EHA-TSH Hematology Tutorial on Lymphoma Systemic T-cell lymphoma: Diagnosis and treatment (first line and relapse disease)
Massimo Federico, Tatiana Skripets, Martina Manni University of Modena and Reggio Emilia, Modena
İzmir, Turkey April 6-7, 2019 My Disclosures
Company Research funding Consultancy Honoraria
Takeda Oncology X X X
Seattle Genetics X
Celgene x x x
Millennium x
Spectrum/Allos x x x T-cell lymphomas. Key facts
‒ Approximately 10% - 15% of all NHL ‒ Rare in Western population, slightly higher in Asia and Central-South America ‒ The incidence of PTCLs is growing significantly • may be driven by an aging population • improvements in diagnosis techniques may also be driving the apparent growth in incidence Massimo Federico Certainties of Life
▪ Death ▪ Taxes ▪ The lymphoma classification will change
Leonard Prosnitz, MD James Armitage, MD Duke University University of Nebraska
▪ If you were confused before, the updated WHO classification was just published online Blood 2016…
Courtesy of A. Zelenetz The 2016 WHO classification
New Diagnostic categories and criteria
Basis for Biological future and clinical thepapeutic futures advances Mature T- and NK- cell neoplasm (29 entities) 2014 ;32(27):3059-3068 2014 ;32(27):3048-3058 2014 ;32(27):3059-3068 Overall Survival
Median follow-up: 43 months 5-yrs OS: 44% (95% CI 41-47) Median OS: 37 months (95% CI 29-46) Deaths: 690 (47%) Main cause of death: Lymphoma (68%)
PTCL: 34% OS at 5 yr AILT: 42% OS at 5-yr ALCL – 49% OS at 5-yr ALCL + 77% OS at 5-yr PTCL-NOS AITL ALCL, ALK- ALCL, ALK+
Investigator Meeting ••• Montevideo April 12-13, 2018 Prognostic factors from the IPTCLP
IPI, Prognostic indices IPI, PIT IPI IPI, PIT PIT IPI PIT, PIAI K-PI Age > 60 yrs ECOG ≥ 2 B-symptoms LDH > ULN CRP > ULN Hb< 11g/dL) Plt < 150K/μL Lymphopenia (ALC <103/μL) * Tranformed tumor cells (>40%) (>70%) Stage III-IV Extranodal sites > 1 Bulky disease (≥10cm) (≥5cm) Ki67 > 50% ATLL* ALCL. ALK+ NKTCL ATLL PTCL-U EATL PTCL-U* AITL PTCL subset ALCL.ALK- (Nasal) AITL PTCL NOS. A new prognostic model developed by the International T cell Project Network
OS by risk group ECOG PS 0-1 AA STAGE 1-2 Albumin > 3.5 g 1 Absolute N Count < 6,500
.75
Low Risk 0 factors .5 Intermediate risk 1-2 High risk 3-4
Cumulative probability .25
0 0 12 24 36 48 60 72 84 Follow-up, months
Low Interm. High
Federico et al, BJH 2018 Score T-cell PIT IPI 1.00 1.00 1.00
0.75 0.75 0.75
0.50 0.50 0.50
Overall survival in records0.25 complete0.25 for 0.25
0.00 0.00 0.00 the five scores (n=208; events0 12 24 36 48 60 72 84n=107)0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84 Low Interm. High Low Interm. High Low Interm. High
Score T-cell PIT IPI IPTCLP mPIT 1.00 1.00 1.00 1.00 1.00
0.75 0.75 0.75 0.75 0.75
probability Cumulative probability Cumulative 0.50 0.50 0.50 0.50 0.50
0.25 0.25 0.25 0.25 0.25
0.00 0.00 0.00 0.00 0.00 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84 Cumulative Cumulative 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84
Low Interm. High Low Interm. High Low Interm. High Low Interm. High Low Interm. High Follow-up. months Follow-up, months IPTCLP mPIT 2 1.00 Score 1.00 c-Harrell D-Royston R AIC AUC (95CI) (SE) (95CI) 3 -yrs OS 0.75 0.75
Cumulative probability Cumulative Score t-Cell 0.666 (0.618-0.713) 1.152 (0.191) 0.31 (0.14-0.46) 983 0.714 0.50 0.50 0.696 0.25 PIT 0.25 0.614 (0.563-0.664) 0.750 (0.195) 0.15 (0.06-0.31) 1004
0.00 IPI 0.00 0.645 (0.594-0.696) 0.883 (0.191) 0.22 (0.08-0.38) 987 0.704 0 12 24 36 48 60 72 84 0 12 24 36 48 60 72 84
