Low-dose thalidomid in refractory and relapsing multiple myeloma

Introduction:
Thalidomide is one of the drugs which are newly used in the therapy of multiple myeloma. Its immunomodulating action and a number of additional effects have been proven in the treatment of advanced and refractory stage of the disease. However, the best dosing scheme has not yet been discovered and is the subject of research in a number of clinical studies today.

Patients and methods:
On a retrospective basis, we evaluated results for 59 patients with multiple myeloma who were treated with thalidomide in our facility (median dose of 100 mg), in monotherapy or in combination with corticosteroids, between 2000 and 2005. The objective was to determine the percentage of responses to treatment in patients at different stages of the disease. Response to treatment was evaluated in accordance with EBMT standards.

Results:
Thalidomide was used as 2^nd line therapy (1^st relapse or primarily resistant disease) in 59 % of cases (35 patients), and as 3^rd line therapy (2^nd relapse) in 37 % of cases (22 patients). 2 patients were receiving thalidomide as 4^th line therapy. None of the patients had taken thalidomide as part of previous treatment. The response rate at 1^st relapse (CR - complete remission, PR - partial remission, MR - minimum response) was 60 % (21 patients), of which CR was recorded in 2 patients (6 %), PR was recorded in 12 patients (35 %) and MR in 6 patients (17 %). The response rate at 2^nd relapse was 45 % (10 patients), of which CR was recorded in 3 patients (14 %), PR in 1 patient (5%) and MR in 5 patients (23 %). Even though we did not record any statistically significant difference in the response of the evaluated group of patients to the treatment with thalidomide at 1^st and 2^nd relapse, a higher percentage or progression during treatment (32 % vs. 14 %) was observed in patients at 2^nd relapse. 2 patients treated with thalidomide at 3^rd relapse did not have a satisfactory response to the treatment (progression or short stabilisation of the disease with subsequent progression). Only 3 patients (5 %) of the evaluated group had to discontinue the treatment due to severe adverse events (neuropathy, allergic reaction, leukopenia). The follow up time for Thalidomide therapy ranged between 3 and 62 months for both groups (with a median of 10 months) and spanned from 3 to 60 months at 1^st relapse (median of 12 months) and from 3 to 57 months at 2^nd relapse (median of 6 months). No statistically significant differences were observed between the 1^st and 2^nd relapse groups of patients in terms of response rates or length of effect.

Conclusion:
Thalidomide is highly efficient in the treatment of multiple myeloma. The results of study document effectiveness of thalidomide regardless of the disease stage. Comparison of study data with the results of other studies shows that the effectiveness of lower doses we used is comparable with that of higher doses. The fact that lower doses of thalidomide reduce the incidence of adverse events is a clear advantage.

Keywords: thalidomide; low doses; multiple myeloma; treatment; relapse