Frequent Good Partial Remissions From Thalidomide Including Best Response Ever in Patients With Advanced Refractory and Relapsed Myeloma

Abstract

Twenty‐three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR; nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine‐doxorubicin‐dexamethasone (VAD)‐based treatment in all but one and high‐dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15–50 weeks). Sedation was common but usually tolerable, and some patients continued full‐ or part‐time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.

Long‐term results of thalidomide in refractory and relapsed multiple myeloma with emphasis on response duration

“…It must be pointed out that if our 11 patients with EMP are excluded, the response rate increases up to 58%. As previously reported, both the lack of response of soft-tissue plasmacytomas to thalidomide as well as the existence of cases of extramedullary progression despite serological response, even in patients with no extramedullary involvement at the start of thalidomide therapy, indicate that the homing of myeloma cells in the bone marrow is essential for the anti-myeloma effect of the drug and support the importance of the bone marrow microenvironment in the mechanism of anti-myeloma action of thalidomide (13,20,21,34).…”

“…On the rationale of its antiangiogenic activity, thalidomide was the first of these new drugs. A response rate of about 40% has been consistently reported when using thalidomide as a single agent in myeloma patients with refractory or relapsed disease (11)(12)(13)(14)(15)(16)(17). When thalidomide is combined with other anti-myeloma agents the response rate increases to 50-63% (25)(26)(27)(28)(29)(30)(31)(32).…”

“…Thalidomide was the first of these new drugs and has been followed by others such as bortezomib (Velcade TM , Johnson and Johnson Pharmaceutical Research & Development, Beerse, Belgium), recently approved for the treatment of relapsed and refractory MM (8), and lenalidomide (Revlimid TM , Celgene Corporation, Summit, NJ, USA), an immunomodulatory drug (IMiD) which is showing highly promising results (9,10). A response rate of about 40% has been consistently reported when using thalidomide as a single agent in patients with advanced MM (11)(12)(13)(14)(15)(16)(17). However, the information on the duration of such responses is scarce (18,19).…”

Thalidomide for the treatment of multiple myeloma

“…Numerous other investigators have reported similar results (Table 1) (Alexanian et al . 2000;Juliusson et al . 2000;Kneller et al .…”

“…1999). Since then, a number of reports have demonstrated the efficacy of thalidomide in 25-58% of refractory MM cases; treatment was associated with only minor complications such as somnolence, constipation, peripheral neuropathy, and skin rash (Alexanian & Weber 2000;Juliusson et al . 2000;Kneller et al .…”