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In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs. [ABSTRACT FROM AUTHOR]

Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials. [ABSTRACT FROM AUTHOR]

Background Human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurological condition characterized by progressive myelopathic symptoms including spasticity, pain, weakness, and urinary symptoms, without proven treatments. Mogamulizumab (MOG) is a monoclonal antibody that binds CCR4 and leads to the clearance of HTLV-1-infected CCR4+ cells. A phase 1-2a study in Japan evaluated MOG for the treatment of HAM/TSP and reported decreases in HTLV-1 proviral load and neuroinflammatory markers, with clinical improvement in some participants. Methods We administered MOG 0.1 mg/kg every 8 weeks to individuals with HAM/TSP as a compassionate and palliative treatment. Patients who received MOG had (1) a positive peripheral HTLV-1 antibody, (2) progressive myelopathic symptoms, and (3) a diagnosis of HAM/TSP. Results Four female patients, ages 45–68, received MOG (range, 2–6 infusions) between 1 November 2019 and 30 November 2022. Two patients with <3 years of symptoms had milder disease, with Osame scores <4. The other 2, with >7 years of symptoms, had Osame scores >5. One patient, with 6 total treatments, received dose-reduced MOG after she developed a rash at the initial dose. The 2 patients with milder baseline disease reported symptomatic improvement and saw reductions in Osame and/or modified Ashworth scale scores during follow-up. The other 2 patients showed no improvement. All 4 developed rashes after receiving MOG—a treatment-limiting event in some cases. Conclusions Clinical trials are needed including diverse patient populations to assess the potential role of MOG for HAM/TSP. Our findings may help inform the development of these trials. [ABSTRACT FROM AUTHOR]

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Summary: Background and Objectives: The effect of mogamulizumab in cutaneous T‐cell lymphoma (CTCL) on T cells (TC) in the peripheral blood and its potential role to navigate treatment intervals are explored. Methods: We investigated within a retrospective monocentric analysis the effect of mogamulizumab on the CD3+ TC and the aberrant T cell population (TCP), i.e., the CD4+/CD7– and the CD4+/CD26– TC, analyzed by flow cytometry. Results: Thirteen patients with CTCL were included. After four cycles there was a mean reduction of 57% in CD3+ TC, 72% in the CD4+/CD7– and 75% in the CD4+/CD26– TCP compared to the individual baseline of each patient. The reduction in CD4+/CD7+ and CD4+/CD26+ TC was lower, averaging 54% and 41%. A significant decrease in aberrant TCP was already evident after the first administration. A median plateau of TCP already occurred during the IP. Progressive disease occurred in 5/13 patients without a clear correlation to aberrant TCP. Conclusions: Already after one dose of mogamulizumab, aberrant TCP and, to a lesser extent, normal TC decrease. We did not observe a clear correlation between TCP and the efficacy of mogamulizumab, but further studies with larger numbers of patients are needed. [ABSTRACT FROM AUTHOR]

Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.

We present a case report of a 56-year-old woman who was diagnosed with biopsy-proven left thalamic glioblastoma multiforme (GBM). She was treated with standard concurrent chemotherapy and radiation, as well as a 2-year period of adjuvant temozolomide. She relapsed 2 ½ years after starting her initial therapy and was treated with bevacizumab and lomustine, but she relapsed. She was then placed on a phase 1/2 clinical trial that included KHK2455 and mogamulizumab-kpkc individually and in combination for almost 4 years. She had a rapid demise due to the development of a neutropenic pneumonia and treatment-induced acute myeloid leukemia (AML) and elected for hospice care. [ABSTRACT FROM AUTHOR]

Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a phase 1–2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1 or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, CSF inflammatory markers and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the phase 1–2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1–2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and four (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (P = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effects on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment. [ABSTRACT FROM AUTHOR]

Patients with recurrent adult T‐cell leukemia/lymphoma (ATL) after allogeneic hematopoietic cell transplantation (allo‐HCT) have a dismal prognosis. We retrospectively evaluated the safety and efficacy of lenalidomide (LEN) in 11 consecutive patients with recurrent ATL after allo‐HCT. The median time from allo‐HCT to ATL recurrence was 111 days (range, 20–1476), and that from allo‐HCT to the initiation of LEN was 162 days (range, 43–1560). The median initial daily dose of LEN was 10 mg (range, 5–25), and the median duration of LEN treatment was 37 days (range, 3–1078). Three patients (27%) achieved complete response and two (18%) achieved partial response (PR). The rates of complete or PR according to the involved site were 57% for skin and 50% for nodal or extranodal lesions. With a median follow‐up of 1033 days (range, 601–1465) among survivors, the 1‐year probability of overall survival (OS) after ATL recurrence was 55%. Grade ≥3 toxicities included cytopenia (n = 4), superficial vein thrombosis (n = 1), and deep vein thrombosis (n = 1). Graft‐versus‐host disease (GVHD) newly developed in five patients (45%) and worsened in four patients (36%). The median duration from the initiation of LEN to GVHD onset or worsening was 5 days (range, 1–9). GVHD was manageable in all patients. Seven patients received mogamulizumab (MOG) for recurrent ATL before LEN treatment. The overall response rates to LEN were 57% in patients who had previously received MOG and 25% in those who had not. The 1‐year probabilities of OS after recurrent ATL were 71% in patients who had previously received MOG and 25% in those who had not. Although cytopenia and GVHD are common among patients with recurrent ATL after allo‐HCT, LEN may improve survival. Administering MOG before LEN may augment treatment efficacy in the allo‐HCT population. [ABSTRACT FROM AUTHOR]

