Significant impact of HLA class I allele expression on outcome in melanoma patients treated with an allogeneic melanoma cell lysate vaccine. Final analysis of SWOG-9035

Abstract

7501 Background: SWOG-9035 compared 2 years of an allogeneic melanoma lysate (Melacine™) to observation in patients (pts) with stage II melanoma 1.5–4.0 mm thick. We also analyzed the effects of expression of certain HLA antigens (≥2 of HLA-A2, A28, B44, B45, C3 - called M5 - or either HLA-A2 and or C3). Now we report the mature overall survival (OS) analysis as planned. Methods: Primary analyses were conducted on the eligible pt population (intent to treat, ITT) using a Cox model adjusted for stratification and recognized prognostic factors. HLA analyses were \(\underline{\mathrm{prospective}}\), involved all typed pts and were adjusted for stratification and prognostic factors. Results: In total, 689 pts were entered over 4.5 years (598 eligible). Median follow-up time is 7.8 years (maximum 10.9 years). Ninety-one patients are ineligible, mostly (n=75) by pathology (tumor too thin or too thick). For the ITT analysis, the 5-year OS for the observation arm is 77% and for the vaccine arm is 81% (p=.98). For all randomized pts, the 5-year OS for the observation arm is 76% and for the vaccine arm is 82% (p=.49). We HLA typed 553 of the total 689 pts enrolled (80% of the total). There was a significant interaction of M5 status (≥2 vs 0–1) and treatment (p=.02). Among pts with 2 or more of the M5, 5-year OS for vaccine pts is 93% and for observation pts is 74% (p=.009). Among patients with 0–1 of the M5, 5-year OS for vaccine pts is 83% and for observation pts is 82% (p=.68). The interaction remained significant when only HLA A2/C3 status was considered (A2+ and/or C3+ vs A2- and C3-, p=.004). In the A2+ and/or C3+ group, 5-year OS for vaccine pts is 90% and for observation pts is 76% (p=.007). In the A2- and C3- group, 5-year OS for vaccine pts is 80% and for observation pts is 84% (p=.16). Conclusion: There was no significant benefit of vaccine therapy overall, but this prospective analysis indicates significant survival benefit of vaccine therapy among early-stage melanoma pts expressing ≥2 of the M5 alleles. HLA-A2 and C3 were the predominant alleles contributing to this effect. A prospective confirmatory trial in pts expressing HLA-A2 and/or HLA-C3 is planned. No significant financial relationships to disclose.