1. Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies.
- Author
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Van Not, Olivier J., van den Eertwegh, Alfons J.M., Haanen, John B., van Rijn, Rozemarijn S., Aarts, Maureen J.B., van den Berkmortel, Franchette W.P.J., Blank, Christian U., Boers-Sonderen, Marye J., van Eijs, Mick J.M., de Groot, Jan-Willem B., Hospers, Geke A.P., Kapiteijn, Ellen, de Meza, Melissa, Piersma, Djura, Stevense-den Boer, Marion, van der Veldt, Astrid A.M., Vreugdenhil, Gerard, Wouters, Michel W.J.M., Suijkerbuijk, Karijn P.M., and Blokx, Willeke A.M.
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PROGRAMMED cell death 1 receptors , *IMMUNE checkpoint inhibitors , *CONFIDENCE intervals , *MELANOMA , *MULTIVARIATE analysis , *PATIENT-centered care , *IPILIMUMAB , *CANCER patients , *TREATMENT effectiveness , *RISK assessment , *HEMATOLOGIC malignancies , *SURVIVAL analysis (Biometry) , *NIVOLUMAB , *PROGRESSION-free survival , *PROPORTIONAL hazards models , *PHARMACODYNAMICS - Abstract
Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction. All advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM−). A cox model was used to account for confounders associated with PFS and MSS. In total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM− (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM− (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HR adj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HR adj 1.74; 95% CI 1.09–2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM− patients were not significantly different. Patients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM. • Largest cohort of metastatic melanoma (MM) and haematologic malignancy (HM) patients. • Immunotherapy-treated MM patients with a concurrent HM had significantly worse PFS. • PFS was not worse for patients with HM treated with targeted therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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