Novel immunotherapies in lymphoid malignancies Journal Article


Authors: Batlevi, C. L.; Matsuki, E.; Brentjens, R. J.; Younes, A.
Article Title: Novel immunotherapies in lymphoid malignancies
Abstract: The success of the anti-CD20 monoclonal antibody rituximab in the treatment of lymphoid malignancies provided proof-of-principle for exploiting the immune system therapeutically. Since the FDA approval of rituximab in 1997, several novel strategies that harness the ability of T cells to target cancer cells have emerged. Reflecting on the promising clinical efficacy of these novel immunotherapy approaches, the FDA has recently granted 'breakthrough' designation to three novel treatments with distinct mechanisms. First, chimeric antigen receptor (CAR)-T-cell therapy is promising for the treatment of adult and paediatric relapsed and/or refractory acute lymphoblastic leukaemia (ALL). Second, blinatumomab, a bispecific T-cell engager (BiTE ®) antibody, is now approved for the treatment of adults with Philadelphia-chromosome-negative relapsed and/or refractory B-precursor ALL. Finally, the monoclonal antibody nivolumab, which targets the PD-1 immune-checkpoint receptor with high affinity, is used for the treatment of Hodgkin lymphoma following treatment failure with autologous-stem-cell transplantation and brentuximab vedotin. Herein, we review the background and development of these three distinct immunotherapy platforms, address the scientific advances in understanding the mechanism of action of each therapy, and assess the current clinical knowledge of their efficacy and safety. We also discuss future strategies to improve these immunotherapies through enhanced engineering, biomarker selection, and mechanism-based combination regimens. © 2015 Macmillan Publishers Limited. All rights reserved.
Keywords: cancer survival; event free survival; treatment failure; overall survival; fludarabine; prednisone; fatigue; neutropenia; review; hepatitis; doxorubicin; drug dose reduction; drug efficacy; drug safety; drug withdrawal; unspecified side effect; drug targeting; cytarabine; rituximab; neurotoxicity; antigen expression; interleukin 2; ipilimumab; cancer immunotherapy; progression free survival; infection; multiple cycle treatment; anemia; cell infiltration; etoposide; leukopenia; lung disease; thrombocytopenia; bendamustine; cyclophosphamide; dexamethasone; immunoglobulin; melphalan; steroid; vincristine; autologous stem cell transplantation; kidney failure; continuous infusion; carmustine; acute lymphoblastic leukemia; hodgkin disease; drug dose escalation; febrile neutropenia; fever; pneumonia; rash; hypoxia; hypokalemia; hypotension; hematologic malignancy; nonhodgkin lymphoma; genetic engineering; minimal residual disease; cytotoxic t lymphocyte; drug response; graft versus host reaction; brain disease; mental disease; sepsis; chimeric antigen receptor; donor lymphocyte infusion; cell therapy; colitis; electroporation; autoimmunity; lymphoproliferative disease; seizure; headache; large cell lymphoma; maximum tolerated dose; lymphatic leukemia; drug half life; hypothyroidism; aphasia; t cell depletion; leukemia relapse; drug treatment failure; joint swelling; chronic lymphatic leukemia; immunoglobulin deficiency; tremor; ataxia; follicular lymphoma; t lymphocyte activation; lymphocyte depletion; immunopathology; clofarabine; tachycardia; pentostatin; peripheral blood mononuclear cell; transposon; pre b lymphocyte; opportunistic infection; adult respiratory distress syndrome; respiratory distress syndrome; recurrence free survival; programmed death 1 ligand 1; central nervous system disease; tumor microenvironment; myeloid leukemia; central nervous system infection; lymphatic system disease; disorientation; hypophysitis; thyroiditis; capillary leak syndrome; cytokine release syndrome; lymphocytosis; antibody combining site; aplasia; tocilizumab; consolidation chemotherapy; brentuximab vedotin; blinatumomab; nivolumab; pidilizumab; urelumab; human; priority journal; checkpoint kinase inhibitor; pembrolizumab; macrophage activation syndrome
Journal Title: Nature Reviews Clinical Oncology
Volume: 13
Issue: 1
ISSN: 1759-4774
Publisher: Nature Publishing Group  
Date Published: 2016-01-01
Start Page: 25
End Page: 40
Language: English
DOI: 10.1038/nrclinonc.2015.187
PROVIDER: scopus
PUBMED: 26525683
PMCID: PMC4916838
DOI/URL:
Notes: Review -- Export Date: 3 February 2016 -- Source: Scopus
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MSK Authors
  1. Renier J Brentjens
    237 Brentjens
  2. Connie Wing-Ching Lee
    73 Lee
  3. Anas Younes
    250 Younes