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  • Review Article
  • Published:

The landscape of new drugs in lymphoma

Nature Reviews Clinical Oncology volume 14, pages 335–346 (2017)Cite this article

Subjects

Key Points

  • The availability of novel small-molecule inhibitors and immunotherapies has changed the landscape of drug development in lymphoma

  • The most effective small-molecule inhibitors target B-cell-receptor signalling, PI3K signalling, and the BCL2 protein

  • Multiple immunotherapy platforms have demonstrated promising clinical activity, including immune-checkpoint inhibitors, CAR T cells, and bispecific antibodies

  • Many companies are developing similar drugs, which inhibit the same target, necessitating a more focused drug development strategy, with prioritization of clinical investigations

  • Owing to the high number of drugs in development, the potential number of drug combinations is becoming unmanageable; prioritization should focus on mechanism-based combinations that are potentially safer and more effective

Abstract

The landscape of drugs for the treatment of lymphoma has become crowded in light of the plethora of new agents, necessitating the efficient prioritization of drugs for expedited development. The number of drugs available, and the fact that many can be given for an extended period of time, has resulted in the emergence of new challenges; these include determining the optimal duration of therapy, and the need to balance costs, benefits, and the risk of late-onset toxicities. Moreover, with the increase in the number of available investigational drugs, the number of possible combinations is becoming overwhelming, which necessitates prioritization plans for the selective development of novel combination regimens. In this Review, we describe the most-promising agents in clinical development for the treatment of lymphoma, and provide expert opinion on new strategies that might enable more streamlined drug development. We also address new approaches for patient selection and for incorporating new end points into clinical trials.

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Figure 1: Therapeutic targeting of the B-cell receptor (BCR) signalling pathway in patients with lymphoma.
Figure 2: Therapeutic targeting of the PI3K/AKT/mTOR pathway.
Figure 3: Therapeutic induction of cell death through targeting of the mitochondrial apoptosis pathway.
Figure 4: Autologous T-cell activation strategies.
Figure 5: A representative high-throughput screening experiment involving drug combinations with the BET inhibitor JQ1.

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Author information

Authors and Affiliations

  1. Lymphoma Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, New York, USA

    Anas Younes

  2. Division of Haematology, Mayo Clinic, 200 1st St Sw, Rochester, 55905, Minnesota, USA

    Stephen Ansell

  3. Department of Lymphoma and Myeloma, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, 77030, Texas, USA

    Nathan Fowler

  4. Lymphoid Malignancies Branch, National Cancer Institute, 9000 Rockville Pike, Bethesda, 20892, MD, USA

    Wyndham Wilson

  5. Department of Medicine, Ronald Reagan UCLA Medical Center, Santa Monica, 90404, California, USA

    Sven de Vos

  6. Department of Haematology, Peter MacCallum Cancer Centre, A'Beckett Street, East Melbourne, 8006, Victoria, Australia

    John Seymour

  7. Division of Oncology, Stanford University Cancer Center, 875 Blake Wilbur Drive, Stanford, 94305, California, USA

    Ranjana Advani

  8. Division of Haematology and Oncology, University of Alabama School of Medicine, 1720 2nd Avenue South, NP2540, Birmingham, 35294–3300, Alabama, USA

    Andres Forero

  9. Department of Haematology, Hôpital Claude Huriez, F-59037, Lille, France

    Franck Morschhauser

  10. Department of Haematology, Academic Medical Center and LYMMCARE, Amsterdam, Netherlands

    Marie Jose Kersten

  11. Haematology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, 104–0045, Tokyo, Japan

    Kensei Tobinai

  12. Institute of Haematology “L. e A. Seràgnoli,” University of Bologna, Via Massarenti, 9–40138, Bologna, Italy

    Pier Luigi Zinzani

  13. Oncology Institute of Southern Switzerland, Ospedale San Giovanni, 6500, Bellinzona, Switzerland

    Emanuele Zucca

  14. Massachusetts General Hospital Cancer Center, Yawkey Center for Outpatient Care, Mailstop: Yawkey 9A, 32 Fruit Street, Boston, 02114, Massachusetts, USA

    Jeremy Abramson

  15. UNMC Oncology/Haematology Division, 987680 Nebraska Medical Center, Omaha, 681980–7680, Nebraska, USA

    Julie Vose

Authors
  1. Anas Younes
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  2. Stephen Ansell
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  3. Nathan Fowler
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  4. Wyndham Wilson
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  5. Sven de Vos
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  6. John Seymour
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  7. Ranjana Advani
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  8. Andres Forero
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  9. Franck Morschhauser
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  10. Marie Jose Kersten
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  11. Kensei Tobinai
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  12. Pier Luigi Zinzani
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  13. Emanuele Zucca
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  14. Jeremy Abramson
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  15. Julie Vose
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Contributions

All authors researched data for article, contributed to discussion of the content, wrote the manuscript and reviewed/edited the article before submission.

Corresponding author

Correspondence to Anas Younes.

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Competing interests

A.Y. receives honouraria and/or consults for Abbvie, Bayer, BMS, Celgene, Gilead, Incyte, Janssen R&D, Sanofi, Seattle Genetics, Merck, and Takeda Millenium, and research support from the John and Barbara Vogelstein Foundation. The other authors declare no competing interests.

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Younes, A., Ansell, S., Fowler, N. et al. The landscape of new drugs in lymphoma. Nat Rev Clin Oncol 14, 335–346 (2017). https://doi.org/10.1038/nrclinonc.2016.205

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