Peripheral T-cell lymphoma. Matt Ahearne Clinical Lecturer, Leicester

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1 Peripheral T-cell lymphoma Matt Ahearne Clinical Lecturer, Leicester

2 PTCL Objectives To understand the natural history of PTCL To appreciate the importance of accurate diagnosis of PTCL including recent advances in subclassification To understand current treatment options for PTCL used in the UK and appreciate the lack of evidence base available To explore future directions in the diagnosis and management of PTCL

3 PTCL - background

4 PTCL background Adapted from Swerdlow et al Blood 2016

5 PTCL background Vose et al J Clin Oncol Sep 1;26(25):

6 PTCL work-up

7 PTCL work-up Aims of work-up are to: Establish an accurate diagnosis Assess for the presence of clinical complications Assign prognostic score/risk assess Establish baseline parameters to guide disease response assessment With the intention of: Guiding treatment decisions Counselling patients appropriately

8 PTCL work-up Blood-based Routine bloods Immunoglobulins and autoantibodies HTLV serology PCR for EBV DNA Imaging CT and PET Bone marrow biopsy Calculation of prognostic score Federico et al J Clin Oncol Jan 10;31(2):240-6 Broccoli et al Blood Mar 2;129(9):

9 PTCL - diagnosis

10 PTCL diagnosis Challenging Complex subclassification. Rarity Multiple pathological mimics Low tumour burden Tissue sampling Beware clonality High discordance rates Warnke et al Morphologic and Immunophenotypic Variants of Nodal T-Cell Lymphomas and T- Cell Lymphoma Mimics Am J Clin Path 2007;127:

11 Advances in diagnosis Tfh lymphoma PTCL-NOS TFH LYMPHOMA 30% AITL Iqbal et al Blood Feb 4;115(5): Sakata-Yaganimoto Nat Genet Feb;46(2):171-5

12 Advances in diagnosis refining prognosis Javeed Iqbal et al. Blood 2014;123: Parilla Castellar et al Blood Aug 28;124(9):

13 PTCL - management

14 PTCL treatment Is CHOP the best chemotherapy backbone? Do additional agents improve CHOP? Should all fit patient undergo upfront autologous stem cell transplant?

15 Is CHOP the best backbone? About 80% patients treated with CHOP-based chemo Achieves adequate initial response in majority ORR with CHOP-based chemo ~65-80% CR rates variable (35-60%) Durable responses uncommon No alternative chemo regimen has clearly shown superior activity Gemcitabine-based Intensified approaches

16 Do additional agents improve CHOP? Data that etoposide induces deeper and more durable response Better EFS in young ALK +ve ALCL with normal LDH Better PFS in younger PTCL No impact on OS Clear increase in toxicity in older patients Many centres use CHOEP CHOP + Alemtuzumab CHOP + Romidepsin d-amore et al ESMO guidelines 2015

17 Upfront ASCT for all? Widely adopted No randomised data Conflicting prospective and retrospective data Key determinant may well be induction response rather than ASCT itself Urgent need for: Randomised trial Predictive markers of patient subgroups likely to benefit Fossard et al. Ann Onc 2018; 29:

18 PTCL relapse/refractory disease Dismal clinical outcomes Salvage chemotherapy options ICE/GDP/ESHAP Durable responses rare Strong consideration for allogeneic stem cell transplant Aim should be entry into a clinical trial RomiCar AVAIL-T Early integration of palliative care where appropriate

19 PTCL future directions

20 PTCL future directions Evolving diagnostics Molecular tools Tissue-based vs blood-based Increasing array of therapeutic options Beyond CHOP with novel backbones Stratified patient cohorts National/international collaboration Progress will only be made through high quality clinical trials

21 Any questions