Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia

Geffen Kleinstern; Abdul Rishi; Sara J. Achenbach; Kari G. Rabe; Neil E. Kay; Tait D. Shanafelt; Wei Ding; Joe F. Leis; Aaron D. Norman; Timothy G. Call; James R. Cerhan; Sameer A. Parikh; Christian L. Baum; Susan L. Slager

doi:10.1016/j.jaad.2020.06.1024

Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia

Geffen Kleinstern, Abdul Rishi, Sara J. Achenbach, Kari G. Rabe, Neil E. Kay, Tait D. Shanafelt, Wei Ding, Joe F. Leis, Aaron D. Norman, Timothy G. Call, James R. Cerhan, Sameer A. Parikh, Christian L. Baum, Susan L. Slager

Research output: Contribution to journal › Article › peer-review

Abstract

Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. Objective: To evaluate the association of factors associated with SCC risk. Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). Limitations: The sample size decreases when combining all risk factors in a single model. Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.

Original language	English
Pages (from-to)	1581-1589
Number of pages	9
Journal	Journal of the American Academy of Dermatology
Volume	83
Issue number	6
DOIs	https://doi.org/10.1016/j.jaad.2020.06.1024
State	Published - Dec 2020
Externally published	Yes

Bibliographical note

Funding Information:
Funding sources: Funding was provided by National Institutes of Health National Cancer Institute ( CA-97274 , CA-235026 ), Specialized Programs of Research Excellence (SPORE) in Human Cancer ( P50-CA-97274 ), the Henry J. Predolin Foundation ( R01-CA-92153 ), the National Center for Advancing Translational Science ( UL1-TR-000135 ), and Mayo Clinic Cancer Center Support grant P30-CA-15083 . Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation .

Funding Information:
Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics , MorphoSys , Janssen , AstraZeneca , and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm , Pharmacyclics , MEI Pharma , and Tolero ; is on a data safety monitoring committee for Agios Pharm , Celgene , Sunesis , Cytomx Therapeutics , Morpho-Sys , Rigel Pharm , and Juno Therapeutics ; and is on an advisory board for AstraZeneca , Cytomx Therapeutics , Pharmacyclics Dava Oncology , Acerta Pharma BV , and Juno Therapeutics . Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare.

Funding Information:
Funding sources: Funding was provided by National Institutes of Health National Cancer Institute (CA-97274, CA-235026), Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50-CA-97274), the Henry J. Predolin Foundation (R01-CA-92153), the National Center for Advancing Translational Science (UL1-TR-000135), and Mayo Clinic Cancer Center Support grant P30-CA-15083. Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation.Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm, Pharmacyclics, MEI Pharma, and Tolero; is on a data safety monitoring committee for Agios Pharm, Celgene, Sunesis, Cytomx Therapeutics, Morpho-Sys, Rigel Pharm, and Juno Therapeutics; and is on an advisory board for AstraZeneca, Cytomx Therapeutics, Pharmacyclics Dava Oncology, Acerta Pharma BV, and Juno Therapeutics. Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare.

Publisher Copyright:
© 2020 American Academy of Dermatology, Inc.

Keywords

chronic lymphocytic leukemia
cutaneous squamous cell carcinoma

ASJC Scopus subject areas

Dermatology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaad.2020.06.1024

Cite this

Kleinstern, G., Rishi, A., Achenbach, S. J., Rabe, K. G., Kay, N. E., Shanafelt, T. D., Ding, W., Leis, J. F., Norman, A. D., Call, T. G., Cerhan, J. R., Parikh, S. A., Baum, C. L., & Slager, S. L. (2020). Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia. Journal of the American Academy of Dermatology, 83(6), 1581-1589. https://doi.org/10.1016/j.jaad.2020.06.1024

