And Now for Something Completely Different: Immunotherapy Beyond Checkpoints in Melanoma.

Advances in the understanding of biology and therapy of melanoma have occurred at an astonishing pace over the past approximately 15 years, and successful melanoma therapy has led the way for similar advances in many other solid tumors that are continuing to improve outcomes for all patients with cancer. Although the 2018 Nobel Prize was awarded to two investigators who discovered that therapeutic targeting of immune checkpoints held the key to major patient benefits, there are many additional immunotherapeutic strategies that warrant further study and discussion at scientific and medical meetings. This article provides the newest information on three areas of immunotherapy that have been successfully applied to melanoma and continue to pave the way for new developments: cytokines, adoptive cell therapies (ADTs), and intratumoral injection of immunomodulatory agents.

Plasma cell enrichment enhances detection of high-risk cytogenomic abnormalities by fluorescence in situ hybridization and improves risk stratification of patients with plasma cell neoplasms.

CONTEXT: Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy. OBJECTIVE: To evaluate the utility of plasma cell enrichment combined with FISH for detection of high-risk cytogenomic abnormalities in patients with PCNs after therapy. DESIGN: Twenty-eight patients with PCNs, of whom 22 received treatment, were included in this study. Plasma cells were enriched in BM aspirates by using a magnetic cell-sorting procedure to select CD138(+) cells. Probes were chosen to assess for del(17p13/TP53), del(13q14/RB1), 1q21/CKS1B gain, IgH/FGFR3, and IgH/MAF. Clinicopathologic data were collected during clinical follow-up after plasma cell enrichment. RESULTS: Plasma cells in nonenriched BM specimens ranged from 1% to 28% (median, 8%) compared with 28% to 96% (median, 73%) in enriched BM specimens (P < .001). In a subset of treated patients in clinical remission, FISH detected high-risk cytogenomic abnormalities only in plasma cell-enriched samples. This approach also detected abnormalities in cases of solitary plasmacytoma and monoclonal gammopathy of undetermined significance. CONCLUSIONS: Plasma cell enrichment of BM specimens increases FISH sensitivity for detecting high-risk cytogenomic abnormalities, particularly in treated patients, and these results, in combination with clinical follow-up data, can be of value to improve risk stratification and patient management.