Sezary Syndrome and Combination Immunomodulatory Therapy: Improving Clinical Outcomes
Authors: Piliotis Eugenia , Govas Panayiota , Imrie Kevin R , Cheung Matthew C , Shear Neil , Walsh Scott , Fairlie Cathy , Barth David 
Published: April 2020

Introduction: Sezary syndrome is a rare, aggressive and advanced stage of cutaneous T cell lymphoma where patients exhibit total body erythroderma and peripheral blood involvement. Patients can progress from preexisting mycoses fungoides or present de-novo. Historically median survival has been less than two years however with current combinations of skin directed and immunomodulatory therapy median survival has been documented up to 3–4 years, however randomized trials are lacking given the rarity of this disorder. We describe the outcomes 23 patients followed in our centre diagnosed with sezary syndrome based on peripheral blood involvement and erythroderma who have been treated primarily with combination skin and immunomodulatory therapy.

Methods: A review of all patients diagnosed with sezary syndrome in our centre was conducted. Base line characteristics, survival, number and type of therapies as well as responses to treatments were recorded

Results: 23 patients were identified. 11 male, 12 female, average age at diagnosis 64.7 yrs (range 47–85). Therapies included total skin electron beam (TSEB), PUVA, Interferon, oral retinoids, and extracorporeal photophoresis (ECP). 5 patients had received prior traditional chemotherapy including CHOP, chlorambucil and purine analogues with either no or transient responses. 19 patients received a combination of all 5 therapies. 19 patients received IFN, 13 TSEB, 21 PUVA, 18 ECP and 16 oral retinoids. 7 patients received 3 or fewer therapies (3 in process of escalating therapy, 1 CR to TSEB, 3 pts refused multiagent therapy as elderly and stable on PUVA +/− retinoids). 6 patients achieved a durable complete remission while on therapy (4 received IFN/TSEB/PUVA/ECP, 1 IFN/PUVA/ECP, 1 TSEB alone), 3 patients had progressive disease, and the remainder either had partial responses or stable disease. Median follow-up was 44 months (range 9–127). Median survival of the entire cohort was 37 months (mean 52 months, range 6–108 months, 5 patients have been diagnosed in the last 12 months). There have been 5 deaths to date, median 43 months (range 33–101) from the time of diagnosis. Cause of death included 2 cardiac, 1 renal, 1 infection, and 1 progressive disease. There was no correlation between survival and LDH at presentation, sezary cell count or number of therapies. There was a modest correlation between survival and age at diagnosis (R2=0.1263). Patients who received TSEB had an average of 57 months survival vs. 33.5 months than those who did not, however this was not statistically significant. Reasons not to receive TSEB included 5 patient refusal, 3 still escalating therapy, 2 had adequate response to other therapies. Patients who achieved a CR to therapy had a median survival of 63 months (average 65 months) vs. those who did not achieve a CR had a median survival of 22 months (average 65 months).

Conclusions: Patients receiving combination immunotherapy and skin based treatments for sezary syndrome appear to be living longer than historical series. Given the small number of this cohort it was not possible to statistically determine variables predictive of prolonged survival, however patients who received TSEB and or achieved a CR to treatment had median survival of approximately 5 years. The majority of patients received maintenance immunotherapy to sustain disease control.