Is there a Role for Upfront Stem Cell Transplantation in Peripheral T-Cell Lymphoma: YES!

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1 Is there a Role for Upfront Stem ell Transplantation in Peripheral T-ell Lymphoma: YES! Norbert Schmitz Dep. Hematology, Oncology and Stem ell Transplantation AK St. Georg Hamburg, Germany

2 OS in the common subtypes of T-cell lymphoma

3 Proportion T-cell lymphomas in DSHNHL trials EFS - IPI score for patients without ALK + (n=242) Months p<0.001 IPI 0. 1 (n=118) IPI 2 (n=59) IPI 3 (n=38) IPI 4. 5 (n=27) DSHNHL Schmitz et al., Blood 2010;116:

4 (A) Second progression-free survival (median, 3.7 months) of patients treated with chemotherapy (n = 89) with relapsed or progressive peripheral T-cell lymphoma (PTL) and (B) overall survival (median, 6.5 months) after first relapse or progression of PTL. Mak V et al. JO 2013;31: by American Society of linical Oncology

5 No randomized studies to support use of autologous or allogeneic transplantation in T-cell lymphoma

6 Autologous Tx in T-cell lymphoma

7 MegaHOEP T vs B: time to treatment failure B-ell (n = 146) T-ell ( Alk -) (n = 24) p= Year TTTF B-ell: 59.8% T-ell ( Alk-): 25.0% Time (years) GERMAN HIGH-GRADE NHL STUDY GROUP Nickelsen et al., Ann. Oncol. 2009; 20:

8 Autologous Stem ell Transplantation as First-line Therapy in T-cell lymphoma PFS Reimer et al., JO 2009; 27:106

9 Nordic PTL project NLG-T-01: Design and schedule Excluded: 1) alk-1 pos ALL T/0 2) TL 3) Leukemic T- NHL HOEP-14d x 3 R, PR HOEP-14d x 3 R, PR (stem cell collection) N,PD N,PD HDT (BEAM) Follow-up d'amore F et al. JO 2012;30:

10 Kaplan-Meier estimates of (A) overall (OS) and (B) progression-free survival (PFS) for the entire NLG-T-01 cohort and () OS and (D) PFS for the four largest histologic subtypes. d'amore F et al. JO 2012;30: by American Society of linical Oncology

11 Allogeneic Tx in T-cell lymphoma

12 Survival Outcomes N= 30 alive (54%): 26 in R, 1 in PR, 3 in PD N= 26 deaths (46%): 20 for disease progression and 6 for NRM Dodero et al. Leukemia 2011

13 (A) Adjusted progression-free survival (PFS), (B) adjusted overall survival (OS), and () nonrelapse mortality (NRM) for all patients (n = 241). Smith S M et al. JO 2013;31: by American Society of linical Oncology

14 (A) Adjusted progression-free survival (PFS), (B) adjusted overall survival (OS), and () nonrelapse mortality (NRM) for all patients (n = 241). Smith S M et al. JO 2013;31: by American Society of linical Oncology

15 RI-allo in ptl. The French Experience Le Gouill et al., JO 2008

16 allost in AITL -- PFS Kyriakou et al., JO 2009

17 Myeloablative hemotherapy Followed by Allogeneic Stem ell Transplantation in Relapsed / Refractory T-ell Lymphoma n=95 OS PFS patients at risk (OS) Wulf et al. (manuscript in preparation)

18 Results in Allogeneic Transplantation for Relapsed / Refractory T-ell Lymphoma Author Patients onditioning NRM REL PFS OS Dodero (2011) 8 Le Gouill (2008) 10 Kyriakon (2009) 11 Glass (2011) 12 Jacobsen (2011) 14 Delioukina (2012) 15 zajczynska (2013) 16 Smith (2013) 9 52 (33) TT/y/Flu 12% 49% 40% 50% 77 (60) Myeloablative 34% N.E. N.E. 57% 45 (26) Various 25% 20% 20% 64% AITL only 63 Flu/Bu/y 32% 43% 42% 29 refractory pts 52 (24) TBi/y (31) 36% 33% 30% 41% Myeloablative Bu/Flu (21) 14% 57% RI 27 (15) Flu/Mel 22% 30% 47% 55% TL in 11 pts 24 (5) BEAM/ALEMT 25% 25% N.E. 42% 74 MA 32% 32% 36% 39% 45 RI 27% 40% 33% 42% Schmitz et al. Sem. Hematol. (in press)

19 OS (proportion) Survival of relapsed patients after first-line therapy with MegaHOEP or HOEP-14 (n=25) DSHNHL Allo ST Time after progression (months)

20 Overall survival (proportion) Survival of relapsed patients after first-line therapy with MegaHOEP or HOEP-14 (n=25) DSHNHL Xxxxxxxxx Log-Rank-test p = allogeneic Tx. n= no allogeneic Tx. n= time after progression (months)

21 Treatment Strategies in Peripheral T-cell Lymphoma hemotherapy DHAP High-dose therapy / autologous Tx BEAM A S T DHAP Allogeneic Tx FB S T romidepsin, brentuximab vedotin...

22 DSHNHL A: study design First-line treatment of mature (peripheral) T-cell lymphoma (PTL) for patients 60 years Inclusion criteria Peripheral T-cell lymphoma, unspecified Angioimmunoblastic T-cell lymphoma Anaplastic large cell lyphoma, ALK negative Extranodal NK/T-cell lymphoma, nasal type Enteropathy type T-cell lymphoma Hepatosplenic T-cell lymphoma Subcutaneous panniculitis type T-cell lymphoma All stages and IPI except stage I with aalp10 R H O E P H O E P H O E P H O E P H O E P H O E P H O E P H O E P R, PR, N R, PR, N Days D H A P D H A P PBS harvest No donor available 4 6 weeks B E A M F B A S T S T R = At diagnosis, patients are randomized to allogeneic or autologous transplantation (tx). Donor search (family or unrelated) will be initiated only in patients randomized to allogeneic transplantation. Patients randomized to allogeneic tx but without a donor will receive autologous tx. Peripheral blood stem cells are harvested after DHAP in patients who are to receive autologous tx (randomized or crossed over [dotted line in the diagram] from the transplant arm because no donor is available). Available from: