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Author: Admin | 2025-04-28
For Medical Oncology. Please visit: www.esmo.org. Close modal Retreatment Retreatment with an agent used previously is considered feasible, if the treatment produced a clinically meaningful response of adequate duration and with acceptable toxicity. In general, the minimal depth of the initial response should be partial response, whereas the minimal duration of response should have been at least 6 months. Trials and retrospective analyses have shown that retreatment with bortezomib is feasible and effective and does not incur cumulative toxicity. Lenalidomide retreatment is also feasible and may induce responses in up to 44% of relapsed patients and is better than retreatment with thalidomide. Tolerability is another important consideration. Residual toxicity from prior treatment such as neuropathy, myelosuppression, and thrombosis may prohibit retreatment. For some patients a change to a less-intensive schedule or dose may make the treatment better tolerated. For bortezomib, changing to a weekly and subcutaneous schedule will reduce toxicity. If an effective alternative treatment is available at relapse, switching drug class is preferable, and previously used agents may then be considered again at a later relapse. Patients may even become sensitive to (escalated dosages of) drugs to which they were previously refractory, on the basis of the appearance of different tumor clones during subsequent stages of the disease. IMiDs Thalidomide-based treatments. A meta-analysis of thalidomide monotherapy limited to trials of ≥50 patients reported an ORR of 28% (CR 2% and PR 26%).22 A phase 3 comparison of low-dose (100 mg) and high-dose (400 mg) thalidomide showed similar activity, with a better safety profile associated with low-dose thalidomide. Retreatment with thalidomide was associated with a 30% ORR. Combining thalidomide with dexamethasone improves its efficacy in relapsed MM, which is further improved when thalidomide is combined with VTD; dexamethasone and cyclophosphamide (CTD); bortezomib plus melphalan and prednisone or dexamethasone; lenalidomide, melphalan, and prednisone; or VTD with pegylated liposomal doxorubicin. These regimens have an ORR of 63% to 90% with CR being reported in 2% to 35% of patients. In conclusion, thalidomide combined with dexamethasone is an option for relapsed patients who are thalidomide-naïve, when an oral treatment schedule is needed and who are not eligible for bortezomib or lenalidomide-based treatment. Thalidomide is now less frequently used because of relatively poor tolerability, the risk of venous thrombotic events, fatigue, and peripheral neuropathy as well as the availability of more effective alternative treatments. In spite of this, thalidomide plus dexamethasone may be an effective and affordable alternative in specific environments. Lenalidomide-based treatments. Lenalidomide is active as a single agent, and it is well tolerated in patients with relapsed MM with 25% to 27% ORR and 23 to 27 months OS. Its main toxicities are myelosuppression, diarrhea, and risk of venous thrombosis. Adding dexamethasone
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