EERSTE LIJN
<65-70
stadium I: 3x R-CHOP-14 + IF-RT (30 Gy)
stadium >I: schema HOVON 75, arm A (zonder bortezomib-onderhoud)
>65-70
stadium I: 3x R-CHOP-21 + IF-RT (30 Gy)
stadium >I: 8x R-CHOP-21 gevolgd door rituximabonderhoud (2 jaar, HOVON 55)

RECIDIEF
indicatie therapie: symptomatische progressie.
liefst: studieverband
bij respons op lijn 2+: allogene stamceltransplantatie overwegen worden (relapse rate 26%, NRM 28%, 5 jr OS 55% en 10 jr 45%)
[10,13]

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.

Rituximab-bendamustine. 
- Response rate 82%, PFS 17 maanden, OS 3 jr 55%.[14] 75% na R-CHOP
- Eenzelfde PFS van 17 maanden is gevonden in een studie waarin R-bendamustine is vergeleken met R-fludarabine.[15]
R-FC
- ernstige hematotoxiciteit en bijkomende infectieproblematiek
- RR 75%, mediane duur 11 maanden)[16]
R-FCM 4x
- Response rate 58%, PFS 8 maanden.[17]
Ibrutinib
- 560 mg eenmaal daags tot progressie
- RR 72%, PFS 14 maanden.[4,18]
- bij voorkeur verdient bij chemo-refractaire patiënten in 2e of latere lijn. 

Andere opties, meestal voor 3e of latere lijn: 
Indien nog geen R-CHOP is gegeven is dit een goede optie.
Indien nog geen cytarabine is gegeven kan dat overwogen worden (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]

Frail patienten: 
chloorambucil lage dosis continu palliatief gebruikt worden. 

Voor lokale palliatie kan 2 x 2 Gy radiotherapie worden overwogen. 
Supportive care.


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.
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.
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.
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