Open-label, single arm, multicenter phase II study of VIDL induction chemotherapy followed by upfront autologous stem cell transplantation in patients with advanced stage extranodal NK/T-cell lymphoma

Song, Ga‐Young; Yoon, Dok Hyun; Suh, Cheolwon; Moon, Joon Ho; Baek, Dong Won; Kim, Jin Seok; Lee, Gyeong‐Won; Yi, Jun; Park, Yong; Jung, Ki Sun; Kim, Seok Jin; Yang, Deok‐Hwan; Kim, Won Seog

doi:10.1038/s41409-020-01160-2

Cited by 14 publications

(11 citation statements)

References 9 publications

(9 reference statements)

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“…In another phase II study of stage III/IV patients, treatment with VIDL was followed by autologous HSCT. For patients who proceeded to autologous HSCT, only 47% of cases remained in remission after a short median follow-up of 31 months [ 80 ]. Although there was no direct comparison, these results did not appear to be different from those obtained with asparaginase-containing regimens alone, suggesting that autologous HSCT in these settings did not improve outcome.…”

Section: Haematopoietic Stem Cell Transplantation (Hsct)mentioning

confidence: 99%

How we treat NK/T-cell lymphomas

et al. 2022

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Natural killer (NK)/T-cell lymphomas are aggressive malignancies with a predilection for Asian and South American populations. Epstein–Barr virus (EBV) infection in lymphoma cells is universal. Predominantly extranodal, NK/T-cell lymphomas are divided clinically into nasal (involving the nose and upper aerodigestive tract), non-nasal (involving the skin, gastrointestinal tract, testes, and other organs), and aggressive leukaemia/lymphoma (involving the marrow and multiple organs) subtypes. Initial assessment should include imaging with positron emission tomography computed tomography (PET/CT), quantification of plasma EBV DNA as a surrogate marker of lymphoma load, and bone marrow examination with in situ hybridization for EBV-encoded small RNA. Prognostication can be based on presentation parameters (age, stage, lymph node involvement, clinical subtypes, and EBV DNA), which represent patient factors and lymphoma load; and dynamic parameters during treatment (serial plasma EBV DNA and interim/end-of-treatment PET/CT), which reflect response to therapy. Therapeutic goals are to achieve undetectable plasma EBV DNA and normal PET/CT (Deauville score ≤ 3). NK/T-cell lymphomas express the multidrug resistance phenotype, rendering anthracycline-containing regimens ineffective. Stage I/II nasal cases are treated with non-anthracycline asparaginase-based regimens plus sequential/concurrent radiotherapy. Stage III/IV nasal, and non-nasal and aggressive leukaemia/lymphoma cases are treated with asparaginase-containing regimens and consolidated by allogeneic haematopoietic stem cell transplantation (HSCT) in suitable patients. Autologous HSCT does not improve outcome. In relapsed/refractory cases, novel approaches comprise immune checkpoint blockade of PD1/PD-L1, EBV-specific cytotoxic T-cells, monoclonal antibodies, and histone deacetylase inhibitors. Future strategies may include inhibition of signalling pathways and driver mutations, and immunotherapy targeting the lymphoma and its microenvironment.

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Section: Haematopoietic Stem Cell Transplantation (Hsct)mentioning

confidence: 99%

How we treat NK/T-cell lymphomas

et al. 2022

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“…No standard treatment has been defined for consolidated treatment of advanced ENKTCLassociated HLH [11]. Previous studies have reported that autologous hematopoietic stem cell transplantation does not significantly reduce the recurrence rate of advanced ENKTCL [12]. If the complete response can be achieved, allogeneic HSCT can be attempted for consolidation therapy in young patients with lymphoma-associated HLH.…”

Section: Discussionmentioning

confidence: 99%

Nasal type extranodal natural killer/T-cell lymphomaassociated hemophagocytic lymphohistiocytosis: A Case report and literature review

