brentuximab vedotin
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2022 ◽  
pp. 1-6
Werner Kempf ◽  
Christina Mitteldorf

Kutane T-Zell-Lymphome (CTCL) machen den Großteil aller primären kutanen Lymphome (CL) aus. 80 % aller Fälle von CTCL wiederum entfallen auf Mycosis fungoides (MF) und CD30-positive lymphoproliferative Erkrankungen der Haut. Das klinische Bild der verschiedenen Formen von CTCL zeigt Überschneidungen. Darum ist die klinisch-pathologische Korrelation von großer Bedeutung für die finale Diagnosestellung. Die MF zeigt einen charakteristischen Verlauf mit makuläre Läsionen (Patches), infiltrierte Plaques und, bei einem Teil der Patienten (10–20 %), Tumoren. Die Behandlung erfolgt stadienorientiert mit auf die Haut gerichteten Therapien wie UV-Lichttherapien und Kortikosteroiden in frühen Stadien der Erkrankung (Patch- und begrenztes Plaque-Stadium) und systemischen Therapien (Retinoide bzw. Rexinoide, Interferon, Monochemotherapie, zielgerichtete Therapie) und/oder Strahlentherapie (lokal oder Ganzkörperbestrahlung mit Elektronen) in fortgeschrittenen Stadien. Neuartige Ansätze umfassen zielgerichtete Therapien wie Mogamulizumab (Antikörper gegen CCR4) oder Brentuximab Vedotin (Antikörper gegen CD30) sowie Histon-Deacetylase-Inhibitoren. Angesichts des Impacts von zielgerichteten Therapien sind Biomarker wie CD30 nicht nur für die Diagnosestellung und korrekte Klassifikation eines Lymphoms im Einzelfall von großer Bedeutung, sondern als potenzielle Wirkstoff-Zielmoleküle auch für die Therapie. In der kürzlich überarbeiteten WHO-Klassifikation von 2017 und der aktualisierten WHO-EORTC-Klassifikation der CL von 2018 ist erstmals das CD8-positive akrale T-Zell-Lymphom als eigene, noch provisorische Entität aufgeführt. Diese Form zeigt charakteristische klinische, histologische und phänotypische Merkmale und eine hervorragende Prognose. Zu den seltenen, aber aggressiven CTCL zählen das primär kutane aggressive epidermotrope CD8-positive T-Zell-Lymphom und das kutane Gamma/Delta-T-Zell-Lymphom, die durch rasches Auftreten nekrotischer oder ulzerierender Plaques und Tumoren gekennzeichnet sind. Da bei diesen Formen die Prognose ungünstig ist, umfasst die Behandlung Polychemotherapien und hämatopoetische Stammzelltransplantationen.

2022 ◽  
Vol 12 ◽  
Chunting Zhu ◽  
Yi Zhao ◽  
Fang Yu ◽  
Weijia Huang ◽  
Wenjun Wu ◽  

BackgroundTumor flare reaction (TFR) is a clinical syndrome, which is mainly associated with painful and swollen lymph nodes or splenomegaly, slight fever, bone pain, and skin rash during treatment with immune-related drugs, causing difficulty in distinguishing TFR from disease progression. Brentuximab vedotin (BV) and programmed death 1 (PD-1) inhibitor are two ideal drugs used for the treatment of classic Hodgkin lymphoma, but few studies have reported their adverse effects in association with TFR. The efficacy and safety of monotherapy or combination therapy with these drugs needs to be further evaluated. It is essential to determine whether treated patients can develop TFR, thus enabling more accurate diagnosis and treatment.Case presentationA 26-year-old female patient, diagnosed with classic Hodgkin lymphoma, had received 2 + 3 cycles of ABVD chemotherapy (a combination of adriamycin, bleomycin, vinblastine, and dacarbazine) and 4 cycles of PD-1 inhibitor (tislelizumab) therapy but exhibited poor efficacy. Subsequently, she was given combination therapy of BV (100 mg) + tislelizumab (200 mg). However, a slight fever, painful and swollen axillary lymph nodes, multiple skin rashes with pruritus, joint pain, and fatigue with poor appetite appeared during the treatment. Ultrasound (US) scans revealed that multiple lymph nodes were significantly enlarged. After treatment with low-dose dexamethasone and cetirizine, the symptoms were alleviated. A biopsy of the left axillary lymph node revealed that lymphoid tissue exhibited proliferative changes, without tumor cell infiltration. These findings were consistent with the clinical and pathological manifestations of TFR.ConclusionCombination therapy with BV and PD-1 inhibitor was effective in the treatment of relapsed or refractory classic Hodgkin lymphoma. The results suggest that the combination therapy may cause TFR, and biopsy and also continuous imaging observation are important to determine the disease stage. This approach allows clinicians to decide whether to continue the current treatment plan, and alerts them to the occurrence of excessive activation of the immune system.

