Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

Cass, Samuel; Tobin, Joshua W.D.; Seo, Yongwoo David; Gener-Ricos, Georgina; Keung, Emily Z.; Burton, Elizabeth M.; Davies, Michael A.; McQuade, Jennifer L.; Lazar, Alexander J.; Mason, Robert M.; Millward, Michael; Sandhu, Shahneen; Khoo, Christine; Warburton, Lydia; Guerra, Veronica; Haydon, Andrew; Dearden, Helen; Menzies, A.M.; Carlino, Matteo S.; Smith, Jessica L.; Mollee, Peter; Burgess, Melinda; Mapp, Sally; Keane, Colm; Atkinson, Victoria; Markovic, Svetomir N.; Ding, Wei; Call, Timothy G.; Hampel, Paul J.; Long, Georgina V.; Wargo, Jennifer A.; Ferrajoli, Alessandra

doi:10.1016/j.annonc.2023.06.007

Cited by 3 publications

(3 citation statements)

References 30 publications

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“…There are often concerns about the tolerability of chemotherapy in elderly and immunocompromised patients and, thus, the exploration of the efficacy of ICIs in these patients is desirable. In our cohort, four patients were immunocompromised, a group where there have been historical concerns about reduced response rates to ICIs [42]. However, despite this, durable responses were seen in three out of four (75%) of these patients.…”

Section: Discussionmentioning

confidence: 92%

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors

McLean,

Lim,

Angel

et al. 2024

Cancers

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Non-melanomatous cutaneous spindle cell neoplasms are a rare group of malignancies that present a diagnostic challenge, and for which there is a lack of consensus on how to best manage patients with advanced disease and only limited reports of immune-checkpoint inhibitor (ICI) responses. In this study, we performed a single-center retrospective review of treatment outcomes for all advanced non-melanomatous cutaneous spindle cell neoplasms treated with ICIs. Blinded histopathology reviews occurred to confirm each diagnosis. Comprehensive tumour profiling included whole exome sequencing for tumour mutational burden (TMB) and ultraviolet(UV) signatures, and immunohistochemistry for immune-cell infiltration (CD4/CD3/CD8/CD103/CD20) and immune-checkpoint expression (PD-L1/LAG3/TIGIT). Seven patients were identified. The objective response rate was 86% (6/7) with five complete responses (CR). Responses were durable with two patients in CR > 30 months after ICI commencement. All patients had high TMB and UV signatures. One patient had PD-L1 100% (combined positive score) with abundant immune-cell infiltration and LAG3 expression. In advanced non-melanomatous cutaneous spindle cell neoplasms, excellent responses to ICIs with durable disease control were observed. ICIs are worthy of further exploration in these patients. UV signatures and high TMB could be used to help select patients for treatment.

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Section: Discussionmentioning

confidence: 92%

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors

McLean,

Lim,

Angel

et al. 2024

Cancers

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“…Before development of immune checkpoint receptor inhibitors (ICIs), there was a large difference in median survival between patients with melanoma alone compared to those with melanoma and CLL (91.4 months vs. 59.3 months, respectively) 70 . Studies investigating effect of ICIs (including nivolumab, pembrolizumab, and ipilimumab) on advanced melanoma in CLL patients indicate comparable objective response rates and PFS compared to patients without hematologic malignancy, although prior CLL treatment (particularly fludarabine) and high/intermediate risk CLL have been associated with poorer melanoma‐specific outcomes following checkpoint blockade 71–74 . ICIs have no demonstrated effect on CLL 75 …”

Section: Epidemiology Of Melanoma In Cll Patientsmentioning

confidence: 99%

“…with poorer melanoma-specific outcomes following checkpoint blockade. [71][72][73][74] ICIs have no demonstrated effect on CLL. 75 Melanoma is more prevalent in patients with CLL and other types of NHL.…”

Section: Epidemi Ology Of Mel Anoma In Cll Patientsmentioning

confidence: 99%

Cutaneous malignancies in chronic lymphocytic leukemia

Zilberg,

Ferguson,

Lyons

et al. 2024

The Journal of Dermatology

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Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy that is associated with an increased risk of developing cutaneous malignancies. Clinical outcomes for these malignancies, including melanoma and keratinocyte cancers (KC), are worse for patients with CLL. Individuals with CLL develop an immunodeficiency of both the adaptive and innate immune system, which plays a role in the increased prevalence of skin cancers. This review focuses on the complex interplay between genetics, immunity, and pathogens that influence the cellular composition and biology of skin tumors and their microenvironment in CLL patients, and in comparison with other chronic hematological malignancies. It is paramount for dermatologists to be aware of the association between CLL (and chronic hematological malignancies more broadly) and cutaneous malignancies. This is a high‐risk population who require regular and vigorous dermatologic follow‐up.

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Clinical and histopathological features of advanced cutaneous squamous cell carcinoma with varying responses to cemiplimab

Hempel,

Vladimirova,

Horn

et al. 2024

J Deutsche Derma Gesell

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SummaryBackgroundMost patients with unresectable locally advanced cutaneous squamous cell carcinoma (cSCC) benefit from cemiplimab, but some do not respond. Our study aims to identify clinical and histopathological features predicting response to cemiplimab.Patients and MethodsWe analyzed 15 patients treated with cemiplimab, assessing clinical, demographic, histopathological, and immunohistochemical characteristics and correlating them with treatment response. Furthermore, effectiveness and safety were evaluated in our cohort.ResultsOur cohort included 12 males and 3 females, with a mean age of 78.1 years. The majority of tumors, accounting for 66.7%, were located in the head and neck region. Treatment was well‐tolerated, with only one grade 3 colitis. There was no correlation between immune‐related adverse events and treatment response. Non‐responders were younger (69.4 vs. 82.5 years). A history of hematological malignancy correlated with poorer response. High mitotic rate, poor tumor differentiation, high vimentin and p53, and low E‐cadherin expression were associated with worse response. Conversely, higher intratumoral inflammatory infiltrate density, presence of necrotic areas, and lower mismatch repair‐protein staining correlated with better response.ConclusionsCemiplimab is a safe and effective therapy, particularly in elderly patients. Well‐differentiated tumors with low proliferative index, intratumoral inflammatory infiltrate, and tumor necrosis may predict better clinical response.

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Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia

Cited by 3 publications

References 30 publications

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors

A Retrospective Review and Comprehensive Tumour Profiling of Advanced Non-Melanomatous Cutaneous Spindle Cell Neoplasms Treated with Immune-Checkpoint Inhibitors

Cutaneous malignancies in chronic lymphocytic leukemia

Clinical and histopathological features of advanced cutaneous squamous cell carcinoma with varying responses to cemiplimab

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