Checkpoint Inhibitors Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Hu, Bei; Jacobs, Ryan; Ghosh, Nilanjan

doi:10.1007/s11899-018-0484-4

Cited by 34 publications

(37 citation statements)

References 91 publications

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“…Since anti-PD-1 therapy is effective in the treatment of several solid tumors, 32 and PD-1 was the most conspicuous checkpoint inhibitor elevated in our model system, the two single and combined therapies were compared (Figure 6a). ICK alone was more effective than anti-PD-1 alone therapy, but the combined therapy was no better than the ICK monotherapy ( Figure 6b).…”

Section: Effect Of Combined Anti-pd-1 and Ick Therapy In The E0771 Modelmentioning

confidence: 99%

Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation

et al. 2020

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While anti-CEA antibodies have no direct effect on CEA-positive tumors, they can be used to direct potent antitumor effects as an antibody-IL-2 fusion protein (immunocytokine, ICK), and at the same time reduce the toxicity of IL-2 as a single agent. Using a fusion protein of humanized anti-CEA with human IL-2 (M5A-IL-2) in a transgenic murine model expressing human CEA, we show high tumor uptake of the ICK to CEA-positive tumors with additional lymph node targeting. ICK treated CEA-positive tumors exhibit significant tumor eradication. Analysis of tumor-infiltrating lymphocytes shows a high frequency of both CD8 + and CD4 + T cells along with CD11b positive myeloid cells in ICK treated mice. The frequency of tumor-infiltrating FoxP3 + CD4 + T cells (Tregs) is significantly reduced vs anti-CEA antibody-treated controls, indicating that ICK did not preferentially stimulate migration or proliferation of Tregs to the tumor. Combination therapy with anti-PD-1 antibody did not improve tumor reduction over ICK therapy alone. Since stereotactic tumor irradiation (SRT), commonly used in cancer therapy has immunomodulatory effects, we tested combination SRT+ICK therapy in two tumor model systems. Use of fractionated vs single high dose SRT in combination with ICK resulted in greater tumor inhibition and immunity to tumor rechallenge. In particular, tumor microenvironment and myeloid cell composition appear to play a significant role in the response rate to ICK+SRT combination therapy.

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Section: Effect Of Combined Anti-pd-1 and Ick Therapy In The E0771 Modelmentioning

confidence: 99%

Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation

et al. 2020

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“…Immunotherapy has reformed the treatment of solid tumors and hematological neoplasms over the past decade with numerous agents approved by the FDA in recent years. While various approaches are used to modify the antitumor immunity of the host, perhaps the most commonly studied and used is the checkpoint block (15,(56)(57)(58)(59). The motivation for adopting ICIs in the treatment of lymphoma relies on the existence in such malignancies of mechanisms that escape immune surveillance due to genetic variance.…”

Section: Immune Checkpoint Inhibitors (Icis)mentioning

confidence: 99%

“…Researches on solid tumors report hepatitis, pneumonia, colitis, thyroiditis, hypophysitis, and other inflammatory reactions. Patients receiving therapies with checkpoint inhibitors should regularly be checked for thyroid function and ACTH/cortisol levels if they experience symptoms such as fatigue or hyponatremia (58,59,74).…”

Section: Immune Checkpoint Inhibitors-toxicitiesmentioning

confidence: 99%

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

et al. 2019

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The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis and the discovery of the critical role of tumor microenvironments have enabled the design of new drugs against cell targets and pathways. The Food and Drug Administration (FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) for targeted therapy in hematology. This review focuses on the efficacy results of the currently available targeted agents and recaps the main ongoing trials in the setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the different classes of novel agents approved for mature B-cell lymphomas, to describe in synoptic tables the results they achieved and, finally, to draw future scenarios as we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation (CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for improving survival outcome in lymphoid neoplasms, as well as the trade-offs between efficacy and toxicity. The hope for clinical advantages should carefully be coupled with mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes severe, toxicities.

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“…Derzeit gibt es einige vielversprechende Ergebnisse bei der Therapie von Patienten mit Non Hodgkin-Lymphomen (NHL) mit Immun-Checkpoint-Inhibitoren. Obwohl die Mehrzahl der NHL eine geringe Empfindlichkeit gegenüber einer PD1/PDL1-Blockade zeigen, weisen einige Subtypen wie das primäre ZNS-Lymphom, das primäre Hodenlymphom und das primäre mediastinale Lymphom Veränderungen von 9p21.1 auf, womit sie für eine PD1-Blockade empfänglicher werden [18].…”

Section: Non Hodgkin-lymphomeunclassified

Standard- oder Therapieverändernde Erkenntnisse in der Hämatologie

Haas

Jäger

2018

Klinikarzt

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ZusammenfassungEin Umdenken von Diagnostik oder bisherigen Standardtherapien verschiedener Erkrankungen erfolgt in der Regel aufgrund neuer Erkenntnisse und Ergebnisse klinischer Studien. Um bisherige Standardtherapien zu verändern, müssen die neuen Erkenntnisse auf einer breiten Basis erzielt und von solcher Signifikanz sein, dass die Wissenschaft eine neue Richtung einschlägt. Im Folgenden wird eine Auswahl von Publikationen für verschiedene hämatologische Erkrankungen vorgestellt: so zeigen bei der chronischen myeloischen Leukämie (CML) Tyrosinkinase-Inhibitoren (TKI) der zweiten Generation eine bessere Effektivität und wurden daher in einigen Ländern als Erstlinientherapie zugelassen. Bei den Myelodysplastischen Syndromen (MDS) sind die Ergebnisse mit Luspatercept vielversprechend und bestätigen die bisher erhobenen Daten. Bei akuten myeloischen Leukämien (AML) erhielt das neu geschaffene CPX-351 (Verbindung aus Cytarabin und Daunorubin) die Zulassung für die Therapie von Patienten mit neu diagnostizierter sekundärer AML. Beim Multiplen Myelom (MM) wird die sequentielle Behandlung aus Induktionstherapie, Cyclophosphamid und einer anschließenden autologen Blutstammzelltransplantation (ASCT) weiterhin als Standard betrachtet. Bei der Therapie von Patienten mit Non Hodgkin-Lymphomen (NHL) gibt es derzeit einige vielversprechende Ergebnisse mit Immun-Checkpoint-Inhibitoren, die eine therapeutische Wirksamkeit ohne die sonst üblichen zytotoxischen Nebenwirkungen ermöglicht. Bei Patienten mit chronisch lymphatischer Leukämie (CLL) kann Venetoclax andauernde Remissionen induzieren und ist deshalb eine vielversprechende und gut verträgliche Behandlungsoption bei Hoch-Risiko-CLL. Auch CAR (chimäre Antigenrezeptor)-modifizierte T-Zell-Therapie konnte bei therapierefraktären aggressiven Lymphomen mit einem akzeptablen Sicherheitsprofil ein hohes Maß an Remissionen erreichen.

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Checkpoint Inhibitors Hodgkin Lymphoma and Non-Hodgkin Lymphoma

Cited by 34 publications

References 91 publications

Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation

Potent immunomodulatory effects of an anti-CEA-IL-2 immunocytokine on tumor therapy and effects of stereotactic radiation

Overview of Targeted Drugs for Mature B-Cell Non-hodgkin Lymphomas

Standard- oder Therapieverändernde Erkenntnisse in der Hämatologie

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