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
- (voorheen werd Sox11 bepaald: past bij indolent MCL, waarde zeer beperkt)
2 Therapie
2.1 eerste lijn
- stadium I: 3x R-CHOP-14 + IF-RT (30 Gy)
- stadium >I:
- indolent MCL: expectatief
- indolent beloop niet te voorspellen
- proxies: Ki-67 <30%, geen blastoide of pleiomorfe histologie, maximale tumor diameter < 3 cm, normaal LDH en beta2microglobuline, geen B-symptomen.[13]
- <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
- standaardarm R-CHOP alternerend met R-DHAP (totaal 6 kuren), hierin geen evaluaties middels PET
- na laatste R-DHAP ferese
- gevolgd door BEAM[3][22], hierna PET-CT
- rituximab-onderhoud bij PR of CR, 1x per 2 maanden, gedurende 3 jaar[2]
- oxaliplatin bij nierfunctiestoornis en geen carboplatin vanwege een verminderde effectiviteit
- TRIANGLE-studie: 3 armen
- >65-70:
- 8x R-CHOP-21 gevolgd door rituximabonderhoud a 2 maanden tot progressie
- BR zonder R-onderhoud bij contra-indicatie anthracyclinen [23]
- in de toekomst? R-BAC[25]
- in de toekomst? VR-CAP[24]
- indolent MCL: expectatief
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
Na >1 lijn therapie: Atalanta-1
- R-bendamustine
- response rate 82%, PFS 17 maanden, 3-jr OS 55%[14][15]
- R-FC
- gekenmerkt door hematotoxiciteit en hoge incidentie ernstige infecties
- response rate 75%, mediane duur 11 maanden[16]
- 4x R-FCM
- response rate 58%, PFS 8 maanden[17]
- 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
- LYM1002
- indien nog geen cytarabine gegeven: cytarabine (R-DHAP, of bij ouderen R-HAD)
- lenalidomide
- RR 40%, PFS 8 maanden[19]
- bortezomib
- RR 50%, PFS 5 maanden[20]
- 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 |
- study of 455 patients with MCL diagnosed between 1996 and 2004 (Hoster, Blood, 2008)
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 |
- zie ook Hoster (JCO, 2016)
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