Replacing/potentiating Keytruda

A very interesting topic is the fact that Leronlimab can potentiate and, arguably, replace Keytruda. From a hypothesis letter (Blockade of CCR5 in melanoma: An alternative immune checkpoint modulator) in the link (emphasis are mine):

https://onlinelibrary.wiley.com/doi/pdf/10.1111/exd.14065

Quote:

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For instance, Pembrolizumab, an anti-PD-1 antibody, showed over 34% progression-free survival at 6 months vs 16% progression-free survival on chemotherapy in an early clinical trial of pembrolizumab. The mechanisms of action of immunotherapy encompass blocking PD-1/PDL-1 and CTLA-4 receptors, which mediate the interaction of melanoma and T cells. Blockade of these pathways allows T cells to mount an immune response against melanoma cells. Immunotherapy is widely used as no other therapy provides longterm survival benefit (40% of patients alive at 3 years) even after stopping the medication. However, a significant downside of immunotherapy is toxicity. Immune side effects manifest in all organs and systems including skin rashes, pneumonitis, colitis, hepatitis, nephritis, encephalitis, endocrine and rheumatologic side effects and reactivation of immune diseases.
Therefore, pursuing treatment alternatives with fewer side effects is warranted .

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The paper goes on to add:

Quote:

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The addition of CCR5 blockade could help decrease the dose of PD1 inhibitors and therefore improve the side effect profile, which is a major obstacle to the use of immunotherapy . While anti-PD-1/PD-L1 enables T-cell anti-tumor activity, blockade of CCR5 can prevent MDSCs and T-regs immune modulation and prevent neutrophilic-mediated inflammation in the tumor microenvironment.

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The point here is that little has been done on Melanoma with Leronlimab, this is a common condition (large market) and Keytruda has serious adverse effects. The Hypotesis letter rightly points out that there is urgent need to start a trial with Leronlimab (well, with a CCR5 antagonist) for Melanoma.

And, more broadly, I think Leronlimab should start soon to show that it con replace or complement PD1 inhibitors (like Keytruda) in some indications (sorry Merck) reducing the serious adverse effects associated with the latter.