Mantelcellymfoom (MCL)

Inhoudsopgave

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1 Verplicht aanvullend onderzoek

  • laboratoriumonderzoek inclusief M-proteine
  • PET-CT (als bij het DGBCL)
  • beenmergonderzoek
  • prognostische markers
    • MIPI
    • blastoide variant
    • Ki67 >30%
    • p53: zeer slechte prognose
    • Sox11: indolent MCL

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.[13]
      • Sox11-negatief vereist
    • <65-70:
      • TRIANGLE-studie: 3 armen
        • R-CHOP/DHAP + AuSCT +/- R-onderhouds
        • R-i-CHOP/DHAP + AuSCT +/- R-onderhouds
        • R-i-CHOP/DHAP zonder AuSCT +/- R-onderhouds
      • R-CHOP alternerend met R-DHAP (totaal 6 kuren) gevolgd door autologe stamceltransplantatie[3][22] en rituximab-onderhoud bij PR of CR, 1x per 2 maanden, gedurende 3 jaar[2]
        • oxaliplatin bij nierfunctiestoornis en geen carboplatin vanwege een verminderde effectiviteit
    • >65-70:
      1. 8x R-CHOP-21 gevolgd door rituximabonderhoud a 2 maanden tot progressie
      2. BR zonder R-onderhoud bij contra-indicatie anthracyclinen [23]
      3. in de toekomst? R-BAC[25]
      4. in de toekomst? VR-CAP[24]

2.2 recidief

2.2.1 algemeen

  • symptomatische progressie pas indicatie therapie
  • indien geschikte kandidaat bij respons op tweedelijns therapie: allogene stamceltransplantatie[1]
    • 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%[14][15]
  2. R-FC
    • gekenmerkt door hematotoxiciteit en hoge incidentie ernstige infecties
    • response rate 75%, mediane duur 11 maanden[16]
  3. 4x R-FCM
    • response rate 58%, PFS 8 maanden[17]
  4. ibrutinib 1dd 560 mg tot progressie
    • bij voorkeur pas bij chemo-refractaire patiënten in 2e of latere lijn
    • RR 72%, PFS 14 maanden[18]
    • 20% CR

2.2.3 andere opties, meestal voor 3e of latere lijn

  1. LYM1002
  2. indien nog geen cytarabine gegeven: cytarabine (R-DHAP, of bij ouderen R-HAD)
  3. lenalidomide
    • RR 40%, PFS 8 maanden[19]
  4. bortezomib
    • RR 50%, PFS 5 maanden[20]
  5. temsirolimus
    • RR 40%, PFS 6 maanden[18]

2.2.4 palliatief

  • chloorambucil lage dosis continu
  • palliatieve lokale radiotherapie / steroiden

3 Mantle cell lymphoma international prognostic index (MIPI)

Points Age (years) ECOG LDH:ULN ratio WBC (109/L)
0 <50 0 to 1 <0.67 <6.7
1 50 to 59   0.67 to 0.99 6.7 to 9.9
2 60 to 69 2 to 4 1.00 to 1.49 10.0 to 14.9
3 ≥70   ≥1.50 ≥15.00
Score Risk group Median survival Five-year OS
0 to 3 points Low risk Not reached 60 percent
4 to 5 points Intermediate risk 58 months 35 percent
6 to 12 points High risk 37 months 20 percent

4 voetnoten

[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. [14] 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. [15] 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.

[16] 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.

[17] 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. [18]

  • 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.
  • Wang, NEJM, 2013

[19] 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. [20] 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 [22] Dreyling, Blood, 2005: consolidatie met AuSCT, verlenging OS [2]

  • Le Gouill. Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma. N Engl J Med. 2017;377(13):1250-60.
  • - HOVON 75

[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.

[13]

  • 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.

[23] Rummel, Lancet oncol, 2017 [24] Robak, NEJM, 2015; frequent trombocytentransfusie [25] Visco, JCO, 2013

Auteur: Koen de Heer

Created: 2021-07-06 di 19:30