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  • American Society of Hematology  (9)
  • 1
    Online Resource
    Online Resource
    The Tetraspanin CD81 Facilitates Tumor Metastasis By Modulating Immune Suppression
    American Society of Hematology ; 2014
    In:  Blood Vol. 124, No. 21 ( 2014-12-06), p. 4136-4136
    Details
    In: Blood, American Society of Hematology, Vol. 124, No. 21 ( 2014-12-06), p. 4136-4136
    Abstract: Tumor metastasis is the major cause of cancer mortality. While immune cells are aimed at halting metastases, the proliferating cancer cells at the primary tumor site recruit cells that counteract the adaptive anti-tumor immune response. Indeed, it is well established that tumors induce the accumulation and proliferation of immune suppressive cells, such as regulatory T cells (Tregs) and Myeloid Derived Suppressor cells (MDSC). The tetraspanin CD81 belongs to a family of proteins that play an important role in the immune system as evident by impaired immune functions of DCs, B and T cells in several tetraspanin-deficient mice (CD37, CD81, CD151, and CD82). While many studies have addressed the function of CD81 in infection and in the immune system, few have focused on its role in tumorigenesis and metastasis. Here we report that the growth of subcutaneously implanted breast cancer tumors (4T1) is slightly impaired in CD81 knockout (CD81KO) compared to wild type mice. Moreover, CD81KO mice develop very few lung metastases compared to their wild type and heterozygous counterparts. Both wild type and CD81KO tumor-bearing mice show substantial increases in Tregs, and MDSCs. However, these Tregs and MDSCs differ functionally - those derived from wild type mice are effective suppressors of T cell proliferation. By contrast, Tregs and MDSCs derived from tumor-bearing CD81KO mice do not suppress the proliferation of Teff cells. Thus, it is highly likely that while Teff cells are greatly restrained by Tregs and MDSCs in wild type tumor-bearing mice, the impairment of both suppressive cell populations in CD81KO mice enables the anti-tumor function thereby opposing metastases. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V124.21.4136.4136
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 2
    Online Resource
    Online Resource
    Local Treg Immunomodulation Cures Metastatic Lymphoma Including CNS Sites
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. LBA-2-LBA-2
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. LBA-2-LBA-2
    Abstract: Abstract LBA-2 Background: CD4+CD25+FOXP3+ regulatory T-cells (Tregs) protect cancers from the immune system. They express important functional molecules such as CTLA-4 and Ox40 on their surface. Anti-CTLA4 monoclonal antibody (mAb) is the first drug to improve survival of refractory metastatic melanoma. Its recent approval by the FDA/EMEA inaugurates a paradigm shift in cancer therapy where the immune system is targeted rather than the tumor itself. Scientific question: Does local immunomodulation of tumor specific Tregs trigger a systemic anti-tumor immune response and cure disseminated lymphoma? Results: The Tregs that infiltrate the tumor site preferentially express CTLA4 and OX40 compared to their counterparts in the blood and other lymphoid organs, both in mice and in humans. Upon injection of low doses of anti-CTLA4 and anti-OX40 together with CpG, a TLR-9 agonist, directly into the tumor, tumor-specific Tregs are depleted from the tumor-infiltrate. This immunomodulatory combination therapy triggers an anti-tumor immune response able to cure mice with established disseminated disease. The triple combination is uniquely required as neither CpG alone nor mAbs without CpG are effective. The local Treg immunomodulation with anti-CTLA4+anti-OX40+CpG in a single sub-cutaneous tumor eradicates disease in mice with established CNS lymphoma, even with leptomeningeal and spinal cord metastases, whereas chemotherapies or mAb therapy directed against the tumor cells have little effect in the CNS site. Moreover, these cured mice have a long term intra-cranial anti-tumor immunity since they are protected against late intra-cranial re-challenge. Significance: Immunomodulatory