IPITCLPLow Interm. High 0.606Low (0.549Interm. High-0.663) 0.631 (0.188) 0.12 (0.03-0.28) 1006 0.704 0.681 mPIT 0.640Follow-up, (0.586 months-0.694) 0.762 (0.170) 0.16 (0.05-0.33) 999
R2: explained randomness; 95CI: 95% confidence interval; SE: standard error; c-Harrel: Harrel’s concordance index; AUC: Area under curve according to Heagerty et al (Biometrics. 56. 337 – 344 . 2000) T-cell lymphoma is an orphan disease and needs more care! The relevance of data collection
Where to get the data? Vose J, et al. JCO 2008;26(25): 4124-4130 2008 by American Society of Clinical Oncology a project by the International T-Cell non-Hodgkin's Lymphoma Study Group
Study start: September 1, 2006 Status of the T-cell Project
▪ 89 authorized sites ▪ 77 active sites (at least 1 Pt in) ▪ 15 active countries (at least 1 Pt in) ▪ 5 geographic areas ✓ Europe ✓ North America ✓ South America ✓ Middle/Far East ✓ Oceania ▪ 1,611 cases of PTCL or NK/T-cell lymphoma registered Registrations by Region Recruiting 77 1611 Pts 100% Sites Active, Not Yet Recruiting 7 - - USA Middle East 2 39 3% *active. not yet recruiting 8 391 24% Sheba Medical Center-Israel Europe Haifa RAMBAM MSKCC Sourasky Medical Center-Israel* 56 703 44% MDACC Italy (39 + 2*) UNMC UK (4) Stanford Switzerland (3) CCF Slovakia (1) FHCRC Spain (8 + 3*) WUStL France (1) Yale Ukraine (1) SKCC*
South America Asia 7 328 20% % Argentina (3) 2 144 9 Brazil (2) SMC-South Korea Chile (1) QMH-Hong Kong Uruguay (1) Oceania 1 6 <1% Concord Hospital, Australia Histotype distribution (confirmed diagnosis, N=1459)
PTCL-NOS 521 36% Enteropathy type 63 4%
AITL 260 18% Hepatosplenic 29 2%
ALCL. ALK- 218 15% Subcutaneous pann-like 22 2%
ALCL. ALK + 122* 8% Peripheral γδ 18 1%
NKTCL 164 11% Unclassifiable T-cell 42 3%
*Updated to December 2017 Lessons from the T-cell project v.1
✓ The outcome of PTCL continues to be dismal in the majority of cases
✓ No improvement in OS in the majority of subtypes, compared to older series
✓ Treatment remains challenging
✓ New therapies are welcome! Now this is not the end. It is not even the beginning of the end. but it is, perhaps, the end of the beginning.
The Lord Mayor's Luncheon, Mansion House "The End of the Beginning" November 10, 1942
Advances in Malignant lymphomas: The case of extranodal and T-cell lymphomas ♦ Santiago de Chile - April 5-6, 2016 T-CELL PROJECT 2.0 The more you register, the more you learn, the more your patients will benefit Executive Committee Histopathology review panel
Massimo Federico (Modena, Italy) Stefano Pileri (Bologna/Milano, Italy) Attilio Guarini (Bari, Italy) John Chan (Duarte, USA) Julie Vose (Nebraska, USA) Eric Hsi (Cleveland, USA) Steven Horwitz (New York, USA) Miguel A Piris (Madrid, Spain) Miles Prince (Melbourne, Australia) Young-Hyeh Ko (Seoul, South Korea) Kim Won Seog (Seoul, South Korea) Stephen Lade (Melbourne, Australia) Dolores Caballero (Salamanca, Spain) Francesco Zaya (Udine, Italy) Stefano Luminari (Reggio Emilia, Italy) Ranjana Advani (Stanford, USA) Andrei Shustov (Seattle, USA) Trial Office Pierluigi Porcu (Philadelphia, USA) Astrid Pavlovsky (Buenos Aires, Argentina) Martina Manni (Modena, Italy) Carlos Chiattone (Sao Paulo, Brazil) Monica Civallero (Modena, Italy) Francine Foss (New Haven, USA) Athina Lymboussakis (Modena, Italy) Christopher Fox (Nottingham, UK) GOALS
• To better define the clinical relevance of the new WHO Classification;
• To better define the role of FDG-PET in staging and response assessment;
• To define the prognosis of different entities;
• To define the genomic landscape of different subtypes;
