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  1. Article: Checkpoint inhibition in hematologic malignancies.

    Tsumura, Aaron / Levis, Daniel / Tuscano, Joseph M

    Frontiers in oncology

    2023  Volume 13, Page(s) 1288172

    Abstract: Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint ... ...

    Abstract Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings. Checkpoint inhibition also appears to have a role as a synergistic agent to augment clinical responses to other forms of therapy such as hematopoietic stem cell transplant. Moreover, alternative checkpoint molecules that bypass the well-studied CTLA-4 and PD-1/PD-L1 pathways have emerged as exciting new therapeutic targets. Most excitingly is the use of anti-CD47 blockade in the treatment of high risk MDS and TP-53 mutated AML. Overall, there has been tremendous progress in understanding the benefits of checkpoint inhibition in hematologic malignancies, but further studies are needed in all areas to best utilize these agents. This is a review of the most recent developments and progress in Immune Checkpoint Inhibition in Hematologic Malignancies in the last decade.
    Language English
    Publishing date 2023-10-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2023.1288172
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: A phase II trial of decitabine, bortezomib and pegylated liposomal doxorubicin for the treatment of relapsed or refractory AML.

    Jonas, Brian A / Potter, Laura A / Galkin, Maria / Tuscano, Joseph M

    Leukemia research reports

    2023  Volume 19, Page(s) 100374

    Language English
    Publishing date 2023-06-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2706248-X
    ISSN 2213-0489
    ISSN 2213-0489
    DOI 10.1016/j.lrr.2023.100374
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: A Novel bispecific T-cell engager (BiTE) targeting CD22 and CD3 has both in vitro and in vivo activity and synergizes with blinatumomab in an acute lymphoblastic leukemia (ALL) tumor model.

    Meckler, Joshua F / Levis, Daniel J / Vang, Daniel P / Tuscano, Joseph M

    Cancer immunology, immunotherapy : CII

    2023  Volume 72, Issue 9, Page(s) 2939–2948

    Abstract: Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. ... ...

    Abstract Immunotherapy has revolutionized cancer therapy. Two recently FDA-approved immunotherapies for B-cell malignancies target CD19, in the form of a Bispecific T-Cell Engager (BiTE) antibody construct or chimeric antigen receptor T (CAR-T) cells. Blinatumomab, an FDA-approved BiTE, binds to CD19 on B cells and to CD3 on T cells, mediating effector-target cell contact and T-cell activation that results in effective elimination of target B cells. Although CD19 is expressed by essentially all B-cell malignancies at clinical presentation, relapses with loss or reduction in CD19 surface expression are increasingly recognized as a cause of treatment failure. Therefore, there is a clear need to develop therapeutics for alternate targets. We have developed a novel BiTE consisting of humanized anti-CD22 and anti-CD3 single chain variable fragments. Target binding of the anti-CD22 and anti-CD3 moieties was confirmed by flow cytometry. CD22-BiTE promoted in vitro cell-mediated cytotoxicity in a dose and effector: target (E:T)-dependent fashion. Additionally, in an established acute lymphoblastic leukemia (ALL) xenograft mouse model, CD22-BiTE demonstrated tumor growth inhibition, comparable to blinatumomab. Further, the combination of blinatumomab and CD22-BiTE yielded increased efficacy in vivo when compared to the single agents. In conclusion, we report here the development of a new BiTE with cytotoxic activity against CD22
    MeSH term(s) Humans ; Animals ; Mice ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Antineoplastic Agents/therapeutic use ; T-Lymphocytes ; Antibodies, Bispecific/pharmacology ; Antibodies, Bispecific/therapeutic use ; Antigens, CD19
    Chemical Substances blinatumomab (4FR53SIF3A) ; Antineoplastic Agents ; Antibodies, Bispecific ; Antigens, CD19
    Language English
    Publishing date 2023-05-29
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 195342-4
    ISSN 1432-0851 ; 0340-7004
    ISSN (online) 1432-0851
    ISSN 0340-7004
    DOI 10.1007/s00262-023-03444-0
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  4. Article ; Online: Phase I trial of the combination of ibrutinib and lenalidomide of the treatment of patients with MDS who have failed standard therapy or who are unfit for or refuse standard therapy.

    Fisch, Samantha C / Tuscano, Joseph M / Qi, Lihong / Jonas, Brian A

    Leukemia research

    2022  Volume 122, Page(s) 106947

    MeSH term(s) Humans ; Lenalidomide ; Piperidines ; Adenine ; Chromosome Deletion
    Chemical Substances Lenalidomide (F0P408N6V4) ; ibrutinib (1X70OSD4VX) ; Piperidines ; Adenine (JAC85A2161)
    Language English
    Publishing date 2022-09-06
    Publishing country England
    Document type Clinical Trial, Phase I ; Letter
    ZDB-ID 752396-8
    ISSN 1873-5835 ; 0145-2126
    ISSN (online) 1873-5835
    ISSN 0145-2126
    DOI 10.1016/j.leukres.2022.106947
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A Fermented Wheat Germ Extract Contains Protein Components Active against NSCLC Xenografts In Vivo.

