTRACT: Résumé: Nous assistons depuis 20 ans à des progrès continus dans la prise en charge des patients atteints de myélome multiple (MM). Le traitement intensif avec autogreffe de cellules souches du sang périphérique constitue maintenant le traitement de référence des patients de moins de 65 ans. Depuis 1999, l’arsenal thérapeutique s’est renforcé de trois molécules majeures, le thalidomide, le bortézomib (Velcade®) et le lénalidomide (Revlimid®), qui vont à l’évidence améliorer le pronostic des patients. Selon toute vraisemblance, les associations melphalan-prednisone-thalidomide, melphalan-prednisone-bortézomib ou melphalan-prednisone-lénalidomide seront amenées à remplacer l’association historique melphalanprednisone comme traitement de référence du MM du sujet âgé. Ces molécules prendront également leur place dans les procédures de traitement intensif, dans la réduction tumorale avant greffe ou en traitement d’entretien. Le traitement du MM bénéficie aussi des traitements par bisphosphonates, pour prise en charge de l’ostéopathie, et des érythropoïétines recombinantes pour traitement ou prévention de l’anémie. Toutes ces avancées ne doivent pas faire oublier que le traitement symptomatique conserve une importance majeure.Oncologie 05/2006; 8(4):357-361. DOI:10.1007/s10269-006-0404-4 · 0.08 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The combination of thalidomide and dexamethasone has yielded an about 50% response rate as salvage therapy in multiple myeloma patients. The aim of the present study was to evaluate, after a median follow up of 22 months, the long term outcome of 50 patients with progressive myelo- ma, who were treated with the combination of intermediate dose thalidomide (200-400 mg/d) and high dose dexamethasone (40 mg 4d/ 2wks). Overall response rate was 58% (complete response: 4%, very good partial response 20% and partial response: 34%). The median time to response was 42 days and the median response duration was 16 months. The median event free survival was 8 months (19 months for responders vs. 3 months for non-responders, p=0.001) and the median overall survival was 19 months (28 months for responders vs. 9 months for non responders, p=0.0001). The most common adverse effects were constipation, peripheral neuropathy, somnolence and skin rash, ob- served in 60%, 54%, 40% and 22% of the patients respectively. Thrombotic events occurred in 6 (12%) patients, 4 of which not receiving any anticoagulant prophylaxis. Long term administration of thalidomide/dexamethasone combination can induce and maintain long lasting responses in myeloma patients with progressive disease, while toxicity remains acceptable.