Open Access

Treatment outcome of thalidomide based regimens in newly diagnosed and relapsed/refractory non-transplant multiple myeloma patients: a single center experience from Thailand

  • Pimjai Niparuck1Email author,
  • Ladda Sorakhunpipitkul1,
  • Vichai Atichartakarn1,
  • Suporn Chuncharunee1,
  • Artit Ungkanont1,
  • Pantep Aungchaisuksiri1,
  • Teeraya Puavilai1 and
  • Saengsuree Jootar1
Journal of Hematology & Oncology20103:1

DOI: 10.1186/1756-8722-3-1

Received: 14 December 2009

Accepted: 5 January 2010

Published: 5 January 2010

Abstract

Background

Thalidomide based regimen is an effective and well tolerated therapy in multiple myeloma (MM) patients, however, there were a small number of studies written about the results of thalidomide therapy in non-transplant MM patients. We therefore conducted a retrospective study of 42 consecutive patients with newly diagnosed and relapsed/refractory MM treated with thalidomide- based induction regimens followed by thalidomide maintenance therapy.

Results

Induction regimens with thalidomide and dexamethasone, and the oral combination of melphalan, prednisolone and thalidomide were administrated in 22 and 16 patients, respectively. The remaining 4 patients received other thalidomide- containing regimens. Twenty-nine patients received thalidomide as a salvage regimen. Twenty-three out of 26 patients achieving complete remission (CR) and very good partial remission (VGPR) received thalidomide maintenance. Of the 41 evaluable patients, median time of treatment was 21 months (3- 45 months), ORR was 92.7% with a 63.4% CR/VGPR. With a median follow up of 23 months, 3-year- PFS and 3-year-OS were 58.6 and 72.6%, respectively. Median time to progression was 42 months. While 3-year-PFS and 3-year-OS in non-transplant patients receiving thalidomide maintenance therapy were 67 and 80%, respectively.

Conclusions

Prolonged thalidomide therapy enhanced survival rate and less frequently developed serious toxicity in non-transplant multiple myeloma patients.

To the editor:

Thalidomide based therapy for multiple myeloma (MM) improves the response and the complete remission (CR) rates in previously untreated and relapsed/refractory MM (overall response rate was 48- 73% with a 5- 10% CR) [1, 2]. In this study, we performed a retrospective study of 42 newly diagnosed and relapsed/refractory MM patients treated with thalidomide based regimens without upfront ASCT at Ramathibodi Hospital during January 2005-October 2008. Thirteen and 29 patients were previously untreated and relapsed/refractory MM, respectively (Table 1). Twenty-two patients received thalidomide 200 mg/day and oral dexamethasone 20- 40 mg/day (d1-4) every 2 weeks, 16 patients received oral melphalan 4 mg/m2/day (d1-7), prednisolone 40 mg/m2/day (d1-7) and thalidomide 100 mg/day every 4 weeks, 3 patients received thalidomide 200-400 mg/day and the remaining 1 patient received thalidomide 100 mg/day, pegylated liposomal doxorubicin i.v. 40 mg/m2/day (d1) and oral dexamethasone 40 mg/day (d1-4, 9-12) every 4 weeks. Eighty-eight percents (23/26 patients) achieving CR/VGPR (very good partial remission) received thalidomide maintenance therapy (100-200 mg/day). Aspirin 65- 325 mg/day or warfarin 1.5 mg/day was given to all patients for deep vein thrombosis prophylaxis. Of the 41 evaluable patients, median treatment period was 21 months (3- 45 m). The ORR (overall response rate) was 92.7%, with a 63.4% CR/VGPR. Median number of courses to achieve PR and CR/VGPR were 4 (range, 2-13) and 6 courses (range, 2-16), respectively. There was no difference in ORR and CR between frontline and salvage therapy groups (92.3% vs 93%) and (39% vs 23%), respectively. The ORR and CR rate for those treated with thal/dex were slightly higher than those treated with MPT (95.2% vs 87.5% and 38% vs 25%). Median follow up was 23 months, 3-year-OS and 3-year-PFS were 72.6 and 58.6%, respectively. Median TTP was 42 months, non- VGPR/CR patients had significant poorer PFS by multivariate analysis (p = 0.01) and non-responders had significant shorter OS (p = 0.01). In maintenance group, median treatment duration was 14 months (4-37 m). Three-year-PFS and 3-year-OS were 67 and 80%, respectively. Toxicities were constipation (81%), neuropathy (67%), muscle weakness in the legs (5%), infection (7%) and thrombosis (5%). New agents for treatment of MM with no planned ASCT show the CR/VGPR rates of 50- 80% with a PFS of 2 years [35]. The CR/VGPR rates in our patients were also high that might be associated with a prolonged use of thalidomide induction. Thalidomide maintenance in CR/VGPR patients provided impressive survival benefit. Hence, thalidomide is an effective therapy for MM and prolonged thalidomide use had the survival benefit and had minimal serious toxicity in non-transplant MM patients. To date, MM remains incurable. Novel agents continue to be developed and are eagerly awaited [57].
Table 1

Patients' characteristics and treatment outcomes of previously untreated and relapsed/refractory multiple myeloma

Characteristics

 

ORR

CR/VGPR

PFS

OS

Total patients (N = 42)