antibodies are currently under clinical development for cancer treatment, and their major side effect is the triggering of auto-immune diseases. We show here that injecting very little doses of these antibodies in combination with CpG at one tumor site is sufficient to trigger a systemic anti-tumor response able to eradicate distant sites, including in the CNS which is usually considered a sanctuary site for conventional systemic therapies. Impact: We recently have published positive results of intra-tumoral CpG in patients with follicular Lymphoma (Brody,Levy, et al. JCO, 2010). Anti-CTLA4 has just been FDA approved in patients with metastatic melanoma, and anti-Ox40 antibodies are currently being tested in phase I/II clinical trials. Therefore, the combination described here can be tested in patients with injectable sites of lymphoma, even if they have CNS disease. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.LBA-2.LBA-2
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
    Online Resource
    Online Resource
    A Phase 1 Study Evaluating BI 765063, a First in Class Selective Myeloid Sirpa Inhibitor, As Stand-Alone and in Combination with BI 754091, a Programmed Death-1 (PD-1) Inhibitor, in Patients with Advanced Solid Tumours
    American Society of Hematology ; 2019
    In:  Blood Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1040-1040
    Details
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 1040-1040
    Abstract: Introduction: Signal Regulatory Protein α [SIRPα] is a polymorphic protein, strongly expressed on myeloid suppressive cells. BI 765063 (OSE172), a humanized IgG4 monoclonal antibody (mAb), is a selective antagonist of SIRPα/CD47 interaction, it does not bind to SIRP ɣ, known to assist T cell co-stimulation and migration. BI 765063 strongly binds V1 allele, one of the 2 major functional allele of SIRPα expressed in more than 80% of general population and Asian (in 60%). Anti-tumor effect was shown in various in vivo cancer models using the validated anti-mouse SIRPα mAbs surrogate, as single agent. The effect was more pronounced in combination with T checkpoint inhibitors (Gauttier V et al, 2018). BI 765063 mechanism of action includes promotion of tumor-antigen-presentation while preserving T-cell activation and increase tumor phagocytosis. This first in human (FIH) study is aiming at evaluating the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of BI 765063 as monotherapy and in combination a mAb antagonist to PD-1 receptor (with BI 754091), in patients with advanced solid tumours. Methods: This study comprises a dose escalation (step 1) to determine the Dose-Limiting Toxicities, Maximum Tolerated Dose (MTD), and Recommended Phase 2 Dose (RP2Ds) of BI 765063 monotherapy and with BI 754091, and dose-confirmation expansion cohorts (step 2). In Step 1, ascending dose of BI 763063 once every 3 weeks intravenously (iv) using a Bayesian approach with overdose control are tested. When MTD determined, BI 763063 will be tested with BI 754091, a PD1 mAb inhibitor. In step 2, 2 parallel randomized, non-comparative mono and combination cohorts will further confirm the RP2Ds and assess the safety and preliminary efficacy (RECIST 1.1 and iRECIST). Patients ≥ 18 years, PS:0-1, with advanced solid tumor who failed or are not eligible to standard therapy will be included. V1/V1 and V1/V2 patients (central testing) are evaluated in separate cohorts in step 1. In step 2 selected population of V1/V1 patients with advanced-stage cancers (e.g. non-small cell lung cancer, triple negative breast cancer, or gastro-intestinal cancers) will be included. Pharmacokinetics (PK), SIRPα receptor occupancy (RO) and a comprehensive translational program (in blood and tumour) will assess PK/PD profile and biomarkers of activity. A total of 116 (56 in step 1 and 60 in step 2) patients will be enrolled. Results: This trial is currently in progress. Conclusions: The trial is currently active and plans to assess the safety profile and preliminary efficacy of BI 765063, a first in class myeloid check point inhibitor antagonist of SIRPα on myeloid cells. Disclosures Marabelle: Merck Serono: Honoraria, Speakers Bureau; Merus: Research