Invited study discussant of the use of ipilimumab plus nivolumab in resistant melanoma, at the AACR Annual Meeting 2022, Mario Sznol, MD, of Yale University Cancer Center, indicated that the substantial increase in progression-free survival at 6 months was not maintained. “The durable progression-free survival difference [with the combination] declines to less than 10% over 18 to 34 months. This is not as impressive as we would like. There is no overall survival difference, but the study was small and not powered for that endpoint.”

Mario Sznol, MD

Dr. Sznol noted that the lack of a survival advantage was surprising because the prior larger retrospective studies showed improved overall survival for the combination compared with ipilimumab alone. “Nevertheless, the differences in overall response rate are important,” he continued.

Dr. Sznol raised the possibility that activity of the combination can be maintained but toxicity reduced with alternate-dose regimens or new approaches to mitigating adverse events. He also pointed out there is still no predictive biomarker for when to use the ipilimumab-plus-nivolumab combination after disease progression on single-agent anti–PD-1, or when to add ipilimumab to anti–PD-1 in the first-line metastatic setting.

“This study suggests that nivolumab plus ipilimumab is an appropriate next-line treatment after single-agent anti–PD-1,” he said. “But other anti–PD-1 combinations will likely be added to the standard of care options for the first-line setting—for example, nivolumab plus relatlimab. Studies to demonstrate the activity of the ipilimumab/nivolumab combination will be required for patients who have progression on nivolumab/relatlimab.”

Pros and Cons of Intratumoral Therapy

Stefania Scala, MD

Invited study discussant of the phase II SPOTLIGHT-203 trial, Stefania Scala, MD, of the Istituto Nazionale Per Lo Studio dei Tumori-“Pascale,” Naples, said that intratumoral therapy had both advantages (eg, bypasses systemic trafficking, and tumor penetration reduces toxicity) and disadvantages compared with current systemic approaches. “Intratumoral therapies take advantage of the entire tumor antigenic repertoire by local injection of multiple tumor lesions and can induce a polyclonal immune response against all subclones,” she noted.

“The viral-like nanoparticles of therapies such as BO-112 have the theoretical advantage of lacking immunogeni­city. The toxicity is promising,” she added. “However, most response reflected results in the injected lesions, not systemic disease. And while intralesional injections can have a valuable role, this is usually only in a limited number of patients. Meaningful success requires responses in lesions other than those injected,” she said

DISCLOSURE: Dr. Sznol and Dr. Scala reported no conflicts of interest.