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Despite the improved survival rates of patients with advanced stage melanoma since the introduction of ICIs, many patients do not have (long‐term) benefit from these treatments. There is evidence that the exposome, an accumulation of host‐extrinsic factors including environmental influences, could impact ICI response. Recently, a survival benefit was observed in patients with BRAF wild‐type melanoma living in Denmark who initiated immunotherapy in summer as compared to winter. As the Netherlands lies in close geographical proximity to Denmark and has comparable seasonal differences, a Dutch validation cohort was established using data from our nationwide melanoma registry. In this study, we did not observe a similar seasonal difference in overall survival and are therefore unable to confirm the Danish findings. Validation of either the Dutch or Danish findings in (combined) patient cohorts from other countries would be necessary to determine whether this host‐extrinsic factor influences the response to ICI‐treatment. [ABSTRACT FROM AUTHOR]

We collected peripheral blood stem cells (PBSC) in 19 early chronic phase CML patients following each of two consecutive cycles of intensive chemotherapy (CT) to evaluate whether an additional cycle of CT would increase Philadelphia (Ph)-negativity of the PBSC harvest. Autologous SCT (autoSCT) was performed if a major cytogenetic response (MCR) of the PBSC harvest was obtained. CT consisted of cytarabine 200 mg/ m2/day (days 1–7)/idarubicin 12 mg/m2/day (days 1–2) (cycle one) and cytarabine 2000 mg/m2/day (days 1–6)/amsacrine 120 mg/m2/day (days 1–3) (cycle two). One patient died of fungal pneumonia after the first cycle. Stem cells were harvested in 18 patients after cycle one and in 16 patients after cycle two. After the first cycle, all patients showed a cytogenetic response of their graft (MCR in eight patients: three complete, five partial), after cycle two, seven patients obtained an MCR (one complete, six partial). Seven patients became eligible for autoSCT. All patients proceeded with IFNα maintenance. Currently, 16 patients are alive. At the latest cytogenetic examination of bone marrow, four patients showed an MCR and four a minor response. In conclusion, although a second cycle of CT may contribute to elimination of leukemia residing in the patient, it appeared to be ineffective in improving the Ph-negativity of the PBSC graft. Bone Marrow Transplantation (2000) 25, 1147–1155. [ABSTRACT FROM AUTHOR]

Background: Adjuvant anti-PD-1 therapy improves relapse free survival in stage III melanoma, but also leads to immune-related adverse events (irAEs). Older patients are of particular interest due to comorbidities and frailty, which may impact their ability to tolerate irAEs and benefit from anti-PD-1 therapy. This study aimed to explore associations between clinical parameters and the occurrence of grade ≥ 3 irAEs and recurrence-free survival (RFS) in older patients with radically resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy., Methods: Patients aged ≥ 65 with resected stage III/IV cutaneous melanoma treated with adjuvant anti-PD-1 therapy between 2018 and 2022 were selected using real-world data from the nationwide Dutch Melanoma Treatment Registry (DMTR). A univariate and multivariable logistic regression was used to compare determinants of grade ≥ 3 irAEs, and univariate and multivariable Cox-proportional hazard models were fitted to identify factors influencing RFS., Results: The study included 885 patients, with 280 aged 75 and older. The incidence of grade ≥ 3 irAEs was 15.5 % in the 65-74 age group and 13.9 % in the ≥ 75 age group. No significant correlation was found between age and grade ≥ 3 irAEs. However, an increasing number of comorbidities was associated with a higher risk of grade ≥ 3 irAEs (multivariable analyses: OR 1.83, 95 % C.I. 0.99-3.40). The 1-year RFS rate of 80.0 % of this study was comparable to those reported in previous registration trials and real-world data. Having ≥ 3 comorbidities was significantly associated with a decrease in RFS (HR: 1.68, 95 % C.I. 1.15-2.44)., Conclusion: Older patients had similar benefit of adjuvant immunotherapy compared to older subgroups in previous trials. However, patients