Effects of mogamulizumab in adult T‐cell leukemia/lymphoma in clinical practice

Sekine, Masaaki; Kubuki, Yoko; Kameda, Takuro; Takeuchi, Masanori; Toyama, Takanori; Kawano, Noriaki; Maeda, Kouichi; Sato, Seiichi; Ishizaki, Junzo; Kawano, Hiroshi; Kamiunten, Ayako; Akizuki, Keiichi; Tahira, Yuki; Shimoda, Haruko; Shide, Kotaro; Hidaka, Tomonori; Kitanaka, Akira; Yamashita, Kiyoshi; Matsuoka, Hitoshi; Shimoda, Kazuya

doi:10.1111/ejh.12863

Cited by 16 publications

(17 citation statements)

References 18 publications

(71 reference statements)

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“…This could possibly be due to the inclusion of patients with poor conditions such as unfavorable laboratory findings, PS of 3‐4, and poor response to prior therapy, as this postmarketing surveillance did not have prespecified eligibility criteria for patients unlike the prospective clinical trial. According to retrospective studies analyzing data from clinical practice for patients with r/r ATL who received various treatments, including mogamulizumab, the median OS was reported to be within the range of 3.9‐5.4 months, which was consistent with our results. Of note, some of the previous publications suggested a survival benefit of mogamulizumab in patients who received mogamulizumab therapy compared with those who did not based on the result from the subgroup analyses; however, the sample sizes of the mogamulizumab‐treated populations in these studies were small (<100 patients).…”

Section: Discussionsupporting

confidence: 90%

“…According to retrospective studies analyzing data from clinical practice for patients with r/r ATL who received various treatments, including mogamulizumab, the median OS was reported to be within the range of 3.9‐5.4 months, which was consistent with our results. Of note, some of the previous publications suggested a survival benefit of mogamulizumab in patients who received mogamulizumab therapy compared with those who did not based on the result from the subgroup analyses; however, the sample sizes of the mogamulizumab‐treated populations in these studies were small (<100 patients). In addition, some articles have demonstrated that mogamulizumab administration before allogeneic HSCT may be associated with increased risks of severe GVHD.…”

Section: Discussionsupporting

confidence: 90%

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Safety and effectiveness of mogamulizumab in relapsed or refractory adult T‐cell leukemia‐lymphoma

Ishitsuka

Yurimoto

Tsuji

et al. 2019

European J of Haematology

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ObjectiveThis prospective, observational, postmarketing surveillance was conducted to evaluate the safety and effectiveness of mogamulizumab, an anti‐CC chemokine receptor 4 (CCR4) monoclonal antibody, in patients with CCR4‐positive, relapsed or refractory (r/r) adult T‐cell leukemia‐lymphoma (ATL) in Japan.MethodAll patients were scheduled to receive intravenous infusions of mogamulizumab 1.0 mg/kg once weekly for 8 weeks, alone or in combination with other modalities.ResultsIn the safety analysis population comprising 572 patients, mogamulizumab therapy was started between May 29, 2012, and April 30, 2013, and adverse drug reactions (ADRs) were reported in 73.4% (38.6% serious cases) of patients. The most common ADRs were skin disorders (33.2% [10.8% serious cases]), infusion‐related reactions (30.1% [4.7% serious cases]), and infections (22.0% [14.7% serious cases]). In the effectiveness analysis population comprising 523 patients, the best overall response rate and the response rate at the end of therapy were 57.9% and 42.0%, respectively. The median overall survival was 5.5 months. Safety and effectiveness results were similar between patients aged ≥70 and <70 years.ConclusionThis postmarketing surveillance confirmed the safety and effectiveness of mogamulizumab for the treatment of patients with r/r ATL, including elderly patients, in clinical practice.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Safety and effectiveness of mogamulizumab in relapsed or refractory adult T‐cell leukemia‐lymphoma

Ishitsuka

Yurimoto

Tsuji

et al. 2019

European J of Haematology

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“…Therapeutic modulation of some of these targets is hypothesized to synergize with PD‐1 by their alternative mechanism of action with lower anticipated toxicity than CTLA‐4 inhibitors. The combination of nivolumab and the anti‐CCR4 antibody, mogamulizumab, which has shown efficacy in T‐cell lymphomas, is being tested in an open phase I/II trial in HCC (NCT02705105). Targeting the cytokine drive toward immunosuppression may be especially relevant in view of the inflammatory nature of HCC, and the combination of the TGF‐β inhibitor, galunisertib, with nivolumab in patients with refractory HCC (NCT02423343) is under investigation.…”

