Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response

Kooij, Monique K. Van der; Wetzels, Marjolein J A L; Aarts, Maureen J.B.; Berkmortel, Franchette W P J van den; Blank, Christian U.; Boers‐Sonderen, Marye J.; Dierselhuis, Miranda P.; Groot, Jan Willem B. de; Hospers, Geke A.P.; Piersma, Djura; Rijn, Rozemarijn S. van; Suijkerbuijk, Karijn P M; Tije, Albert J. ten; Veldt, Astrid A.M. van der; Vreugdenhil, Gerard; Wouters, Michel W. J. M.; Haanen, John B.A.G.; Eertwegh, A.J.M. van den; Bastiaannet, E.

doi:10.3390/cancers12082072

Cited by 23 publications

(24 citation statements)

References 42 publications

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“…Our data show that advanced melanoma in women more frequently harbors a BRAF V600E mutation, while melanoma in men more frequently has a NRAS or BRAF V600K mutation. Our data strengthen data from previously published smaller cohorts [ 37 , 38 , 39 ].…”

Section: Discussionsupporting

confidence: 91%

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study

Kooij

Dekkers

Aarts

et al. 2021

Cancers

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Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013–July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3–4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients ≥60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference.

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Section: Discussionsupporting

confidence: 91%

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study

Kooij

Dekkers

Aarts

et al. 2021

Cancers

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“…Younger patients may have a more active immune system which can lead to hepatitis or other IRAEs [ 32 ]. A recent study showed no increased rate of grade 3–4 side effects in general in younger patients compared to older adults [ 33 ]. However, for combination therapy-induced hepatitis it does seem a relevant risk factor.…”

Section: Discussionmentioning

confidence: 99%

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

et al. 2021

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Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.

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“…Australia; 6 School of Public Health, The University of Queensland, Brisbane, Australia; 7 Queensland Melanoma Project (Princess Alexandra Hospital), The University of Queensland, Brisbane, Australia; and 8 Cancer Research UK Manchester and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK Email: reza.ghiasvand@kreftregisteret.no…”

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confidence: 99%

“…Likewise, a recent cohort study found that baseline characteristics differed between young and old with advanced melanoma, but once treatment was initiated, tumour responses and melanoma-specific survival were similar. 6 Table 1 Risk of recurrence and association between sex, tumour characteristics and recurrence of primary melanoma, total and by age at diagnosis Total (n = 700)…”

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Patient age and risk of recurrence of primary melanoma at high risk of spread

et al. 2020

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underlying haematological condition. To our knowledge, this is the first report describing efficacy of ICI for NMSC in this context. The successful experiences with ICI in our cases provide important insights relevant to the clinical management of such patients. Firstly, our cases add to the scant literature supporting that patients with NMSC who may be relatively immunocompromised due to concurrent haematological malignancies can still respond to ICI. 7 Secondly, our experiences suggest that JAK inhibition with ruxolitinib, which possibly facilitated the development of NMSC in these patients, may not automatically confer ICI resistance. It has been reported that mutations of JAK1 and JAK2 do not result in primary resistance to ICI in melanoma. 8 It is plausible that NMSC developing in a relatively immune-suppressed environment may not need to develop sophisticated mechanisms to evade the immune system, and hence, retains susceptibility to ICI.In conclusion, the durable response to ICI in our three patients, who were also receiving ruxolitinib, suggests that concurrent treatment with JAK inhibitors may not fully suppress the immune effector mechanisms of PD-1/PD-L1 blockade. A trial of ICI is a reasonable treatment option for treating advanced NMSC in these patients.

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Age Does Matter in Adolescents and Young Adults versus Older Adults with Advanced Melanoma; A National Cohort Study Comparing Tumor Characteristics, Treatment Pattern, Toxicity and Response

Cited by 23 publications

References 42 publications

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study

Sex-Based Differences in Treatment with Immune Checkpoint Inhibition and Targeted Therapy for Advanced Melanoma: A Nationwide Cohort Study

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

Patient age and risk of recurrence of primary melanoma at high risk of spread

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