Stereotactic radiosurgery and combined immunotherapy with ipilimumab and nivolumab for melanoma brain metastases
Raphael Bodensohn,
Germany
PO-1159
Abstract
Stereotactic radiosurgery and combined immunotherapy with ipilimumab and nivolumab for melanoma brain metastases
Authors: Raphael Bodensohn1, Simone Werner1, Jonas Reis2, Montserrat Pazos Escudero1, Anna-Lena Kaempfel1, Indrawati Hadi1, Robert Forbrig2, Farkhad Manapov1, Stefanie Corradini1, Claus Belka1, Sebastian Theurich3, Lucie Heinzerling4, Max Schlaak5, Maximilian Niyazi1
1University Hospital LMU Munich, Department of Radiation Oncology, Munich, Germany; 2University Hospital LMU Munich, Institute of Neuroradiology, Munich, Germany; 3University Hospital LMU Munich, Department of Medicine III, Munich, Germany; 4University Hospital LMU Munich, Department of Dermatology and Allergology, Munich, Germany; 5Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Berlin, Germany
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Purpose or Objective
Adding stereotactic radiosurgery (SRS) to combined immune checkpoint therapy with ipilimumab and nivolumab (IPI+NIVO) has led to promising results for patients with melanoma brain metastases (MBM). Previous studies have shown a synergistic effect. However, the toxicity especially with regard to radionecrosis has been unclear. This study retrospectively analyzes the toxicity profile depending on the timing of SRS during IPI+NIVO.
Material and Methods
For this study, the clinical database was searched for all patients with MBM who were treated with SRS and IPI+NIVO. The patients were separated into three groups: group 1 received IPI+NIVO (usually up to four cycles) more than 14 days before SRS, group 2 IPI+NIVO more than 14 days after SRS, and group 3 received SRS concurrently to IPI+NIVO. All groups were compared with respect to overall survival, progression-free survival and toxicity. Toxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5. The follow-up MRIs were evaluated by two experienced neuroradiologists. Relation between groups and toxicity was analyzed using the Fisher-Yates-test.
Results
In total, 31 patients were assessed including six (19.4%) patients in group 1, seven (22.6%) in group 2 and 18 (58.1%) patients in group 3. Median follow-up was not reached in group 1, 55.7 months in group 2 and 33.1 months in group 3. Median overall survival after diagnosis of MBM was 13.9 months (95% CI 11.4-16.3) in group 1, not reached in group 2 and 16.3 months (95% CI 12.1-23.7) in group 3. Intracranial progression-free survival was 2.5 months (95% CI 2.4-2.5) for group 1, 10.9 months (95% CI 2.3-19.5) for group 2 and 1.5 months (95% CI 1.2-7.2) for group 3. In total, there were ten (32.3%) patients with reported CTCAE grade 3 toxicities. Five (16.1%) of them were related to SRS (radionecrosis or hemorrhage CTCAE grade 3). All of these five patients were in group 3, which was significantly related to CTCAE grade 3 toxicities (p=0.050). Moreover, all of these patients received SRS within seven days of IPI+NIVO treatment; to receive SRS within seven days of IPI+NIVO treatment was therefore significantly related to grade 3 toxicities (p=0.036),
Conclusion
The patient group in which SRS was applied during or less than seven days before or after IPI+NIVO showed significantly higher grade 3 toxicities than the patient groups with sequential treatment. Due to the small cohort and the retrospective nature of this study, there is however a relevant selection bias with concomitant treatment mainly chosen for patients with dismal prognosis of MBM. Thus, the results should be confirmed in a larger prospective cohort.