Low-dose thalidomid in refractory and relapsing multiple myeloma


Authors: J. Radocha;  V. Maisnar
Authors‘ workplace: Oddělení klinické hematologie II. interní kliniky Lékařské fakulty UK a FN, Hradec Králové, přednosta prof. MUDr. Jaroslav Malý, CSc.
Published in: Vnitř Lék 2007; 53(2): 129-164
Category: Original Contributions

Overview

Background:
Thalidomide is one of the novel agents used in the therapy of multiple myeloma. Its immunomodulatory activity and several other effects have been recently shown to be highly effective in the treatment of refractory and advanced disease. However the best way of using this drug has yet to be estimated.

Patients and methods:
We retrospectively evaluated 59 patients who were treated for multiple myeloma with Thalidomide (median dose 100 mg daily) as monotherapy or in combination with corticosteroids from 2000 to 2005. The primary goal was to compare the overall response to Thalidomide in various settings. The response to therapy was estimated according to EBMT standards.

Results:
Thalidomide was used as the second line treatment (first relapse or primary resistance to convetional chemotherapy) in 59 % of patients (35 patients), as the third line (second relapse) in 37 % of patients (22 patients). 2 patients recieved Thalidomide as the fourth line treatment. No patient recieved Thalidomide in previous therapy. In the first relapse the overall response rate (complete remissions - CR, partial remissions - PR and minimal response - MR) was reached in 64 % of patients (21 patients), 1 patient (3 %) reached CR, 12 patients PR (35 %) and 6 patients (17 %) reached MR. In the second relapse the overall response rate was 45 % with 14 % of CR (3 patients), 5 % PR (1 patient) and 23 % (5 patients) reached MR (5 patients). We observed that in the second relapse group there was higher rate of progressive disease during treatment compared to first relapse group (32 % vs. 14 %). 2 patients who recieved Thalidomide for third relapse shown either progressive disease or short stable disease with soon progression. Only 5 % of patients (3 patients) from all groups had to withdraw treatment with Thalidomide because of sevsere adverse reactions (grade III and IV neuropathy, allergic reaction, neutropenia). Follow-up of Thalidomide use was 3 - 62 months (median 10), in the 1st relapse group 3 - 60 months (median 12) and in the 2nd relapse group 3 - 57 months (median 6). No statistical differences were found in response rate and effect duration between first and second relapse group.

Conclusion:
Thalidomide is very promising agent for therapy of multiple myeloma. The higher response rate in the first relapse group also indicates, that the profit from using Thalidomide is comparable regardless the course of the disease. Lower doses of Thalidomide show similar efficiency when compared with the data from other studies using higher doses. Also less adverse reactions occur in the group of patients recieving lower doses of Thalidomide.

Key words:
thalidomide - low dose - multiple myeloma - relapsing - therapy


Sources

1. Barlogie B, Tricot GJ, van Rhee F et al. Long-term outcome results of the first tandem autotransplant trial for multiple myeloma. Br J Haematol 2006; 135: 158-164.

2. Attal M, Harousseau JL, Stoppa AM et al. A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 1996; 335: 91-97.

3. Krejčí M, Adam Z, Mayer J et al. Autologní transplantace periferních kmenových buněk v terapii relapsu mnohočetného myelomu Vnitř Lék 1998; 44: 698-701.

4. Ráčil Z, Adam Z, Hájek R et al. Vysokodávkovaná chemoterapie s podporou autologních hemopoetických buněk v terapii mnohočetného myelomu - přehled současných možností. Vnitř Lék 2001; 47: 92-98.

5. Richardson PG, Blood E, Mitsiades CS et al. A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma. Blood 2006; 18: in print

6. San-Miguel J, Blade J. Perspective on the current use of bortezomib in multiple myeloma. Haematologica 2006; 91: 871-872.

7. Singhal S, Mehta J, Desikan R et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med 1999; 341: 1565-1571.

8. Hájek R, Maisnar V, Krejčí M. Thalidomid. Klin Farm 2005; 19: 43-46.

9. Strupp C, Germing U, Scherer A et al. Thalidomide for the treatment of idiopathic myelofibrosis. Eur J Haematol 2004; 72: 52-57.

10. Palumbo A, Falco P, Ambrosini MT et al. Thalidomide plus dexamethasone is an effective salvage regimen for myeloma patients relapsing after autologous transplant. Eur J Haematol 2005; 75: 391-395.

11. Neuwirtová R, Špička L, Karban J et al. Naše zkušenosti s léčbou myelomu thalidomidem. Transfuze dnes 2002; 8: 13-19.

12. Palumbo A, Bringhen S, Caravita T et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet 2006; 367: 825-831.

13. Foldyna D, Kamelander J, Krejčí M et al. Žádoucí a nežádoucí účinky thalidomidu u pacientů s mnohočetným myelomem. Vnitř Lék 2003; 49: 859-868.

14. Grover JK, Uppal G, Raina V. The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma. Ann Oncol 2002; 13: 1636-1640.

15. Palumbo A, Rus C, Zeldis JB et al. Enoxaparin or aspirin for the prevention of recurrent thromboembolism in newly diagnosed myeloma patients treated with melphalan and prednisone plus thalidomide or lenalidomide. J Thromb Haemost 2006; 4: 1842-1845.

16. Durie BGM, Stepan DE. Low Dose Thalidomide Alone and in Combination: Long Term Follow-Up. Blood 2001; 98(Suppl 1): 163a.

17. Blade J, Samson D, Reece D et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. Br J Haematol 1998; 102: 1115-1123.

18. Barlogie B, Tricot G, Anaissie E et al. Thalidomide and hematopoietic-cell transplantation for multiple myeloma. N Engl J Med 2006; 354: 1021-1030.

19. Attal M, Harousseau JL, Leyvraz S et al. Maintenance therapy with thalidomide improves survival in multiple myeloma patients. Blood 2006; 108: 3289-3294.

20. Barlogie B, Desikan R, Eddlemon P et al. Extended survival in advanced and refractory multiple myeloma after single-agent thalidomide: identification of prognostic factors in a phase 2 study of 169 patients. Blood 2001; 98: 492-494.

21. Juliusson G, Celsing F, Turesson I et al. Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. Br J Haematol 2000; 109: 89-96.

22. Rajkumar SV, Dispenzieri A, Fonseca R et al. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia 2001; 15: 1271-1276.

23. Oakervee HE, Gupta V, Smith ML et al. Response to thalidomide can be predicted by paraprotein quantitation 14 days after initiating therapy. Br J Haematol 2001; 113(Suppl 1): 40.

24. Grosbois B, Bellissant E, Moreau P et al. Thalidomide (Thal) in the Treatment of Advanced Multiple Myeloma (MM). A Prospective Study of 120 Patients. Blood 2001; 98(Suppl 1): 163a.

25. Weber DM, Rankin K, Delasalle K et al. Thalidomide Alone and in Combination for Previously Untreated Myeloma. VIIIth International Myeloma Workshop, Banff, Alberta, Canada 2001.

Labels
Diabetology Endocrinology Internal medicine
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account