@article{46c0990174a3474b85a2ffb53cbcb73d,

title = "Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia",

abstract = "Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. Objective: To evaluate the association of factors associated with SCC risk. Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). Limitations: The sample size decreases when combining all risk factors in a single model. Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.",

keywords = "chronic lymphocytic leukemia, cutaneous squamous cell carcinoma",

author = "Geffen Kleinstern and Abdul Rishi and Achenbach, {Sara J.} and Rabe, {Kari G.} and Kay, {Neil E.} and Shanafelt, {Tait D.} and Wei Ding and Leis, {Joe F.} and Norman, {Aaron D.} and Call, {Timothy G.} and Cerhan, {James R.} and Parikh, {Sameer A.} and Baum, {Christian L.} and Slager, {Susan L.}",

note = "Funding Information: Funding sources: Funding was provided by National Institutes of Health National Cancer Institute ( CA-97274 , CA-235026 ), Specialized Programs of Research Excellence (SPORE) in Human Cancer ( P50-CA-97274 ), the Henry J. Predolin Foundation ( R01-CA-92153 ), the National Center for Advancing Translational Science ( UL1-TR-000135 ), and Mayo Clinic Cancer Center Support grant P30-CA-15083 . Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation . Funding Information: Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics , MorphoSys , Janssen , AstraZeneca , and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm , Pharmacyclics , MEI Pharma , and Tolero ; is on a data safety monitoring committee for Agios Pharm , Celgene , Sunesis , Cytomx Therapeutics , Morpho-Sys , Rigel Pharm , and Juno Therapeutics ; and is on an advisory board for AstraZeneca , Cytomx Therapeutics , Pharmacyclics Dava Oncology , Acerta Pharma BV , and Juno Therapeutics . Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare. Funding Information: Funding sources: Funding was provided by National Institutes of Health National Cancer Institute (CA-97274, CA-235026), Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50-CA-97274), the Henry J. Predolin Foundation (R01-CA-92153), the National Center for Advancing Translational Science (UL1-TR-000135), and Mayo Clinic Cancer Center Support grant P30-CA-15083. Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation.Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm, Pharmacyclics, MEI Pharma, and Tolero; is on a data safety monitoring committee for Agios Pharm, Celgene, Sunesis, Cytomx Therapeutics, Morpho-Sys, Rigel Pharm, and Juno Therapeutics; and is on an advisory board for AstraZeneca, Cytomx Therapeutics, Pharmacyclics Dava Oncology, Acerta Pharma BV, and Juno Therapeutics. Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2020 American Academy of Dermatology, Inc.",

year = "2020",

month = dec,

doi = "10.1016/j.jaad.2020.06.1024",

language = "English",

volume = "83",

pages = "1581--1589",

journal = "Journal of the American Academy of Dermatology",

issn = "0190-9622",

publisher = "Mosby Inc.",

number = "6",

}

Kleinstern, G, Rishi, A, Achenbach, SJ, Rabe, KG, Kay, NE, Shanafelt, TD, Ding, W, Leis, JF, Norman, AD, Call, TG, Cerhan, JR, Parikh, SA, Baum, CL & Slager, SL 2020, 'Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia', Journal of the American Academy of Dermatology, vol. 83, no. 6, pp. 1581-1589. https://doi.org/10.1016/j.jaad.2020.06.1024

TY - JOUR

T1 - Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia

AU - Kleinstern, Geffen

AU - Rishi, Abdul

AU - Achenbach, Sara J.

AU - Rabe, Kari G.

AU - Kay, Neil E.

AU - Shanafelt, Tait D.

AU - Ding, Wei

AU - Leis, Joe F.

AU - Norman, Aaron D.

AU - Call, Timothy G.

AU - Cerhan, James R.

AU - Parikh, Sameer A.

AU - Baum, Christian L.

AU - Slager, Susan L.

