DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMAS Morton Coleman, M.D. Director, Center for Lymphoma and Myeloma New York-Presbyterian Hospital Weill Cornell Medical Center Clinical Professor of Medicine Weill Cornell Medical College Chairman, Medical Affiliates Board Lymphoma Research Foundation
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DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMAS
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DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMAS
DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMAS
Morton Coleman, M.D.Director, Center for Lymphoma and Myeloma
New York-Presbyterian Hospital Weill Cornell Medical Center
Clinical Professor of Medicine
Weill Cornell Medical College
Chairman, Medical Affiliates Board
Lymphoma Research Foundation
Morton Coleman, M.D.Director, Center for Lymphoma and Myeloma
New York-Presbyterian Hospital Weill Cornell Medical Center
Clinical Professor of Medicine
Weill Cornell Medical College
Chairman, Medical Affiliates Board
Lymphoma Research Foundation
Chromosomal translocations in lymphoma and MYC
40% of B cell lymphomas have recurrent reciprocal translocations– May be subtype specific– Often oncogene plus Ig loci enhancer t(8;14)(q24;q32) – lymphoma initiating in BL MYC breakpoints may be secondary events in other
lymphomas At diagnosis or at progression In MYC+ DLBCL and DH lymphoma, often non Ig-MYC
breakpoints
“Double hit”
Chromosomal breakpoints in DLBCL
Aukema et al, Blood 2011
Chromosomal breakpoints in DLBCL
Aukema et al, Blood 2011
Study NMYC+ total %
MYC+ SH %
BCL2/ MYC+ DH %
BCL6/ MYC+ DH %
BCL2/ BCL6/
MYC+ TH %
All DH and TH %
Barrans 2010 245 14% 2% 8% 1% 3% 12%
Obermann 2009
220 4% 3% 0 0 0 1%
Yoon 2008 137 7% 7% 1% 1% 1% 3%
Tibiletti 2009 74 16% 4% 7% 7% 1% 12%
Copie-Bergman 2009
68 3% 3% 0 0 0 0
Van Imhoff 2006
58 15% 8% 5% 2% 0 7%
Savage 2009 135 9% 7% 2% NA NA NA
Klapper 2008 117 8% NA NA NA NA NA
What is a “double hit” lymphoma?
Recurrent breakpoints activating multiple oncogenes, one being MYC
BCL2+/MYC+ most common
BCL6, CCND1 and BCL3 may also occur
Can also have “triple hit”
B cell lymphoma, unclassifiable, with features intermediate between diffuse
large B cell lymphoma and Burkitt lymphoma
WHO 2008 classification 35-50% of cases have a MYC translocation,
15% have a BCL2 translocation Increasing incidence with age Many are DH
Phase II study of dose adjusted R-EPOCH in previously untreated BL and
c-MYC + DLBCL
Inclusion criteria– Burkitt lymphoma or B-cell lymphoma,
unclassifiable, with features intermediate between Diffuse Large B-cell lymphoma and Burkitt Lymphoma
– c-MYC + DLBCL– c-MYC+ plasmablastic lymphoma
NCT01092182
Approach to “variant” DLBCL GCB vs non-GCB
– R-CHOP is standard– Various randomized trials underway
MYC+, DH, TH– Consider FISH for MYC, BCL2, BCL6– Less favorable with R-CHOP– Unclear if other approaches better– Prospective studies underway– Analysis needs incorporation in clinical trials
Intensive BL type regimens
R-EPOCH
Less favorable outcome than other DLBCL with R-CHOP– Risk seems to be beyond age, IPI