Diffuse Large B-Cell Lymphoma (DLBCL)

Transcription

1 Diffuse Large B-Cell Lymphoma (DLBCL) DLBCL/MCL Dr. Anthea Peters, MD, FRCPC University of Alberta/Cross Cancer Institute

2 Disclosures Honoraria from Janssen, Abbvie, Roche, Lundbeck, Seattle Genetics

3 Objectives Diffuse Large B Cell Lymphoma (DLBCL) Prognosis IPI Molecular subtypes Treatment DLBCL NOS vs. double hit lymphoma Relapse Mantle Cell Lymphoma (MCL) Prognosis MIPI Treatment Young vs. elderly

4 Diffuse Large B Cell Lymphoma The most common non-hodgkin lymphoma subtype (40%) A group of clinically, morphologically, and molecularly heterogenous aggressive B- cell non-hodgkin lymphomas Aggressive clinical course Over 50% of patients are cured with RCHOP* chemoimmunotherapy Poor prognosis for refractory or relapsed patients *RCHOP: rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone

5 International Prognostic Index IPI R-IPI NEJM 1993;329:987 Sehn L, et al. Blood 2007;109:1857

6 Molecular Subgroups Gene expression profiling experiments have identified 3 molecular subgroups, referring to their cell of origin. Subgroups have distinct prognoses. Germinal centre B-cell-like Activated B-cell-like other Rosenwald A, NEJM 2002;346:1937

7 Molecular Subgroups Cell of Origin Germinal-centre B-cell subtype Activated B-cell subtype Unclassified subtype c-myc Double/triple hit (FISH) MYC BCL2 +/- BCL6 Double expressor (IHC) MYC BCL2 and/or BCL6 Friedberg J. Blood 2017;130(5):590-9 FISH: fluorescence in situ hybridization IHC: immunohistochemistry

8 Molecular Subgroups c-myc Double/triple hit (FISH) MYC BCL2 +/- BCL6 Double expressor (IHC) MYC BCL2 and/or BCL6 Sarkozy et al., Lancet Oncology 2015;16(15):e555-7 Johnson et al., J Clin Oncol 2012;30:3452-9

9 Treatment of DLBCL CoiffierB, et al., NEJM 2002;346:245

10 Landsburg et al. J Clin Oncol 2017;35(20): Treatment of DHL RCHOP alone is inferior treatment Intensified treatment is required No consensus on which regimen AutoSCT only beneficial after RCHOP

11 Relapsed DLBCL NOS PARMA Trial: Philip T et al., NEJM 1995; 333:1540

12 Risk of CNS Relapse HistologicSubtype DLBCL NOS Risk Factors CNS-IPI 4 or involvement of breast, testis, uterus, epidural, kidney/ adrenals Double-expressor lymphoma CD5+ DLBCL Intravascular DLBCL High-grade B-cell lymphoma with BCL2 and/or BCL6 rearrangements All Adapted from Chin C et al. Blood 2017;130(7):867-74

13 DLBCL Treatment Algorithm DLBCL NOS Double Hit Lymphoma High risk of CNS relapse AND age <70 Ø RCHOP x 6 Ø RCHOP x 6 + HD-MTX* Intensified chemotherapy + rituximab Ø Magrath Ø DA-EPOCH-R** Ø RCHO(E)P +MTX +ASCT in CR/PR1 *HD-MTX: high dose methotrexate **DA-EPOCH-R: dose-adjusted EPOCH-R

14 DLBCL Treatment Algorithm DLBCL NOS Double Hit Lymphoma High risk of CNS relapse AND age <70 Ø RCHOP x 6 Ø RCHOP x 6 + HD-MTX Ø Intensified chemotherapy + rituximab Systemic Relapse Age 65 Age 65 Ø Salvage chemo + ASCT Ø Clinical trial Ø Palliation

15 Mantle Cell Lymphoma A rare subtype of NHL that predominantly occurs in the 5 th or 6 th decade and in males (3:1). Overexpression of CD5 and cyclin D1 (t(11;14) by FISH Morphologic variants: classical, pleomorphic, blastoid Aggressive clinical behavior but not curable with chemoimmunotherapy Blastoid variant particularly aggressive Rare leukemic non-nodal subtype with indolent clinical behaviour

16 MIPI Score Dreyling M, et al. Ann Oncol 2017;28 (Suppl 4): iv62-71 HosterE., et al. Blood 2008;111:558-65

17 Mantle Cell Lymphoma Hoster E, et al. JCO 2016;34:1386

18 Mantle Cell Lymphoma Hoster E, et al. JCO 2016;34:1386

19 MCL Younger Trial HermineO, et al. Lancet 2016;388:565-75

20 MCL Younger Trial Time to treatment failure (TTF) and progression-free survival (PFS) were significantly superior in the cytarabine group Median PFS 9.1 years vs. 4.3 years (cytarabine vs. control) There was no significant difference between the groups with regards to overall survival (OS) HermineO, et al. Lancet 2016;388:565-75

21 Maintenance rituximab significantly improved both PFS and OS in patients that received cytarabine-based chemotherapy and autosct. Le Gouill S, et al. NEJM 2017;337:

22 Rummel M, et al. Lancet 2013; 381: Robak T et al. NEJM 2015;372(10): RCHOP Not Standard Chemo For Elderly B-R= Bendamustine + rituximab VR-CAP=Velcade, rituximab, cyclophosphamide, doxorubicin, prednisone

23 Other Treatment Options Watch and wait may be appropriate for patients with: Non-nodal CLL-like presentation with no cytopenias No disease-related symptoms No adverse pathology features Stage I-IIA non-bulky May consider abbreviated chemotherapy course +/- radiation Dreyling M, et al. Ann Oncol 2017;28 (Suppl 4): iv62-71 Alberta Provincial Lymphoma Guidelines 2017

24 Relapsed MCL There is no accepted standard therapy for relapsed mantle cell lymphoma. Immunochemotherapy or targeted therapy are accepted options. This phase 3 trial showed that ibrutinib is superior to temsirolimus with respect to PFS and tolerability. Dreylinget al., Lancet 2016;387:770-8

25 MCL Treatment Algorithm Young 65 Elderly > 65 Ø RCHOP/ RDHAP x 6 Ø Watch & wait Ø Bendamustine + R Ø ASCT in CR/PR1 Ø Maint-R Ø Maint-R

26 MCL Treatment Algorithm Young 65 Elderly > 65 Ø RCHOP/ RDHAP x 6 Ø Watch & wait Ø Bendamustine + R Ø ASCT in CR/PR1 Ø Maint-R Ø Maint-R Relapse Allogeneic SCT Chemoimmunotherapy: VR-CAP, BR, RBAC Targeted therapies: Ibrutinib, lenalidomide