Systemic virotherapy for multiple myeloma

ABSTRACT

Introduction: The multiple myeloma (MM) treatment scenario has changed considerably over the past few years. Several novel targeted therapies are currently under consideration including oncolytic virotherapy.

Areas covered: This review provides an analysis of the mechanisms of action of virotherapy, and summarizes the preclinical and clinical studies of systemic virotherapy developed for the treatment of MM. Different types of viruses have been identified, including: adenovirus, vaccinia virus, herpes simplex virus 1, myxoma virus, reovirus, measles virus, vesicular stomatitis virus and coxsackievirus A21.

Expert opinion: The above-mentioned viruses can do more than simply infect and kill malignant plasma cells alone or in combination with chemo and/or radiotherapy. In fact, some of them can also be used to purge myeloma cells from an autologous bone marrow (BM) transplant. Further investigations are required to better explore the best therapeutic combinations for MM and to also overcome antiviral response immunity that can limit the efficacy of this therapeutic strategy.

KEYWORDS:

• Multiple myeloma
• oncolytic viruses
• virotherapy
• treatment

Article highlights

• Oncolytic virotherapy represents a promising therapeutic approach for Multiple Myeloma exploiting naturally or genetically engineered viruses able to infect, transduce and consequently kill myeloma cells.

• OVs can mediate antitumor activity through the direct infection and lysis of tumor cells, exploiting the presence of signaling pathways or targeted molecules aberrant in cancer cells, and induction of systemic antitumor immunity.

• Several preclinical and some clinical studies have tested, or are currently assessing, DNA and RNA oncolytic viruses agents alone or in combination with chemo- and/or radiotherapy, and as purging agents in MM patients.

• To date, reovirus and MV have demonstrated a deeper activity in myeloma cells both in preclinical and clinical trials.

• Synergistic potential strategies with OVs and immunomodulatory drugs can increase cytolytic activities in MM cells. The combination with ICIs, adoptive cell therapies and other immune-modulating strategies is an effective option in the MM treatment armamentarium.

This box summarizes key points contained in the article.

Declaration of interest

S Oliva has received honoraria from Takeda, Amgen Inc. and Celgene. Furthermore, M Boccadoro has received honoraria from Sanofi, Celgene, Amgen Inc, Janssen Pharmaceuticals, Novartis, AbbVie and Bristol-Myers Squibb, while they have also received research funding from Celgene, Janssen Pharmaceuticals, Amgen Inc, Bristol-Myers Squibb, Mundipharma, Novartis and Sanofi. Finally, S Bringhen has received honoraria from Celgene and Janssen-Cilag in addition to acting as a consultant for Onyx. S Bringhen is also on the advisory board of Mundipharma. 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 apart from those disclosed.

Additional information

Funding

This manuscript was not funded.