Mogamulizumab is being increasingly prescribed for the treatment of T-cell lymphomas (MF/SS/ATLL). We conducted a retrospective cohort study to identify muscular immune-related adverse events (irAEs) associated with mogamulizumab in patients with T-cell lymphoma followed at Dana-Farber Cancer Institute from January 2015 to June 2022. We identified 5 cases of mogamulizumab-associated myositis and/or myocarditis (MAM/Mc), 2 additionally affected by myasthenia gravis, among 42 patients with T-cell lymphoma. Three cases experienced -mogamulizumab-associated rash (MAR) prior to developing MAM/Mc. The incidence (n = 5/42, 11.9%) of muscular mogamulizumab-associated irAEs may be higher than has been previously reported in clinical trials and may be of late onset (a median of 5 cycles and as late as 100 days from the last infusion). We highlight the utility of IVIG, together with systemic corticosteroids, for the treatment of these potentially fatal side effects associated with mogamulizumab therapy. [ABSTRACT FROM AUTHOR]

Opinion Statement: Adult T-cell leukemia/lymphoma (ATL) is a rare, aggressive subtype of peripheral T-cell lymphoma developing after many years of chronic, asymptomatic infection with the retrovirus human T-cell lymphotropic virus type 1 (HTLV-1). HTLV-1 is endemic to certain geographic areas of the world, and primary infection generally occurs in infancy through mother-to-child transmission via breastfeeding. In less than 5% of infected individuals, a decades-long pathogenic process culminates in the development of ATL. Aggressive subtypes of ATL are life-threatening and challenging to treat, with median overall survival typically less than 1 year in the absence of allogeneic hematopoietic cell transplantation (alloHCT). Owing to the rarity of this illness, prospective large-scale clinical trials have been challenging to perform, and treatment recommendations are largely founded upon limited evidence. Herein, we review the current therapeutic options for ATL, providing a broad literature overview of the foremost clinical trials and reports of this disease. We emphasize our own treatment paradigm, which is broadly based upon disease subtype, patient fitness, and intent to perform alloHCT. Finally, we highlight recent advances in understanding ATL disease biology and important ongoing clinical trials that we foresee as informative and potentially practice-changing. [ABSTRACT FROM AUTHOR]

BACKGROUND:Expressed on activated T and natural killer cells, 4-1BB/CD137 is a costimulatory receptor that signals a series of events resulting in cytokine secretion and enhanced effector function. Targeting 4-1BB/CD137 with agonist antibodies has been associated with tumor reduction and antitumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed in various solid tumor indications and associated with poor prognosis. This phase Ib, open-label study in patients with advanced solid tumors assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of utomilumab (PF-05082566), a human monoclonal antibody (mAb) agonist of the T-cell costimulatory receptor 4-1BB/CD137, in combination with mogamulizumab, a humanized mAb targeting CCR4 reported to deplete subsets of regulatory T cells (Tregs). METHODS:Utomilumab 1.2-5 mg/kg or 100 mg flat dose every 4 weeks plus mogamulizumab 1 mg/kg (weekly in Cycle 1 followed by biweekly in Cycles ≥2) was administered intravenously to 24 adults with solid tumors. Blood was collected pre- and post-dose for assessment of drug pharmacokinetics, immunogenicity, and pharmacodynamic markers. Baseline tumor biopsies from a subset of patients were also analyzed for the presence of programmed cell death-ligand 1 (PD-L1), CD8, FoxP3, and 4-1BB/CD137. Radiologic tumor assessments were conducted at baseline and on treatment every 8 weeks. RESULTS:No dose-limiting toxicities occurred and the maximum tolerated dose was determined to be at least 2.4 mg/kg per the time-to-event continual reassessment method. No serious adverse events related to either treatment were observed; anemia was the only grade 3 non-serious adverse event related to both treatments. Utomilumab systemic exposure appeared to increase with dose. One patient with PD-L1-refractory squamous lung cancer achieved a best overall response of partial response and 9 patients had a best overall response of stable disease. No patients achieved complete response. Objective response rate was 4.2% (95% confidence interval: 0.1-21.1%) per RECIST 1.1. Depletion of Tregs in peripheral blood was accompanied by evidence of T-cell expansion as assessed by T-cell receptor sequence analysis. CONCLUSIONS:The combination of utomilumab/mogamulizumab was safe and tolerable, and may be suitable for evaluation in settings where CCR4-expressing Tregs are suppressing anticancer immunity. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02444793.

