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ESTRO 36 2017
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SP-0015 The impact of tumour infiltrating lymphocytes
on clinical outcome after (chemo)radiotherapy
J. Galon
1
Cordeliers Research Center (CRC), Paris, France
Abstract not received
SP-0016 Radiotherapy and immunotherapy
combination: paradigm changing or just hype?
S.J. Dovedi
1
1
The University of Manchester, Targeted Therapy Group,
Manchester, United Kingdom
Radiotherapy (RT) is a highly effective anti-cancer
treatment forming part of the standard of care for the
majority of patients. In addition to the direct
cytoreductive effect of RT there is increasing evidence
that this treatment may also be immunogenic; however,
the contribution and mechanisms of RT induced immune
responses are unknown. Moreover, as a monotherapy, RT
is rarely able to generate to abscopal responses outside of
the treatment field, suggesting that any immune response
generated may be suboptimal.
Longitudinal profiling of the tumour microenvironment
following RT in syngeneic mouse models, which have a
fully competent immune system, reveals the impact of
local RT on both the innate and adaptive components of
the immune system. Using next-generation sequencing of
the T-cell receptor repertoire (TCR) we show that
treatment with daily low-dose fractionated RT leads to a
T-cell response that is dominated by polyclonal expansion
of pre-existing T-cell clones. Moreover, we show that both
local and distal tumour control following RT can be
improved by combination with immunotherapies that
target both immunosuppressive checkpoints (such as the
PD-1/PD-L1 axis) and immune-stimulatory pathways to
ultimately enhance anti-tumor activity by CD8+ T-cells.
Importantly, preclinical data suggests that RT dose,
fractionation and scheduling with immunotherapy may
impact tumour control.
In this presentation we will review the data from
preclinical models and emerging clinical studies to explore
the immunological effects of RT and how these insights
may be used to guide clinical translation.
OC-0017 Combined High Dose Radiation and
Ipilimumab in Metastatic Melanoma, a Phase I Dose
Escalation Trial.
K. De Wolf
1
, V. Kruse
2
, L. Brochez
3
, N. Sundahl
1
, M. Van
Gele
3
, R. Speeckaert
3
, P. Ost
1
1
University Hospital Ghent, radiotherapy and oncology,
Gent, Belgium
2
University Hospital Ghent, medical oncology, Gent,
Belgium
3
University Hospital Ghent, dermatology, Gent, Belgium
Ipilimumab, a CTLA-4 blocking monoclonal antibody,
induces durable, potentially curative, tumour regressions
in some patients with metastatic melanoma, but
unfortunately the majority of patients do not have long-
term benefit from ipilimumab monotherapy. Preclinical
data and early clinical data suggest synergistic antitumor
activity between ipilimumab and high-dose radiotherapy
(e.g. doses higher than 8 Gy per fraction). Therefore, the
combination of ipilimumab with high-dose radiotherapy
holds substantial promise for improving clinical benefit.
We conducted a phase I trial to determine the safety and
tumour responses of this combination.
Material and Methods
Patients with metastatic
melanoma, with at least three distinct measurable sites of
disease, received four infusions of ipilimumab every three
weeks at 3 mg/kg in combination with dose-escalated
stereotactic body radiotherapy to one lesion after the
second infusion of ipilimumab (level 1: 24 Gy in 8 Gy per
fraction, level 2: 30 Gy in 10 Gy per fraction and level 3:
36 Gy in 12 Gy per fraction). For the patient
randomization, a time-to-event continual reassessment
method was used. The primary endpoint was to determine
the maximum tolerated radiotherapy doses. Secondary
endpoints were local control and tumour response as per
RECIST 1.1. Clinical benefit was defined as complete
response, partial response or stable disease.
Results
From March 18, 2015, to April 7, 2016, 13 patients
with metastatic melanoma were enrolled. Median age was
68 years (range 23 - 80), with 58% male and 42% female
patients. One patient experienced disease progression
before receiving radiotherapy and was not eligible for
evaluation. No dose-limiting toxicities were noted at dose
levels 1, 2 or 3. Grade 3 or 4 ipilimumab-related adverse
events (AEs) occurred in 25% of patients. Treatment-
related AEs are shown in Table 1.
Table 1: Treatment-related adverse events
Local control of the irradiated lesions was achieved in 11
of 12 patients. There was a complete local response in 1
irradiated lesion (8%), a partial response in 6 irradiated
lesions (46%), stable disease in 4 irradiated lesions (31%),
and progressive disease in 1 irradiated lesion
(8%). Evaluation of the non-irradiated lesions
demonstrated that 3 patients (24%) experienced clinical
benefit (one patient (8%) developed a confirmed partial
response and 2 patients (16%) had confirmed stable
disease).
Figure 1: Best local response of irradiated lesions and
overall response of non-irradiated target lesions
Conclusion
Ipilimumab 3 mg/kg with concurrent high-dose
radiotherapy can be delivered safely in patients with