Developmental History, Clinical Considerations, and Future Perspectives

Michael A. Postow, MD; Jedd D. Wolchok, MD, PhD


The Melanoma Letter. 2012;30(1):1-4. 

In This Article

Future Directions: Combination Strategies to Increase the Number of Patients Who Benefit

Research leading to the approval of ipilimumab highlighted the importance of immune regulatory circuits and provided insights into how immunomodulatory antibodies that manipulate these mechanisms can dramatically improve clinical outcomes. Ipilimumab has fundamentally changed the landscape of melanoma treatment, with a substantial subset of patients now achieving long-term disease control and survival. Current research into understanding the pathophysiology of ipilimumab's unique side effect profile and analyzing biomarkers predictive of response will ultimately lead to improved patient selection and clinical care.

Despite the therapy's ability to create durable, long-lasting responses, there is a clear need to increase the number of patients who benefit. One study in treatment-naïve patients showed a trend towards a higher response rate when ipilimumab was combined with dacarbazine compared to ipilimumab alone.[10] Despite the possibility of an additive effect in this study, further studies are necessary. Current and planned clinical trials are combining ipilimumab with chemotherapy, other immunotherapy, radiotherapy, and targeted therapy, such as BRAF inhibition (Table 1). Ipilimumab is also being investigated in the adjuvant setting after surgical resection of high-risk disease. We believe therapeutic strategies combining ipilimumab with other immunotherapeutic agents such as vaccines or other immunomodulatory antibodies that enhance T-cell responses may add to the benefit of ipilimumab, and we are conducting clinical trials to assess this promising possibility.


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