Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma

Summary. Twenty-three patients with advanced and heavilypretreated myeloma were treated with thalidomide. Startingdose was 200 mg/d, and 20 patients had dose escalations upto 400 (n ‹5), 600 (n ‹12) or 800 mg/d (n ‹3), usually individed doses. Nineteen patients were refractory to recentchemotherapy, and four had untreated relapse after priorintensive therapy. Ten out of 23 patients (43%) achievedpartial response (PR; nine with refractory and one withrelapsed disease), six patients had minor response orstabilization of the disease and four had disease progression.Another three patients died early from advanced myeloma atless than 3 weeks of thalidomide therapy. Of the 10 patientswith PR, seven had a better response than after any priortherapy, despite vincristine–doxorubicin–dexamethasone(VAD)-based treatment in all but one and high-dosemelphalan with autologous stem cell support in four. Timeto achieve PR was rapid in patients receiving thalidomide individed doses (median 31 d). Responses also includedreduced bone marrow plasma cell infiltration and improvedgeneral status. Normalized polyclonal gammaglobulin levelswere seen in four cases. Six out of 10 patients with PRremained in remission with a median time on treatment of23 weeks (range 15–50 weeks). Sedation was common butusually tolerable, and some patients continued full- or part-time work. Four patients had skin problems, three patientshad pneumonia, one hypothyrosis, one sinus bradycardiaand one minor sensory neuropathy. Thalidomide may inducegood partial remissions in advanced refractory myelomawith tolerable toxicity, and should be evaluated in othersettings for myeloma patients. Divided thalidomide dosesseem to reduce time to achieve remission and may improveresponse rate.Keywords: myeloma, thalidomide, therapy, refractory,response.Few drug types with documented effect as treatment formyeloma are currently available. Steroids and alkylatingagents, mainly melphalan and cyclophosphamide, havesignificant and dose-related anti-tumour effects. In contrast,clinical benefit of anthracyclins have not been documented,but still they are frequently incorporated into combinationchemotherapies (Barlogie et al, 1984). High-dose dexa-methasone pulse-based therapy (Barlogie et al, 1984)followed by high-dose melphalan with autologous stem cellsupport (Barlogie et al, 1999) leads to a prolonged diseasecontrol with significant improvement in survival (Attal et al,1996; Barlogie et al, 1997; Lenhoff et al, 2000). Still, thecomplete response rate is well below 50%, cure has notbeen documented, as progression-free survival is limitedto a few years, and there is no plateau in the survivalcurves. However, recent studies suggest that allogeneic stemcell transplantation may improve response duration andoutcome.Thalidomide (a-(N-phthalimido)glutarimide; C