Liu

Wei

Yang

et al. 2022

APT

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Hemophagocytic lymphohistiocytosis (HLH) is a clinical syndrome in which a large number of inflammatory cytokines, such as IL-6, TNF-α, and sCD25, are released into the blood circulation due to cytotoxic killing cells and dysfunction of natural killer (NK) cells. HLH can be induced by various infections, cancer, or hereditary disorders. HLH is usually fatal due to severe cytopenia and multiple organ failure. Nasal type extranodal natural killer/T-cell lymphoma (ENKTCL) is an aggressive non-Hodgkin’s lymphoma that is closely related to Epstein-Barr virus. ENKTCL can be complicated by HLH at initial diagnosis and recurrence. However, the optimal treatment strategies for ENKTCL-associated HLH are not well defined. Here, we report a case of ENKTCL-associated HLH that was successfully treated with liposomal doxorubicin, etoposide, methylprednisolone, and pegaspargase (DEPL regimen), followed by immunotherapy. This report aims to contribute to improved recognition, diagnosis, and treatment of lymphoma-associated HLH. Keywords: Hemophagocytic lymphohistiocytosis, extranodal natural killer/T-cell lymphoma, liposomal doxorubicin, pegaspargase, lymphoma-associated HLH

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“…The area of each marker in the figure indicates the sample size of the study. Data are cited from ( 35 , 68 , 69 , 72 , 73 , 82 , 84 , 94 , 98 – 114 ).…”

Section: Survival Trend Of Patients With Enktcl In the Past Two Decadesmentioning

confidence: 99%

Treatment of extranodal NK/T-cell lymphoma: From past to future

et al. 2023

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Extranodal NK/T-cell lymphoma (ENKTCL) is the most common subtype of T/NK-cell lymphoma in Asia and Latin America, but very rare in North American and Europe. Patient survival has improved significantly over the past two decades. However, standard treatment has not yet been established, although dozens of prospective trials have been conducted. To help understand how the treatment of ENKTCL has evolved in the past and what trends lie ahead, we have comprehensively reviewed the treatment of this aggressive malignancy, with a particular focus on neglected or unanswered issues, such as the optimal staging method, the best partner of asparaginase (Asp), the individualized administration of Asp, the preferred sequence of CT and RT and so on. Overall, the 5-year overall survival (OS) of patients with Ann Arbor stage I/II disease increased from < 50% in the early 20th century to > 80% in recent years, and the median OS of patients with Ann Arbor stage III/IV disease increased from < 1 year to more than 3 years. The improvement in patient survival is largely attributable to advances in radiation technology and the introduction of Asp and anti-PD-1/PD-L1 immunotherapy into practice. Radiotherapy is essential for patients with early-stage disease, while Asp-based chemotherapy (CT) and PD-1/PD-L1 inhibitors significantly improved the prognosis of patients with advanced-stage disease. ENKTCL management is trending toward simpler regimens, less toxicity, and higher efficacy. Novel drugs, such as manufactured T cells, monoclonal antibodies, and small molecule inhibitors, are being intensively investigated. Based on the fact that ENKTCL is highly resistant to cytotoxic drugs except Asp, and aggressive CT leads to higher toxicity rather than better outcomes, we recommend it is unnecessary to expend additional resources to compare different combinations of Asp with cytotoxic agents. Instead, more efforts should be made to optimize the use of Asp and immunotherapy to maximize efficacy and minimize toxicity, explore ways to overcome resistance to Asp and immunotherapy, identify novel treatment targets, and define subpopulations who may benefit more from specific treatments.

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Open-label, single arm, multicenter phase II study of VIDL induction chemotherapy followed by upfront autologous stem cell transplantation in patients with advanced stage extranodal NK/T-cell lymphoma

Cited by 14 publications

References 9 publications

How we treat NK/T-cell lymphomas

How we treat NK/T-cell lymphomas

Nasal type extranodal natural killer/T-cell lymphomaassociated hemophagocytic lymphohistiocytosis: A Case report and literature review

Treatment of extranodal NK/T-cell lymphoma: From past to future

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