Laura Caruso,1 Alessia Castellino,2 Daniela Dessì,3 Leonardo Flenghi,4 Antonio Giordano,5 Adalberto Ibatici,6 Cesare Massone,7 Alessandro Pileri,8 Ilaria Proietti,9 Livio Pupo,10 Pietro Quaglino,11 Serena Rupoli,12 Pier Luigi Zinzani13,14 1Hematology and Bone Marrow Transplantation Unit, Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco Di Catania, Catania, Italy; 2Department of Hematology, Santa Croce E Carle Hospital, Cuneo, Italy; 3Department of Hematology, Businco Hospital Arnas AOB, Cagliari, Italy; 4Hematology and Bone Marrow Transplantation Unit, Santa Maria Della Misericordia Hospital, Perugia, Italy; 5Department of Hematology, Fondazione Policlinico Universitario Agostino Gemelli—IRCCS, Rome, Italy; 6Hematology and Transplant Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 7Dermatology Unit, Ospedali Galliera, Genova, Italy; 8Dermatology Unit, IRCCS S. Orsola-Malpighi Polyclinic, Bologna, Italy. Department of Specialistic, Diagnostic and Experimental Medicine (DIMES), Alma Mater Studiorum University of Bologna, Bologna, Italy; 9Dermatology Unit”Daniele Innocenzi”, Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, Terracina, Italy; 10UOC Lymphoproliferative Diseases, Fondazione PTV Policlinico Tor Vergata, Rome, Italy; 11Dermatologic Clinic, Department of Medical Sciences University of Turin Medical School, Turin, Italy; 12Clinic of Hematology, Ospedali Riuniti Ancona, Ancona, Italy; 13IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; 14Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale Università di Bologna, Bologna, ItalyCorrespondence: Pier Luigi Zinzani, IRCCS University Hospital of Bologna, Seràgnoli Institute of Hematology, and Department of Specialized, Diagnostic and Experimental Medicine, University of Bologna, via Massarenti 9, Bologna, 40138, Italy, Tel +39 051 2144042, Fax +39 051 2144037, Email pierluigi.zinzani@unibo.itAbstract: Mycosis fungoides and Sèzary syndrome are the most studied subtypes common cutaneous T-cell lymphomas. The current treatment objective is to improve the clinical manifestations of the disease in the affected areas, to relieve symptoms and to halt disease progression. Patients with early-stage mycosis fungoides are usually managed with skin-directed therapies, whereas patients with resistant or advanced-stage mycosis fungoides or Sèzary syndrome often require systemic drugs. Over the last decade, new drugs have been developed, increasing the breadth of treatment options for cutaneous T-cell lymphomas patients. Mogamulizumab is a first-in-class defucosylated humanized IgG1 κ monoclonal antibody, which exerts its anti-tumour action by selectively binding to C-C chemokine receptor 4 and increasing antibody-dependent cellular cytotoxicity activity against malignant T-cells. Several clinical trials showed that mogamulizumab is able to effectively control the cutaneous T-cell lymphomas in each site (skin, blood, lymph nodes and viscera), improving patients’ symptoms, function and overall quality of life with a manageable safety profile. In this report, we discuss 12 cases of patients with mycosis fungoides or Sèzary syndrome successfully treated with mogamulizumab in real-life clinical practice in Italy.Keywords: cutaneous T- cell lymphoma, mycosis fungoides, Sèzary syndrome, mogamulizumab

Adult T-cell leukemia–lymphoma (ATL) is classified into four clinical subtypes: acute, lymphoma, chronic, and smoldering. Chronic ATL is further divided into unfavorable and favorable chronic types according to serum lactate dehydrogenase, blood urea nitrogen, and serum albumin values. Acute, lymphoma, and unfavorable chronic types are categorized as aggressive ATL, whereas favorable chronic and smoldering types are categorized as indolent ATL. Intensive chemotherapy alone is not sufficient to prevent relapse of aggressive ATL. Allogeneic hematopoietic stem cell transplantation is a potential therapeutic option to cure aggressive ATL in younger patients. Reduced-intensity conditioning regimens have decreased transplantation-related mortality, and increased donor availability has dramatically improved transplant access. New agents, including mogamulizumab, brentuximab vedotin, tucidinostat, and valemetostat, have recently become available for patients with aggressive ATL in Japan. Here, I provide an overview of recent advances in therapeutic strategies for ATL. [ABSTRACT FROM AUTHOR]

Aim: Due to extensive treatment switching in the MAVORIC trial, lack of UK regulatory licence for the comparator, overall survival (OS) with mogamulizumab was compared with patients with previously treated advanced mycosis fungoides/S ´ ezary syndrome (MF/SS) in real-world setting. Design, setting & participants: Data were from the Hospital Episode Statistics database (all patients in NHS secondary care system in 2009–2019). Patients were selected according to trial inclusion criteria, then trial and HES samples were matched on selected variables with significant imbalance. Outcomes: The analysis indicated significant improvement in OS for mogamulizumab treatment compared with UK clinical practice (hazard ratio: 0.36, 95% CI: 0.24, 0.53). Conclusion: Results suggest an OS advantage for patients with advanced MF/SS treated with mogamulizumab in MAVORIC trial compared with UK clinical practice.

Aim: This study assessed the cost–utility of mogamulizumab, a novel monoclonal antibody, versus established clinical management (ECM) in UK patients in previously treated advanced mycosis fungoides (MF)/S ´ ezary syndrome (SS). Materials & methods: Lifetime partitioned survival model based on overall survival, next treatment-free survival and the use of allogeneic stem cell transplant was developed. Inputs were from the pivotal MAVORIC trial, real-world evidence and published literature. Extensive sensitivity analyses were conducted. Results: Discounted incremental quality-adjusted life years (QALYs), costs and incremental cost–effectiveness ratio were 3.08, £86,998 and £28,233. Results were most sensitive to the survival extrapolations, utilities and costs after loss of disease control. Conclusion: Mogamulizumab is a cost-effective alternative to ECM in UK patients with previously treated advanced MF/SS.