• To investigate on most adequate treatment strategies for these neoplasms in the real-world population. TCP2 website https://www.tcellproject2.org/ What’s new: WHO2016
Inclusion Criteria: • Previously-untreated patients with de novo diagnosis of peripheral T-cell or NK/T-cell lymphoma: 1. T-cell large granular lymphocytic leukaemia; 2. Chronic lymphoproliferative disorder of NK cells; 3. Aggressive NK-cell leukaemia; 4. Adult T-cell leukaemia/lymphoma; 5. Extranodal NK/T-cell lymphoma, nasal type; 6. Intestinal T-cell lymphoma; 7. Hepatosplenic T-cell lymphoma; 8. Subcutaneous panniculitis-like T-cell lymphoma; 9. Peripheral T-cell lymphoma, not otherwise specified; 10.Angioimmunoblastic T-cell lymphoma and other nodal lymphomas of T follicular helper cell origin; 11.Anaplastic large cell lymphoma, ALK-positive; 12.Anaplastic large cell lymphoma, ALK-negative; 13.Breast implant-associated anaplastic large cell lymphoma. • Age over 18; • Tissue biopsy adequate for diagnosis and classification and available for centralized review; • Clinical data including baseline information on disease localization and laboratory parameters at staging, features of treatment adopted and assurance of follow-up updating for at least 2 years are requested; • Written informed consent. What’s new: BIOBANK
✓ It is planned to collect blood samples (liquid biopsies) at diagnosis and also at the end of initial therapy ✓ Storage at peripheral sites participating in the study and central testing the samples once a discrete number of them is available What’s new: PET-scan
✓ Through the new webiste, it is also planned to collect information on PET-scan performed at staging and response assessment. What’s new: new countries
• 77 active sites (at least 1 Pt in) • 15 active countries (at least 1 Pt in) TCP v 1.0 • 5 geographic areas – Europe – North America – South America – Middle/Far East – Oceania
TCP v 2.0
Open registrations to countries not represented in the TCP v 1.0 CURRENT STATUS OF TCP2
(updated to April 02, 2019) N° active sites (EC approval/at least 1 pt in)
Country N° active sites (EC N° active sites (at least approval) 1 pt in)
Ukraine 1 1
Argentina 29 12
Chile 2 2 Perù 1 0 Brazil 27 13
Romania 1 1
Italy 3 0
Total 64 29
Update: April 02, 2019 N° countries/sites interested/active/in activation phase 7
28 29 2 1
1 5 countries
1 Australia 1 Netherlands 1
2 in 18 18 in
5 Uruguay Spain China 1
sites 8 1
India Estonia 27 1 124 124 2 1 Update: April 02, 2019 Total n° registered patients: 151
Country N° cases N° active sites (at least 1 pt in)
Ukraine 2 1
Argentina 39 12
Chile 6 2
Brazil 99 13
Romania 5 1
Total 151 29
Update: April 02, 2019 T-cell lymphomas. Key facts
‒ Heterogeneous group of lymphomas ‒ Occur in all age groups ‒ Poor outcome in most cases ‒ No clear definition in treatment options, mostly due to lack of large, prospective, and randomised trials CHOP, CHOP and once more CHO(E)P Meta-analysis of Frontline Anthracycline-Based Therapy for PTCL: overall survival
▪ 31 studies: 2815 Pts; 5-yr OS (all PTCL): 38.5% PTCL Subgroup Study, Yr 5-Yr OS Rate 95% CI 5-Yr OS Rate and 95% CI AITL Pautier et al, 1999 0.360 0.217-0.534 Savage et al, 2004 0.360 0.134-0.672 Sonnen et al, 2005 0.280 0.155-0.451 Vose et al, 2008 0.320 0.264-0.381 AITL summary estimate Fixed 0.321 0.272-0.375 Random 0.321 0.272-0.375 ALCL Gisselbrecht et al, 1998 0.640 0.512-0.751 Savage et al, 2004 0.430 0.275-0.600 Sonnen et al, 2005 0.610 0.394-0.790 ALCL summary estimate Fixed 0.573 0.479-0.662 Random 0.565 0.428-0.692 Alk-neg ALCL Vose et al, 2008 0.490 