Safety considerations with targeted therapy drugs for B-cell non-Hodgkin lymphoma

ABSTRACT

Introduction

B-cell non-Hodgkin lymphomas (B-NHLs) are the most frequent hematologic malignant cancers. Molecular targeted therapy is an important aspect of B-NHL treatment alongside cytotoxic chemotherapy, radiotherapy, and immunotherapy.

Areas covered

Molecular targeted therapies have changed the landscape of treatment strategies for B-NHLs since the approval of rituximab, an anti-CD20 monoclonal antibody, by the US Food and Drug Administration in 1997. Currently, several targeted therapies have been approved or are in the later-phase of clinical trials including naked antibodies, antibody-drug conjugates, and small molecules, such as Bruton’s tyrosine kinase (BTK) inhibitors, phosphatidylinositol 3-kinase (PI3 K) inhibitors, enhancer of zeste homolog 2 (EZH2) inhibitors, and B-cell lymphoma 2 (Bcl-2) inhibitors. These drugs have various toxicities because of their unique mechanisms of action. In this review, the available toxicity data of the targeted therapies for B-NHLs have been summarized.

Expert opinion

Recent clinical developments of targeted therapies for B-NHLs have provided several useful effective therapeutic options for patients. However, there are unique toxicities that need to be resolved. It is necessary to find out the toxicity mechanism; optimal treatment strategy for these toxicities; and novel targeted therapies that might potentially overcome the toxicities of previously approved targeted therapies.

KEYWORDS:

• Polatuzumab vedotin
• ibrutinib
• acalabrutinib
• tirabrutinib
• zanubrutinib
• idelalisib
• duvelisib
• copanlisib
• tazemetostat
• venetoclax

Article highlights

• Molecular targeted therapy is an important B-cell non-Hodgkin lymphoma (B-NHL) treatment along with cytotoxic chemotherapy, radiotherapy, and immunotherapy.

• Antibody-drug conjugates, Bruton’s tyrosine kinase (BTK) inhibitors, phosphatidylinositol 3-kinase (PI3K) inhibitors, enhancer of zeste homolog 2 (EZH2) inhibitor, and B-cell lymphoma 2 (Bcl-2) inhibitor have been approved or are actively being developed in the later-phase of clinical trials.

• These drugs have various toxicities that are completely different from those of conventional cytotoxic chemotherapies because of their unique mechanism of action.

• Several novel targeted therapies are actively being developed and might potentially overcome the toxicities of previously approved targeted therapies.

This box summarizes key points contained in the article.

Acknowledgments

The authors sincerely thank the patients, their families, and all the health-care workers involved in lymphoma care at the National Cancer Center Hospital.

Declaration of interest

S Makita has received honoraria from Celgene, Chugai Pharma, Daiichi-Sankyo, Eisai, Novartis, and Takeda. K Tobinai has received honoraria from Zenyaku Kogyo, Eisai, Takeda, Mundipharma, HUYA Bioscience International, Kyowa Hakko Kirin, Celgene, Chugai Pharma, Ono Pharmaceutical, Yakult, Daiichi-Sankyo, and Solasia Pharma; and plays a consulting/advisory role for Celgene, Zenyaku Kogyo, HUYA Bioscience International, Daiichi-Sankyo, Takeda, Mundipharma, and Ono Pharmaceutical. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a co-author of the registration studies of ibrutinib, acalabrutinib, zanubrutinib, idelalisib, and venetoclax. All other peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.