Simple Summary: Patients with erythrodermic cutaneous T-cell lymphoma often experience severe symptoms. This study provides an insight into the impact of the disease, mogamulizumab treatment, and essential patient-reported outcomes. The data on patients' expectation, quality of life, and treatment satisfaction can especially be used in the counseling of future patients. Background: Erythrodermic cutaneous T-cell lymphoma (E-CTCL) is associated with a poor prognosis and severe symptoms. Objective: To establish insights into the quality of life (QoL), expectations, and treatment satisfaction of E-CTCL patients receiving mogamulizumab. Methods: Outcomes of this prospective cohort study conducted between September 2020 and August 2021 at the Leiden University Medical Center included the dermatology-specific QoL (Skindex-29), health-related QoL (RAND-12), degree of itch, pain, and fatigue (Visual Analogue Scale), patient's expectations, and treatment satisfaction (Client Satisfaction Questionnaire-8 (CSQ-8)), measured at baseline and after six months. Results: 13 patients with E-CTCL were included. Most patients anticipated a positive treatment effect on symptoms. Five patients (46%) improved one or more clinical categories regarding the symptoms domain, six (55%) regarding emotions, four (36%) regarding functioning, and four (36%) regarding the overall Skindex-29 score compared to baseline. The Mental Component Score clinically improved from 31 (IQR 29–51) at baseline to 38 (IQR 25–51). The median VAS itch improved significantly from baseline (8 (IQR 7–10) vs. 3 (IQR 1–8), p = 0.024). Most patients (n = 7) were "very satisfied" with their treatment. Limitations: There was a limited number of patients due to the rarity of the disease. Conclusion: In general, mogamulizumab has a favorable effect on biochemical- and dermatology-specific QoL and physical functioning in some patients, with high treatment satisfaction. Itch especially improved over time in most patients. The treatment satisfaction was generally high. Mogamulizumab seems to be an effective treatment that improves the QoL in patients with E-CTCL. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Adult T‐cell leukemia/lymphoma (ATL) patients have a very poor prognosis. The humanized anti‐CCR4 therapeutic monoclonal antibody, mogamulizumab, is a key agent for ATL treatment. Our previous integrated molecular analysis demonstrated that among all the driver genes in ATL, CCR7 gene alterations were significantly associated with clinical response to mogamulizumab. Accordingly, here we investigated the detailed clinical impact of CCR7 alterations in a larger cohort of ATL patients. These CCR7 alterations, most of which lead to C‐terminus truncations, were observed in 27 of 223 patients (12%). For patients receiving mogamulizumab but not allogeneic hematopoietic stem cell transplantation (HSCT), CCR7 alterations were significantly associated with worse survival (median survival from the first dose of mogamulizumab of 0.7 years for 12 patients with CCR7 alterations vs. 1.6 years for 72 patients without, p = 0.020). On the other hand, the presence or absence of CCR7 alterations had no significant impact on survival in the entire cohort (median overall survival of 1.4 and 1.8 years, respectively, p = 0.901), or on the survival of patients receiving allogeneic HSCT (median survival from the day of transplantation of 0.9 years for 6 patients with CCR7 alterations and 1.4 years for 48 without, p = 0.543). Multivariate analysis indicated that patients with CCR4 alterations but lacking CCR7 alterations (n = 20) had significantly better survival after receiving mogamulizumab‐containing treatments (hazard ratio for survival, 0.437, 95% confidence interval, 0.192–0.994). This study contributes to the establishment of precision medicine for ATL. [ABSTRACT FROM AUTHOR]

Sézary syndrome (SS) is a rare and aggressive T-cell lymphoma with a poor prognosis in advanced stages. Allogeneic hematopoietic cell transplantation (allo-HCT) offers a potential cure, but complications such as graft-versus-host disease (GvHD) remain a clinical challenge. Mogamulizumab, a humanized anti-CC chemokine receptor 4 (CCR4) antibody, is sometimes used as a bridge to transplantation, but its potential interactions with allo-HCT are unclear. This report describes the case of a 37-year-old man with advanced SS who received mogamulizumab therapy followed by allo-HCT from an HLA-identical sibling donor. The patient developed severe gastrointestinal acute GvHD, which was treated with steroids and infliximab. However, the condition rapidly progressed to severe intestinal symptoms and life-threatening haemorrhagic shock, ultimately resulting in the patient's death. This case highlights a potential link between mogamulizumab and severe acute GvHD promoted by drug-induced suppression of regulatory T cells. Further research is required to fully understand the interaction between mogamulizumab and allo-HCT and to determine whether it is an optimal approach as a bridge to transplant therapy. This paradigmatic case suggests the need of personalizing transplant strategies by selecting appropriate conditioning therapy and GvHD prophylaxis to minimize potential toxicity. [ABSTRACT FROM AUTHOR]

