ISHL10 Abstract P088

PET-adapted therapy with Brentuximab vedotin (BV) and Augmented ICE for relapsed/refractory Hodgkin lymphoma – Lack of improvement with 3 versus 2 cycles of weekly BV

Introduction: PET-adapted salvage therapy with brentuximab vedotin (BV) and augmented ICE (augICE) produced a PET-negative (neg) rate of 76% (Moskowitz, AJ. Lancet Oncology 2015). In this study, 45 patients (pts) received 2 cycles of BV (1.2mg/Kg weekly, 6 doses over 8 weeks) and those with residual PET-avidity received 2 cycles of augICE (ifosfamide 5000mg/m2 x2 doses, carboplatin AUC 5, etoposide 200mg/m2 x3 doses) prior to ASCT. With a median follow-up of 40 months, 44 of 45 patients proceeded to ASCT and 3-year event free survival (EFS) and overall survival (OS) were 80% and 93%, respectively. 27% achieved PET-neg status following BV and received no additional chemotherapy before ASCT. We enrolled a second cohort aimed at improving the PET-neg rate to BV by administering 3 rather than 2 cycles. Methods: On cohort 2, pts received 3 cycles of weekly BV (1.2mg/Kg weekly, 9 doses over 12 weeks). PET-neg pts (by Deauville 1-2) proceeded to ASCT while those with residual PET-avidity received augICE for 2 cycles before ASCT. Transplant conditioning included involved field radiation for eligible patients. Results: 20 pts enrolled onto cohort 2. Characteristics appear in the table. After BV, 6 (30%) pts were PET-neg (by Deauville 1-2) and 7 (6 Deauville 2, 1 Deauville 3) proceeded directly to ASCT. 13 pts received additional treatment before ASCT; 10 received augICEx2, 2 received ICEx2, and 1 received ICEx1 and augICEx1. All patients proceeded to ASCT and pre-transplant PET was negative by Deauville 1-2 for 16 (80%) pts. The median follow-up for cohort 2 was 24 months and 2-year EFS and OS were 85% and 100%, respectively. For cohorts 1 plus 2, the PET-neg rate following BV and before transplant were 28% and 78%, respectively. The 2 year EFS was 82%. By multivariate analysis, factors predictive of EFS included age>40 (p<0.001), advanced stage (p=0.001), refractory disease (p=0.001), and pre-transplant PET (0.003). Conclusion: PET-adapted salvage therapy with BV followed by augICE produces a PET-neg rate of 78%. With this treatment program, 28% patients achieved PET-neg status and proceeded to ASCT following BV alone. Increasing the number of weekly BV cycles from 2 to 3 did not improve the PET-neg rate achieved with single-agent BV. Pre-transplant PET remains an important prognostic factor for relapsed/refractory HL and achievement of PET-negative status should continue to be the primary objective of studies evaluating novel salvage regimens.

Authors

  • A.J. Moskowitz
  • H.r. Schode
  • J. Yahlom
  • S.J. McCall
  • S.Y. Fox
  • J. Gerecitano
  • R. Grewal
  • P.A. Hamlin
  • S. Horwitz
  • R. Kobos
  • A. Kumar
  • M. Matasar
  • A. Noy
  • M.L. Palomba
  • M.A. Merales
  • C.S. Portlock
  • C. Sauter
  • N. Shukla
  • P. Steinherz
  • D. Straus
  • T. Trippett
  • A. Younes
  • A. Zelenetz
  • C.H. Moskowitz