with multiple comorbidities were at increased risk of grade ≥ 3 irAEs and had a lower RFS. This should be considered when deciding upon adjuvant treatment., Competing Interests: Declaration of Competing Interest All remaining authors have declared no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors., Methods: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression., Results: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m 2 cyclophosphamide/>300 mg/m 2 doxorubicin versus ≤2250 mg/m 2 /≤150 mg/m 2 , respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab., Conclusion: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m 2 cyclophosphamide/>300 mg/m 2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients., Competing Interests: Disclosure MJK has received research support from Kite/Gilead and financial compensation for attending advisory boards and/or presentations from Roche, Kite/Gilead, Novartis, BMS/Celgene, Miltenyi Biotec, Takeda and Adicet Bio. All other authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The objective of this study was to evaluate trends in survival and health care costs in metastatic melanoma in the era of targeted and immunotherapeutic drugs., Materials and Methods: Data on survival and health care resource use were retrieved from the Dutch Melanoma Treatment Registry. The Kaplan-Meier method was used to estimate overall survival. Health care costs and budget impact were computed by applying unit costs to individual patient resource use. All outcomes were stratified by year of diagnosis., Results: Baseline characteristics were balanced across cohort years. The percentage of patients receiving systemic treatment increased from 73% in 2013 to 90% in 2018. Patients received on average 1.85 [standard deviation (SD): 1.14] lines of treatment and 41% of patients received at least two lines of treatment. Median survival increased from 11.8 months in 2013 [95% confidence interval (CI): 10.7-13.7 months] to 21.1 months in 2018 (95% CI: 18.2 months-not reached). Total mean costs were €100 330 (SD: €103 699); systemic treatments accounted for 84% of the total costs. Costs for patients who received systemic treatment [€118 905 (SD: €104 166)] remained reasonably stable over the years even after the introduction of additional (combination of) novel drugs. From mid-2013 to 2018, the total budget impact for all patients was €452.79 million., Conclusion: Our study shows a gain in survival in the era of novel targeted and immunotherapeutic drugs. These novel drugs came, however, along with substantial health care costs. Further insights into the cost-effectiveness of the novel drugs are crucial for ensuring value for money in the treatment of patients with metastatic melanoma., Competing Interests: Disclosure ACJvA reports grants and personal fees from Amgen and Merck-Pfizer; and personal fees from Bristol-Myers Squibb, Novartis, MSD-Merck, Pierre Fabre, Sanofi, and 4SC, outside the submitted work. AJMvdE reports personal fees from BMS, MSD, Merck, Sanofi, Roche, Novartis, Eisai, Ipsen, Pfizer, and Pierre Fabre; and grants from Grant for clinical studies, outside the submitted work. MGF reports grants from Roche Nederland B.V., Daiichi Sankyo, Abbvie, Gilead Sciences Netherlands BV, and Astellas Pharma BV, outside the submitted work. JWBdG reports personal fees from BMS, MSD, Pierre Fabre, and Servier, outside the submitted work. JBAGH reports grants and other from BMS, MSD, Novartis, BioNTech, and Amgen; other from Achilles Tx, GSK, Immunocore, Ipsen, Merck Serono, Molecular Partners, Pfizer, Roche/Genentech, Sanofi, Seattle Genetics, Third Rock Ventures, and Vaximm; and personal fees from Neogene Tx, outside the submitted work. GAPH reports consulting and advisory role: Amgen, Roche, MSD, BMS, Pfizer, Novartis, Pierre Fabry, paid to the institution (UMCG); and research grant from BMS and Seerave, paid to the institution (UMCG). DP reports personal fees from BMS advisory board and Pierre Fabre advisory board, outside the submitted work. KPMS reports personal fees from Novartis, Roche, Pierre Fabre, MSD, BMS, and Abbvie, outside the submitted work. AAMvdV reports other from BMS, MSD, Merck, Sanofi, Roche, Novartis, Eisai, Ipsen, Pfizer, and Pierre Fabre, outside the submitted