Funding; Sotio: Honoraria; Imcheck: Honoraria; Bayer: Honoraria; GSK: Honoraria; Boehringer Ingelheim: Honoraria, Research Funding; Deerfield: Honoraria; Amgen: Honoraria, Speakers Bureau; Astra Zeneca/Medimmune: Honoraria, Other: Travel expenses, Speakers Bureau; Transgene: Honoraria, Research Funding; Corus: Honoraria; Imaxio: Honoraria; Bioncotech: Honoraria; Roche/Genentech: Honoraria, Other, Speakers Bureau; Servier: Honoraria; Daichii: Honoraria; BMS: Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; T3 Pharma: Honoraria; OSE Immunotherapeutics: Honoraria; MSD: Honoraria, Other, Research Funding, Speakers Bureau; Oncovir: Honoraria; Molecular Partners: Honoraria; Novartis: Honoraria; Genticel: Honoraria; System Analytics: Honoraria; Eisei: Honoraria; GLG: Honoraria; Pillar Partners: Honoraria; Sanofi: Honoraria, Speakers Bureau; Rigontel: Honoraria; BioNtech: Honoraria; Pierre Fabre: Honoraria; Innate Pharma: Honoraria; Edimark: Honoraria; Onxeo: Honoraria; Guide Point Global: Honoraria. Vinceneux:UBS: Consultancy. Champiat:Astra Zeneca: Honoraria, Research Funding; BMS: Honoraria, Research Funding; MSD: Honoraria, Research Funding; Sanofi: Research Funding; Boehringer Ingelheim: Research Funding; Amgen: Honoraria; Novartis: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Pfizer: Research Funding. Huhn:Boehringer Ingelheim Pharmaceuticals: Employment. Poirier:OSE Immunotherapeutics: Employment. Costantini:OSE Immunotherapeutics: Employment, Membership on an entity's Board of Directors or advisory committees. Vasseur:OSE Immunotherapeutics: Employment. Cassier:Blueprint Medecine: Honoraria, Research Funding; Celgene: Research Funding; Abbvie: Research Funding; Roche/Genentech: Honoraria, Other, Research Funding; Astra Zeneca: Research Funding; BMS: Other: Travel expenses, Research Funding; Innate Pharma: Research Funding; Plexxikon: Research Funding; Merck Sereno: Research Funding; Taiho Pharmaceuticals: Research Funding; Transgene: Research Funding; Toray industries: Honoraria; Janssen: Research Funding; MSD: Other: Travel expenses, Research Funding; Novartis: Honoraria, Other: travel expenses, Research Funding; Amgen: Honoraria, Other: travel expenses; Lilly: Research Funding; Bayer: Research Funding; Loxo: Research Funding; GSK: Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2019-124876
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
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  • 4
    Online Resource
    Online Resource
    Anti-KIR Antibody Enhancement Of Anti-Lymphoma Activity Of Natural Killer Cells As Monotherapy and In Combination With Anti-CD20 Antibodies
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 4417-4417
    Details
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 4417-4417
    Abstract: Natural killer (NK) cells mediate anti-lymphoma activity by spontaneous cytotoxicity and antibody-dependent cell-mediated cytotoxicity (ADCC) when triggered by rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B cell lymphomas. The balance of inhibitory and activating signals determines the magnitude of NK cell's efficacy by spontaneous cytoxicity. Using a killer cell immunoglobulin-like receptor (KIR) transgenic murine model, we show that blockade of the interface of inhibitory KIRs with MHC class I antigens on lymphoma by anti-KIR antibodies prevents a tolerogenic interaction and augments NK cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR treatment induces enhanced NK cell-mediated, rituximab-dependent cytotoxicity against lymphoma in vitro and in vivo in syngeneic and KIR transgenic murine lymphoma models. Specifically targeting murine NK cells in vitro, anti-Ly49C/I F(ab')2 increased anti-CD20 mAb-mediated NK cell degranulation as measured by CD107a mobilization and interferon-γ release, as well as increased cytotoxicity as assessed by chromium release. In the syngeneic EL4-huCD20 lymphoma model, anti-Ly49C/I F(ab')2 enhanced the anti-lymphoma activity of anti-CD20 mAb in vivo (Fig 1A-1B) and was NK cell-dependent with efficacy abrogated by NK cell depletion with anti-Asialo-GM1. To validate these observations and the potential efficacy of a fully human anti-KIR mAb (IPH2101, lirilumab), we