Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma

Fuji, Shigeo; Shindo, Takero

doi:10.21037/sci.2016.09.13

Cited by 40 publications

(22 citation statements)

References 76 publications

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“…A recent retrospective study from Japan also reported that pre-transplant mogatherapy increases the risk of severe and steroid-refractory graft-versus-host disease (GVHD), which leads to increases in nonrelapse mortality and the overall mortality. It was proposed that mogatherapy depletes Treg cells for at least a few months, which may increase the risk of GVHD after allohematopoietic stem cell transplantation (Fuji and Shindo 2016). Therefore, it is possible that fatal OIs in case no.…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Mohammed

Chagan-Yasutan

Ashino

et al. 2017

Tohoku J. Exp. Med.

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Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients. Gal-9, soluble interleukin (IL)-2 receptor, tumor necrosis factor-α, and IL-10 levels were increased before chemotherapy, and Gal-9 levels were associated with the sIL-2 receptor, which reflects tumor burden. Inflammatory levels decreased after chemotherapy. After mogatherapy, 5 of 6 patients attained complete remission (CR), whereas 1 patient showed no response (NR) and died. Among 5 patients with CR, the biomarkers remained low during mogatherapy, except for a 3-5-fold increment in Gal-9 (associated with skin eruptions). A skin biopsy showed infiltration by inflammatory cells and Gal-9 synthesis in areas with CD8 cell infiltration. In the patient with NR, increased levels of Gal-9 and the aforementioned biomarkers were noted 3 days after mogatherapy, followed by opportunistic infections resembling immune reconstitution inflammatory syndrome. Therefore, an increased Gal-9 plasma level in ATL/ATLL indicates tumor burden and reflects immune activation by mogatherapy. These findings may indicate that an increase in the Gal-9 level, a novel immune checkpoint molecule, can reflect immune-related adverse effects of various biotherapies.

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Section: Discussionmentioning

confidence: 99%

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Mohammed

Chagan-Yasutan

Ashino

et al. 2017

Tohoku J. Exp. Med.

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“…A few studies showed that the number of Tregs decreased after the administration of Moga, in which Tregs were monitored using multicolor flow cytometry . In patients with scarce Tregs before allo‐HSCT, which reflects significant depletion of host‐derived Tregs, it is expected that the recovery of donor‐derived Tregs will be suppressed after allo‐HSCT . Thus, we must take into consideration the risks of aggravated immune reactions during the engraftment period and afterward.…”

Section: Key Scientific Statement To the Clinical Questions Regardingmentioning

confidence: 99%

“…Importance of the interval between the administration of mogamulizumab (Moga) and allo‐ HSCT . (A) With a short interval between Moga and allo‐ HSCT , the concentration of Moga at allo‐ HSCT might be high, which is sufficient to deplete donor‐derived regulatory T cells (Tregs) as well as recipient‐derived Tregs; (B) with a long interval between Moga and allo‐ HSCT , the concentration of Moga at allo‐ HSCT might be low enough that Moga no longer depletes donor‐derived Tregs but still depletes recipient‐derived Tregs…”

Section: Key Scientific Statement To the Clinical Questions Regardingmentioning

confidence: 99%

“…We use Moga before or after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) in patients with aggressive ATL, based on the label. When administered before allo‐HSCT, Moga can deplete regulatory T cells (Tregs), potentially increasing the risk of graft‐versus‐host disease (GVHD) . 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 (OS) .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…Recently, mogamulizumab (anti‐CCR4 monoclonal antibody, Moga) was approved as a treatment for ATL in Japan . However, in case we plan to perform allo‐HSCT, Moga should be carefully used as Moga depletes regulatory T cells in vivo and the effects of Moga persist for months even after allo‐HSCT . Fuji et al reported that the use of Moga before allo‐HSCT was associated with a significantly inferior clinical outcome mainly because of an increased risk of severe/corticosteroid‐refractory acute GVHD and NRM .…”

Section: Other Types Of T‐cell Lymphomamentioning

confidence: 99%

Hematopoietic stem cell transplantation for T-cell lymphoma

Shichijo

Fuji

2018

Adv Cell Gene Ther

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As peripheral T-cell lymphomas (PTCL) are rare and heterogeneous groups of non-Hodgkin lymphomas, it is practically difficult to conduct randomized controlled trials to establish standard treatment strategies. There is still no consensus regarding the optimal treatment strategy for patients with PTCL. Moreover, the survival outcomes of PTCL, excluding anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma, remain disappointing although novel agents have become available recent years. The aim of this review is to summarize the information regarding hematopoietic stem cell transplantation (HSCT) for PTCL including both autologous (auto-) and allogeneic (allo-) HSCT. In the first-line setting, up-front auto-HSCT is generally recommended for patients with PTCL, especially with complete remission 1 (CR1). On the other hand, up-front allo-HSCT might be recommended for patients with highrisk PTCL, although the study incorporating up-front allo-HSCT is limited. In the salvage setting, auto-HSCT might be considered in patients with chemosensitive disease, especially with CR. Allo-HSCT might also be considered, although the data of allo-HSCT in the salvage setting is still limited. Further investigation to optimize the application of HSCT in patients with PTCL is warranted in the future.

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Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma

Cited by 40 publications

References 76 publications

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

Galectin-9 as a Predictive Marker for the Onset of Immune-Related Adverse Effects Associated with Anti-CCR4 MoAb Therapy in Patients with Adult T Cell Leukemia

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

Hematopoietic stem cell transplantation for T-cell lymphoma

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