PD Dr Anastasios Stathis, MD Head-New Drugs Development Unit Chair-Clinical Research Oncology Institute of Southern Switzerland Bellinzona, Switzerland Advances in the management of non-Hodgkin’s Lymphomas 6th ESO-ESMO Eastern Europe and Balkan Region Masterclass in Medical Oncology 12/04/2019 - 17/04/2019, Sibenik, Croatia ESO-ESMO EEBR Masterclass 2019
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Advances in the management of non-Hodgkin’s Lymphomas€¦ · PD Dr Anastasios Stathis, MD Head-New Drugs Development Unit . Chair-Clinical Research. Oncology Institute of Southern
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PD Dr Anastasios Stathis, MDHead-New Drugs Development Unit
Chair-Clinical ResearchOncology Institute of Southern Switzerland
Bellinzona, Switzerland
Advances in the management of non-Hodgkin’s Lymphomas
6th ESO-ESMO Eastern Europe and Balkan RegionMasterclass in Medical Oncology
12/04/2019 - 17/04/2019, Sibenik, Croatia
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Outline
• The different lymphoma subtypes• Diagnosis and staging• Principles of lymphoma therapy• Management of DLBCL: how to tailor
treatment based on clinical and biologicalfactors
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90 entities !!!
The 2016 revision of the 2008 WHO classification
(Swerdlow et al, Blood 2016)
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Incidence and mortality lymphomas
Siegel et al, CA Cancer J Clin. 2019ESO-E
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Lymphoma Database (Bellinzona and Novara), 2803 patients and 10 yrs follow-up
The most frequent subtypes
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• „Rapidly growing but curable“ (diffuse large B-cell)
Risk of CNS relapseage > 60 y, LDH > N, stage 3 or 4, extranodal sites > 1,
kidney/adrenal gland involvement
Savage KJ et al. (Abs) Blood. 2014ESO-E
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Treatment based on clinical features
Characteristic TreatmentaaIPI=0 non bulky disease 4x RCHOP +2RaaIPI≥1 and/or bulky disease 6x RCHOP (+RT?)aaIPI=3 6xRCHOP (+auto SCT?)Older and fit patients 6x RCHOP with pre-phaseOlder not-fit 6x R-miniCHOP, or R-CEOP, or
R-Bendamustine
Testis involvement, multiple extranodal sites, close to SNC, ≥4 risk factors of the IPI score
SNC prophylaxis with HD-MTX
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Can we improve over R-CHOP21?
• Shorter treatment intervals • Maintenance rituximab • Intensive 1st line regimen • Front-line autotransplant• Infusional regimens • Replace rituximab with other MoAb
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Can we improve over R-CHOP21?
• Shorter treatment intervals NO• Maintenance rituximab NO• Intensive 1st line regimen YES but..• Front-line autotransplant In selected pts• Infusional regimens NO• Replace rituximab with other MoAb NO
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How can we tailor treatment in DLBCL?
CLINICAL FACTORS
Age, comorbidityStage (eg short course
chemo + RT)Extranodal sites (eg CNS
prophylaxis for some sites; different treatment for PCNSL)
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How can we tailor treatment in DLBCL?
CLINICAL FACTORS
Age, comorbidityStage (eg short course
chemo + RT)Extranodal sites (eg CNS
prophylaxis for some sites; different treatment for PCNSL)
BIOLOGICAL FACTORS??
COO (ABC vs GCB)Myc , BCL2, BCL6
translocationsMYC/BCL2 IHC double
expression (DE)
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Myc, Bcl-2 and Bcl-6
Rosenthal and Younes, Blood Reviews 2016
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Myc, Bcl-2 and Bcl-6
• MYC is a transcription factor which regulates the expression of several target genes involved in the cell cycle, DNA damage repair, metabolism, protein synthesis, and response to stress– MYC translocation can be detected in approximately 10% of DLBCL
(range 4% to 14%)
• BCL2 normally serves an anti-apoptotic function– BCL2 translocations are found in 20–30% of de novo DLBCL and the
vast majority of cases are observed in the GCB subtype
• BCL6 is expressed in normal mature germinal center B-cells and acts as a transcription repressor
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Adverse impact on survival of MYC translocations
Rosenthal and Younes, Blood Reviews 2016
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Swerdlow et al, Blood 2016
MYC+MYC+
DH+
DH+
DH+ DH+
Aggressive B-cell lymphomas in the new classification
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Landsburg DJ. Et al, J Clin Oncol, 2017
MYC +/- BCL2 +/- BCL6 rearrangements(role of intensive 1st line R-chemo)
RFS OS
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MYC +/- BCL2 +/- BCL6 rearrangements(role of auto-SCT in 1st line)
Landsburg DJ. Et al, J Clin Oncol, 2017
RFS OS
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Double-expressor lymphoma
19-34% of cases
IHC expression(40% MYC)(50% BCL2)
Rosenthal and Younes, Blood Reviews 2016
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Coexpression of MYC and BCL2 considered new prognostic marker (double-expressor lymphoma)
• R-CHOP remains the standard of care• Consolidation with ASCT in selected young high IPI• R-CHOP + CNS prophylaxis based on CNS risk factors• No data to support MTAs added to R-CHOP based on
COO• Intensified treatment and CNS prophylaxis in HGBL
with MYC +/- BCL2 +/- BCL6 rearrangements
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In conclusion
• Treatment outcomes improved for many different lymphomas
• In DLBCL RCHOP remains the standard of care• All phase III trials have failed to imrpove treatment
outcomes in 1st line• CARTs have shown great activity in r/r DLBCL patients
(problem of costs!!!)• Need to direct treatment to specific genetic