PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

Kwong, Yok–Lam; Chan, Thomas S. Y.; Tan, Daryl; Kim, Seok Jin; Poon, Limei; Mow, Benjamin; Khong, Pek‐Lan; Loong, Florence; Au-Yeung, Rex; Iqbal, Jabed; Phipps, Colin; Tse, Eric

doi:10.1182/blood-2016-12-756841

Cited by 420 publications

(356 citation statements)

References 21 publications

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“…In parallel, studies have focused on analyzing of the PD1/ PD-L1 axis for prognostic relevance and prediction of treatment response. 4,[6][7][8][9][10] With regards to lymphoid malignancies, tumor cell PD-L1 expression is frequently reported in classic Hodgkin lymphoma (CHL), primary mediastinal large B-cell lymphoma, and Epstein-Barr virus (EBV)-associated lymphomas, including EBV-positive diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) type, and extranodal NK/T-cell lymphoma, nasal type 11 according to the WHO 2017 classification. 1 Moreover, a recent report describes a higher incidence of neoplastic PD-L1 overexpression in primary DLBCL of the CNS (PCNS-DLBCL) compared to systemic ordinal cases.…”

Section: Introductionmentioning

confidence: 99%

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Sakakibara

Inagaki

Imaoka

et al. 2018

J Clin Exp Hematopathol

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Intravascular large B-cell lymphoma (IVLBCL) is a rare and clinically distinctive entity characterized by the almost exclusive growth of large cells within the lumen of blood vessels in particular capillaries. Reports of this peculiar disease, do not commonly address the PD-L1 expression on IVLBCL tumor cells. Here, we describe a 51-year-old Japanese woman who presented with rapidly progressive cognitive decline and higher brain dysfunction. CT scan and MRI revealed multiple ischemic foci in the cerebral hemispheres, ground-glass opacity in the lungs, and splenomegaly. Random skin biopsy for IVLBCL diagnosis yielded negative results. The patient experienced a rapidly deteriorating clinical course with no treatment, and died from the disease after 3 months of hospitalization. Post-mortem examination revealed systemic intravascular plugging of lymphoma cells, without mass lesions in the central nervous system or in visceral organs such as the lungs, liver, pituitary gland, ovaries, and uterus. The tumor cells were positive for CD10, CD20, BCL2, BCL6, and MUM1, but not other lineage-specific markers. Notably, the tumor cells showed strong PD-L1 expression. Our case was diagnosed as IVLBCL with neoplastic PD-L1 expression. These findings suggest that PD-L1 is associated with immune evasion of IVLBCL and may play a role in the pathogenesis and peculiar biological behavior of this unique disease. Additionally, PD-L1 may represent a possible therapeutic target for immune check-point inhibitors.

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Section: Introductionmentioning

confidence: 99%

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Sakakibara

Inagaki

Imaoka

et al. 2018

J Clin Exp Hematopathol

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“…Pembrolizumab, a humanised antibody that targets and blockades the programmed cell death-1 receptor, has been shown to be effective for relapse or refractory disease in some cases 9. It is also imperative to treat the underlying cause of secondary HLH syndrome with antiviral medications, intravenous immunoglobulin or chemotherapy 4…”

Section: Discussionmentioning

confidence: 99%

Natural killer/T-cell lymphoma and secondary haemophagocytic lymphohistiocytosis in pregnancy

Neistadt

Carrubba

Zaretksy³

2018

BMJ Case Reports

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Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially fatal disorder. It is challenging to diagnose due to its rarity and variation in clinical presentation, laboratory abnormalities and underlying aetiologies. A reproductive-aged woman, gravida 2 para 1001 at 27 weeks gestation presented with fever, hypotension and subacute upper respiratory infection. She delivered a male infant by caesarean section secondary to fetal distress. Subsequently, she was diagnosed with T-cell lymphoma and secondary HLH. Despite management with supportive care and multiple chemotherapeutic agents, she ultimately died of multiorgan failure. Patients with HLH secondary to malignancy have a particularly poor prognosis. This case highlights the importance of considering secondary HLH in the differential diagnosis of a patient with fever, pancytopenia and systemic symptoms of unclear aetiology in pregnancy.

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“…PD-L1 status was available in 5 of the patients, 4 of whom had high PD-L1 expression and 1 with weak expression by IHC. Of the patients with high PD-L1 expression, 3 achieved a CR 105 . Similar results have been observed following treatment with nivolumab 106 .…”

Section: Checkpoint Inhibitorsmentioning

confidence: 99%

New developments in immunotherapy for lymphoma

Heyman

Yang

2018

Cancer Biology & Medicine

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The development of immunotherapies for lymphoma has undergone a revolutionary evolution over the past decades. Since the advent of rituximab as the first successful immunotherapy for B-cell non-Hodgkin lymphoma over two decades ago, a plethora of new immunotherapeutic approaches to treat lymphoma has ensued. Four of the most exciting classes of immunotherapies include: chimeric antigen receptor T-cells, bispecific antibodies, immune checkpoint inhibitors, and vaccines. However, with addition of these novel therapies the appropriate timing of treatment, optimal patient population, duration of therapy, toxicity, and cost must be considered. In this review, we describe the most-promising immunotherapeutic approaches for the treatment of lymphoma in clinical development, specifically focusing on clinical trials performed to date and strategies for improvement.

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PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase

Abstract: Key Points NK/T-cell lymphomas failing L-asparaginse, generally fatal, showed a high CR rate to PD1 blockade with pembrolizumab. Comprehensive clinical, radiologic, pathologic, and molecular assessments showed different patterns of CRs and PRs.

Cited by 420 publications

References 21 publications

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Autopsy case report of intravascular large B-cell lymphoma with neoplastic PD-L1 expression

Natural killer/T-cell lymphoma and secondary haemophagocytic lymphohistiocytosis in pregnancy

New developments in immunotherapy for lymphoma

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