FRANCESCO(D’AMORE((AARHUS)
HOW(CLINICAL(TRIALS(AND(THE(LATEST(UPDATE(OF(THE(WHO(
CLASSIFICATION(ARE(SHAPING(CURRENT(AND(FUTURE(THERAPIES(FOR(T?CELL(
LYMPHOMA(–(TOWARDS(MORE(SUBTYPE?SPECIFIC(APPROACHES?(
(
Peripheral! T>cell! lymphomas! (PTCL)! are! a! rare! and! heterogeneous! group! of! entities! with!
marked! differences! in! biological! backgrounds! and! clinical! presentation! features.! The! PTCL!
subtype!definition!we!use!today!is!a!result!of!basic!and!translational!researchperformed!over!
the! last! three! decades! leading! not! only! to! PTCL! specific! but! PTCL( subtype>specific!
approaches.!
A! number! of! novel! agents! has! been! tested! as! monotherapy! at! phase1>2! level! in!
relapsed/refractory! PTCL,! and! 3! of! them,! alemtuzumab,! brentuximab! vedotin,! romidepsin!
were!investigated!in!upfront!phase!3!trials.!
From! the! updated! PTCL! entities! of! the! revised! 2017! WHO! classification,! three! areas! with!
specific! therapeutic! aspects! will! be! discussed:! (i)! the! T>follicular! helper! (TFH)! cell! derived!
PTCL!(including!AITL!and!TFH>derived!PTCL>NOS),!(ii)!the!intestinal!lymphomas!and!(iii)!the!
anaplastic!large!cell!lymphomas!(ALCL).!
TFH>derived! TCL:! Angioimmunblastic! TCL! (AITL)! is! a! disease! considered! to! originate! from!
follicular!helper!T>cells!with!a!typical!phenotype!often!displaying!CD3+,!CD10+,!BCL6+,!PD1+,!
CXCL13! and! a! vivid! meshwork! of! CD21+! follicular! dendritic! cells.! Presence! of! clonal! B>cell!
populations!with!EBV+!large!B>cell!blasts!is!common!and!a!secondary!EBV+!DLBCL!can!occur.!
Molecular! genomic! studies! have! helped! clarifying! the! interrelationship! between! nodal!
entities!of!TFH!origin!and!provided!the!ration!for!common!therapeutic!targeting.!TFH!derived!
PTCL!is!often!mutated!in!epigenetic!modifier!genes!such!as!DNMT3A!and>B,!TET2!and!IDH2.!
Mutations!in!these!genes!were!known!to!occur!in!myeloid!neoplasias,!where!they!seem!to!
be!mutually!exclusive,!while!they!often!co>occurr!in!TFH>derived!TCL.!Early!treatment!results!
with!histone!deacetylase!inhibitors!(HDACi)!in!r/r!PTCL!seemed!to!favour!TFH>derived!PTCL.!
Therefore,! an! upfront! phase! 1b/2! randomized! study! combining! romidepsin! with! CHOP! vs!
CHOP!alone!was!launched.!The!hypomethylating!agent!5>aza>cytidine!has!also!been!tested!in!
AITL! and! TFH>derived! PTCL>NOS! with! encouraging! anecdotal! results! and! is! currently!
investigated!in!the!randomized!phase!2!ORACLE!trial!in!comparison!with!physician’s!choice!
monotherapy!(bendamustine,!gemcitabine!or!romidepsin).!!
Intestinal!TCL:!In!the!context!of!T>cell!lymphomas!of!the!gastrointestinal!tract!(GIT),!the!2017!
WHO!classification!has!modified!the!terminology!with!regard!to!the!entity!earlier!referred!to!
as!type!2!enteropathy>associated!TCL!to!monomorphic!epitheliotropic!intestinal!lymphoma,!
underscoring!the!fact!that!this!usually!TCR!γδ!rearranged,!CD8+,CD56+!and!SETD2!mutated!
disease! is! most! commony! not! associated! with! a! pre>/co>existing! enteropathy.! Importantly!
the! 2017! WHO! classification! also! introduces! a! provisional! entity! (‘indolent!
lymphoproliferative! disease! og! the! gastrointestinal! tract),! which! is! a! CD8+! disease!
characterized! by! a! chronic,! indolent! clinical! course! with! mostly! local! relapses! and! rarely!
disseminating!outside!the!GIT.!It!is!relevant!for!lymphoma!clinician!to!know!that!this!disease!
is!usually!chemorefractory!and!best!managed!with!a!watchful!(e.g.!endoscopic!control!x1/yr)!
waiting!strategy.!Local!relapses!can!be!managed!by!local!radiotherapy.!
ALCL:!!A!novel!entity!in!the!2017!WHO!classification!is!the!breast>implant!associated!ALCL.!
Often!identified!as!a!cytological!finding!in!a!seroma!developed!around!the!implant!capsule,!it!
SCIENTIFIC PROGRAMME
SESSION I
HODGKIN’S DISEASE
DEBATE I
IS THERE STILL A ROLE
FOR COMBINED MODALITY
THERAPY FOR EARLY
STAGE CHL?
SESSION II
T-CELL LYMPHOMA
ROUNDTABLE I
FUTURE DIRECTIONS IN
T-CELL LYMPHOMA
SESSION III
FOLLICULAR LYMPHOMA
DEBATE II
CAN WE AVOID
CHEMOTHERAPY IN
THE MANAGEMENT OF
FOLLICULAR LYMPHOMA?
SESSION IV
RARE LYMPHOMAS –
MARGINAL ZONE
LYMPHOMA AND
WALDENSTRÖM M
ACROGLOBULINEMIA
ROUNDTABLE II – WHERE
TO GO IN RARE B-CELL
LYMPHOMAS
SESSION V
MANTLE CELL LYMPHOMA
SESSION VI
DIFFUSE LARGE B-CELL
LYMPHOMA
DEBATE III
DO WE STILL NEED ASCT
IN MCL?
SESSION VII
NOVEL THER APEUTIC
CONCEPTS IN B-CELL
LYMPHOMAS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES