Hodgkin

Brentuximab Vedotin Combined With Chemotherapy in Patients With Newly Diagnosed Early-Stage, Unfavourable-Risk Hodgkin Lymphoma - PDF Version

Kumar A, Casulo C, Advani RH, Budde E, Barr PM, Batlevi CL, Caron P, Constine LS, Dandapani SV, Drill E, Drullinsky P, Friedberg JW, Grieve C, Hamilton A, Hamlin PA, Hoppe RT, Horwitz SM, Joseph A, Khan N, Laraque L, Matasar MJ, Moskowitz AJ, Noy A, Palomba ML, Schöder H, Straus DJ, Vemuri S, Yang J, Younes A, Zelenetz AD, Yahalom J, Moskowitz CH.

J Clin Oncol. 2021 Apr 28:JCO2100108. doi: 10.1200/JCO.21.00108

PURPOSE

To improve curability and limit long-term adverse effects for newly diagnosed early-stage (ES), unfavourable-risk Hodgkin lymphoma.

METHODS

In this multicenter study with four sequential cohorts, patients received four cycles of brentuximab vedotin (BV) and doxorubicin, vinblastine, and dacarbazine (AVD). If positron emission tomography (PET)-4-negative, patients received 30-Gy involved-site radiotherapy in cohort 1, 20-Gy involved-site radiotherapy in cohort 2, 30-Gy consolidation-volume radiotherapy in cohort 3, and no radiotherapy in cohort 4. Eligible patients had ES, unfavourable-risk disease. Bulk disease defined by Memorial Sloan Kettering criteria (> 7.0 cm in maximal transverse or coronal diameter on computed tomography) was not required for cohorts 1 and 2 but was for cohorts 3 and 4. The primary end point was to evaluate safety for cohort 1 and to evaluate complete response rate by PET for cohorts 2-4.

RESULTS

Of the 117 patients enrolled, 116 completed chemotherapy, with the median age of 32 years: 50% men, 98% stage II, 86% Memorial Sloan Kettering-defined disease bulk, 27% traditional bulk (> 10 cm), 52% elevated erythrocyte sedimentation rate, 21% extranodal involvement, and 56% > 2 involved lymph node sites. The complete response rate in cohorts 1-4 was 93%, 100%, 93%, and 97%, respectively. With median follow-up of 3.8 years (5.9, 4.5, 2.5, and 2.2 years for cohorts 1-4), the overall two-year progression-free and overall survival were 94% and 99%, respectively. In cohorts 1-4, the two-year progression-free survival was 93%, 97%, 90%, and 97%, respectively. Adverse events included neutropenia (44%), febrile neutropenia (8.0%), and peripheral neuropathy (54%), which was largely reversible.

CONCLUSION

BV + AVD × four cycles is a highly active and well-tolerated treatment program for ES, unfavourable-risk Hodgkin lymphoma, including bulky disease. The efficacy of BV + AVD supports the safe reduction or elimination of consolidative radiation among PET-4-negative patients.