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.

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 1Patients characteristicsAll patientsALCLCTCLPTCL(n=26)(n=15)(n=5)(n=6)Sexemale15 (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-II4 (15%)3 (20%)-1 (17%)III-IV16 (62%)11 (73%)-5 (83%)unknown1 (4%)1 (7%)--NA5 (19%)-5 (100%)-Auto-HSCT (before BV)patients8 (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)refractory18 (69%)9 (60%)5 (100%)4 (66%)relapsing8 (31%)6 (40%)-2 (34%)cycles of BVmedian (ranges)4 (1-8)4 (1-8)4 (4-6)4 (1-4)Treatment associated with BVno20 (77%)11 (73%)5 (100%)4 (66%)GVD2 (8%)2 (13%)--CHP2 (8%)--2 (33%)DHAP1 (4%)1 (7%)--Radiotherapy1 (4%)1 (7%)--Time between diagnosis and Allo-HSCTMonths (range)21 (6-93)13 (6-93)23 (21-43)23 (12-76)Status before Allo-HSCTCR16 (62%)13 (87%)-3 (50%)PR6 (23%)2 (13%)4 (80%)-SD/PD3 (12%)-1 (20%)2 (33%)Donor typeMRD15 (57%)5 (33%)4 (80%)6 (100%)MUD7 (27%)6 (40%)1 (20%)-CBU2 (8%)2 (13%)--Haploidentical2 (8%)2 (13%)--Conditioning3 (50%)RIC17 (65%)9 (60%)5 (100%)MAC9 (35%)6 (40%)-3 (50%)Immunosuppressive agentsCyA5 (19%)4 (27%)-1 (17%)CyA/MMF10 (38%)4 (27%)5 (100%)1 (17%)CyA/MTX11 (42%)7 (47%)-4 (66%)Anti-thymocyte globulin11 (42%)8 (53%)1 (20%)2 (33%) DisclosuresOff Label Use: Brentuximab used for CD30+ cutaneous and peripheral T cell lymphoma.