Paolo Cotzia: The safety and effectiveness of combining two intratumoral immunotherapies for treating high-risk DCIS
Paolo Cotzia, Medical Director of Molecular Pathology and Head of Molecular Excellence at Sonic Healthcare USA, shared an article by Kirithiga Ramalingam et al. on LinkedIn:
“High-risk ductal carcinoma in situ (DCIS) involves factors such as large tumor size, high nuclear grade, hormone receptor negativity, and overexpression of certain proteins like ERBB2 (HER2).
While DCIS can often be treated successfully with surgery and radiation, aggressive cases may require more advanced treatment strategies to reduce recurrence or progression to invasive cancer.
One promising strategy is intratumoral immunotherapy, which could potentially shrink or eliminate high-risk DCIS while reducing the need for extensive surgery.
This phase 1 clinical trial, recently published on JAMA Oncology, evaluated the safety and effectiveness of combining two intratumoral immunotherapies—pembrolizumab (an anti-PD-1 antibody) and mRNA-2752 (a combination of interleukins and OX40L mRNA)—for treating high-risk DCIS. The trial included 10 female patients aged 35-80 with DCIS tumors, all meeting high-risk criteria such as large tumor size or hormone receptor negativity.
The patients received between 2 to 4 doses of the immunotherapy combination, administered directly into the tumors.
The trial showed that 8 out of the 10 patients responded positively to treatment. Notably, three patients experienced complete responses, with two of them remaining disease-free for 1 to 2 years after declining surgery. The treatment was generally well-tolerated (common side effects included mild flu-like symptoms, fever, and injection site reactions).
A reduction in the doses of both pembrolizumab and mRNA-2752 was required to enhance patient tolerability, with the final recommended doses being 4 mg of pembrolizumab and 1 mg of mRNA-2752.
Multiplex immunofluorescence analysis revealed that tumors with high baseline levels of immune cells (specifically tumor-infiltrating lymphocytes and PD-L1-positive cells) were more likely to respond well to the treatment.
The findings from this early-phase trial suggest that intratumoral immunotherapy using pembrolizumab and mRNA-2752 is a safe and potentially effective treatment for high-risk DCIS, particularly in tumors associated with a strong immune infiltrate.
Further research is necessary to confirm these promising results, paving the way for reducing the need for invasive surgery in high-risk DCIS patients.”
Intratumoral Injection of mRNA-2752 and Pembrolizumab for High-Risk Ductal Carcinoma In Situ.
Authors: Kirithiga Ramalingam, et al.
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