N1 - Funding Information: Funding sources: Funding was provided by National Institutes of Health National Cancer Institute ( CA-97274 , CA-235026 ), Specialized Programs of Research Excellence (SPORE) in Human Cancer ( P50-CA-97274 ), the Henry J. Predolin Foundation ( R01-CA-92153 ), the National Center for Advancing Translational Science ( UL1-TR-000135 ), and Mayo Clinic Cancer Center Support grant P30-CA-15083 . Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation . Funding Information: Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics , MorphoSys , Janssen , AstraZeneca , and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm , Pharmacyclics , MEI Pharma , and Tolero ; is on a data safety monitoring committee for Agios Pharm , Celgene , Sunesis , Cytomx Therapeutics , Morpho-Sys , Rigel Pharm , and Juno Therapeutics ; and is on an advisory board for AstraZeneca , Cytomx Therapeutics , Pharmacyclics Dava Oncology , Acerta Pharma BV , and Juno Therapeutics . Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare. Funding Information: Funding sources: Funding was provided by National Institutes of Health National Cancer Institute (CA-97274, CA-235026), Specialized Programs of Research Excellence (SPORE) in Human Cancer (P50-CA-97274), the Henry J. Predolin Foundation (R01-CA-92153), the National Center for Advancing Translational Science (UL1-TR-000135), and Mayo Clinic Cancer Center Support grant P30-CA-15083. Dr Kleinstern was supported by the National Institutes of Health National Cancer Institute grant R25-CA-92049 (Mayo Cancer Genetic Epidemiology Training Program). Dr Baum is supported by a Career Development Award through the Dermatology Foundation.Conflicts of interest: Research funding has been provided to the institution from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in advisory board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, and AbbVie (but was not personally compensated for his participation). Dr Kay has research funding from Acerta Pharm, Pharmacyclics, MEI Pharma, and Tolero; is on a data safety monitoring committee for Agios Pharm, Celgene, Sunesis, Cytomx Therapeutics, Morpho-Sys, Rigel Pharm, and Juno Therapeutics; and is on an advisory board for AstraZeneca, Cytomx Therapeutics, Pharmacyclics Dava Oncology, Acerta Pharma BV, and Juno Therapeutics. Wei Ding has research funding from Merck and is on an advisory board for Merck and Octapharma (no personal compensation). Authors Kleinstern, Rishi, Achenbach, Rabe, Shanafelt, Leis, Norman, Call, Cerhan, Baum, and Slager have no conflicts of interest to declare. Publisher Copyright: © 2020 American Academy of Dermatology, Inc.

PY - 2020/12

Y1 - 2020/12

N2 - Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. Objective: To evaluate the association of factors associated with SCC risk. Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). Limitations: The sample size decreases when combining all risk factors in a single model. Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.

AB - Background: The incidence of cutaneous squamous cell carcinoma (SCC) in patients with chronic lymphocytic leukemia (CLL) is significantly higher compared with age- and sex-matched controls. Objective: To evaluate the association of factors associated with SCC risk. Methods: Clinical CLL and SCC data were obtained from Mayo Clinic CLL Resource and self-reported questionnaires among patients with newly diagnosed CLL. We computed the CLL International Prognostic Index (CLL-IPI) from CLL prognostic factors, and a polygenic risk score from SCC susceptibility variants. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Among 1269 patients with CLL, the median follow-up was 7 years, and SCC subsequently developed in 124 patients. Significant associations with SCC risk were history of skin cancer (HR=4.80; 95% CI: 3.37-6.83), CLL-IPI (HR=1.42; 95% CI: 1.13-1.80), and polygenic risk score (HR=2.58; 95% CI: 1.50-4.43). In a multivariable model, these factors were independent predictors (C statistic = 0.69; 95% CI: 0.62-0.76). T-cell immunosuppressive treatments were also associated with SCC risk (HR=2.29; 95% CI: 1.47-3.55; adjusted for age, sex, and prior SCC). Limitations: The sample size decreases when combining all risk factors in a single model. Conclusion: SCC risk includes history of skin cancer, an aggressive disease at time of CLL diagnosis, receiving T-cell immunosuppressive treatments, and high polygenic risk score. Future studies should develop prediction models that include these factors to improved screening guidelines.

KW - chronic lymphocytic leukemia

KW - cutaneous squamous cell carcinoma

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U2 - 10.1016/j.jaad.2020.06.1024

DO - 10.1016/j.jaad.2020.06.1024

M3 - Article

C2 - 32682027

AN - SCOPUS:85091926759

SN - 0190-9622

VL - 83

SP - 1581

EP - 1589

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

IS - 6

ER -

Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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