Evaluation of Maintenance Therapy in Cutaneous T-Cell Lymphoma Patients Receiving Total Skin Electron Beam Radiation Therapy
Authors: Kudelka Matthew , Lechowicz Mary Jo , Khan Mohammad K , Esiashvili Natia , Flowers Christopher R , Allen Pamela 
Published: October 2019

Abstract
Introduction: Total skin electron beam (TSEB) therapy is a well-established treatment modality for patients suffering from cutaneous T-cell lymphoma (CTCL). It is often augmented with maintenance therapy, including skin directed and systemic therapies. However, the utility of maintenance therapy remains controversial. We performed a retrospective analysis in patients with CTCL to assess whether maintenance therapy following TSEB improved outcomes.
Methods: We conducted a single center retrospective analysis at the Winship Cancer Center of Emory University analyzing CTCL patients who received TSEB from 1998 - 2018. Patients who received TSEB were selected from an existing cutaneous lymphoma database, and cross referenced with a list of patients obtained from the Emory Cancer registry through the Lymphoid Malignancies Enterprise Architecture Database (LEAD) under an IRB-approved protocol. Consent was waived due to the retrospective nature of the project. The primary objective was to assess progression free survival in patients who received maintenance therapy following TSEB (PFS-TSEB) compared to those who did not. Maintenance therapy was defined as therapy started either concurrently or within 1 month of the initiation of TSEB. Secondary objectives were to assess overall survival following TSEB (OS-TSEB), and OS following diagnosis (OS). Additionally, we evaluated patient demographics, number of treatments, and time to TSEB from diagnosis. Equality of variances between groups was assessed with F-test. Numerical variables were analyzed with unpaired two-tailed t-tests or Welch's t-test and categorical variables were analyzed with chi-squared tests.
Results: 101 patients with a median age of diagnosis of 55 years (range 10 - 89, 95% CI 52 - 58) underwent TSEB. 52% of patients were male, 48% female; 50% were black, 46% white/Hispanic, 65 % had MF, 16% SS, 16% CTCL NOS, 1% CD30+ CTCL, and 2% other. At diagnosis, 33% were stage 1, 39% stage 2, 10% stage 3, and 18% stage 4.
48% of patients received maintenance treatment and 52% did not; 36% of maintenance was given concurrently with TSEB, 34% after, and 30% unknown. The most common maintenance therapies were bexarotene (29%), interferon (23%), and PUVA (15%). From diagnosis, median time to first treatment was 48 days (IQR 11 - 152), time to TSEB was 429 days (IQR 136 - 1225), and median time to first treatment after TSEB was 51 days (IQR 18 - 115). A median of 2 therapies were received prior to TSEB (IQR 1 - 4; 1 skin-directed, 1 systemic, 0 RT). A median of 2 therapies occurred following TSEB (IQR 0 - 4.5; 0 skin-directed, 1 systemic, 0 RT). The most common skin directed and systemic treatments overall were topical steroids (pre, post-TSEB), PUVA (pre-TSEB), and retinoids (post-TSEB).
Overall, 80% of patients progressed after TSEB with a median time to progression of 118 days (IQR 36.5 - 231.5). OS-TSEB and OS were 642.5 d (IQR 248 - 1587.5) and 1523 (IQR 785 - 2698), respectively, with 46% of patients alive and 54% dead. In comparing outcomes of maintenance to no maintenance, PFS-TSEB was 171 days (IQR 30.25 - 333.75) versus 66.5 days (IQR 30 - 178.75) (Welch's t-test, P = .067), OS-TSEB was 1135 days (IQR 476.5 - 1845.5) versus 433.5 (IQR 219 - 1309.75) (t-test, P = .046), and OS was 1871 (IQR 961 - 2698) versus 1329.5 days (IQR 676.5 - 2830.75) (t-test, P = 0.74), respectively. We found no difference in gender, race, diagnosis, stage, or age at diagnosis between maintenance and no maintenance groups. However, in comparing maintenance to no maintenance, time to initiate TSEB from diagnosis was shorter in the maintenance group (322 days [109.5 - 772] versus 456 days [IQR 152 - 1784]) (t-test, P = 0.041). Median total number of treatments was 8 (IQR 4 - 10) versus 5 (IQR 3-9) (t-test, P = 0.052), respectively.
Conclusion:
We defined demographics, diagnoses, stage, treatment number, treatment type, and outcomes in a cohort of CTCL patients undergoing TSEB. Patients receiving maintenance therapy had an increase in overall survival and a trend towards an increase in progression-free survival measured after TSEB. A possible limitation to these findings is that patients receiving maintenance therapy in our cohort received TSEB earlier than those without maintenance, with a trend towards more overall treatments. Our retrospective findings suggest a benefit of maintenance therapy in CTCL following TSEB and provide a basis for initiating prospective studies to further evaluate this approach.

Disclosures
Flowers: Gilead: Research Funding; Burroughs Wellcome Fund: Research Funding; Abbvie: Consultancy, Research Funding; Pharmacyclics: Research Funding; Gilead: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech/Roche: Consultancy; BeiGene: Research Funding; Janssen Pharmaceutical: Research Funding; Pharmacyclics/ Janssen: Consultancy; Spectrum: Consultancy; Karyopharm: Consultancy; Abbvie: Research Funding; Genentech/Roche: Research Funding; OptumRx: Consultancy; Millennium/Takeda: Research Funding; Celgene: Research Funding; Denovo Biopharma: Consultancy; TG Therapeutics: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding. Allen:Merck: Research Funding; Bayer: Consultancy.