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

Since the efficacy of mogamulizumab has been confirmed by a phase III, randomized study, mogamulizumab is one of the promising first‐line therapies for advanced cutaneous T cell lymphoma (CTCL), though its efficacy is not completely satisfactory. Therefore, several anti‐lymphoma drugs such as etoposide were recently used to enhance the anti‐tumor effects of mogamulizumab for the treatment of mycosis fungoides (MF). In this report, the anti‐tumor effects of mogamulizumab and post mogamulizumab therapy were retrospectively evaluated in 11 cases of CTCL in real‐world clinical practice. The best response rate (RR) was 45.5% (95% confidence interval [CI], 21.3%–72.0%) for the total cohort, 50.0% (95%CI, 21.5%–78.5%) for the MF cohort, and 33.3% (95%CI, 5.6%–79.8%) for the primary cutaneous peripheral T cell lymphoma not otherwise specified (PCPTCL‐NOS) cohort. The objective response rate (ORR) at 1 month (ORR1) for the total cohort was 45.5% (95%CI, 21.3%–72.0%), and ORR at 4 months (ORR4) was 27.3% (95%CI, 9.2%–57.1%). The mean time to next treatment (TTNT) was 16.0 weeks (3–100 weeks) for all patients, 16.5 months (3–100 weeks) for the MF cohort, and 9.0 (7–16) weeks for the PCPTCL‐NOS cohort. The efficacy rate of etoposide‐based therapy was 71.4% (95%CI, 35.9%–98.0%) for all patients, 80% (95%CI, 35.9%–98.0%) in the MF cohort, and 50% (95%CI, 9.5%–90.5%) in the PCPTCL‐NOS cohort. The median duration of response was 182 (45–323) weeks. The safety profile of mogamulizumab monotherapy in the present cohort was comparable to the previous phase III, randomized trial. The present study suggests that the efficacy and safety profiles of mogamulizumab monotherapy as second‐line therapy and beyond in a real‐world Japanese cohort were comparable to those in the previous phase III, randomized trial. [ABSTRACT FROM AUTHOR]

Mycosis fungoides (MF) is a subtype of cutaneous T‐cell lymphoma (CTCL). Topical or systemic treatment with psoralen, such as 8‐methoxypsoralen (8‐MOP), followed by ultraviolet A (UVA) irradiation (PUVA therapy) is an effective phototherapy for early‐stage MF. However, the efficacy of PUVA therapy for advanced‐stage MF is not satisfactory, and the ideal combination partner for PUVA therapy has not yet been found. In this study, we developed a new mouse model of CTCL in which efficacy of PUVA was detected and further evaluated the efficacy of combination treatment of PUVA and mogamulizumab, an anti‐CCR4 monoclonal antibody. Cytotoxicity of PUVA therapy against HH cells, a CTCL cell line, was observed in vitro. The cytotoxicity was dependent on both 8‐MOP and UVA. Using HH cells, we developed a mouse model in which HH cells were subcutaneously inoculated in the ear. In this model, PUVA therapy suppressed tumour growth with statistical significance, while 8‐MOP or UVA alone did not. Combination therapy of PUVA and mogamulizumab showed greater antitumor activity than either monotherapy with statistical significance. In the histological analysis of the tumour tissue, PUVA accelerated tumour necrosis and then induced the infiltration inflammatory cells in the necrotic area, suggesting that these cells served as effector cells for mogamulizumab. This combination therapy is expected to be a beneficial option for CTCL therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Treatment choices for patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) who have failed first-line systemic therapies can be challenging, as several options are available. However, most evidence is based on observational and early phase studies due to the rarity of the disease. Mogamulizumab has recently been approved for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy; it has a good tolerability profile prompting its use in combination with other agents. This article aims at describing the role of the concomitant use of bexarotene with mogamulizumab in this setting. CASES PRESENTATION: To add information in the field, we describe our experience with four patients with MF/SS who failed first- and second-line treatments and started the combination mogamulizumab in addition to bexarotene. The combination of bexarotene with mogamulizumab in patients with advanced MF/SS after the failure of bexarotene alone obtained a response in all the four patients observed. The response was maintained longer than expected. CONCLUSIONS: The combination is promising and deserves further study. [ABSTRACT FROM AUTHOR]

Cancer patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are at high risk of viral reactivation after cancer treatment. However, there is a paucity of data regarding HBV or HCV reactivation in cancer patients who receive newer anticancer drugs such as immune checkpoint inhibitors; Bruton tyrosine kinase (BTK) inhibitors; agents targeting CD22, CD38, and CC chemokine receptor 4 (CCR4); and chimeric antigen receptor (CAR) T-cell therapies. In this narrative review article, we describe the rate, characteristics, and outcomes of HBV and HCV reactivation in patients receiving novel systemic anticancer therapies. We searched MEDLINE for all original research articles, case reports, and systematic reviews published in English between July 2013 and December 2021 on cancer patients with HBV or HCV infection receiving novel systemic anticancer therapy. The risk of HBV or HCV reactivation is not well defined in cancer patients receiving immune checkpoint inhibitors (durvalumab, atezolizumab, nivolumab, pembrolizumab, ipilimumab, and tremelimumab); BTK inhibitors (ibrutinib and acalabrutinib); agents targeting CD22 (inotuzumab ozogamicin), CD38 (daratumumab, isatuximab), and CCR4 (mogamulizumab); and CAR T-cell therapy (axicabtagene-ciloleucel). However, screening for chronic HBV and HCV infections and routine monitoring of patients with such infections during novel anticancer therapy are recommended for early identification of viral reactivation, which can impact outcomes of oncologic treatment or be fatal. Specific strategies for risk assessment, monitoring, and management should be designed to reduce the risk of reactivation after novel anticancer therapy in patients with chronic HBV or HCV infections. [ABSTRACT FROM AUTHOR]