work. HMW reports non-financial support from Ipsen; personal fees from Roche; and personal fees and non-financial support from Astellas, outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The treatment landscape has completely changed for advanced melanoma. We report survival outcomes and the differential impact of prognostic factors over time in daily clinical practice., Methods: From a Dutch nationwide population-based registry, patients with advanced melanoma diagnosed from 2013 to 2017 were analysed (n = 3616). Because the proportional hazards assumption was violated, a multivariable Cox model restricted to the first 6 months and a multivariable landmark Cox model from 6 to 48 months were used to assess overall survival (OS) of cases without missing values. The 2017 cohort was excluded from this analysis because of the short follow-up time., Results: Median OS of the 2013 and 2016 cohort was 11.7 months (95% confidence interval [CI]: 10.4-13.5) and 17.7 months (95% CI: 14.9-19.8), respectively. Compared with the 2013 cohort, the 2016 cohort had superior survival in the Cox model from 0 to 6 months (hazard ratio [HR] = 0.55 [95% CI: 0.43-0.72]) and in the Cox model from 6 to 48 months (HR = 0.68 [95% CI: 0.57-0.83]). Elevated lactate dehydrogenase levels, distant metastases in ≥3 organ sites, brain and liver metastasis and Eastern Cooperative Oncology Group performance score of ≥1 had stronger association with inferior survival from 0 to 6 months than from 6 to 48 months. BRAF-mutated melanoma had superior survival in the first 6 months (HR = 0.50 [95% CI: 0.42-0.59])., Conclusion(s): Prognosis for advanced melanoma in the Netherlands has improved from 2013 to 2016. Prognostic importance of most evaluated factors was higher in the first 6 months after diagnosis. BRAF-mutated melanoma was only associated with superior survival in the first 6 months., Competing Interests: Conflict of interest statement AvdE reports advisory relationships with Amgen, Bristol-Myers Squibb, Roche, Novartis, MSD, and Pierre-Fabre. AvA reports consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, and 4SC and research grants not related to this paper from Amgen, BMS, and Novartis. JdG reports personal fees outside the submitted work from Bristol-Myers Squibb, Roche, Pierre-Fabre, Servier, and MSD, Novartis. GH reports consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Roche, MSD, Pfizer, and Novartis and research grants not related to this paper from Bristol-Myers Squibb, and Seerave. EK has consultancy/advisory relationships with Amgen, Bristol-Myers Squibb, Novartis, Roche, Merck, Pierre-Fabre, EISAI, Bayer, and Genzyme-Sanofi and research grants not related to this paper from Novartis and Bristol-Myers Squibb. KS advisory relationships with Bristol-Myers Squibb, Roche, Novartis, MSD, and Pierre-Fabre. AvdV reports consultancy relationships with Bristol-Myers Squibb, MSD, Roche, Novartis, Pierre-Fabre, Pfizer, Sanofi, Ipsen, and Eisai. JH reports advisory relationships with Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Celsius Therapeutics, GSK, Immunocore, Ipsen, MSD, Merck Serono, Novartis, Neon Therapeutics, Pfizer, Roche/Genentech, Sanofi, and Seattle Genetics and research grants not related to this paper from Novartis, Bristol-Myers Squibb, MSD, and Neon Therapeutics. All grants were paid to the institutions. The funders had no role in the writing of this article or decision to submit it for publication., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Two patients, men aged 77 and 66 years, presented with a vasculitis. Due to an abnormal blood smear they were referred to the internist, who subsequently diagnosed a myelodysplastic syndrome (MDS). They were initially treated with a high dose of corticosteroids and this dosage later became a maintenance dose. Immunological phenomena occur in 10-14% of MDS patients and seem to have a poor prognosis. Most patients respond well to treatment with corticosteroids. Occasionally, favourable haematological responses to corticosteroid therapy are seen, although this was not the case in the two patients described. When patients present with an immunological disorder, such as a vasculitis or an autoimmune disease, it is important to be aware of the possibility of an underlying MDS.