Delineation of clinical and biological factors associated with cutaneous squamous cell carcinoma among patients with chronic lymphocytic leukemia - 29/09/20

Doi : 10.1016/j.jaad.2020.06.1024

Geffen Kleinstern, PhD ^a, Abdul Rishi, MBBS ^b, Sara J. Achenbach, MS ^a, Kari G. Rabe, MS ^a, Neil E. Kay, MD ^c, Tait D. Shanafelt, MD ^d, Wei Ding, MBBS ^c, Joe F. Leis, MD, PhD ^e, Aaron D. Norman, MPH ^a, Timothy G. Call, MD ^c, James R. Cerhan, MD, PhD ^a, Sameer A. Parikh, MBBS ^c, Christian L. Baum, MD ^f, Susan L. Slager, PhD ^a,^⁎
^a Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota
^b Department of Internal Medicine, Mercy Hospital, Saint Louis, Missouri
^c Division of Hematology, Mayo Clinic, Rochester, Minnesota
^d Division of Hematology, Department of Medicine, Stanford University, Stanford, California
^e Department of Hematology and Oncology, Mayo Clinic, Phoenix, Arizona
^f Department of Dermatology, Mayo Clinic, Rochester, Minnesota

^∗Correspondence to: Susan L. Slager, PhD, Mayo Clinic, 200 1st St SW, Rochester, MN, 55905.Mayo Clinic200 1st St SWRochesterMN55905

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Tuesday 29 September 2020
Cet article a été publié dans un numéro de la revue, cliquez ici pour y accéder

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.

Le texte complet de cet article est disponible en PDF.

Key words : chronic lymphocytic leukemia, cutaneous squamous cell carcinoma

Abbreviations used : BCC, CI, CLL, HR, IPI, NMSC, PRS, SCC, SNP

Plan

Methods

Study population

CLL clinical and prognostic data

	Authors Kleinstern and Rishi contributed equally.
	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.
	IRB approval status: The cohort protocol was approved by the Mayo Clinic Institutional Review Board.
	Reprints not available from the authors.