Summary: Chemotherapy in combination with mogamulizumab (Mog) was approved in Japan in 2014 for untreated aggressive adult T‐cell leukaemia‐lymphoma (ATL), but the survival benefit remains unclear. Therefore, we retrospectively analysed clinical outcomes in 39 transplant‐ineligible patients with untreated aggressive ATL at Kumamoto University Hospital between 2010 and 2021. The probability of four‐year overall survival was 46.3% in the first‐line Mog‐containing treatment group compared to 20.6% in the chemotherapy‐alone group (p = 0.033). Furthermore, this survival benefit was observed even in the elderly. In conclusion, first‐line Mog‐containing treatment can be a promising strategy for transplant‐ineligible patients with ATL, especially in the elderly. [ABSTRACT FROM AUTHOR]

Competing Interests: Dr Guenova received honoraria and/or grant support from Mallinckrodt, Helsinn, Takeda Pharmaceuticals, Recordati Rare Diseases, Novartis, Sanofi, Stemline Therapeutics, and Kyowa Kirin. Dr Maël Blanchard received honoraria from Kyowa Kirin. Dr Boulinguez received honoraria and/or is a scientific committee member for Recordati, Pierre Fabre Dermatologie, Sanofi, Amgen, UCB, and Novartis. Drs Cortés, Doms, Bernard, and Gabriela Blanchard have no conflicts of interest to declare.

Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, professional organizations suggested extending dosing intervals for systemic cancer therapies to limit in-person visits. Mogamulizumab, indicated for adults with relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS) after ≥1 prior systemic therapy, should be administered every 7 days of the first 28-day cycle (loading) and every 14 days of each subsequent cycle (maintenance) according to the approved prescribing information in the United States (US). This study examined the real-world use of mogamulizumab before and during the COVID-19 pandemic in the US., Methods: Using Symphony Health's Integrated Dataverse (IDV) database, adults with ≥1 diagnosis of MF or SS and ≥1 mogamulizumab claim between October 1, 2018 and December 22-, 2022 were identified. Patients in MF and SS cohorts were divided into 3 subgroups based on the date they initiated mogamulizumab treatment: pre-COVID-19 (October 1, 2018-March 31, 2020), COVID-19 Phase 1 (April 1, 2020-July 31, 2021), and COVID- 19 Phase 2 (August 1, 2021-December 22, 2022)., Findings: During the study, 270 patients with MF and 337 patients with SS initiated mogamulizumab. The pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups included 95, 81, and 94 patients with MF and 124, 119, and 94 patients with SS, respectively. In the MF cohort, mean loading dosing intervals were 13, 12, and 9 days for the pre-COVID-19, COVID-19 Phase 1, and COVID-19 Phase 2 subgroups, respectively, and mean maintenance dosing intervals were 16, 16, and 16 days, respectively. In the SS cohort, mean loading dosing intervals were 16, 11, and 11 days, and mean maintenance dosing intervals were 19, 18, and 16 days, respectively. For both cohorts, more patients in the COVID-19 Phase 1 and Phase 2 subgroups than in the pre-COVID-19 subgroup had gaps of ≤10 days between loading doses and ≤21 days between maintenance doses., Implications: In patients with MF and SS, loading dosing intervals in the pre-COVID-19 period were longer than the loading schedule per the approved prescribing information, but there was a trend towards closer concordance in the COVID-19 periods. Maintenance dosing intervals in patients with MF were consistently similar to the approved schedule across treatment periods, and in patients with SS became more closely aligned over time. Thus, dosing intervals for mogamulizumab in both loading and maintenance cycles do not appear to have been extended during the COVID-19 Phase 1 and Phase 2 periods compared with the pre-COVID-19 period, despite recommendations to extend dosing intervals for systemic cancer therapies during COVID-19., Competing Interests: Declaration of competing interest Chunlan Chang is a salaried employee of Kyowa Kirin, Inc. Robert Ristuccia is a salaried employee of Kyowa Kirin, Inc. Zhishui Zheng is a salaried employee of KMK Consulting, which was engaged by Kyowa Kirin Inc., to conduct the study analyses. Takeshi Takahashi is a salaried employee of Kyowa Kirin Co., Ltd. Takanobu Nomura is a salaried employee of Kyowa Kirin Co., Ltd. Eslie Dennis is a salaried employee of Kyowa Kirin, Inc., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Mogamulizumab (Mog), an anti-C-C motif chemokine receptor 4 (CCR4) antibody, is a therapeutic for adult T-cell leukemia/lymphoma (ATL). Injuries of normal regulatory T cells (Tregs) which express CCR4 by Mog could result in immune-related adverse events including graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this study, we retrospectively analyzed 25 patients among 39 patients with ATL who received allo-HSCT. We found that the risk of grade II to IV GVHD was higher in patients who received Mog before or after allo-HSCT (Mog+) than in those who did not (Mog−). The incidence of severe intestinal GVHD and cytomegalovirus (CMV) enteritis were significantly higher in Mog + patients and resulted in death from GVHD or CMV enteritis. Treg numbers were suppressed until Mog serum concentrations became undetectable. Measuring the concentration of Mog and/or the number of Tregs at the time of allo-HSCT might predict the risk of GVHD. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia-lymphoma (ATL) is an aggressive malignancy with a poor prognosis, especially for patients with the aggressive subtype. While conventional chemotherapy offers short-term disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most promising curative approach for young, transplant-eligible patients. This review focuses on current treatment strategies for aggressive ATL in this specific population. We discuss the rationale for early upfront allo-HSCT following induction chemotherapy. The advent of allo-HSCT using alternative donors, particularly haploidentical HCT, has broadened the applicability of early upfront allo-HSCT in patients with aggressive ATL worldwide. Finally, we address emerging therapies that may improve outcomes in the context of allo-HSCT, paving the way for further advancements in the treatment of aggressive ATL. • Patients with aggressive ATL have a poor prognosis with conventional chemotherapy. • There is a general consensus on early upfront allo-HSCT in patients with aggressive ATL. • Further development of pre- and post-transplant treatment and allo-HSCT is needed. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphoma, drug-related side effect, mogamulizumab, mycosis fungoides, rash, recurrence, Sézary syndrome Keywords: cutaneous T-cell lymphoma; drug-related side effect; mogamulizumab; mycosis fungoides; rash; recurrence; Sézary syndrome EN cutaneous T-cell lymphoma drug-related side effect mogamulizumab mycosis fungoides rash recurrence Sézary syndrome e191 e193 3 05/12/23 20230501 NES 230501 Dear editor, Mogamulizumab is a humanized anti-CCR4 monoclonal antibody approved for treatment of mycosis fungoides (MF) and Sézary syndrome (SS). Mogamulizumab-associated rash (MAR) occurred in 24% of patients in the MAVORIC clinical trial, and it has been reported as the second most frequent adverse effect of mogamulizumab.[1] The clinical suspicion and pathological confirmation are important to enable differentiation of MAR from cutaneous T-cell lymphoma (CTCL) progression, which may be particularly challenging. [Extracted from the article]

