mcl

Table of Contents

Mantelcellymfoom

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1 Verplicht aanvullend onderzoek

  • laboratoriumonderzoek inclusief M-proteine
  • PET-CT
  • beenmergonderzoek
  • aaIPI
    • bij een aaIPI >1 wordt soms de therapie geintensiveerd
    • criteria:
      • stadium III/IV
      • performance status >2
      • verhoogd LDH
  • IPI, verplicht als kwaliteitscriterium bij statusvoering
    • kent dezelfde punten als aaIPI, plus
      • >60 jaar oud
      • >1 extranodale lokalisatie

1.1 PET-CT

  • wordt verricht als eindevaluatie
  • zo mogelijk ook voor start therapie (en voor start prednison)
  • Deauville-score
    1. no uptake or no residual uptake (when used interim)
    2. slight uptake, but below blood pool (mediastinum)
    3. uptake above mediastinal, but below or equal to uptake in the liver
    4. uptake slightly to moderately higher than liver
    5. markedly increased uptake or any new lesion (on response evaluation)
  • Deauville t/m 3 geldt als mCR bij eindevaluatie 1

2 Therapie

2.1 eerste lijn

  • stadium I: 3x R-CHOP-14 + IF-RT (30 Gy)
  • stadium >I:
    • indolent MCL: expectatief
      • Ki-67 < 30%, geen blastoide of pleiomorfe histologie, maximale tumor diameter < 3 cm, normaal LDH en beta2microglobuline, geen B-symptomen.2
    • <65-70: R-CHOP alternerend met R-DHAP (totaal 6 kuren) gevolgd door autologe stamceltransplantatie3 en rituximab-onderhoud bij PR of CR, 1x per 2 maanden, gedurende 3 jaar4
    • >65-70:
      1. 8x R-CHOP-21 gevolgd door 2 jaar rituximabonderhoud1
      2. BR zonder R-onderhoud

2.2 recidief

2.2.1 algemeen

  • symptomatische progressie pas indicatie therapie
  • indien geschikte kandidaat bij respons op tweedelijns therapie: allogene stamceltransplantatie1
    • recidiefkans 26%, NRM 28%, 5-jr OS 55% en 10-jr 45%

2.2.2 geaccepteerde opties voor de tweedelijn

  1. R-bendamustine
    • response rate 82%, PFS 17 maanden, 3-jr OS 55%5, 6
  2. R-FC
    • gekenmerkt door hematotoxiciteit en hoge incidentie ernstige infecties
    • response rate 75%, mediane duur 11 maanden7
  3. 4x R-FCM
    • response rate 58%, PFS 8 maanden8
  4. ibrutinib 1dd 560 mg tot progressie
    • bij voorkeur pas bij chemo-refractaire patiĆ«nten in 2e of latere lijn
    • RR 72%, PFS 14 maanden9

2.2.3 andere opties, meestal voor 3e of latere lijn

  1. indien nog geen cytarabine gegeven: cytarabine (R-DHAP, of bij ouderen R-HAD)
  2. lenalidomide
    • RR 40%, PFS 8 maanden10
  3. bortezomib
    • RR 50%, PFS 5 maanden11
  4. temsirolimus
    • RR 40%, PFS 6 maanden9

2.2.4 palliatief

  • chloorambucil lage dosis continu
  • palliatieve lokale radiotherapie / steroiden

Footnotes:

1

Vaughn JE, Sorror ML, Storer BE, et al. Long-term sustained disease control in patients with mantle cell lymphoma with or without active disease after treatment with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. Cancer. 2015;121(20):3709-16. Robinson S, Dreger P, Caballero D, et al. The EBMT/EMCL consensus project on the role of autologous and allogeneic stem cell transplantation in mantle cell lymphoma. Leukemia. 2015;29(2):464-73.

2
  • Cohen. Deferred therapy is associated with improved overall survival in patients with newly diagnosed mantle cell lymphoma. Cancer. 2016.
  • Cheah. Mantle Cell Lymphoma. J Clin Oncol. 2016;34(11):1256-69.
3

Hermine. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-75.

4

Le Gouill. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. N Engl J Med. 2017;377(13):1250-60.

5

Czuczman MS, Kahanic S, Forero A, et al. Results of a phase II study of bendamustine and ofatumumab in untreated indolent B cell non-Hodgkin's lymphoma. Ann Hematol. 2015;94(4):633-41. 75% na R-CHOP Czuczman. Phase II study of bendamustine combined with rituximab in relapsed/refractory mantle cell lymphoma: efficacy, tolerability, and safety findings. Ann Hematol. 2015 Dec;94(12):2025-32.

6

Rummel M, Kaiser U, Balser C, et al. Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open -label, non-inferiority phase 3 trial. Lancet Oncol. 2016;17(1):57-66.

7

Thomas DW, Owen RG, Johnson SA, et al. Superior quality and duration of responses among patients with mantle-cell lymphoma treated with fludarabine and cyclophosphamide with or without rituximab compared with prior responses to CHOP. Leuk Lymphoma. 2005;46(4):549-52.

8

Forstpointner R, Dreyling M, Repp R, et al. The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2004;104(10):3064-71.

9

Dreyling M, Jurczak W, Jerkeman M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387(10020):770-8.

10

Trneny M, Lamy T, Walewski J, et al. Lenalidomide versus investigator's choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol. 2016;17(3):319-31.

11

O'Connor OA, Moskowitz C, Portlock C, et al. Patients with chemotherapy-refractory mantle cell lymphoma experience high response rates and identical progression-free survivals compared with patients with relapsed disease following treatment with single agent bortezomib: results of a multicentre Phase 2 clinical trial. Br J Haematol. 2009;145(1):34-9

Author: Koen de Heer

Created: 2018-10-14 zo 19:06

Emacs 25.2.2 (Org mode 8.2.10)

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