    Levis, Daniel J / Meckler, Joshua F / O'Donnell, Robert T / Tuscano, Joseph M

    Current issues in molecular biology

    2023  Volume 45, Issue 9, Page(s) 7087–7096

    Abstract: Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due ... ...

    Abstract Non-small cell lung cancer (NSCLC) continues to be the leading cause of cancer-related deaths. Although advances have been made in the past decade to treat such tumors, most options induce multiple side effects, and many patients discontinue therapy due to toxicity. Thus, the need remains for non-toxic, effective NSCLC therapies, especially in an elderly patient population. Our lab has previously identified a protein fraction from the nutraceutical Avemar
    Language English
    Publishing date 2023-08-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2000024-8
    ISSN 1467-3045 ; 1467-3037
    ISSN (online) 1467-3045
    ISSN 1467-3037
    DOI 10.3390/cimb45090448
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  6. Article: Multiple myeloma: epidemiology and therapeutic options.

    Tuscano, Joseph M

    Managed care (Langhorne, Pa.)

    2008  Volume 17, Issue 7 Suppl 6, Page(s) 9–15

    Abstract: Myeloma remains an incurable disease, but its management has significantly improved with the introduction of novel treatment agents. Variations in both disease manifestation and patient response to treatment have personalized approaches to care. ...

    Abstract Myeloma remains an incurable disease, but its management has significantly improved with the introduction of novel treatment agents. Variations in both disease manifestation and patient response to treatment have personalized approaches to care.
    MeSH term(s) Age Factors ; Antineoplastic Combined Chemotherapy Protocols ; Chronic Disease ; Dexamethasone/administration & dosage ; Hematopoietic Stem Cell Transplantation ; Humans ; Medical Oncology/trends ; Multiple Myeloma/diagnosis ; Multiple Myeloma/drug therapy ; Multiple Myeloma/epidemiology ; Multiple Myeloma/therapy ; Patient Care Management ; Prognosis ; Thalidomide/administration & dosage ; Thalidomide/analogs & derivatives
    Chemical Substances Thalidomide (4Z8R6ORS6L) ; Dexamethasone (7S5I7G3JQL) ; lenalidomide (F0P408N6V4)
    Language English
    Publishing date 2008-07
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Review
    ZDB-ID 2220044-7
    ISSN 1062-3388
    ISSN 1062-3388
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Adverse health effects of marijuana use.

    Thompson, George R / Tuscano, Joseph M

    The New England journal of medicine

    2014  Volume 371, Issue 9, Page(s) 878–879

    MeSH term(s) Cannabinoids/therapeutic use ; Humans ; Marijuana Smoking/adverse effects
    Chemical Substances Cannabinoids
    Language English
    Publishing date 2014-08-28
    Publishing country United States
    Document type Comment ; Letter
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc1407928#SA2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Outcomes of Adults With Relapsed/Refractory Acute Myeloid Leukemia Treated With Venetoclax Plus Hypomethylating Agents at a Comprehensive Cancer Center.

    Tenold, Matthew E / Moskoff, Benjamin N / Benjamin, David J / Hoeg, Rasmus T / Rosenberg, Aaron S / Abedi, Mehrdad / Tuscano, Joseph M / Jonas, Brian A

    Frontiers in oncology

    2021  Volume 11, Page(s) 649209

    Abstract: Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using ... ...

    Abstract Relapsed/refractory acute myeloid leukemia (AML) is a devastating disease with a poor prognosis and represents a major unmet medical need. We report on a real-world academic center experience of treating 25 patients with relapsed/refractory AML using venetoclax in combination with decitabine or azacitidine, which is not otherwise widely evaluated in the current literature. Our patients come from a large, socioeconomically and geographically diverse area including the majority of Northern California. Most had ELN Adverse Risk (52%) or Intermediate Risk (44%) AML, and most had an ECOG Performance Status of 1 (64%). Over half (52%) had prior hypomethylating agent exposure, and 40% had Secondary AML. We observed an overall response rate of 52%, with eight patients (32%) achieving composite complete remission. Median overall survival was 5.5 months, and for patients achieving composite complete remission this was 21.6 months. One-year estimated overall survival was 38%. Three patients were able to proceed directly to stem cell transplant for consolidation, and all three were alive at last follow-up, ranging 13.8-24.0 months. We found venetoclax in combination with hypomethylating agents to be well tolerated and potentially efficacious in securing long-term remissions for patients with relapsed/refractory AML.
    Language English
    Publishing date 2021-03-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.649209
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  9. Article ; Online: Retrospective Analysis of Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia Treated with FLAG at a Comprehensive Cancer Center.

