Long-term survival of patients after ipilimumab and hypofractionated brain radiotherapy for brain metastases of malignant melanoma: sequence matters

Heinz Schmidberger,Matthias Rapp,Carmen Loquai,Silla Hey-Koch,Arnulf Mayer,Anne Ebersberger,Stephan Grabbe

doi:10.1007/s00066-018-1356-5

Abstract

PurposeSince the introduction of ipilimumab (IPI) for the treatment of patients with metastatic malignant melanoma, we have observed remarkable responses after hypofractionated whole brain irradiation (WBRT) or stereotactic radiotherapy (STX) for brain metastases of malignant melanoma. We sought to investigate the impact of the sequence of these treatment modalities.MethodsWe retrospectively evaluated the survival of melanoma patients with brain metastases who were treated with WBRT or STX and received IPI in close temporal relation between October 2010 and March 2015. Follow-up was obtained until November 2016. A total of 27 patients with advanced melanoma and brain metastases who were treated with WBRT before 2010, and who had not received IPI, served as historical controls.ResultsWe identified a total of 41 patients of whom 15 were treated with STX, 7 with a combination of STX and WBRT and 19 with WBRT alone. All patients received at least 2 doses of IPI. The median time interval between radiotherapy and IPI was 2 months. Patients treated with IPI after radiotherapy had a censored median survival of 11 months, compared with 3 months for the patients who received IPI prior to radiotherapy. Patients who received IPI before radiotherapy showed a similar survival as historical controls, who had not received IPI. We observed long-term survivors after radiotherapy of brain metastases followed by IPI.ConclusionsThese data suggest that the sequence of RT and immune checkpoint inhibition with IPI may be crucial for the success of combined modality treatment of melanoma brain metastases.

Highlights

Over one-third of patients with malignant melanoma eventually develop clinically apparent brain metastases during the course of their disease [1]
The first group consisted of all patients who had been treated at our institution with a combination of radiotherapy to the brain and IPI (n = 41) between October 2010 and March 2015
The median overall survival (OS) in the cohort treated with radiotherapy plus IPI was 9.0 months, the median cerebral progression-free survival (CPFS) was 3.0 months

Summary

Introduction

Over one-third of patients with malignant melanoma eventually develop clinically apparent brain metastases during the course of their disease [1]. Methoden Wir haben retrospektiv das Überleben von Melanompatienten mit Hirnmetastasen untersucht, die zwischen Oktober 2010 und März 2015 mit WBRT oder STX behandelt worden waren und in engem zeitlichen Zusammenhang damit IPI erhalten hatten. Siebenundzwanzig Patienten mit fortgeschrittenem Melanom und Hirnmetastasen, die vor 2010 mit WBRT behandelt worden waren und kein IPI erhalten hatten, dienten als historische Kontrollen. Die nach einer Strahlentherapie mit IPI behandelt wurden, hatten eine mediane Überlebenszeit von 11 Monaten, während diese für Patienten, die vor der Strahlentherapie IPI erhielten, nur 3 Monate betrug. Schlussfolgerungen Diese Daten legen nahe, dass die zeitliche Abfolge der Applikation von Radiotherapie und Immun-Checkpoint-Hemmung mit IPI ein entscheidender Faktor für den Erfolg dieser Kombinationstherapie bei Hirnmetastasen eines malignen Melanoms sein könnte

Methods

Results

Conclusion