Pre- and posttransplant use of mogamulizumab in patients with aggressive adult T-cell leukemia-lymphoma: A statement from key opinion leaders in Japan

Abstract

Recently, the anti-CCR4 antibody mogamulizumab (Moga, Kyowa Hakko Kirin Co., Ltd, Tokyo, Japan) was approved as a treatment for CCR4-positive adult T-cell leukemialymphoma (ATL) in Japan. We use Moga before or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with aggressive ATL. A recent retrospective analysis using a database from a nationwide survey showed that the use of Moga before allo-HSCT was associated with an increased risk of severe/steroid-refractory acute GVHD and inferior overall survival. Meanwhile, it was reported that a number of patients with chemotherapy-refractory ATL achieved disease control with Moga, including those who subsequently underwent allo-HSCT. To address these issues pertaining to Moga in transplant-eligible patients with ATL, a key opinion leader (KOL) meeting comprising hematologists and transplant physicians was conducted by Kyowa Hakko Kirin Co., Ltd. in Japan. The goal of this KOL meeting was to design a framework to guide decision-making on the use of Moga in transplant-eligible patients with ATL. KOLs first presented their experiences, and after a subsequent discussion, the KOLs agreed on the key scientific statement as summarized in this Expert Commentary. Our experiences suggest that a good number of patients benefited from Moga, achieving disease control that was often unattainable by conventional chemotherapies. However, as our statement is based largely on retrospective studies and real clinical practice, it requires further validation. Nevertheless, we believe that this statement should help efficiently guide decision-making concerning Moga use in transplant-eligible patients with ATL.

Progress in Allogeneic Hematopoietic Cell Transplantation in Adult T-Cell Leukemia-Lymphoma

“…Conversely, at our institution, the 1-year OS rate of nine patients with ATL who underwent allo-HCT after 1–2 times of mogamulizumab administration was not less than that of 113 patients who did not receive mogamulizumab (55.6 vs. 37.2%, P = 0.843; Fuji et al, 2018a). Recently, hematologists and transplant physicians in Japan discussed the appropriate use of mogamulizumab for patients with aggressive ATL who planned to undergo allo-HCT, regarding the frequency and timing of mogamulizumab administration and the interval between the last mogamulizumab administration and transplantation.…”

“…Recently, hematologists and transplant physicians in Japan discussed the appropriate use of mogamulizumab for patients with aggressive ATL who planned to undergo allo-HCT, regarding the frequency and timing of mogamulizumab administration and the interval between the last mogamulizumab administration and transplantation. Thus, we proposed the appropriate use of mogamulizumab for patients with aggressive ATL before allo-HCT as follows: (1) mogamulizumab should not be administered to patients with aggressive ATL who plan to undergo transplantation if patients can obtain CR or PR without mogamulizumab; (2) mogamulizumab should be administered a few times only when patients cannot obtain remission by ordinary combination chemotherapy; (3) allo-HCT should be recommended with at least 50-day interval, if possible, between last mogamulizumab administration and transplant, and (4) no consensus about GVHD prophylaxis, choice of stem cell source and prophylaxis for infectious diseases (Fuji et al, 2018a).…”

Recent advances in T-cell lymphoid neoplasms

“…Aberrant PD-L1 expression found in 27% ATLL cases, similar to other T-cell leukemias, supports the use of immune checkpoint therapy 143 . Unfortunately, 3 patients treated with nivolumab showed an aggressive progression 144 .…”

Sensitive Photodynamic Detection of Adult T-cell Leukemia/Lymphoma and Specific Leukemic Cell Death Induced by Photodynamic Therapy: Current Status in Hematopoietic Malignancies

“…Mogamulizumab has a strong cytotoxic effect that can kill not only ATL cells, but also CCR4-positive normal regulatory T (T-reg) cells; therefore, severe acute GVHD might be induced in association with reduced T-reg cells in recipients [43]. An appropriate use of mogamulizumab for patients with ATL who plan to undergo allo-HCT is now developing in Japan [44]. In patients with ATL who have CCR4 mutations of ATL cells, mogamulizumab therapy confers better OS compared to that in patients without CCR4 mutations [45].…”