Letter to the Editor

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Blood Res 2019; 54(2):

Published online June 30, 2019

https://doi.org/10.5045/br.2019.54.2.153

© The Korean Society of Hematology

What is the most appropriate regimen for untreated Waldenström macroglobulinemia? - An updated analysis of rituximab and half-dose CHOP therapy and cost effectiveness

Naohiro Sekiguchi1,2, Airi Hamano3, Tomoko Kitagawa2, Kenichi Ito1, Kazuhiko Hirano4, Kazuaki Yamada4

1Hematology Division, 2Clinical Research Division, 3Pharmaceutical Division, 4Laboratory and Pathology Division, National Hospital Organization Disaster Medical Center, Tokyo, Japan

Correspondence to : Naohiro Sekiguchi
Hematology Division, National Hospital Organization Disaster Medical Center, 3256 Midori-cho, Tachikawa, Tokyo 190-0014, Japan
E-mail: nao26nao26@gmail.com

Received: January 31, 2019; Revised: February 25, 2019; Accepted: March 8, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Fig. 1.

Survival curve. (A) Progression-free survival (PFS). The median PFS of half-dose R-CHOP therapy was not reached, and the estimated 2-year PFS was 72% and 3-year PFS was 64%. The estimated 3-year second PFS by a bendamustine-containing regimen was 89%. (B) Overall survival (OS). The estimated 3-year OS was 96%.


Fig. 2.

Swimmer plot for 25 patients who received half-dose R-CHOP therapy. Nine patients developed refractory disease or progression and 3 patients received third-line therapy.


Table. 1.

Table 1 Summary of responses to each regimen, survival, and drug prices.

a)Ibrutinib is not approved in Japan for WM. b)Data relapsed/refractory WM.

Abbreviations: R, rituximab; DRC, dexamethasone, R, cyclophosphamide; R-CHOP, R, cyclophosphamide, hydroxyl-doxorubicin, vincristine, prednisone; BDR, bortezomib, dexamethasone, R; ORR, overall response rate; JPY, japanese yen; PFS, progression-free survival; TTF, time to treatment failure; TTP, time to progression; PD, progressive disease; NA, not applicable; NR, not reached.


  1. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012;367:826-833.
    Pubmed
  2. Sekiguchi N, Nomoto J, Nagata A, et al. Gene expression profile signature of aggressive Waldenström macroglobulinemia with chromosome 6q deletion. Biomed Res Int 2018;2018:6728128.
    Pubmed
  3. Sekiguchi N, Hamano A, Kitagawa T, et al. Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent. Blood Res 2018;53:117-122.
    Pubmed
  4. Buske C, Hoster E, Dreyling M, et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia 2009;23:153-161.
    Pubmed
  5. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 2013;381:1203-1210.
    Pubmed
  6. Buske C, Sadullah S, Kastritis E, et al. Treatment and outcome patterns in European patients with Waldenström's macroglobulinaemia: a large, observational, retrospective chart review. Lancet Haematol 2018;5:e299-e309.
    Pubmed
  7. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol 2007;25:3344-3349.
    Pubmed
  8. Olszewski AJ, Treon SP, Castillo JJ. Application and outcomes of bendamustine- or bortezomib-based therapy for Waldenstrom's macroglobulinemia. Blood (ASH Annual Meeting Abstracts) 2017;130:abst 348.
  9. Lee HS, Kim K, Yoon DH, et al. Clinical factors associated with response or survival after chemotherapy in patients with Waldenström macroglobulinemia in Korea. Biomed Res Int 2014;2014:253243.
    Pubmed
  10. Saito A, Isoda A, Kojima M, et al. Retrospective analysis of prognostic factors for Waldenström macroglobulinemia: a multicenter cooperative study in Japan. Int J Hematol 2017;106:681-690.
    Pubmed
  11. Treon SP, Ioakimidis L, Soumerai JD, et al. Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol 2009;27:3830-3835.
    Pubmed
  12. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med 2015;372:1430-1440.
    Pubmed
  13. Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenström's macroglobulinemia. N Engl J Med 2018;378:2399-2410.
    Pubmed
  14. Olszewski AJ, Castillo JJ. Ibrutinib and rituximab in Waldenström's macroglobulinemia. N Engl J Med 2018;379:1973-1974.
  15. Aiello A, D'Ausilio A, Lo Muto R, Randon F, Laurenti L. Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy. J Mark Access Health Policy 2017;5:1393308.
    Pubmed

Article

Letter to the Editor

Blood Res 2019; 54(2): 153-156

Published online June 30, 2019 https://doi.org/10.5045/br.2019.54.2.153

Copyright © The Korean Society of Hematology.