    Tenold, Matthew E / Moskoff, Benjamin N / Krishnan, Rajeev / Rosenberg, Aaron S / Hoeg, Rasmus T / Abedi, Mehrdad / Tuscano, Joseph M / Jonas, Brian A

    Clinical lymphoma, myeloma & leukemia

    2021  Volume 21, Issue 7, Page(s) e611–e618

    Abstract: Background: FLAG ± Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), is a salvage chemotherapy regimen for relapsed or refractory (R/R) acute myeloid leukemia (AML), with complete remission (CR) rates historically ... ...

    Abstract Background: FLAG ± Ida (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin), is a salvage chemotherapy regimen for relapsed or refractory (R/R) acute myeloid leukemia (AML), with complete remission (CR) rates historically ranging from 52% to 63%. We review the outcomes for patients with R/R AML treated with FLAG ± Ida at the University of California Davis Comprehensive Cancer Center.
    Patients and methods: Adult patients (≥ 18 years) with R/R AML who received FLAG or FLAG + Ida from January 1, 2012 to October 31, 2016 were identified via chart review. Outcomes evaluated were CR, CR with incomplete hematologic recovery (CRi), overall response rate, overall survival (OS), relapse-free survival, and adverse events.
    Results: Forty-two patients were included. The median age was 52 years (range, 23-73 years), and 57% were male. Sixteen (38.1%) patients had relapsed disease, and 26 (61.9%) had refractory disease. Most (n = 35; 83.3%) patients had European LeukemiaNet intermediate-risk AML. Responses were CR in 20 (47.6%) and CRi in 6 (14.3%). The median OS was 10 months (range, 0.8-51 months), and the median relapse-free survival was 12 months (range, 1-51 months) for responders. The median OS for patients who achieved CR was not reached, and the estimated 48-month survival rate was 56%. The median OS after CRi or no response was 3.47 and 2.17 months, respectively. The median OS was not significantly different when censored for stem cell transplant following chemotherapy, nor with use/deferral of idarubicin. The most common adverse effects were pancytopenia and infection.
    Conclusion: Patient outcomes after treatment with FLAG ± Ida for R/R AML remain similar to prior reports, confirming its role as a salvage regimen for these patients.
    MeSH term(s) Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Cancer Care Facilities/statistics & numerical data ; Cytarabine/administration & dosage ; Cytarabine/adverse effects ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Female ; Granulocyte Colony-Stimulating Factor/administration & dosage ; Granulocyte Colony-Stimulating Factor/adverse effects ; Hematopoietic Stem Cell Transplantation/statistics & numerical data ; Humans ; Idarubicin/administration & dosage ; Idarubicin/adverse effects ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/pathology ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Neoplasm Recurrence, Local/mortality ; Neoplasm Recurrence, Local/pathology ; Neoplasm Recurrence, Local/therapy ; Pancytopenia/chemically induced ; Pancytopenia/epidemiology ; Retrospective Studies ; Salvage Therapy/methods ; Salvage Therapy/statistics & numerical data ; Survival Rate ; Vidarabine/administration & dosage ; Vidarabine/adverse effects ; Vidarabine/analogs & derivatives ; Young Adult
    Chemical Substances Cytarabine (04079A1RDZ) ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Vidarabine (FA2DM6879K) ; Idarubicin (ZRP63D75JW)
    Language English
    Publishing date 2021-03-02
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2540992-X
    ISSN 2152-2669 ; 2152-2650
    ISSN (online) 2152-2669
    ISSN 2152-2650
    DOI 10.1016/j.clml.2021.02.007
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  10. Article ; Online: Phase I study of escalating doses of carfilzomib with HyperCVAD in patients with newly diagnosed acute lymphoblastic leukemia.

    Jonas, Brian A / Fisch, Samantha C / Rosenberg, Aaron S / Hoeg, Rasmus T / Tuscano, Joseph M / Abedi, Mehrdad

    American journal of hematology

    2021  Volume 96, Issue 4, Page(s) E114–E117

    MeSH term(s) Adult ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/administration & dosage ; Cyclophosphamide/adverse effects ; Dexamethasone/administration & dosage ; Dexamethasone/adverse effects ; Doxorubicin/administration & dosage ; Doxorubicin/adverse effects ; Female ; Hematologic Diseases/chemically induced ; Humans ; Hypocalcemia/chemically induced ; Hyponatremia/chemically induced ; Male ; Middle Aged ; Neoplasm, Residual ; Oligopeptides/administration & dosage ; Oligopeptides/adverse effects ; Peripheral Nervous System Diseases/chemically induced ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology ; Rituximab/administration & dosage ; Treatment Outcome ; Vincristine/administration & dosage ; Vincristine/adverse effects ; Young Adult
    Chemical Substances Oligopeptides ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; carfilzomib (72X6E3J5AR) ; Dexamethasone (7S5I7G3JQL) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P)
    Language English
    Publishing date 2021-02-26
    Publishing country United States
    Document type Clinical Trial, Phase I ; Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 196767-8
    ISSN 1096-8652 ; 0361-8609
    ISSN (online) 1096-8652
    ISSN 0361-8609
    DOI 10.1002/ajh.26105
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