Abstract Background CC chemokine receptor 4 (CCR4), the receptor for CCL22 and CCL17, is expressed on the surface of effector Tregs that have the highest suppressive effects on antitumor immune response. CCR4 is also widely 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 Tregs and tumor cells, the mogamulizumab can reduce tumor burden and boost antitumor immunity to achieve antitumor effects. Methods We examined the PubMed and ClinicalTrials.gov until 1 February 2020. Considering variability in different studies, we selected the adverse events (AEs), overall survival (OS), progression-free survival (PFS), objective responses rate (ORR) and Hazard Ratio (HR) for PFS to evaluate the safety and efficacy profile of mogamulizumab. Results When patients were treated with mogamulizumab monotherapy, the most common all-grade AEs were lymphopenia, infusion reaction, fever, rash and chills while the most common grade ≥ 3 AEs were lymphopenia, neutropenia and rash. When patients were treated with combined therapy of mogamulizumab and other drugs, the most common all-grade AEs were neutropenia, anaemia, lymphopenia and gastrointestinal disorder, while the most common grade ≥ 3 AEs was lymphopenia. For patients treated with mogamulizumab monotherapy, the pooled ORR and mean PFS were 0.430 (95% CI: 0.393–0.469) and 1.060 months (95% CI: 1.043–1.077), respectively. For patients treated with combined therapy of mogamulizumab and other drugs, the pooled ORR was 0.203 (95% CI: 0.022–0.746) while the pooled 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 Based on present evidence, we believed that mogamulizumab had clinically meaningful antitumor activity with acceptable toxicity which is a novel therapy in treating patients with cancers.

Simple Summary: Mogamulizumab is a recent monoclonal antibody prescribed in the second line to treat advanced mycosis fungoides and Sézary syndromes. We collected data from all patients who used mogamulizumab in six French university hospitals until 1 September 2021. Our primary objective was to determine the median progression free survival (PFS). Secondary objectives were to consider tolerance regarding side effect occurrence and severity. Twenty-one patients were included, with a median time of follow-up of 11.6 months, and progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. Our study suggests that mogamulizumab is a significant treatment option to extend PFS in patients with advanced refractory cutaneous T-cell lymphomas (CTCL). The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III–IV adverse events (AEs) compared to other systemic treatments. Background: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared. Methods: Data on patients with advanced cutaneous T-cell lymphomas were collected since French Authorization, in six French university hospitals. Patients were followed until they stopped mogamulizumab because of relapse or toxicity. For those still treated by mogamulizumab, the end point was 1 September 2021. We excluded 3 patients as they had already been included in the MAVORIC study and data was not available. Results: The median time of follow-up was 11.6 months. Of the 21 patients included, we reported four full-response patients, eight in partial response, one in stability, three in progression, and five were deceased. One patient had visceral progression, and seven had new lymphadenopathy. Progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe, i.e., grade III-IV. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. Conclusions: Our study suggests that mogamulizumab can give patients with advanced refractory CTCL a consequent PFS, estimated at 22 months. The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III–IV AEs, comparable with other studies. No other study using real-life data has been performed to investigate the AEs of mogamulizumab. [ABSTRACT FROM AUTHOR]

