BackgroundPatients 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...Show moreBackgroundPatients 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.MethodsAll 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.ResultsIn 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 (HRadj 1.62; 95% confidence interval [95% CI] 1.15–2.29; p = 0.006) and melanoma-related death (HRadj 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.ConclusionsPatients 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. Show less
Rauwerdink, D.J.W.; Doorn, R. van; Hage, J. van der; Eertwegh, A.J.M. van den; Haanen, J.B.A.G.; Aarts, M.; ... ; Kapiteijn, E. 2022
Simple Summary Nodular melanoma is associated with a higher locoregional recurrence rate and worse overall survival outcomes. Whether this histologic subtype affects the efficacy of immunotherapy... Show moreSimple Summary Nodular melanoma is associated with a higher locoregional recurrence rate and worse overall survival outcomes. Whether this histologic subtype affects the efficacy of immunotherapy or targeted therapy is unclear. The aim of our multi-center nationwide study is to identify the efficacy of immunotherapy and BRAF/MEKi therapy in metastatic nodular melanoma compared with the efficacy in metastatic superficial spreading melanoma. Our study results demonstrate no difference between the effectiveness of immunotherapy and BRAF/MEKi in metastatic nodular versus superficial melanoma patients. A shorter distant metastasis-free survival and reduced overall survival (measured as the time between primary melanoma up to death or last follow-up) was observed in the nodular melanoma patient group, suggesting worse overal survival of nodular melanoma is mainly driven by propensity of metastatic outgrowth of nodular melanoma after primary diagnosis. Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7-4.2) compared with SSM patients at 3.1 years (CI 95% 1.3-6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85-1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81-1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis. Show less
Rauwerdink, D.J.W.; Doorn, R. van; Hage, J. van der; Eertwegh, A.J.M. van den; Haanen, J.B.A.G.; Aarts, M.; ... ; Kapiteijn, E. 2022
Nodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic... Show moreNodular melanoma (NM) is associated with a higher locoregional and distant recurrence rate compared with superficial spreading melanoma (SSM); it is unknown whether the efficacy of systemic therapy is limited. Here, we compare the efficacy of immunotherapy and BRAF/MEK inhibitors (BRAF/MEKi) in advanced NM to SSM. Patients with advanced stage IIIc and stage IV NM and SSM treated with anti-CTLA-4 and/or anti-PD-1, or BRAF/MEKi in the first line, were included from the prospective Dutch Melanoma Treatment Registry. The primary objectives were distant metastasis-free survival (DMFS) and overall survival (OS). In total, 1086 NM and 2246 SSM patients were included. DMFS was significantly shorter for advanced NM patients at 1.9 years (CI 95% 0.7–4.2) compared with SSM patients at 3.1 years (CI 95% 1.3–6.2) (p < 0.01). Multivariate survival analysis for immunotherapy and BRAF/MEKi demonstrated a hazard ratio for immunotherapy of 1.0 (CI 95% 0.85–1.17) and BRAF/MEKi of 0.95 (CI 95% 0.81–1.11). A shorter DMFS for NM patients developing advanced disease compared with SSM patients was observed, while no difference was observed in the efficacy of systemic immunotherapy or BRAF/MEKi between NM and SSM patients. Our results suggests that the worse overall survival of NM is mainly driven by propensity of metastatic outgrowth of NM after primary diagnosis. Show less
