Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma

Hradská, Katarína; Kaščák, Michal; Jelı́nek, Tomáš

doi:10.1080/17474086.2020.1733405

Cited by 6 publications

(9 citation statements)

References 105 publications

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“…Additionally, it is of extreme relevance the identification of potential immunomodulatory activities of drugs currently used for the treatment of advanced disease (such as proteasome inhibitors [88]) and of novel molecules (hypomethylating agents, HDAC inhibitors, checkpoint inhibitors) [16,49,60,62]. This will lead to the translational design of innovative combination strategies tailored to each patient's "immune status" and to the development of personalized immune therapy for symptomatic (or asymptomatic) MM disease.…”

Section: Discussionmentioning

confidence: 99%

“…MM-associated T-cells could present a mixed phenotype, which ranges from a "senescent" effector phenotype, characterized by positivity to KLRG-1, CD57, CD160 associated to low or negative CD28, CTLA4, and PD1, up to an "exhaustion" phenotype, which includes the positivity for PD1, CTLA-4, CD57 and the lack of CD28 [22,25,43,60]. Unfortunately, the failure of trials including anti-PD1 mAbs (even if some interesting results have been observed from IMiDs-anti-PD1 combinatory strategies) revealed a dismal clinical role for the axis PDL1-PD1 in MM [61][62][63]. Several trials are now exploring the activity MM-associated T-cells could present a mixed phenotype, which ranges from a "senescent" effector phenotype, characterized by positivity to KLRG-1, CD57, CD160 associated to low or negative CD28, CTLA4, and PD1, up to an "exhaustion" phenotype, which includes the positivity for PD1, CTLA-4, CD57 and the lack of CD28 [22,25,43,60].…”

Section: Cytotoxic T Lymphocytes (Ctls)mentioning

confidence: 99%

“…Several trials are now exploring the activity MM-associated T-cells could present a mixed phenotype, which ranges from a "senescent" effector phenotype, characterized by positivity to KLRG-1, CD57, CD160 associated to low or negative CD28, CTLA4, and PD1, up to an "exhaustion" phenotype, which includes the positivity for PD1, CTLA-4, CD57 and the lack of CD28 [22,25,43,60]. Unfortunately, the failure of trials including anti-PD1 mAbs (even if some interesting results have been observed from IMiDs-anti-PD1 combinatory strategies) revealed a dismal clinical role for the axis PDL1-PD1 in MM [61][62][63]. Several trials are now exploring the activity of anti-CTLA4 mAbs alone or in combination with anti-PD1.…”

Section: Cytotoxic T Lymphocytes (Ctls)mentioning

confidence: 99%

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Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Botta

Mendicino

Martino

et al. 2021

Cancers

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Multiple myeloma (MM) is the second most common hematologic malignancy, characterized by a multi-step evolutionary path, which starts with an early asymptomatic stage, defined as monoclonal gammopathy of undetermined significance (MGUS) evolving to overt disease in 1% of cases per year, often through an intermediate phase known as “smoldering” MM (sMM). Interestingly, while many genomic alterations (translocation, deletions, mutations) are usually found at early stages, they are not sufficient (alone) to determine disease evolution. The latter, indeed, relies on significant “epigenetic” alterations of different normal cell populations within the bone marrow (BM) niche, including the “evasion” from immune-system control. Additionally, MM cells could “educate” the BM immune microenvironment (BM-IM) towards a pro-inflammatory and immunosuppressive phenotype, which ultimately leads to disease evolution, drug resistance, and patients’ worse outcome. Indeed, it is not a case that the most important drugs for the treatment of MM include immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide) and monoclonal antibodies (daratumumab, isatuximab, and elotuzumab). On these bases, in this review, we describe the most recent advances in the comprehension of the role of the different cells composing the BM-IM, and we discuss the potential molecular targets, which could represent new opportunities to improve current treatment strategies for MM patients.

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Section: Discussionmentioning

confidence: 99%

Section: Cytotoxic T Lymphocytes (Ctls)mentioning

confidence: 99%

Section: Cytotoxic T Lymphocytes (Ctls)mentioning

confidence: 99%

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Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Botta

Mendicino

Martino

et al. 2021

Cancers

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“…Cemiplimab (Libtayo) is the most recent antibody in this category which was approved in 2018. It is an anti-PD-1 monoclonal antibody used for metastatic cutaneous squamous cell carcinoma, lung cancer, and myeloma (97)(98)(99). Administering cemiplimab in a study on 78 patients with locally advanced cutaneous squamous cell carcinoma and no accepted standard of care showed 13% of complete response, 31% of partial response, and one treatment-related death (97).…”

Section: Cemiplimabmentioning

confidence: 99%

“…For the patients with NSCLC and tumors expressing PD-L1 >50%, a comparative study between pembrolizumab monotherapy vs. combinations of cemiplimab, ipilimumab, and platinum-based doublet chemotherapy is performing in Phase 3 (98). Cemiplimab combined with isatuximab is in phase 1/phase 2 to treat relapsed/refractory multiple myeloma patients (99). For hormone receptor-positive HER2 negative or triple-negative breast cancer, the first clinical trial was launched.…”

Section: Cemiplimabmentioning

confidence: 99%

A Review of Therapeutic Antibodies in Breast Cancer

Eini¹,

Zainodini²,

Montazeri³

et al. 2021

J Pharm Pharm Sci

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Since the first production of monoclonal antibodies about 35 years ago, researchers have found them useful in the treatment and diagnosis of various diseases such as cancer. By developing different types of monoclonal antibodies such as humanized, drug conjugated, or bispecific ones, researchers, have achieved remarkable success in treating several complicated and challenging diseases, targeting specific antigens or receptors makes monoclonal antibodies the right choice to inhibit signaling pathways like programmed death-ligand 1 (PD-L1) or programmed death1 (PD-1) and changing cell behavior. As one of the most common types of malignancies among women, breast cancer is one of the most critical conditions which different types of monoclonal antibodies were designed and produced to treat. Therefore, we reviewed these antibodies in breast cancer, their targets, and their efficacy and toxicity, with more focus on recent PD-L1or PD-1 inhibitor antibodies in breast cancer and beyond.

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Monoclonal antibodies used for the management of hemataological disorders

Ghosh

2022

Expert Review of Hematology

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Identifying and treating candidates for checkpoint inhibitor therapies in multiple myeloma and lymphoma

Cited by 6 publications

References 105 publications

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

Mechanisms of Immune Evasion in Multiple Myeloma: Open Questions and Therapeutic Opportunities

A Review of Therapeutic Antibodies in Breast Cancer

Monoclonal antibodies used for the management of hemataological disorders

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