demonstrated, in vitro, dose-dependent KIR2DL3 saturation and tumor lysis following blockade of KIR2DL3/HLA-C with lirilumab. In the transgenic KIR murine model, lirilumab therapy improved survival in an NK cell-dependent manner in both a prophylactic and therapeutic HLA+ (221 HLA-Cw3) lymphoma model. In combination, lirilumab therapy synergistically enhanced rituximab's anti-lymphoma efficacy in vivo in an NK cell-dependent manner (Fig 2A-C). These results support a therapeutic strategy of combination, rituximab and KIR blockade through lirilumab, illustrating the potential efficacy of combining a tumor targeting therapy with an NK cell agonist thus stimulating the post-rituximab anti-lymphoma immune response. Disclosures: Thielens: Innate Pharma: Employment, Equity Ownership. Sola:Innate Pharma: Employment, Equity Ownership. Chanuc:Innate Pharma: Employment, Equity Ownership. Fuseri:Innate Pharma: Employment. Bonnafous:Innate Pharma: Employment, Equity Ownership. Vivier:Innate Pharma: Membership on an entity’s Board of Directors or advisory committees. Romagne:Innate Pharma: Employment, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees. Andre:Innate-Pharma: Employment, Equity Ownership. Blery:Innate Pharma: Employment, Equity Ownership.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V122.21.4417.4417
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 5
    Online Resource
    Online Resource
    Local Treg Immunomodulation Cures Metastatic Lymphoma Including CNS Sites
    American Society of Hematology ; 2011
    In:  Blood Vol. 118, No. 21 ( 2011-11-18), p. LBA-2-LBA-2
    Details
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. LBA-2-LBA-2
    Abstract: Abstract LBA-2 Background: CD4+CD25+FOXP3+ regulatory T-cells (Tregs) protect cancers from the immune system. They express important functional molecules such as CTLA-4 and Ox40 on their surface. Anti-CTLA4 monoclonal antibody (mAb) is the first drug to improve survival of refractory metastatic melanoma. Its recent approval by the FDA/EMEA inaugurates a paradigm shift in cancer therapy where the immune system is targeted rather than the tumor itself. Scientific question: Does local immunomodulation of tumor specific Tregs trigger a systemic anti-tumor immune response and cure disseminated lymphoma? Results: The Tregs that infiltrate the tumor site preferentially express CTLA4 and OX40 compared to their counterparts in the blood and other lymphoid organs, both in mice and in humans. Upon injection of low doses of anti-CTLA4 and anti-OX40 together with CpG, a TLR-9 agonist, directly into the tumor, tumor-specific Tregs are depleted from the tumor-infiltrate. This immunomodulatory combination therapy triggers an anti-tumor immune response able to cure mice with established disseminated disease. The triple combination is uniquely required as neither CpG alone nor mAbs without CpG are effective. The local Treg immunomodulation with anti-CTLA4+anti-OX40+CpG in a single sub-cutaneous tumor eradicates disease in mice with established CNS lymphoma, even with leptomeningeal and spinal cord metastases, whereas chemotherapies or mAb therapy directed against the tumor cells have little effect in the CNS site. Moreover, these cured mice have a long term intra-cranial anti-tumor immunity since they are protected against late intra-cranial re-challenge. Significance: Immunomodulatory antibodies are currently under clinical development for cancer treatment, and their major side effect is the triggering of auto-immune diseases. We show here that injecting very little doses of these antibodies in combination with CpG at one tumor site is sufficient to trigger a systemic anti-tumor response able to eradicate distant sites, including in the CNS which is usually considered a sanctuary site for conventional systemic therapies. Impact: We recently have published positive results of intra-tumoral CpG in patients with follicular Lymphoma (Brody,Levy, et al. JCO, 2010). Anti-CTLA4 has just been FDA approved in patients with metastatic melanoma, and anti-Ox40 antibodies are currently being tested in phase I/II clinical trials. Therefore, the combination described here can be tested in patients with injectable sites of lymphoma, even if they have CNS disease. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V118.21.LBA-2.bld0076_P1_LBA-2
