283MO - Leptomeningeal disease (LMD) in patients (pts) with metastatic melanoma (MM): Survival analysis of a contemporary cohort

Background

Previous review of the overall survival (OS) of 178 pts with LMD from MM diagnosed between 1999-2015 showed a dismal OS of only 3.5 months (mos). Here we present a contemporary analysis to assess if outcomes had improved with the many changes in systemic therapies for MM pts with LMD since 2015.

Methods

Clinical characteristics, treatment (tx) and OS data were collected for MM pts diagnosed with LMD from 2015-2020. The Kaplan-Meier method was used to estimate OS and multivariable Cox proportional hazards regression modeling was used to evaluate associations with OS.

Results

172 melanoma pts were identified. LMD diagnosis was confirmed with CSF cytology in 53% (n=44) of the 83 pts that underwent analysis, with MRI brain in 128 (74%) pts and MRI spine in 69 (40%) pts. Median age at LMD diagnosis was 53 years (range: 20-79 years), and most pts were male (n=103, 60%). 93 (54%) had a history of primary cutaneous melanoma; the majority had a BRAF mutation (n=113, 66%). With a median follow-up of 4.0 mos (range: 0.1-65.3 mos), the median OS from LMD diagnosis for all pts was 4.9 mos (95% CI: 3.4, 6.5). The majority of patients (n=142; 83%) received at least one LMD directed tx following LMD diagnosis. Systemic tx for LMD was used in 118 (69%) pts. The median OS from LMD diagnosis was 7.9 mos for all pts who received any systemic tx; 10.2 mos for those receiving immunotherapy alone (n=57, 48%), 8.0 mos for pts receiving targeted therapy alone (n=60, 51%), and 5.6 mos for those receiving chemotherapy alone (n=30, 25%). Forty-two (24%) pts received intrathecal (IT) immunotherapy tx. Median OS for pts receiving IT tx was 8.0 mos. 92 (64%) pts received radiation therapy (RT) for LMD, whole-brain RT (n=71, 49%), spine RT (n=23, 16%), and stereotactic RT (n=9, 6%). Improved OS was observed in pts with negative baseline CSF cytopathology (hazard ratio (95% CI): 0.52 (0.27, 0.99); p=0.046), normal LDH (0.47 (0.30, 0.73); p<0.001) and no tx with WBRT (0.20 (0.09, 0.44); p<0.001).

Conclusions

Despite overall poor OS even with available contemporary MM tx, a subset of MM pts with LMD achieve better survival. Further investigation of this specific pts population is needed, as it might guide management and to inform the design of future clinical trials for this population.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

I.C. Glitza: Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb. R. Amaria: Financial Interests, Personal, Advisory Board: Iovance Biotherapeutics, Novartis, Bristol Myers-Squibb; Financial Interests, Institutional, Invited Speaker: Merck, Bristol Myers Squibb, Novartis, Iovance. M. Davies: Financial Interests, Personal and Institutional, Other, Consultant: Bristol Myers Squibb, Pfizer, Novartis; Financial Interests, Institutional, Principal Investigator: Merck. A. Diab: Financial Interests, Personal, Advisory Board: Nektar Therpaeutics, Apexigen, Idera Pharmaceuticals. J. Mcquade: Financial Interests, Personal and Institutional, Other, Consultant: Merck; Financial Interests, Personal and Institutional, Other, Honorarium: Bristol Myer Squibb. S. Patel: Financial Interests, Personal, Invited Speaker, Peer discussion group leader for melanoma (non-promotional speaker / leader): Merck; Financial Interests, Personal, Advisory Board, Scientific Advisory Board: TriSalus; Financial Interests, Personal, Advisory Board: Cardinal Health; Financial Interests, Personal, Other, Independent Data Monitoring Committee: Immunocore; Financial Interests, Institutional, Invited Speaker: Provectus, Lvgen, Bristol Myers Squibb, InxMed, Foghorn Therapeutics, Ideaya. H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Merck, Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. M. Wong: Financial Interests, Personal and Institutional, Advisory Board: Merck, Pfizer, Bristol Myers Squibb. All other authors have declared no conflicts of interest.