Treatment of metastatic melanoma has changed dramatically in the past 5 years with the approval of six new agents (vemurafenib, dabrafenib, trametinib, ipilimumab, pembrolizumab, and nivolumab) by the US Food and Drug Administration (FDA). This review will compare the immunotherapies recently approved by the FDA (ipilimumab, nivolumab and pembrolizumab) with the long-approved immunotherapy, interleukin-2. Additional consideration will be given to the evolving landscape, including the opportunities for combination regimens. Immunotherapies have distinct mechanisms of action and unique response kinetics that differ from conventional cytotoxic and targeted therapies, and have a range of adverse events that can be safely managed by experienced health care providers. Data suggest immunotherapies can result in long-term survival in a proportion of patients. This dynamic and evolving field of immunotherapy for melanoma will continue to offer challenges in terms of optimal patient management for the foreseeable future.

High-dose interleukin-2 (HD IL-2) is an approved immunotherapy agent for metastatic melanoma and renal cell carcinoma resulting in objective responses in 15-20% of patients. An additional subset of patients achieves stable disease and the natural history of these patients has not been well documented. We hypothesized that stable disease following HD IL-2 is associated with a survival advantage. To explore this hypothesis, a retrospective chart review of 305 patients diagnosed with metastatic melanoma or renal cell carcinoma treated with HD IL-2 was conducted. Patient characteristics, response based on standard RECIST criteria and overall survival were analyzed using the Kaplan-Meier method and associations with clinical response were compared using a log-rank test. 245 patients had melanoma and 60 had renal cell carcinoma. Of these, 217 had complete data available for analysis. 59% had progressive disease (PD), 26% had stable disease (SD) and 15% had an objective complete (CR) or partial response (PR). Median overall survival was 16.8 months for all patients with available survival data; patients with progressive disease had a median survival of 7.9 months compared to 38.2 months for stable disease, while the median has not been reached for those with objective responses. This retrospective data supports an association between overall survival and stable disease, suggesting that clinical benefit may be underestimated for patients treated with HD IL-2. The data further supports the use of disease control rate (CR+PR+SD) as a more meaningful endpoint for future clinical studies of tumor immunotherapy, including future studies of HD IL-2.

When index of suspicion is high or when biopsy is performed for patient previously diagnosed with lymphoma and recurrence/transformation is suspected, LB safely and consistently provides adequate tissue for initial diagnosis and for ancillary studies. In contrast, image-guided PB may be more appropriate for patients for whom ancillary studies are unlikely to add to planned treatments or when there is a high risk of complications from either general anesthesia or patient comorbidities.

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Recurrent cytogenetic abnormalities involving chromosomes 1, 6q, and 18 are present in greater than 50% of ILBCL.