0.377-0.604 Alk-neg ALCL summary estimate Fixed 0.490 0.377-0.604 Random 0.490 0.377-0.604 ETTL Savages et al, 2004 0.220 0.055-0.577 Vose et al, 2008 0.200 0.118-0.318 ETTL summary estimate Fixed 0.203 0.125-0.312 Random 0.203 0.125-0.312 Non-ALCL PTCL Gisselbrecht et al, 1998 0.350 0.291-0.414 Rudiger et al, 2002 0.260 0.182-0.357 PTCL-NOS Savage et al, 2004 0.350 0.269-0.440 Sonnen et al, 2005 0.450 0.338-0.567 Vose et al, 2008 0.320 0.273-0.371 PTCL combined Karakas et al, 1996 0.480 0.303-0.663 Kim et al, 2002 0.526 0.415-0.633 Reiser et al, 2002 0.550 0.429-0.665
0% 50% 100% 2010
EFS of Pts <60 years and with normal LDH (NHL-B1 and HiCHOEP phase II/III trials)
▪ The addition of etoposide to CHOP (CHOEP) improves the EFS of young Pts with normal LDH, but not OS (P=0.176) ▪ In Pts >60 years neither shortening the time interval (CHOP-21 vs CHOP- 14), number of cycles (8 vs 6 CHOP-14), or the addition of etoposide (CHOEP) yielded any advantage, mainly due to added toxicities 2010
▪ For patients < 60 years with lactate dehydrogenase < UNV, etoposide improved 3-year EFS: 75.4% versus 51.0%, P = .003 ▪ In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the standard therapy ▪ Patients with ALK-neg ALCL, PTCLU, or AITL presenting with IPI > 1 have a poor prognosis and should be considered candidates for novel treatment strategies A prospective Cohort Study of Patients with Peripheral T-cell Lymphoma in the United States (COMPLETE)
Induction Regimen for Patients with PTCL-NOS, AITL, and ALCL (N = 234)
Carson KR, et al. Cancer, 2017 123(7): 1174-1183 Carson KR, et al. Cancer, 2017 123(7): 1174-1183 A prospective Cohort Study of Patients with Peripheral T-cell Lymphoma in the United States (COMPLETE)
Overall Survival for Patients with PTCL-NOS, AITL, and ALCL, Stratified by Anthracycline Use
Carson KR, et al. Cancer, 2017 123(7): 1174-1183 First line chemotherapy and ASCT in PTCL: prospective phase II studies
Authors N° Pts Regimen TX rate CR rate PFS OS
Rodriguez 26 Mega CHOP+/- IFE 73% 89% 53 % ( 3yrs) 73% (3yrs) 2007 BEAM ASCT
Corradini 62 HDS or MACOP-B + Mito- Arac 74% 66% 30 % (12yrs) 34 % ( 3yrs) 2006 Mito/ Alk or BEAM ASCT
Mercadel 41 Mega CHOP/ESHAP 70% 51% 30 % ( 3yrs) 39 % ( 3yrs) 2008 BEAM ASCT
Reimer 83 CHOP 66% 58% 36 % ( 3yrs) 48 % ( 3yrs) 2008 CTX-TBI ASCT
D’ Amore 160 CHOEP14-BEAM ASCT 71% 56% 44 % ( 5yrs) 51 % ( 5yrs) 2011 Sieniawsky 26* IVE/MTX 53% 65% 52 % ( 5yrs) 60 % ( 5yrs) 2010 Mito /Melph TBI or BEAM-ASCT Corradini 61 A-CHOP + HyperCHIDAM 60% 54% 44 % ( 4yrs) 49 % ( 4yrs) 2014 ASCT (14) Allo ASCT (23)
*All patients with diagnosis of EATL CHOEP14 x 6 + BEAM-ASCT
❖ 160pts included
❖ Excluded ALK+, CTCL, precursor TCL, primary leukemic PTCL
❖ <60 yrs: CHOEP – 14 (n=118)
❖ >60 yrs: CHOP-14 (n=42)
❖ If CR/PR = HDT/ASCT (115 pts)
D’Amore F, et al. JCO 2012; 30:3093-3099 • 83 pts with PTCL • 4-6 x CHOP • If response – Cy-TBI+ASCT • ORR 66% • CR 56% Role of HDT ASCT – still an open issue, however, already in guidelines How I treat Peripheral T Cell Lymphomas
Outside of clinical trials
CHOEP-14 x 3 Reccomendation Included • Age <65 yrs Patients aged 65 yrs or younger • PTCL nos with nodal PTCL, except for Alk + ALCL, CHOEP-14 x 3 six courses of CHOP/CHOEP ( induction phase) • Alk neg ALCL followed by ASCT ( consolidation phase ) is the • AITL (stem cell collection) reccomended therapy • EATL CR+PR • All stages and IPI except stage I with aalPI-0 HDT –ASCT( BEAM)
New national clinical trial Follow-up • ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active- comparator phase 3 study;
