Brentuximab Vedotin Followed By Allogeneic Stem-Cell Transplantation for Patients with CD30 Anaplastic or T Cell Non Hodgkin Lymphomas: A Study on Behalf of the SFGM-TC.
Authors: Garciaz Sylvain , Loschi Michael , de Masson Adele , François Sylvie , Tomowiak Cecile , Fegueux Nathalie , Labussière-Wallet Hélène , Sibon David , Cassuto Ophelie , Borel Cecile , Cornillon Jérôme , Nibumona Stanislas , Charbonnier Amandine , Brice Pauline , Socie Gerard , Blaise Didier , Peffault de la Tour Regis , Sicre de Fontbrune Flore 
Published: October 2019

Abstract
Brentuximab vedotin (BV), an anti-CD30 antibody-drug conjugate, has demonstrated efficacy alone or in combination with chemotherapy in CD30 refractory Non-Hodgkin Lymphoma (NHL). It has been approved in anaplastic large cell lymphoma (ALCL) and promising results have also been published in other CD30 positive T-cell lymphomas such as cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL). In patients with relapsing or refractory NHL, BV has mainly been proposed as a bridge for autologous or allogeneic transplantation (Allo-HSCT). Very few data are available about patients with T-cell NHL receiving Allo-HSCT after BV. The aim of our study was to study safety and efficacy of this procedure in a retrospective series of patients treated on behalf of SFGM-TC.
Inclusion criteria were: - CD30 positive T cell NHL including ALCL, CTCL and PTCL, - Partial or Complete response after BV treatment, - Allogeneic HSCT performed after BV as last salvage treatment. BV was administered at 1,8mg/kg dose every 3 weeks in outpatient department. Allo-HSCT was performed according to institutional guidelines.
Twenty-six patients receiving Allo-HSCT in France after salvage therapy including BV were identified. Patients characteristic are summarized in Table 1. With a median follow-up of 13 months (1.5-40), 8 patients relapsed and 7 patients died. Two-year OS and PFS were respectively 76% and 47%. Among patients with ALCL (n=15) 2 patients relapsed and 2 patients died. Whereas in the CTCL group (n=5), 5 patients relapsed and 1 patient died and in the PTCL group (n=6), 1 patient relapsed and 4 patients died. Two-year OS were 93%, 80% and 21% (p<0.001) and two-year PFS were 86%, 20% and 0% (p<0.001) for ALCL, CTCL and PTCL respectively. Two-years PFS for patients in CR before Allo-HSCT (n=16) was 67% whereas patients in PR (n=6) or who progressed before transplantation (n=3) have a 25% and 0% 2-years PFS respectively (p=0,08). In multivariate analysis, only anaplastic histology had a positive impact on OS or PFS. We compared data with a control group of patients with T-cell NHL (n=52) transplanted in the same centers during the same period, not receiving BV as a salvage treatment. Day-100 cumulative incidence of acute Grade 2-4 GVHD and Grade 3-4 GVHD were 39% [20-59] and 16% [1-30] in the BV group and 46% [27-66] and 19% [8-30] in the control group (p=NS). Two-years overall chronic GVHD and extensive chronic GVHD were 33% [9-56] and 22% [0-46] in the BV group and 39% [24-53] and 15% [0-26] in the control group (p=NS). Day-100 and 1-year NRM were 12% [0-25] and 16% [1-30] in the BV group and 4% [0-9] and 8% [1-15] in the control group (p=0,07). One-year relapse incidence was 37% [14-60] and 22% [10-34] in the BV and control groups respectively (p=0,27). BV was not associated with higher GVH, NRM or relapse incidence in multivariate analysis.
In conclusion, BV followed by Allo-HSCT is an option for patients with advanced CD 30 positive T cell NHL. Immunotherapy targeting CD30 before Allo-HSCT is not associated with a higher rate of GVHD, NRM or relapse incidence. Patients with ALCL have a better survival than patients with PTCL or CTCL.
Table 1. Patients characteristics All patients ALCL CTCL PTCL (n=26) (n=15) (n=5) (n=6) Sexe male 15 (58%) 7 (47%) 4 (80%) 4 (67%) Age (at Allo-HSCT) median (range) 47 (21-62) 40 (21-59) 50 (31-62) 50 (46-59) Stade (at diagnosis) I-II 4 (15%) 3 (20%) - 1 (17%) III-IV 16 (62%) 11 (73%) - 5 (83%) unknown 1 (4%) 1 (7%) - - NA 5 (19%) - 5 (100%) - Auto-HSCT (before BV) patients 8 (31%) 5 (33%) - 3 (50%) Lines of chemotherapy (before BV) median (ranges) 2 (1-7) 2 (1-4) 4 (3-7) 2 (1-3) Status (before BV) refractory 18 (69%) 9 (60%) 5 (100%) 4 (66%) relapsing 8 (31%) 6 (40%) - 2 (34%) cycles of BV median (ranges) 4 (1-8) 4 (1-8) 4 (4-6) 4 (1-4) Treatment associated with BV no 20 (77%) 11 (73%) 5 (100%) 4 (66%) GVD 2 (8%) 2 (13%) - - CHP 2 (8%) - - 2 (33%) DHAP 1 (4%) 1 (7%) - - Radiotherapy 1 (4%) 1 (7%) - - Time between diagnosis and Allo-HSCT Months (range) 21 (6-93) 13 (6-93) 23 (21-43) 23 (12-76) Status before Allo-HSCT CR 16 (62%) 13 (87%) - 3 (50%) PR 6 (23%) 2 (13%) 4 (80%) - SD/PD 3 (12%) - 1 (20%) 2 (33%) Donor type MRD 15 (57%) 5 (33%) 4 (80%) 6 (100%) MUD 7 (27%) 6 (40%) 1 (20%) - CBU 2 (8%) 2 (13%) - - Haploidentical 2 (8%) 2 (13%) - - Conditioning 3 (50%) RIC 17 (65%) 9 (60%) 5 (100%) MAC 9 (35%) 6 (40%) - 3 (50%) Immunosuppressive agents CyA 5 (19%) 4 (27%) - 1 (17%) CyA/MMF 10 (38%) 4 (27%) 5 (100%) 1 (17%) CyA/MTX 11 (42%) 7 (47%) - 4 (66%) Anti-thymocyte globulin 11 (42%) 8 (53%) 1 (20%) 2 (33%)

Disclosures
Off Label Use: Brentuximab used for CD30+ cutaneous and peripheral T cell lymphoma.