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.

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%)