2022 ◽  
Vittorio Stefoni ◽  
Cinzia Pellegrini ◽  
Lisa Argnani ◽  
Paolo Corradini ◽  
Anna Dodero ◽  

2022 ◽  
Gabriele Roccuzzo ◽  
Francesco Cavallo ◽  
Gianluca Avallone ◽  
Paolo Fava ◽  
Luca Conti ◽  

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 247-253
Narendranath Epperla ◽  
Mehdi Hamadani

Abstract The approval of brentuximab vedotin (BV) and checkpoint inhibitors (CPI) has revolutionized the management of relapsed/refractory classical Hodgkin lymphoma (cHL) patients. In recent years these agents have rapidly moved to earlier lines of therapy, including post-autologous hematopoietic cell transplant (auto-HCT) consolidation, pre-HCT salvage, and the frontline treatment setting. This shift in practice means that double-refractory (refractory to both BV and CPI) cHL is becoming an increasingly common clinical problem. In patients who are not eligible for clinical trials, conventional cytotoxic and targeted therapies (off label) may be a potential option. In patients who are transplant eligible, early referral to allogeneic HCT should be considered given the significant improvement in transplant outcomes in the contemporary era. Cellular therapy options including CD30.chimeric antigen receptor T cells, Epstein-Barr virus-directed cytotoxic T cells, and CD16A/30 bispecific natural killer cell engagers appear promising and are currently in clinical trials.

2021 ◽  
Vol 11 ◽  
Georg-Nikolaus Franke ◽  
Konstantin Dumann ◽  
Madlen Jentzsch ◽  
Astrid Monecke ◽  
Christine Doehring ◽  

Sezary Syndrome (SS) is a rare leukemic variant of primary cutaneous T-cell lymphoma. Relapsed or refractory disease is generally considered incurable by conventional therapeutic approaches, although durable responses can be achieved with novel monoclonal antibodies. Allogeneic hematopoietic stem cell transplantation (alloHSCT) may have potential value by inducing graft vs-lymphoma (GvL) effects, but there is currently no consensus regarding the timing of alloHSCT or type of conditioning regimen. Here we present the case of a male patient who achieved a complete remission (CR) of primary refractory SS after non-myeloablative alloHSCT. Patient: Two years prior to HSCT, the patient had been refractory to CHOEP-based chemotherapy, interferon, extracorporeal photopheresis (ECP), and bexarotene. Directly prior to alloHSCT brentuximab-vedotin (BV) was applied resulting in a partial remission of the skin compartment and overall in a stable disease. Prior to HSCT, flow cytometry of the bone marrow and peripheral blood showed an infiltration with T-cells positive for CD5, CD4, low CD3, low CD2 and negative for CD7, CD38, HLA-DR and CD8. The trephine biopsy showed a 7% infiltration of SS cells. The CD4:CD8 ratio in peripheral blood (pb) was massively increased at 76.67, with 63.5% of white blood cells expressing a SS immune phenotype. The conditioning regimen included 30 mg/m2 fludarabine on days -5, -4 and -3 and total body irradiation with 2 Gy on day -1. Immunosuppression consisted of cyclosporine A from day-1 and mycophenolate mofetil from day 0. The patient received 6.55x106 CD34+ cells and 1.11x108 CD3+ cells/kg body weight. Bone marrow evaluation on day 28 still showed persistent SS cells by flow cytometry. After tapering immunosuppression until day 169, the CD4:CD8 ratio in pb normalized. CR was documented on day 169 after alloHSCT and is now ongoing for almost 3 years after alloHSCT. Conclusions: We confirm that an alloHSCT can be a curative option for refractory patients with SS. The achievement of a CR after tapering the immunosuppressive therapy indicates a significant role of the GvL effect. In present treatment algorithms for patients with SS, the timing of an alloHSCT and the intensity of conditioning should be further explored.

Tanja Podkonjak ◽  
Holly Cranmer ◽  
Julia Scarisbrick ◽  
Grant McCarthy ◽  
Cameron Lilley ◽  

Aim: To assess the cost–effectiveness of brentuximab vedotin (BV) versus physician’s choice (methotrexate or bexarotene) for treating advanced cutaneous T-cell lymphoma. Materials & methods: A partitioned-survival model was developed from the National Health Service perspective in England and Wales. Model inputs were informed by the ALCANZA trial, real-world UK data, published literature or clinical experts. Results: Over the modeled lifetime, BV dominated physician’s choice and provided an additional 1.58 life-years and 1.09 higher quality-adjusted life years with a net cost saving of £119,565. The net monetary benefit was £152,326 using a willingness-to-pay threshold of £30,000/quality-adjusted life year. Results were robust in sensitivity and scenario analyses. Conclusion: BV is a highly cost-effective treatment for advanced cutaneous T-cell lymphoma.

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