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
    Online Resource
    Online Resource
    Targeting B-Cell Lymphoma with Idiotype-Specific Peptibodies: Toward a Personalized and Tumor-Specific Therapy
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 3713-3713
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 3713-3713
    Abstract: Abstract 3713 Background: The complementarity determining region, or idiotype, of the surface immunoglobulin receptor is a tumor-specific marker on B-cell lymphomas that is unique to each patient. Antibodies against idiotype can induce complete regression of lymphoma in patients, but since this therapeutic approach requires the generation of a custom monoclonal antibody for each patient, it has not been practical. Objective: Here we describe a method for targeting the idiotype on the surface of a B-cell lymphoma by using synthetic idiotype-ligands covalently linked to a recombinant IgG Fc domain (Figure 1A). These peptide idiotype-ligands can be identified through oligopeptide library screens and produced inexpensively by automated solid-phase synthesis. Linkage of idiotype-ligands to the Fc domain serves two purposes: to enhance their pharmacokinetics and to augment their anti-tumor effect by activating immune effector functions. Since each patient-specific peptide can be chemically linked to a common IgG Fc domain, this modular construct design yields a patient-specific therapeutic that does not require the production of a custom biologic macromolecule for each patient. Results: Idiotype peptide-ligands were produced by solid-phase synthesis and covalently linked to the amino-terminus of a recombinant mouse IgG2a Fc domain by native chemical ligation, a method for site-selective polypeptide ligation. The resulting peptibody demonstrated targeted killing of a human lymphoma cell line in vitro by crosslinking surface immunoglobulin and triggering activation-induced death. Additionally, the peptibody triggered complement-mediated cytotoxicity of opsonized lymphoma cells in vitro and activated natural killer cells co-cultured with opsonized lymphoma cells. The peptibody exhibited a favorable pharmacokinetic profile and peptibody treatment was sufficient to clear tumor in SCID mice challenged intravenously with a luciferase-labeled human lymphoma cell line (p = 0.0018; Figure 1B-D). Conclusions: Idiotype-specific peptibodies demonstrate multimodal activity against lymphoma cells in vitro and clear human lymphoma in a disseminated xenograft model. The modular design of this therapeutic may enable a personalized and targeted therapy that is feasible to produce for patients with B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V120.21.3713.3713
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
    Online Resource
    Online Resource
    Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies
    American Society of Hematology ; 2014
    In:  Blood Vol. 123, No. 5 ( 2014-01-30), p. 678-686
    Details
    In: Blood, American Society of Hematology, Vol. 123, No. 5 ( 2014-01-30), p. 678-686
    Abstract: Blockade of inhibitory KIRs with MHC class I antigens on lymphoma cells by anti-KIR antibodies augments NK-cell spontaneous cytotoxicity. In combination with anti-CD20 mAbs, anti-KIR induces enhanced NK cell–mediated, rituximab-dependent cytotoxicity against lymphoma.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2013-08-519199
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2014
    detail.hit.zdb_id: 1468538-3
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  • 8
    Online Resource
    Online Resource
    Immunological Cytopenias Induced By Anti-Programmed Cell Death (ligand) 1 Antibodies
    American Society of Hematology ; 2018
    In:  Blood Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2412-2412
    Details
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2412-2412