• Eligible patients were aged 18 years or older and had previously untreated, CD30- positive peripheral T-cell lymphoma according to the WHO 2008;
• Patients were randomly assigned (1:1) to the A+CHP or CHOP group. Randomisation was stratified by histological subtype according to local pathology assessment (ALK-positive systemic anaplastic large cell lymphoma vs all other histologies) and baseline IPI score (0–1 vs 2–3 vs 4–5). ECHELON-2: Phase III trial in frontline CD30+ mature T- cell lymphomas
Brentuximab Vedotin 1,8 mg/kg q3w + R CHP E A 21-day cycles V N A D L O U M A I CHOP T Z 21-day cycles I E O N
M. Federico, İzmir, April 7, 2019 Progression-free survival according to Blinded Independent Central Review in ITT population
Horwitz et al. Lancet, 2019 Overall survival for the ITT population
Horwitz et al. Lancet, 2019 Summary
❖ A+CHP showed superior PFS and significantly longer OS than CHOP;
❖ These improvements in survival came without an observed increase in
toxicity (although the median time to resolution of peripheral
neuropathy was longer with A+CHP than with CHOP).
❖ The ECHELON-2 trial supports the potential for A+CHP to become a new standard of care for many patients with CD30-positive peripheral T-cell lymphoma.
Horwitz et al. Lancet, 2019 RELAPSED/REFRACTORY PTCL Second PFS and OS of Patients with PTCL Treated at time of Relapse or Progression
V. Mak et al.
31(16):1970-1976,2013 ✓TCL failing first line systemic therapy ✓Diagnosis between 1997 and 2010 ✓53 cases 33: 147-151,2015
Survival after relapse Survival after relapse according to performance status and type of failure median SAR 2.5 mo 3-yr SAR 19% The outcome of peripheral T-cell lymphoma patients failing first line therapy: a report from the prospective, international T-Cell project
Survival After Ref/Rel (SAR), SAR by Status (Ref vs Rel)
Median FU: 38 months (1-100 months) SAR at 3-yrs: 23% (95CI 19-27%) 5-yrs: 20% (95CI 16-24%) 3-yr SA Median SAR (mo) Relapse 28% (95CI 21-35) 11 Median SAR: 5.8 months (95CI 4.9-6.9 months) Refractory 21% (95CI 17-25) 5 # of events: 440 (70%) HR <24 mo 1.50 (95CI 1.21- 1.86) p <0.001 HR >24 mo 0.75 (95CI 0.34-1.64) p = 0.470
Bellei, Foss et al, Haematologica 2018 The outcome of peripheral T-cell lymphoma patients failing first line therapy: a report from the prospective, international T-Cell project.
SAR by 4 most common subtypes SAR by salvage therapy (HCT vs. no-HCT)
1.00 1 PTCL-NOS AITL HCT ALCL (-) ALCL (+) Elig. HCT (CR/PR) Not elig. HCT (CR/PR) NKTCL Other .75 Not elig. HCT ( .5 0.50 .25 Cumulative probability 0.25 0 0 12 24 36 48 60 72 84 HCT 99 56 39 29 18 9 5 1 Elig. HCT 124 48 30 21 13 7 1 0 0.00 Not elig. CR/PR 141 47 31 20 12 4 1 1 0 12 24 36 48 60 72 84 Not elig. Bellei et al, Haematologica 2018 Therapeutic Options for T-Cell Lymphomas Monotherapy with Biological Agents in R/R PTCL Compound ORR Compound ORR Monoclonal antibodies Antibody drug conjugates 1 Alemtuzumab (CD52) 36% Brentuximab vedotin 86%9 (ALCL, approved Siplizumab (CD2) 31%2 (CD30) US, EU) Zanolimumab (CD4) 26%3 Kinase inhibitors 10 Mogamulizumab 34%4 Alisertib 24% 11 HDAC inhibitors Duvelisib 47% 12 Belinostat 26%5 (approved Crizotinib 90% (ALK+ ALCL) US) Sorafenib 42%13 Romidepsin 25%6 (approved US) Farnesyltransferase inhibitor Antifolate Tipifarnib 50%14 Pralatrexate 29%7 (approved Organic arsenic compound US) Darinaparsin 28.6%15 Biologic response modifiers Denileukin Diftitox 40%8 References: 1. Enbald G. et al. Blood. 2004;103:2920-2924. 2. O’Mahony D. et al. CCR. 2009; 15:2514-2522. 3. d’Amore F. et al. BJH. 2010; 150:565-573. 