MMDA-09 PROGNOSTIC DIFFERENCE BETWEEN HOMOGENEOUS VS. HETEROGENEOUS INTRACRANIAL RESPONSE OF MELANOMA BRAIN METASTASES TO IPILIMUMAB AND NIVOLUMAB
Devika Shankar, Troy Kleber, Bikash Panthi, Eleni Konstantinopoulou, Victoria White, Saba Elias, Holly Langshaw, Thomas Beckham, Caroline ChungAbstract
Background
The incidence and implications of heterogeneous intracranial response to immunotherapy in patients with melanoma brain metastases (MBM) are poorly understood, posing a clinical challenge by complicating disease assessment and management. Herein, we compare homogeneous and heterogeneous progression presentations for MBM treated with ipilimumab and nivolumab (ipi-nivo).
Methods
We retrospectively identified UT MD Anderson patients with newly diagnosed MBM treated with ipi-nivo in 2018-2023, with ≥1 evaluable MBM at baseline and ≥1 MRI brain scan following ipi-nivo initiation. The longest axial diameter (LAD) for each MBM was extracted from segmented volumes in RayStation. Intracranial progressive disease (IPD) was defined according to modified RECIST criteria. IPD patients with ≥1 evaluable MBM achieving complete response or LAD shrinkage by ≥ 1.5 mm at the time of IPD were considered heterogeneous IPD; otherwise, IPD cases were considered homogeneous.
Results
Out of 65 MBM patients treated with ipi-nivo, 39 (60%) experienced IPD, including 24 (62%) with homogeneous IPD and 15 (38%) with heterogeneous IPD. Compared to heterogeneous IPD, homogeneous IPD was associated with shorter interval from ipi-nivo start to IPD (median 1.4 vs. 6.0 mo, p < 0.01), simultaneous extracranial progression (50% vs. 13%, p = 0.02), and history of systemic therapy prior to MBM diagnosis (63% vs. 13%, p = 0.01). Patients with homogeneous vs. heterogeneous IPD received similar salvage therapy approaches (p = 1.0): stereotactic radiosurgery (63% vs. 67%); whole brain radiotherapy (25% vs. 20%); systemic therapy alone (13% vs. 13%). However, homogeneous IPD patients had worse three-year overall survival, when measured from start of ipi-nivo (22% vs. 67%, p = 0.02) or date of IPD (22% vs. 60%, p = 0.05).
Conclusion
These findings suggest that patients with heterogeneous IPD represent a clinically distinct subgroup with meaningful differences in long-term outcomes compared to homogeneous IPD. This highlights the need to account for lesion-level response heterogeneity in clinical assessment, risk stratification, and individualized treatment planning.