Highlights of This Issue

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) and high-dose (HD) bolus interleukin-2 (IL2) have shown unprecedented rates of durable complete regression of metastatic melanoma; however, the toxicity associated with HD IL2 has hampered its widespread application. Andersen and colleagues evaluated TIL therapy in combination with an attenuated regimen of IL2 in patients with metastatic melanoma (n = 25). The authors report that classical toxicities associated with previous protocols could be reduced without compromising clinical efficacy. Interestingly, tumor regression was associated with induction and persistence of anti-melanoma T cell responses in peripheral blood. These results warrant further testing of ACT with attenuated doses of IL2 in a randomized setting.

Chronic myelomonocytic leukemia (CMML) is a lethal hematologic neoplasm with no disease-modifying therapies. Preclinical studies suggest that Janus kinase 2 (JAK2) inhibition is a viable therapeutic strategy in CMML. In a phase 1 trial, Padron and colleagues tested ruxolitinib (JAK1/2 inhibitor) in CMML and found no dose-limiting toxicity at doses up to 20 mg twice daily. Significant clinical responses were observed and correlative analysis and pharmacodynamic consequences of JAK2 inhibition were reported, providing a clinical rationale for an ongoing phase II study.

Baselga and colleagues analyzed whether the efficacy of trastuzumab emtasine (T-DM1) was correlated with biomarker expression in patients with HER2-positive metastatic breast cancer participating in a phase III study. Progression-free survival and overall survival were longer with T-DM1 compared with capecitabine plus lapatinib (CL) in all subgroups. PIK3CA mutations were associated with shorter median survival in CL-treated, but not T-DM1-treated, patients. These results suggest that T-DM1 is efficacious in the presence of a biomarker associated with impaired response to other HER2-targeted agents.

Madore and colleagues investigated genomic, transcriptomic, and clinical correlates of programmed cell death ligand-1 (PD-L1) protein levels in melanoma patient tumor samples. PD-L1 negative tumors correlated with lower somatic mutation burden, a reduced immune response gene signature, and worse overall survival in stage III melanoma patients. PD-L1 positive tumors displayed increased expression of T cell and macrophage-specific gene sets, although negative tumors displayed reduced MHC-I antigen presentation genes. This article provides a multiplatform analysis of immune activation/dysfunction in human melanomas.