4. Ogura M. et al. J Clin Oncol. 2014; 32:1157-1163. 5. O’Connor O.A. et al. J Clin Oncol. ASCO 2013; abstract 8507. 6. Coiffier B. et al. J Clin Oncol. 2012; 30:631-636. 7. O’Connor O.A. et al. J Clin Oncol. 2011; 29:1182-1189. 8. Foss F. et al. ASCO 2010; abstract 8045. 9. Pro B. et al. J Clin Oncol. 2012; 30:2190-2196. 10. O’Connor O.A. et al. ASH 2015; abstract 341. 11. Horwitz S. et al. ASH 2014; abstract 803. 12. Gambacorti Passerini C. et al. JNCI. 2014; 106:djt378. 13. Gibson J.F. et al. Br J Haematol. 2014;167(1):141–4. 14. Witzig T.E. et al. Blood. 2011;118(18):4882–9. 15. Hosein P.J. et al. Am J Hematol. 2012;87(1):111–4. V. Mak et al. Impact of Novel therapies in R/R PTCL after Relapse or Progression without HSCT ▪ Median OS and PFS after relapse or progression were 5.5 and 3.1 mos ▪ Median OS and PFS after relapse or progression in pts receiving therapy at relapse were 6.5 and 3.7 mos Alisertib (Aurora A Kinase Inhibitor) • Phase 3 Lumière trial of alisertib versus investigator’s choice (pralatrexate, gemcitabine, romidepsin) in R/R PTCL (NCT01482962) Comparator Response Alisertib (n=96) All pts (n=85) Pralatrexate (n=45) Gemcitabine (n=22) Romidepsin (n=18) ORR 36% 46% 44% 36% 61% CR 19% 28% 29% 23% 33% PR 17% 18% 16% 14% 28% SD 30% 20% 24% 14% 17% PD 34% 34% 31% 50% 22% O’Connor O.A. et al. ASH 2015; abstract 341. 2. Friedberg J.W. et al. J Clin Oncol. 2014; 32(1):44-50. 3. Barr P.M. et al. J Clin Oncol. 2015; 33(21):2399-2404. • The COMPLETE registry is a multicenter prospective observational study of newly diagnosed PTCL patients in the United States; • All subtypes of PTCL were included with the exception of precursor T/NK neoplasms, T-cell large granular lymphocytic leukemia, mycosis fungoides other than transformed mycosis fungoides, Sézary syndrome, and primary cutaneous CD30+ disorders; • Patients were included in the single agent arm if as first retreatment they received any of the following single agents as first retreatment: pralatrexate, romidepsin, belinostat, brentuximab vedotin, bendamustine, alisertib, denileukin diftitox, or lenalidomide. Patients were included in the combination arm if as first retreatment they received any multiagent chemotherapy regimen excluding the above single agents. Overall Survival and Progression-Free Survival After First Retreatment including Sensitivity Analysis Stuver et al. Am J Hematol, 2019 Summary ➢ A trend towards greater complete and objective response rates with the use of single agents versus combination chemotherapy, as well as a statistically significant greater OS and PFS; ➢ More patients receiving single agents were bridged to potentially curative transplantation. More toxicity occurred with the use of combination chemotherapy, as did the need for supportive care measures; ➢ In conclusion, this study demonstrates a role for single agents as the first treatment in the salvage setting for patients with R/R PTCL. The optimal approach in this setting remains unclear, and this report should serve as a catalyst for future studies utilizing larger datasets or randomized designs to identify the truly superior strategy. Stuver et al. Am J Hematol, 2019 CONCLUSIONS ➢ PTCL are rare and mostly aggressive lymphomas ➢ Still poor outcomes in most cases ➢ Sometimes OS improvement in young patients, eldery group still remain difficult to treat ➢ No established effective standard of care to relapsed/refractory PTCL ➢ More trials needed M. Federico, İzmir, April 7, 2019 The more we register, The more we learn, The more our patients will benefit! THANK YOU!