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Immunotherapy strategies for multiple myeloma: the present and the future.

ABSTRACT: Growing knowledge of the complexities of the immune system have led to a better understanding of how it can be harnessed for the purpose of anticancer therapy. Moreover, recent success with immunotherapies for solid tumors, combined with novel therapeutic strategies against myeloma, heighten excitement at the prospect of improving clinical outcomes for myeloma by improving antitumor immunity. Increased understanding of myeloma tumor-associated antigens, availability of more potent vaccines, expanded immune-modulating therapies, development of agents that block immune-suppressive pathways, increased sophistication of adoptive cell therapy techniques and capitalization upon standard autologous transplant are all important standalone or combination strategies that might ultimately improve prognosis of patients with multiple myeloma.

SUBMITTER: Locke FL

PROVIDER: S-EPMC4905571 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Immunotherapy strategies for multiple myeloma: the present and the future.

Locke Frederick L FL Nishihori Taiga T Alsina Melissa M Kharfan-Dabaja Mohamed A MA

Immunotherapy 20130901 9

Growing knowledge of the complexities of the immune system have led to a better understanding of how it can be harnessed for the purpose of anticancer therapy. Moreover, recent success with immunotherapies for solid tumors, combined with novel therapeutic strategies against myeloma, heighten excitement at the prospect of improving clinical outcomes for myeloma by improving antitumor immunity. Increased understanding of myeloma tumor-associated antigens, availability of more potent vaccines, expa ...[more]

PMID: 23998734

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Project description:Simple Summary Multiple myeloma is the second most common hematological malignancy and while patients can have long responses to therapy, most patients will eventually develop treatment-resistant disease. Over the last thirty years, improved understanding of multiple myeloma and therapeutic advancements have dramatically improved outcomes for patients. Recently, advances in immunotherapy have revolutionized standard-of-care therapies and provided therapeutic options for patients with heavily pretreated, relapsed refractory multiple myeloma. Immunotherapy is a rapidly evolving field, and this review encompasses the immunotherapies that are currently used to treat myeloma patients as well as recent advances that are poised to advance myeloma therapeutics in the coming years. Abstract Multiple myeloma is an incurable disease of malignant plasma cells and an ideal target for modern immune therapy. The unique plasma cell biology maintained in multiple myeloma, coupled with its hematological nature and unique bone marrow microenvironment, provide an opportunity to design specifically targeted immunotherapies that selectively kill transformed cells with limited on-target off-tumor effects. Broadly defined, immune therapy is the utilization of the immune system and immune agents to treat a disease. In the context of multiple myeloma, immune therapy can be subdivided into four main categories: immune modulatory imide drugs, targeted antibodies, adoptive cell transfer therapies, and vaccines. In recent years, advances in all four of these categories have led to improved therapies with enhanced antitumor activity and specificity. In IMiDs, modified chemical structures have been developed that improve drug potency while reducing dose limiting side effects. Targeted antibody therapies have resulted from the development of new selectively expressed targets as well as the development of antibody drug conjugates and bispecific antibodies. Adoptive cell therapies, particularly CAR-T therapies, have been enhanced through improvements in the manufacturing process, as well as through the development of CAR constructs that enhance CAR-T activation and provide protection from a suppressive immune microenvironment. This review will first cover in-class breakthrough therapies for each of these categories, as well as therapies currently utilized in the clinic. Additionally, this review will explore up and coming therapeutics in the preclinical and clinical trial stage.

Project description:Although classical Hodgkin lymphoma (cHL) is usually curable, 20-30% of the patients experience treatment failure and most of them are typically treated with salvage chemotherapy and autologous stem cell transplantation (autoSCT). However, 45-55% of that subset further relapse or progress despite intensive treatment. At the advanced stage of the disease course, recently developed immunotherapeutic approaches have provided very promising results with prolonged remissions or disease stabilization in many patients. Brentuximab vedotin (BV) has been approved for patients with relapsed/refractory cHL (rr-cHL) who have failed autoSCT, as a consolidation after autoSCT in high-risk patients, as well as for patients who are ineligible for autoSCT or multiagent chemotherapy who have failed ≥ two treatment lines. However, except of the consolidation setting, 90-95% of the patients will progress and require further treatment. In this clinical setting, immune checkpoint inhibitors (CPIs) have produced impressive results. Both nivolumab and pembrolizumab have been approved for rr-cHL after autoSCT and BV failure, while pembrolizumab has also been licensed for transplant ineligible patients after BV failure. Other CPIs, sintilimab and tislelizumab, have been successfully tested in China, albeit in less heavily pretreated populations. Recent data suggest that the efficacy of CPIs may be augmented by hypomethylating agents, such as decitabine. As a result of their success in heavily pretreated disease, BV and CPIs are moving to earlier lines of treatment. BV was recently licensed by the FDA for the first-line treatment of stage III/IV Hodgkin lymphoma (HL) in combination with AVD (only stage IV according to the European Medicines Agency (EMA)). CPIs are currently being evaluated in combination with AVD in phase II trials of first-line treatment. The impact of BV and CPIs was also investigated in the setting of second-line salvage therapy. Finally, combinations of targeted therapies are under evaluation. Based on these exciting results, it appears reasonable to predict that an improvement in survival and a potential increase in the cure rates of cHL will soon become evident.

Dataset Information

Immunotherapy strategies for multiple myeloma: the present and the future.

Publications

Immunotherapy strategies for multiple myeloma: the present and the future.

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