Long-Term Survival and Absence of Late Relapses in Patients Who Underwent Allogeneic Stem Cell Transplantation for Advanced Cutaneous T-Cell Lymphoma
Authors: Leslie Lori A , Leslie Lori A. , Feldman Tatyana A , Skarbnik Alan P , Vesole David H. , Rowley Scott D. , Pecora Andrew L. , Goy Andre , Donato Michele L. 
Published: October 2019

Abstract
Introduction
Primary cutaneous T-cell lymphomas (CTCL) are rare subtypes of extranodal non-Hodgkin lymphoma for which no conventional curative therapies are available. Patients (pts) with early-stage, limited disease typically experience an indolent course. Pts with advanced or progressive disease are more likely to experience an aggressive course characterized by short-lived responses to therapy, debilitating symptoms that significantly impact quality of life,and limited overall survival. Prior retrospective studies have shown allogeneic stem cell transplantation (alloSCT) may lead to durable remissions in pts with advanced CTCL, the largest of which included 47 pts and reported an overall survival (OS) of 51% and progression-free survival (PFS) of 26% at 4-years (Hosing et al. Ann Oncol 2015). We performed a retrospective analysis of pts who underwent alloSCT for advanced CTCL at our institution.
Methods
We performed a retrospective case analysis of 11 pts with CTCL who underwent alloSCT between 1/1/2008 and 3/1/2016. OS and PFS were estimated using Kaplan-Meier analysis. Other endpoints included transplant-related mortality and morbidity as well as CTCL-related mortality.
Results
Eleven pts were identified including 5 with mycosis fungoides/Sezary syndrome (MF/SS), 2 with CD4+ CTCL not otherwise specified (NOS), and 1 each with CD8+ CTCL-NOS, ALK-negative cutaneous anaplastic large cell lymphoma (cALCL), sub panniculitis-type T-cell lymphoma, and cutaneous smoldering HTLV-1 associated adult T-cell leukemia/lymphoma (ATLL). The median age at diagnosis was 45.4 yr, median time to alloSCT was 2.4 yr. The median follow-up post-alloSCT was 39.2 mo. Prior to alloSCT, pts received a median of 5 lines of therapy (range 2-11). Total skin electron beam radiation (TSEB) was part of the immediate pre-alloSCT regimen for 6 pts (55%), all of whom had persistent disease. Four pts (67%) converted to CR pre-alloSCT with the addition of TSEB. Nine pts (82%) received reduced-intensity and 2 pts (18%) received myeloablative conditioning. Ten pts received peripheral blood stem cells (PBSC) and 1 received bone marrow: 4 pts (36%) received stem cells from HLA-matched unrelated donors, 2 (18%) from mismatched unrelated donors, 4 (36%) from matched sibling donors, and 1 (9%) from a haploidentical sibling. Nine pts (82%) received tacrolimus/mini methotrexate and 2 pts (18%) received tacrolimus/mycophenolate mofetil for graft-versus-host disease (GvHD) prophylaxis. The pt who received haploidentical stem cells also received post-alloSCT cyclophosphamide. At the time of transplantation, disease status included: complete response (CR) in 8/11 pts (73%), partial response (PR) in 2/11 pts (18%), and progressive disease (PD) in 1/11 pts (9%). At day 100, 9/11 pts (82%) were in CR, 1 pt had PD, and 1 pt with CD8+ CTCL-NOS had died on day 26 of PD. Two of the 9 pts (22%) in CR on day 100 relapsed soon thereafter, one on day 105 and one on day 113. Both achieved CR, 1 with withdrawal of immunosuppression, 1 with salvage brentuximab vedotin, bexarotene and donor lymphocyte infusions (DLI). There were no late relapses. Median OS at 36 mo was 72% (Figure 1): 1 pt died of PD on day 26, 2 pts died of non-alloSCT/non-CTCL adverse events (cerebrovascular accident (CVA), suicide). Median PFS at 36 mo was 64% (Figure 2). Fifty percent (2/4) of pts who relapsed/progressed were in CR at time of alloSCT, 86% (6/7) of pts who did not relapse were in CR at time of alloSCT. The incidence of acute cutaneous GvHD was 100%: 30% grade 1, 70% grade 2-3. The incidence of chronic cutaneous GvHD was 50%: 2 pts (20%) have ongoing severe GvHD, 1 pt with severe DLI-induced GvHD died due to CVA, 2 pts (20%) have completed therapy with no further manifestations of chronic GvHD. There were no other significant long-term toxicities of alloSCT identified. Disease-related mortality was 9% (1/11). Transplant-related mortality was 0%.
Conclusion
AlloSCT is well-tolerated and may result in long-term remissions for pts with various, heavily pretreated subtypes of CTCL. In our experience relapses were uncommon, occurred early, and durable CR could again be achieved with immunomodulatory approaches. Depth of response pre-alloSCT correlated with long term PFS and OS. It is likely that TSEB may be omitted safely in pts in CR, but should be administered immediately pre-alloSCT to deepen responses in patients with persistent disease.

Disclosures
Leslie: Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Feldman:Celgene: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding, Speakers Bureau; Abbvie/Pharmacyclics/Janssen: Speakers Bureau. Vesole:Novartis: Speakers Bureau; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau. Goy:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees.