Background: Despite increasing availability of therapeutic agents, Sezary syndrome (SS) remains associated with a generally poor prognosis. Typically, patients endure multi-line treatment, frequently with disappointingly short durations of clinical benefit. Time to next treatment (TTNT) measures the interval from the date of commencement of one therapy to the date of initiation of the next line of therapy, and provides a simple and reliable surrogate for duration of clinical benefit outside of clinical trials [ 1 ]. In this multi-centre collaborative study, we review the clinical outcomes of patients with SS/ mycosis fungoides (MF) with B1-2 blood involvement, and compare the treatment efficacy of the currently available systemic therapies using TTNT. Methods: In this retrospective analysis, eligible patients were identified from University Hospital Birmingham, Birmingham, Peter MacCallum Cancer Centre, Melbourne, and Hopital Saint Louis, Paris. Strict eligibility required biopsy-proven MF/SS, with B1-2 blood involvement, newly diagnosed during 1/1/2012 to 31/12/2020. Studied treatment groups include monotherapy and combination therapies of interferon, methotrexate, ECP, HDAC inhibitors, retinoids, monoclonal antibodies, biologicals, chemotherapy, allogeneic stem cell transplant, and best supportive care. The primary endpoint was TTNT, with the aim to compare the efficacy of these systemic therapies. Results: 178 patients were eligible. 77 (43%) were female, median age was 66 (17–94) years. At diagnosis, 35 (20%) patients had Stage IIIB, 131 (74%) Stage IVA and 12 (7%) Stage IVB MF/SS. Large cell transformation was present in 35 (20%) patients at time of diagnosis. A total of 802 treatment lines were delivered, of which 711 were systemic therapies and were included for analysis. Of the 178 patients, 168 received systemic therapy first-line: the most commonly delivered first-line systemic treatments were ECP-containing regimens in 42 (25%) patients (ECP-monotherapy, 17, ECP-based combination therapy, 25), retinoid monotherapy in 34 (19%), interferon monotherapy in 25 (14%) and methotrexate monotherapy in 25 (14%) patients. TTNT and overall survival data will be presented. Conclusions: As a surrogate for duration of clinical benefit, TTNT is a useful endpoint to retrospectively compare the treatment efficacy of currently available systemic therapies for SS/MF with B1-2 blood involvement. Long-term disease control with durable clinical benefit remains the ultimate goal for patients with SS/MF with blood involvement.