Phase Ib study of brentuximab vedotin (BV) with low-dose total skin electron beam (LD-TSEB) for treatment of mycosis fungoides (MF) and Sezary syndrome (SS).
e20037 Background: MF is generally not curable, causing severe symptoms and eventually leading to patient (pt) death. LD-TSEB is currently used for diffuse skin lesions but with short duration of response. BV is effective and approved for MF but also limited by short duration of response. In this study we proposed to evaluate the feasibility of combining these 2 treatments by assessing the safety and response rate/duration in these pts. Methods: Pts with stage IB - IVA CD30+ MF or SS who were candidates for TSEB were recruited for a 2-cohort open-label phase 1b trial. Cohort A included pts with earlier stage disease; cohort B included pts with more advanced disease. BV was given at 1.8 mg/kg 3 wks before initiation of TSEB and then every 3 wks. Pts in Cohort A received 3 doses of BV; pts in Cohort B continued BV until disease progression or unacceptable toxicity, up to 2 years. Standard 12 Gy TSEB was administered in 6 fractions (2/wk) beginning 3 wks after the first dose of BV. The Modified Severity Weighted Assessment Tool (mSWAT) was used to determine skin involvement at baseline and during and after treatment. Skindex-16 was used to assess pt-reported symptoms and toxicities. Pts were seen weekly during TSEB, monthly after TSEB, and every 3 months after the last dose of BV for response evaluation and time to progression (TTP). Results: Five pts were enrolled and treated in this study. Two were enrolled to Cohort A, and 3 were enrolled to Cohort B. One pt in Cohort B expired before completing study treatment due to comorbidity unrelated to MF. The other pt data is listed in the table. None of the pts developed grade 4 or 5 toxicities; pt 1 developed recurrent neuropathy and stopped BV after 5 cycles. Conclusions: As BV became approved for the indication, accrual slowed, and the trial was stopped with very few pts. These pt cohorts are heavily treated before trial entry, making conclusions regarding response hard to generalize. However, the combination of BV and TSEB is well tolerated with no significant increase in skin toxicity. Response rate seems comparable to current standard of care, though with no improvement in duration of response over BV alone. Clinical trial information: NCT02822586 . [Table: see text]