Section: Classes Of the Forerunner Checkpoint Molecules And Their Inhmentioning

confidence: 99%

Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

Flynn¹,

Sayed

Sharma

et al. 2019

Hepatology

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After a decade of stagnation in drug development, therapeutic reversal of immune-exhaustion with immune checkpoint inhibitors (ICPIs) has been shown to be effective in advanced hepatocellular carcinoma (HCC). The clinical development of novel ICPIs continues at a rapid pace, with more than 50 clinical trials of immunotherapeutic agents registered as of May 2018 for this indication. The development of ICPI is particularly challenging in patients with HCC, a population with unique features which impact on safety and efficacy of immune-modulating therapies. In this review, we discuss the biological foundations supporting the development of ICPIs across the advancing stages of HCC, focusing on the rational positioning of ICPIs across the various Barcelona-Clinic Liver Cancer (BCLC) stages of the disease. Translational studies should guide adequate prioritization of those therapeutic agents and combination strategies which are most likely to achieve patient benefit based on solid mechanistic and clinical justifications. (Hepatology 2019;69:2258-2270).T he role of immune evasion as a pivotal mechanism in the progression of hepatocellular carcinoma (HCC) has long been recognized, but has for many decades remained an "undruggable" domain attributed to the lack of effective therapies capable of reversing cancer-related immunosuppression. (1) Clinical trials of immune checkpoint inhibitors (ICPIs) have ascribed HCC to the expanding list of tumors characterized by intrinsic sensitivity to immunotherapy. In particular, these agents have been proven effective in advanced melanoma, renal cell carcinoma, and non-small-cell lung cancer (NSCLC), with an increasing number of studies demonstrating response rates of up to 25% across hematological and solid malignancies. However, despite the unprecedented efficacy of ICPIs, patients with HCC represent a population with distinct features. The concomitant presence of cirrhosis in >80% of patients is unique and deserves to be considered for its potential safety impact on the delivery of immunotherapy.In terms of efficacy, the presence of a predominantly immunosuppressive microenvironment within

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“…cutaneous T-cell lymphoma (CTCL) [4][5][6][7][8][9]. Mogamulizumab (also named as KW-0761, poteligeo) is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4 [9][10][11]. Previous studies have demonstrated that mogamulizumab can highly enhance antibody-dependent cellular cytotoxicity (ADCC) activity in vitro and antitumor effects against CCR4-expressing leukemic cells in vivo [1].…”

Section: Introductionmentioning

confidence: 99%

Safety and Efficacy Profile of Mogamulizumab (Poteligeo) in the Treatment of Cancers: An Update Evidence From 14 Studies

Zhang

Sun

et al. 2020

Preprint

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Background: CC chemokine receptor 4 (CCR4) is the receptor for CCL22 and CCL17, which is expressed on the surface of tumor cells from patients with adult T-cell leukemia/lymphoma (ATL), peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). Mogamulizumab is a humanized, IgG1 kappa monoclonal antibody that is directed against CCR4. By reducing the number of CCR4 positive Treg cells, the mogamulizumab can boost antitumor immunity and achieve anti-tumor effects.Methods: We examined the PubMed and ClinicalTrials.gov without any language restrictions until 1 February 2020. Considering variability in different studies, the overall survival (OS), progression‐free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) were selected to evaluate the efficacy. Besides, adverse events (AEs) were calculated to assess the safety.Results: When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while lymphopenia, neutropenia and rash were the top 3 grade ≥3 AEs. In combination therapies, the top 3 all-grade AEs were neutropenia, anaemia, and lymphopenia, and lymphopenia is the most common grade ≥3 AE. Besides, the overall ORR is 0.430 (95% CI: 0.393-0.469) and the pooled mean PFS is 1.060 months (95% CI: 1.043-1.077) in mogamulizumab monotherapy. In combination therapies, the overall ORR is 0.203 (95% CI: 0.022-0.746) while the overall PFS and OS were 2.093 months (95% CI: 1.602-2.584) and 6.591 months (95% CI: 6.014-7.167), respectively.Conclusions: On the basis of present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which had a considerable potential in treating patients with cancers.

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Effects of mogamulizumab in adult T‐cell leukemia/lymphoma in clinical practice

Abstract: In clinical practice, mogamulizumab exhibited antitumor activity in patients with relapsed/refractory ATLL, with an acceptable toxicity profile. Mogamulizumab therapy improved the OS of ATLL patients.

Cited by 16 publications

References 18 publications

Safety and effectiveness of mogamulizumab in relapsed or refractory adult T‐cell leukemia‐lymphoma

Safety and effectiveness of mogamulizumab in relapsed or refractory adult T‐cell leukemia‐lymphoma

Challenges and Opportunities in the Clinical Development of Immune Checkpoint Inhibitors for Hepatocellular Carcinoma

Safety and Efficacy Profile of Mogamulizumab (Poteligeo) in the Treatment of Cancers: An Update Evidence From 14 Studies

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