Immunotherapy 'Plus': Adding Radiation and Chemo to Immune Therapies

Robert H. Carlson, MBA


June 27, 2016

In This Article

Immunotherapies are still in their infancy, but as the data mature, oncologists are beginning to face a new question: How do these new therapies fit with what's already available? Is there a future for combining immunotherapy with chemotherapy or radiotherapy, or, for that matter, with surgery or targeted agents?

There is potentially huge promise in these approaches, particularly for the large majority of patients who don't respond robustly to single-agent monotherapy. But because each of these approaches acts on the immune system in complicated ways, they are not without unique risks.

Earlier this month at the 2016 ASCO annual meeting, Michael Weller, MD, PhD, chair of neurology and a brain tumor specialist at University Hospital Zürich in Switzerland, summarized the state of the field in gliomas, but his pro and con arguments could be applied more broadly across tumor types.

On the one hand, Dr Weller said, "combo believers" outlined rationales for combining immunotherapy with the following approaches:

  • chemotherapy, because this may deplete regulatory T cells and may release tumor antigens;

  • radiotherapy, because this may kill via immunogenic cell death pathways and release tumor pathogens;

  • anti-angiogenic therapy, because VEGF is immunosuppressive; and

  • surgery, because minimal residual disease minimizes tumor-emanating immunosuppression.

On the other hand, he said, "combo skeptics" have equally specific fears for resisting combination approaches:

  • chemotherapy, because of lymphopenia and bone marrow toxicity;

  • radiotherapy, because this kills tumor infiltrating immune cells and induces tolerance and the necessity to use steroids;

  • anti-angiogenic therapy, because restoring blood-brain barrier integrity prevents influx of immune cells; and

  • surgery, because minimal residual disease translates to a minimal tumor antigen load to be recognized by the immune system.

Dr Weller's conclusion: "You never know until you try."


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