No. of

Patients

%

p-value

No. of

patients

p-value

HR

95% CI

p-value

HR

95% CI

p-value

Age (years), median (range)

62,(36-75)

          

   ≤ 60

17

15(94)

0.83

9(56.3)

0.45

2.95

0.98-8.81

0.05

0.81

0.09-7.27

0.85

   > 60

25

23(92)

 

17(68)

       

Sex

           

   Male

21

18(85.7)

0.79

13(65)

0.91

0.77

0.25-2.38

0.65

2.06

0.34-12.68

0.44

   Female

21

20(95.2)

 

14(66.7)

       

Prior treatment

           

   Yes

29

26(92.6)

0.95

19(67.9)

0.69

3.68

0.91-10.28

0.06

0.87

0.96-7.88

0.9

   No

13

12(92.3)

 

8(61.5)

       

International staging system

           

   I, II

8, 18

24(92.3)

0.97

15(57.7)

0.93

6.30

0.73-54.01

0.09

2.22

0.20-24.57

0.51

   III

13

12(92.3)

 

8(61.5)

       

   No data

3

          

M-protein subtype

           

   IgG, IgA, IgM

23, 8, 1

27(87.1)

0.32

19(61.3)

0.86

3.19

0.64-15.91

0.16

1.21

0.13-11.65

0.87

   Kappa, Lamda

3, 6

9(100)

 

6(66.7)

       

   Unknown type

1

          

Serum creatinine level

           

   < 2 mg/dl

34

31(91.2)

0.43

22(64.7)

0.57

0.74

0.08-6.72

0.79

0.03

0.01-856.9

0.50

   ≥ 2 mg/dl

8

7(100)

 

4(57.2)

       

Serum β2 M level, μg/ml

           

   ≤ 5

26

24(92.3)

0.53

17(65.4)

0.79

4.89

0.55-43.88

0.16

1.97

0.18-21.81

0.58

   > 5

13

11(84.6)

 

8(61.5)

       

   No data

3

          

Response to treatment

           

   Yes

38

-

-

-

-

0.15

0.04-0.61

0.01

0.03

0.01-0.35

0.01

   No

3

          

CR/VGPR

           

   Yes

26

-

-

-

-

0.14

0.04-0.47

0.01

0.21

0.03-1.48

0.12

   No

15

          

Declarations

Authors’ Affiliations

(1)
Division of hematology, Department of Medicine, Ramathibodi Hospital, Mahidol University

References

  1. David DS, Vincent R, Grzegorz SN, Morie AG, Angela D, Martha QL, Suzanne H, Rafael F, John AL, Robert AK, Philip RG, Thomas EW: Combination therapy with thalidomide and dexamethasone in patients with newly diagnosed multiple myeloma not undergoing upfront autologous stem cell transplantation: a phase II trial, haematologica. 2005, 90: 1650-54.Google Scholar
  2. Rajkumar SV, Hayman S, Gertz MA, Dispenzieri A, Lacy MQ, Greipp PR, Geyer S, Iturria N, Fonseca R, Lust JA, Kyle RA, Witzig TE: Combination therapy with thalidomide plus dexamethasone for newly diagnosed myeloma. J Clin Oncol. 2002, 20: 4319-23. 10.1200/JCO.2002.02.116.View ArticlePubMedGoogle Scholar
  3. Palumbo A, Bringhen S, Caravita T, Merla E, Capparella V, Callea V, Cangialosi C, Grasso M, Rossini F, Galli M, Catalano L, Zamagni E, Petrucci MT, De stefano V, Ceccarelli M, Ambrosini MT, Avonto I, Falco P, Ciccone G, Liberati AM, Musto P, Boccadoro M: Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomized controlled trial. Lancet. 2006, 367: 825-35. 10.1016/S0140-6736(06)68338-4.View ArticlePubMedGoogle Scholar
  4. Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, Renaud M, Harousseau JL, Guillerm G, Chaleteix C, Dib M, Voillat L, Maisonneuve H, Troncy J, Dorvaux V, Monconduit M, Martin C, Casassus P, Jaubert J, Jardel H, Doyen C, Kolb B, Anglaret B, Grosbois B, Yakoub-Agha I, Mathiot C, Avet-Loiseau H: Melphalan and prednisone plus thalidomide versus melphalan and prednisone, or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomized trial. Lancet. 2007, 370: 1209-18. 10.1016/S0140-6736(07)61537-2.View ArticlePubMedGoogle Scholar
  5. Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, Verma A: Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009, 2: 36-10.1186/1756-8722-2-36.PubMed CentralView ArticlePubMedGoogle Scholar
  6. Cang S, Ma Y, Liu D: New clinical developments in histone deacetylase inhibitors for epigenetic therapy of cancer. J Hematol Oncol. 2009, 2: 22-10.1186/1756-8722-2-22.PubMed CentralView ArticlePubMedGoogle Scholar
  7. Siegel D, Hussein M, Belani C, Robert F, Galanis E, Richon VM, Garcia-Vargas J, Sanz-Rodriguez C, Rizvi S: Vorinostat in solid and hematologic malignancies. J Hematol Oncol. 2009, 2: 31-10.1186/1756-8722-2-31.PubMed CentralView ArticlePubMedGoogle Scholar

Copyright

© Niparuck et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement