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Immune checkpoint inhibitors show promise for treatment of lymphomas
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NEW YORK — A “reprogramming approach” may form the basis of the future use of immune checkpoint inhibitors for the treatment of lymphoma, according to a presenter at Lymphoma & Myeloma 2015.
There are three main approaches to treating patients: the inhibition of critical pathways, immune activation and depletion of malignant cells, according to Stephen M. Ansell, MD, PhD, professor of medicine at Mayo Clinic in Rochester, Minnesota, and HemOnc Today Editorial Board member.
Stephen M. Ansell
“Our best strategy to treat patients would be to use all three of these strategies in what I call a ‘reprogramming approach,’” Ansell said. “Unless you target each one of these areas, the likelihood is that the other sides of the three-legged stool will take over.”
Ansell first discussed how the depletion approach can be improved by checkpoint blockade.
Appropriate sequencing is the key question when considering the use of an immune checkpoint inhibitor with chemotherapy, Ansell said. Brentuximab vedotin (Adcetris, Seattle Genetics) may provide a more targeted approach to be used in combination with a PD-1 blockade, and this approach is currently being evaluated in patients with Hodgkin’s’ lymphoma. Pidilizumab (CT-011, CureTech) also may offer a more intense approach after transplantation.
Further, the immune checkpoint blockade can be used to optimize pathway-specific therapies, Ansell said. HDAC inhibitors can upregulate PD-1, which can then be targeted by anti-PD-1 therapy. Ibrutinib (Imbruvica; Pharmacyclics and Janssen) and idelalisib (Zydelig, Gilead) are known to have T-cell function, thus representing another possible combination with checkpoint blockade.
Lastly, the immune optimization approach can be improved through immune checkpoint blockade by the use of more than one immune checkpoint; by blocking an inhibitory signal while simultaneously giving an activating signal; and by using a different immune activator, such as CAR T cells, bispecific antibodies, and vaccines in combination with checkpoint inhibitors.
“This is an encouraging and exciting time for immune checkpoint therapy and for immunotherapies in general,” Ansell said. “This is really the new frontier in lymphomas. Checkpoint inhibitors hold real promise even as a single-agent, but also in combinations, in Hodgkin’s and non-Hodgkin’s lymphomas. Because we have multiple agents, this is going to be a very exciting time to work out how to best use them together in a way that benefits their effects rather than contradicts them.” – by Alexandra Todak
For more information:
Ansell SM. Immune checkpoint inhibitors in Hodgkin’s and non-Hodgkin’s lymphoma: How do they work? Where will we use them? Presented at: Lymphoma & Myeloma 2015: An International Congress on Hematologic Malignancies; Oct. 22-24, 2015; New York, New York.
Disclosure: Ansell reports his institution has received research funding from Bristol-Myers Squibb, Celldex Therapeutics and Seattle Genetics.