What is the most appropriate regimen for untreated Waldenström macroglobulinemia? - An updated analysis of rituximab and half-dose CHOP therapy and cost effectiveness

Naohiro Sekiguchi1,2, Airi Hamano3, Tomoko Kitagawa2, Kenichi Ito1, Kazuhiko Hirano4, Kazuaki Yamada4

1Hematology Division, 2Clinical Research Division, 3Pharmaceutical Division, 4Laboratory and Pathology Division, National Hospital Organization Disaster Medical Center, Tokyo, Japan

Correspondence to:Naohiro Sekiguchi
Hematology Division, National Hospital Organization Disaster Medical Center, 3256 Midori-cho, Tachikawa, Tokyo 190-0014, Japan
E-mail: nao26nao26@gmail.com

Received: January 31, 2019; Revised: February 25, 2019; Accepted: March 8, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

    Fig 1.

    Figure 1.

    Survival curve. (A) Progression-free survival (PFS). The median PFS of half-dose R-CHOP therapy was not reached, and the estimated 2-year PFS was 72% and 3-year PFS was 64%. The estimated 3-year second PFS by a bendamustine-containing regimen was 89%. (B) Overall survival (OS). The estimated 3-year OS was 96%.

    Blood Research 2019; 54: 153-156https://doi.org/10.5045/br.2019.54.2.153

    Fig 2.

    Figure 2.

    Swimmer plot for 25 patients who received half-dose R-CHOP therapy. Nine patients developed refractory disease or progression and 3 patients received third-line therapy.

    Blood Research 2019; 54: 153-156https://doi.org/10.5045/br.2019.54.2.153

    Table 1 . Summary of responses to each regimen, survival, and drug prices..

    a)Ibrutinib is not approved in Japan for WM. b)Data relapsed/refractory WM..

    Abbreviations: R, rituximab; DRC, dexamethasone, R, cyclophosphamide; R-CHOP, R, cyclophosphamide, hydroxyl-doxorubicin, vincristine, prednisone; BDR, bortezomib, dexamethasone, R; ORR, overall response rate; JPY, japanese yen; PFS, progression-free survival; TTF, time to treatment failure; TTP, time to progression; PD, progressive disease; NA, not applicable; NR, not reached..


    References

    1. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012;367:826-833.
      Pubmed
    2. Sekiguchi N, Nomoto J, Nagata A, et al. Gene expression profile signature of aggressive Waldenström macroglobulinemia with chromosome 6q deletion. Biomed Res Int 2018;2018:6728128.
      Pubmed
    3. Sekiguchi N, Hamano A, Kitagawa T, et al. Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent. Blood Res 2018;53:117-122.
      Pubmed
    4. Buske C, Hoster E, Dreyling M, et al. The addition of rituximab to front-line therapy with CHOP (R-CHOP) results in a higher response rate and longer time to treatment failure in patients with lymphoplasmacytic lymphoma: results of a randomized trial of the German Low-Grade Lymphoma Study Group (GLSG). Leukemia 2009;23:153-161.
      Pubmed
    5. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 2013;381:1203-1210.
      Pubmed
    6. Buske C, Sadullah S, Kastritis E, et al. Treatment and outcome patterns in European patients with Waldenström's macroglobulinaemia: a large, observational, retrospective chart review. Lancet Haematol 2018;5:e299-e309.
      Pubmed
    7. Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol 2007;25:3344-3349.
      Pubmed
    8. Olszewski AJ, Treon SP, Castillo JJ. Application and outcomes of bendamustine- or bortezomib-based therapy for Waldenstrom's macroglobulinemia. Blood (ASH Annual Meeting Abstracts) 2017;130:abst 348.
    9. Lee HS, Kim K, Yoon DH, et al. Clinical factors associated with response or survival after chemotherapy in patients with Waldenström macroglobulinemia in Korea. Biomed Res Int 2014;2014:253243.
      Pubmed
    10. Saito A, Isoda A, Kojima M, et al. Retrospective analysis of prognostic factors for Waldenström macroglobulinemia: a multicenter cooperative study in Japan. Int J Hematol 2017;106:681-690.
      Pubmed
    11. Treon SP, Ioakimidis L, Soumerai JD, et al. Primary therapy of Waldenström macroglobulinemia with bortezomib, dexamethasone, and rituximab: WMCTG clinical trial 05-180. J Clin Oncol 2009;27:3830-3835.
      Pubmed
    12. Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med 2015;372:1430-1440.
      Pubmed
    13. Dimopoulos MA, Tedeschi A, Trotman J, et al. Phase 3 trial of ibrutinib plus rituximab in Waldenström's macroglobulinemia. N Engl J Med 2018;378:2399-2410.
      Pubmed
    14. Olszewski AJ, Castillo JJ. Ibrutinib and rituximab in Waldenström's macroglobulinemia. N Engl J Med 2018;379:1973-1974.
    15. Aiello A, D'Ausilio A, Lo Muto R, Randon F, Laurenti L. Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy. J Mark Access Health Policy 2017;5:1393308.
      Pubmed
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