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. 2024 Aug;38(8):1575-1587.
doi: 10.1111/jdv.19941. Epub 2024 Mar 11.

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma

Julian Kött  1   2 , Noah Zimmermann  1   2 , Tim Zell  1   2 , Isabel Heidrich  1   2   3 , Glenn Geidel  1   2 , Alessandra Rünger  1   2 , Daniel J Smit  2   3 , Myriam Merkle  1   2 , Niousha Parnian  1 , Inga Hansen  1   2 , Inka Hoehne  1   2 , Finn Abeck  1 , Leopold Torster  1 , Michael Weichenthal  4 , Klaus Pantel  2   3 , Stefan W Schneider  1   2 , Christoffer Gebhardt  1   2
Affiliations

C-reactive protein flare predicts response to checkpoint inhibitor treatment in melanoma

Julian Kött et al. J Eur Acad Dermatol Venereol. 2024 Aug.

Abstract

Background: The treatment of melanoma has been revolutionized by the use of immune checkpoint inhibition (ICI), but many patients do not benefit. Furthermore, immune-related adverse events may occur during therapy. A predictive biomarker is needed to reliably identify patients benefitting. In lung, renal cell and bladder cancer early C-reactive protein (CRP) kinetics were shown to be a predictive biomarker for ICI.

Objective: Here, we investigate early CRP kinetics as predictive biomarker for ICI in melanoma patients.

Methods: Two independent prospectively collected cohorts were analysed: Cohort 1 (n = 87) with advanced and Cohort 2 (n = 99) with completely resected melanoma. Patients were stratified by in the dynamics of CRP after ICI initiation: A doubling of baseline CRP within 30 days followed by at least a 30% drop within 3 months was classified as a CRP flare. If no doubling of CRP was reported, but a 30% drop within 3 months, patients were classified as CRP responders and all others as CRP non-responders. Analysed factors included clinical characteristics like S100B and LDH. Median follow-up was 1.5 and 1.7 years for Cohorts 1 and 2.

Results: In Cohort 1 CRP flare (n = 12), CRP responders (n = 43) and CRP non-responders (n = 32) with a progression-free survival (PFS) of 0.7, 0.6 and 0.2 years (p = 0.017) and an overall survival (OS) of 2.2, 1.5 and 1.0 years (p = 0.014), respectively. Multivariable Cox analysis showed an independent risk reduction of progression for CRP responders by 62% compared to CRP non-responders (p = 0.001). In Cohort 2 CRP flare (n = 13), CRP responders (n = 70) and CRP non-responders (n = 16) the log-rank analysis showed a significant difference between OS and recurrence-free survival (RFS) curves (p = 0.046 and p = 0.049).

Conclusion: Early CRP kinetics could indicate a response to ICI with improved OS and RFS/PFS. CRP flare and CRP response indicating significantly improved outcomes compared to CRP non-responders.

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References

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