Front-line therapy of DIPG using IDO inhibitor with radiation and chemotherapy

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Published: 25 Apr 2018
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Dr Theodore Johnson - Georgia Cancer Center, Augusta, USA

Dr Johnson speaks with ecancer at AACR 2018 about results from brain cancer patients treated with IDO inhibitor indoximod alongside chemotherapy and radiation.

He describes the cohort of diffuse intrinsic pontine glioma (DIPG) patients, and the tolerability of the trial triplet therapy.

Dr Johnson notes that lower-dose, restricted-field radiotherapy may be beneficial with indoximod in relapse cases.

We presented the first 29 patients who enrolled on a paediatric combined immunotherapy chemotherapy radiation trial with two separate dose escalations of indoximod, one in combination with radiation and one in combination with a chemotherapy drug called temozolomide. We also presented pilot data for the first six patients enrolled with newly diagnosed diffuse intrinsic pontine glioma which is DIPG.

What did the data show?

The relapsed refractory brain tumour patients that were enrolled into the dose escalation cohorts tolerated the treatment very well with few toxic side effects which is important because combining immunotherapy with cytolytic therapies like radiation and chemotherapy which have their own toxicities layers on toxicity profiles. But we’re fortunate that indoximod doesn’t have overlapping toxicities with the radiation or the chemotherapy drugs that we chose. The kids are doing very well. We have a proportion of kids even at the phase I level that have achieved long-term control of their disease and are still on the trial at over a year.

How will this research progress?

Indoximod is an IDO inhibitor drug which works by shutting down one of the natural immune regulatory mechanisms that tumours can hijack in order to avoid immune responses. Combination multimodal therapy with immunotherapy like indoximod plus radiation and chemotherapy, we really felt like the optimal setting for that combination was in front line therapy. We’ve recently opened a pilot cohort enrolling newly diagnosed diffuse intrinsic pontine glioma patients, which is the IPG, in the front line setting and we chose that patient population because essentially it’s a ruthlessly progressive disease, it’s uniformly fatal and there have been no real advances in treating that disease in forty years. Essentially all the patients succumb to their disease by two years and the median survival with the only effective therapy, which is palliative radiation, is 10-12 months.

How is the treatment being tolerated?

For the most part the patients are actually tolerating this treatment platform very well. The newly diagnosed DIPG patients we were concerned about because the brain stem is a particularly bad place to have a tumour. It’s a very tight area; there’s not a lot of room for swelling and any immunotherapy that has on target inflammatory responses in a space as confined as the brain stem can cause local oedema that can drastically worsen presenting symptoms and those can be fatal. So we were very concerned and we watched those patients very closely but fortunately all six that we have that have completed radiation did so without major toxicity and all had improvement in their presenting symptoms. So we’re very happy about that.