Mogamulizumab (Mog) is effective against adult T-cell leukemia–lymphoma (ATL), but as we reported previously, Mog increases the incidence of severe acute GVHD when administered before allogeneic hematopoietic cell transplantation (allo-HCT). Here, we report the cases of two ATL patients who did not develop acute GVHD despite receiving Mog before allo-HCT. Case 1: a 63-year-old female who underwent allo-HCT from an HLA-matched donor 2 months after the last dose of Mog. Case 2: a 47-year-old male with ATL that relapsed 3 months after first allo-HCT. He received eight doses of Mog and underwent a second allo-HCT from a haploidentical donor 4 months after the last dose of Mog. Mog blood levels were measured and lymphocytes analyzed by mass cytometry. Mog blood levels measured before starting the conditioning regimens were low. A small proportion of regulatory T cells (Tregs) was detected before and shortly after allo-HCT. When using Mog before allo-HCT, it is important to consider the number of Mog doses and the interval from the last dose of Mog to allo-HCT. Analyzing Mog blood levels and Treg counts before and after allo-HCT should also be useful. [ABSTRACT FROM AUTHOR]

Objective: Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell lymphotropic virus type I (HTLV-1) infection, is among the most aggressive categories and has the worst prognosis among T-cell lymphomas. Mogamulizumab, an anti-CC chemokine receptor 4 (CCR 4), has been shown to be effective in the treatment of ATL; however, some ATL cases are often resistant, particularly the lymphoma-type ATL. To evaluate drug delivery in vivo and identify the distribution of CCR4-positive cells in the body, we developed a novel mogamulizumab tracer labeled with Indium-111 (111In) via diethylenetriaminepentaacetic acid (DTPA) for single-photon emission computerized tomography (SPECT), named [111In]In-DTPA-mogamulizumab, and evaluated its potential for visualizing CCR4 expression in vivo. Methods: [111In]In-DTPA-mogamulizumab was added to HCT116/CCR4 or HCT116/empty vector (EV) cells, and their radioactivity was measured 1 h after administration. A blocking study was additionally performed by treating HCT116/CCR4 cells with excess mogamulizumab in addition to [111In]In-DTPA-mogamulizumab. The biodistribution and SPECT imaging of [111In]In-DTPA-mogamulizumab in HCT116/CCR4 and HCT116/EV dual-xenografted BALB/c-nu mice were evaluated for 72 h after intravenous injection. Results: [111In]In-DTPA-mogamulizumab was acquired with a radiochemical purity > 95%. The cellular uptake level of [111In]In-DTPA-mogamulizumab by HCT116/CCR4 cells was significantly higher than that by HCT116/EV cells (HCT116/CCR4: 0.951 ± 0.069, HCT116/EV: 0.006 ± 0.001%dose/mg protein, p < 0.01), and the uptake was significantly suppressed by co-incubation with excess mogamulizumab (0.013 ± 0.003%dose/mg protein, p < 0.01). In the in vivo study, the radioactivity of the HCT116/CCR4 tumor tissue was significantly higher than that of the HCT116/EV tumor tissue at 72 h after the administration of [111In]In-DTPA-mogamulizumab (HCT116/CCR4: 20.5 ± 5.4, HCT116/EV: 5.7 ± 1.0%ID/g), and HCT116/CCR4 tumors were clearly and specifically visualized on SPECT imaging. Conclusions: We have successfully developed a novel SPECT imaging tracer targeting CCR4, [111In]In-DTPA-mogamulizumab, which showed good specificity and pharmacokinetics, indicating potential in visualizing CCR4 expression in vivo. [ABSTRACT FROM AUTHOR]

Summary: 'Monitoring of immune responses following mogamulizumab‐containing treatment in patients with adult T‐cell leukaemia–lymphoma (ATL)' (MIMOGA) is a multicentre prospective clinical study (UMIN000008696). In the MIMOGA study, we found that a lower percentage of CD2−CD19+ B cells in peripheral blood mononuclear cells (PBMC) was a significant unfavourable prognostic factor for overall survival (OS). Accordingly, we then analysed the immunoglobulin G (IgG) heavy‐chain repertoire in PBMC by high‐throughput sequencing. Of the 101 patients enrolled in the MIMOGA study, for 81 a sufficient amount of PBMC RNA was available for repertoire sequencing analysis. Peripheral IgG B cells in patients with ATL had a restricted repertoire relative to those in healthy individuals. There was a significant positive correlation between the Shannon–Weaver diversity index (SWDI) for the IgG repertoire and proportions of B cells in the PBMC of the patients. Multivariate analysis identified two variables significantly affecting OS: a higher serum soluble interleukin‐2 receptor level, and a lower SWDI for the IgG repertoire [hazard ratio, 2·124; 95% confidence interval, 1·114–4·049; n = 44]. The present study documents the importance of humoral immune responses in patients receiving mogamulizumab‐containing treatment. Further investigation of strategies to enhance humoral immune responses in patients with ATL is warranted. [ABSTRACT FROM AUTHOR]