Systematic review of survival outcomes for relapsed or refractory adult T‐cell leukemia‐lymphoma

Nosaka, Kisato; Crawford, Bruce; Yi, Jingbo; Kuan, William; Matsumoto, Tomoko; Takahashi, Takeshi

doi:10.1111/ejh.13728

Cited by 5 publications

(3 citation statements)

References 48 publications

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“…Nine subgroups were treated with MOG, two pre-allo-HSCT, and another one was treated with chemotherapy. The median OS were 2.2-17.6 months for MOG, 3.8-6.2 months for MOG + allo-HSCT, and 4.1-20.3 months for other chemotherapy [59].…”

Section: Mogamulizumab Results With Combined Treatments In Atllmentioning

confidence: 97%

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review

Fernández-Guarino,

Ortiz,

Gallardo

et al. 2024

IJMS

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Mogamulizumab (MOG) is an antibody targeting the CCR4 receptor, authorized for relapsed or refractory peripheral T-cell (PTCL) and cutaneous T-cell lymphomas (CTCL). Its adoption in guidelines and endorsement by FDA and EMA established it as a systemic treatment, especially for advanced disease stages due to its comparatively lower toxicity. Clinical trials and real-world evidence have underscored its efficacy in advanced CTCLs, including mycosis fungoides and Sézary syndrome; PTCLs; and adult T-cell leukemia/lymphoma (ATLL), showcasing positive outcomes. Notably, the drug has demonstrated significant response rates, disease stability, and extended periods of progression-free survival, suggesting its applicability in cases with multiple treatment lines. Its safety profile is generally manageable, with adverse events (AEs) primarily related to the skin, infusion-related reactions, drug eruptions, autoimmune diseases, and skin disorders. The latter seem to appear as CCR4 can promote the skin-specific homing of lymphocytes, and MOG is directed against this receptor. While combination with immunostimulatory agents like interferon alpha and interleukin 12 has shown promising results, caution is urged when combining with PD1 inhibitors due to the heightened risk of immune-mediated AEs. The introduction of MOG as a systemic treatment implies a significant advancement in managing these diseases, supported by its favorable safety profile and complementary mechanisms.

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Section: Mogamulizumab Results With Combined Treatments In Atllmentioning

confidence: 97%

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review

Fernández-Guarino,

Ortiz,

Gallardo

et al. 2024

IJMS

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show abstract

“…Recent reports indicate that ATL constitutes ≥30% of all T-cell lymphoma cases in Japan. [4][5][6] ATL is classified into 4 clinical subtypes (acute, lymphoma, chronic, and smoldering), with acute, lymphoma, and unfavorable chronic subtypes among the most aggressive. 4 Current standard first-line treatment for aggressive ATLs is multiagent chemotherapy, including VCAP-AMP-VECP (vincristine, cyclophosphamide, doxorubicin, and prednisone; doxorubicin, ranimustine, and prednisone; and vindesine, etoposide, carboplatin, and prednisone).…”

Section: Introductionmentioning

confidence: 99%

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

Izutsu

Makita

Nosaka

et al. 2023

Blood

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Adult T-cell leukemia/lymphoma (ATL) is an aggressive non-Hodgkin lymphoma with poor prognosis and few treatment options for patients with relapsed, recurrent, or refractory disease. We evaluated the efficacy and safety of valemetostat, a potent EZH1 and EZH2 inhibitor, in treating relapsed/refractory (R/R) ATL. This multicenter phase 2 trial (NCT04102150; https://clinicaltrials.gov/ct2/show/NCT04102150; DS3201-A-J201) enrolled patients with R/R aggressive ATL (acute, lymphoma, unfavorable chronic type). Patients received valemetostat 200 mg/day until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR) centrally assessed by an independent efficacy assessment committee (IEAC). Secondary endpoints included best response in disease compartments, duration of response (DOR), pharmacokinetics, and safety. Twenty-five patients (median age, 69.0) with a median of 3 prior lines of therapy were enrolled; 24 had prior mogamulizumab treatment. The primary endpoint was met with a centrally reviewed ORR of 48.0% (90% CI, 30.5% to 65.9%), including 5 complete and 7 partial remissions. Patients pretreated with mogamulizumab had an ORR of 45.8% (4 complete and 7 partial remissions). IEAC-assessed median DOR was not reached (NR; 95% CI, 1.87 months to NR). Treatment-emergent adverse events (TEAEs) were manageable. TEAEs that occurred in ≥20% of patients included thrombocytopenia, anemia, alopecia, dysgeusia, neutropenia, lymphopenia, leukopenia, decreased appetite, and pyrexia. Grade ≥3 TEAEs included thrombocytopenia, anemia, lymphopenia, leukopenia, and neutropenia. Valemetostat demonstrated promising efficacy and tolerability in heavily pretreated patients, warranting further investigation in treating R/R ATL.

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“…Mogamulizumab (MOG) is a humanized monoclonal anti-C-C chemokine receptor type 4 (CCR4) antibody, which has been demonstrated to be clinically effective for ATLL [13][14][15]. As CCR4 is highly expressed on regulatory T cells (Treg cells) and ATLL cells, pre-transplant MOG use induces severe GvHD.…”

Section: Introductionmentioning

confidence: 99%

Mogamulizumab for post-transplant relapse of adult T-cell leukemia/lymphoma: a case study

et al. 2022

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Mogamulizumab (MOG), a humanized monoclonal anti-CCR4 antibody, exerts strong antibody-dependent cellular cytotoxic effects on CCR4-positive adult T-cell leukemia/lymphoma (ATLL) cells. As CCR4 is highly expressed on regulatory T cells as well as ATLL cells, pre-transplant MOG induces severe graft-versus-host disease (GvHD). However, limited data are available on post-transplant use of MOG for relapsed ATLL. Here we describe the case of a patient with ATLL who experienced post-transplant relapse with involvement of peripheral blood, skin, lungs, and lymph nodes. Neither tacrolimus dose reduction nor cytotoxic chemotherapy was effective, but a single dose of MOG (1 mg/kg) induced complete remission. After treatment with MOG, leukemic cells in the peripheral blood rapidly disappeared, and the skin, lymph node, and lung lesions gradually regressed. Most notably, the long-term remission was accompanied by recurrence of moderate acute GvHD (grade II, skin stage 2, gut stage 1, liver stage 0). Our findings indicate that MOG can augment allogeneic immune-mediated anti-tumor reactions through graft-versus-ATLL (GvATLL) even during post-transplant relapse involving the lymph nodes and lungs, along with inducing GvHD.

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Systematic review of survival outcomes for relapsed or refractory adult T‐cell leukemia‐lymphoma

Cited by 5 publications

References 48 publications

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review

An open-label, single-arm phase 2 trial of valemetostat for relapsed or refractory adult T-cell leukemia/lymphoma

Mogamulizumab for post-transplant relapse of adult T-cell leukemia/lymphoma: a case study

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