Igor Puzanov, MD, director, Early Phase Clinical Trials Program, chief of Melanoma, co-leader, CCSG Experimental Therapeutics Program, professor of Oncology, Department of Medicine, Roswell Park Cancer Institute, discusses ways to manage patients with melanoma who may experience adverse events (AEs) in response to treatment with immunotherapy.

According to Puzanov, it can very difficult to predict which patients will experience AEs in response to certain therapies. Thus, 1 of his goals is to develop a marker that can identify patients who are at a higher risk for experiencing a particular AE in response to a particular treatment.

Puzanov explains that he is keen to tell his patients about past cases involving AEs in response to immunotherapy combinations, so that they can be on the lookout for early signs of toxicity. Additionally, he says he often brings patients into his office weekly, at least when patients first begin treatment, to check and and see if he can detect any signs of toxicity.

When patients do experience AEs in response to immunotherapy, Puzanov says he is encouraged by the fact that treating them with steroids does not have any effect on their responses or progression-free survival rates. Thus, he can treat his patients with what they need without harming them further or lowering their chances of being cured.

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Igor Puzanov, MD, director, Early Phase Clinical Trials Program, chief of Melanoma, coleader, CCSG Experimental Therapeutics Program, professor of Oncology, Department of Medicine, Roswell Park Cancer Institute, discusses ways to manage patients with melanoma who may experience adverse events in response to treatment with immunotherapy.

Dr. Puzanov on Management of Adverse Events in Melanoma

Igor Puzanov, MD, director, Early Phase Clinical Trials Program, chief of Melanoma, coleader, CCSG Experimental Therapeutics Program, professor of Oncology, Department of Medicine, Roswell Park Cancer Institute, discusses an ongoing study exploring the optimal sequence of immunotherapy agents and targeted therapies for patients with melanoma.

One of the most developed combinations is the CTLA-4 inhibitor ipilimumab (Yervoy) plus the PD-1 inhibitor nivolumab (Opdivo), which has been FDA approved for patients with melanoma. The combination has also been explored in these patients who have brain metastases, and it is shown to elicit clinical activity.

Additionally, an Eastern Cooperative Group study is exploring the sequence of BRAF inhibitors plus MEK inhibitors or immunotherapy in 

-positive patients in the frontline setting. Patients will undergo a 1:1 randomization for which treatment they will receive first, and then will switch treatments upon disease progression.

Dr. Puzanov on Sequencing Targeted Therapy and Immunotherapy in Melanoma

Igor Puzanov, MD, medical oncologist, Vanderbilt-Ingram Cancer Center, discusses the rationale behind a phase Ib study to evaluate the efficacy and safety of T-VEC and ipilimumab in previously untreated, unresected stage IIIB-IV melanoma.

Puzanov says researchers used T-VEC, an oncolytic virus, because of previous positive data. Researchers wondered if T-VEC could be combined with ipilimumab, a standard-of-care treatment for patients with stage IV melanoma.

T-VEC can unleash multiple antigens from the lysine tumor regardless of the tumor genotype. These antigens will then be presented to the dendritic cells, which are driven to the event from T-VEC, Puzanov says. These dendritic cells teach T cells to start killing the tumor locally and hopefully throughout the body. In order to augment a response throughout the body, Puzanov says, ipilimumab is used.

 Although ipilimumab helps 25% of patients live longer and have long durable responses, sometimes these responses are slow. Adding T-VEC may help speed up the responses in a safe manner, Puzanov says. 

Igor Puzanov, MD

Articles

Dr. Puzanov on Management of Adverse Events in Melanoma

Dr. Puzanov on Sequencing Targeted Therapy and Immunotherapy in Melanoma

Dr. Puzanov on T-VEC in Combination with Ipilimumab for Melanoma Treatment