    Abstract: Background. Anti-programmed death (ligand) 1 (PD-(L)1) antibodies are novel immunotherapies for cancer. Anti-PD(L)1 can induce immune-related adverse events (irAEs), which most frequently affect the skin, endocrine glands, lung, liver and digestive tract, however all organs including the hematopoietic system can potentially be involved. Hematologic irAEs (hem-irAEs) have not yet been extensively characterized. This study based on a pharmacovigilance academic registry aims to provide a comprehensive report of hem-irAEs. Patients and methods. All grade 2 or higher hem-irAEs recorded in pharmacovigilance databases were recorded in this study over the period 2013-2018. Pharmacovilance database included REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie) and ImmunoTOX committee of Gustave Roussy, and the French nationwide CeReCAI registry (Centre de Référence des Cytopénies Auto-Immunes de l'adulte). Prevalence of hem-irAE was calculated in the prospective REISAMIC registry. The hem-irAE's severity was assessed according to the Common Terminology Criteria for Adverse Events (version 4.03). Results. Thirty-five patients (21 men and 14 women) with hem-irAEs related to anti-PD(L)1s were recorded. The prevalence of grade ≥2 hem-irAEs among patients treated with anti-PD(L)1s was estimated to 0.54%. The patients' median age was 65 years (range: 30-90), tumor types were melanoma (n=15), non-small-cell lung carcinoma (n=12), lymphoma (n=4), and other types (n=4). A concomitant medical history of chronic lymphocytic leukemia was found in 3 (9%) patients. The hem-irAEs were classified as neutropenia (n=9; 26%), auto-immune hemolytic anemia (n=9; 26%), immune thrombocytopenia (IT) (n=9; 26%), pancytopenia or aplastic anemia (n=5; 14%), bicytopenia (n=2; 6%) and pure-red cell aplasia (n=1; 3%). The maximum grade of severity reported was grade 2 in 3 (9%) patients, grade 3 in 8 (23%) patients and grade 4 in 24 (69%) patients. Two patients (6%) had a poor outcome and died in the course of the hem-irAE. Treatments given for the hem-irAE were steroids in 31 (89%) patients, granulocyte colony-stimulating factor in 13 (37%) patients, intravenous immunoglobulins in 6 (17%) patients and rituximab in 2 (6%) patients. The median time to onset from anti-PD(L)1 initiation was 10.1 weeks (range 0.9 - 198.0). With a median follow-up of 19 (range 2-180) weeks, the rate of resolution of hem-irAE was 67% (78% for IT and 40% for aplastic anemia patients, p=0.524). After resolution, 6/35 (17%) patients were rechallenged and 3 of them (50%) recurred the same hem-irAE. Conclusion. The clinical spectrum of hematologic irAE is wide and dominated by neutropenia, hemolytic anemia and immune thrombocytopenia. Aplastic anemia is rarer and present as a life-threatening condition. The prevalence of grade ≥2 hematologic irAEs following anti-PD(L)1 was 0.54%. The recurrence rate after rechallenge was 50%. Further prospective investigations are warranted to better detect and manage hematologic immune-related adverse events. Disclosures Herbaux: Gilead Sciences, Inc.: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Maerevoet:abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; roche: Other: travel grant; takeda: Membership on an entity's Board of Directors or advisory committees, Other: travel grant; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Ribrag:Servier: Consultancy, Honoraria; Amgen: Research Funding; BMS: Consultancy, Honoraria, Other: travel; Incyte Corporation: Consultancy; Infinity: Consultancy, Honoraria; NanoString Technologies: Consultancy, Honoraria; MSD: Honoraria; Gilead: Consultancy, Honoraria; Roche: Honoraria, Other: travel; argenX: Research Funding; epizyme: Consultancy, Honoraria; pharmamar: Other: travel.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2018-99-110875
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
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    Combined targeted and immunotherapy: the future of personalized medicine
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 23 ( 2012-11-29), p. 4454-4455
    Details
    In: Blood, American Society of Hematology, Vol. 120, No. 23 ( 2012-11-29), p. 4454-4455
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2012-09-455105
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
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