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Phenotypic and Functional Analysis of Dendritic Cells and Clinical Outcome in Patients With High-Risk Melanoma Treated With Adjuvant Granulocyte Macrophage Colony-Stimulating Factor

Adil I. Daud, Noweeda Mirza, Brianna Lenox, Stephanie Andrews, Patricia Urbas, Gui X. Gao, Ji-Hyun Lee, Vernon K. Sondak, Adam I. Riker, Ronald C. DeConti, Dmitry Gabrilovich

From the H. Lee Moffitt Cancer Center, Tampa, FL; and Mitchell Cancer Institute, University of South Alabama, Mobile, AL

Corresponding author: Adil I. Daud, MD, Department of Medicine, Division of Hematology-Oncology, University of California San Francisco, 1600 Divisadero St, San Francisco, CA 94143-171; e-mail: adaud{at}medicine.ucsf.edu

Purpose: Granulocyte macrophage colony-stimulating factor (GM-CSF) can induce differentiation of dendritic cells (DCs) in preclinical models. We hypothesized that GM-CSF–stimulated DC differentiation may result in clinical benefit in patients with high-risk melanoma.

Patients and Methods: We conducted a prospective trial in patients with high-risk (stage III B/C, IV), resected melanoma, with GM-CSF 125 µg/m²/d administered for 14 days every 28 days. Patients underwent clinical restaging every four cycles, with DC analysis performed at baseline and at 2, 4, 8, and 12 weeks.

Results: Of 42 patients enrolled, 39 were assessable for clinical outcome and DC analysis. Median overall survival was 65 months (95% CI, 43 to 67 months) and recurrence-free survival was 5.6 months (95% CI, 3 to 11 months). GM-CSF treatment caused an increase in mature DCs, first identified after 2 weeks of treatment, normalizing by 4 weeks. Patients with decreased DCs at baseline had significant increases in DC number and function compared with those with "normal" parameters at baseline. No change was observed in the number of myeloid-derived suppressor cells (MDSCs). Early recurrence (< 90 days) correlated with a decreased effect of GM-CSF on host DCs, compared with late or no (evidence of) recurrence.

Conclusion: GM-CSF treatment was associated with a transient increase in mature DCs, but not MDSCs. Greater increase of DCs was associated with remission or delayed recurrence. The prolonged overall survival observed warrants further exploration.

Supported by Berlex Oncology (now Bayer Corp).

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.