ABVD followed by BV consolidation in risk-stratified patients with limited-stage Hodgkin lymphoma

Abstract

Approximately 90% of limited-stage Hodgkin lymphoma (HL) patients are projected to be cured with standard therapy, but many do not live their expected life span because of late treatment-related complications. New treatment paradigms are needed to reduce the use of radiation therapy (RT) as well as conventional chemotherapy drugs while improving upon current standard-of-care survival outcomes. In this phase 2 multicenter study, patients with non-bulky limited-stage HL received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by brentuximab vedotin (BV) consolidation. Forty-one patients were enrolled, and patient characteristics included median age of 29 years (range, 19 to 67 years), 58% were female, 45% had unfavorable disease, and 98% had stage II disease. Based on positron emission tomography (PET)-based risk stratification, patients received 2 to 6 cycles of ABVD followed by 6 cycles of BV. After ABVD followed by BV, 95% of evaluable patients (37 out of 39; 95% confidence interval [CI], 83%-99%) achieved PET-negative status. In the intent-to-treat patient population, the estimated 3-year progression-free survival (PFS) rate was 92%, and the overall survival (OS) rate was 97%, with a median follow-up of 47 months. All 37 patients who achieved negative PET status after BV consolidation effectively avoided RT and remain in remission with estimated 3-year PFS and OS rates of 100%. In conclusion, BV demonstrates encouraging clinical activity when it follows ABVD therapy in limited-stage HL. Early incorporation of BV may reduce the use of RT as well as conventional chemotherapy drugs while achieving favorable survival outcomes in risk-stratified patients with non-bulky limited-stage HL. This trial was registered at www.clinicaltrials.gov as #NCT01578967.

Conflict of interest statement

Conflict-of-interest disclosure: S.I.P. received honoraria and research funding/grants from Seattle Genetics, Inc., honoraria/research funding from Bristol-Myers Squibb, G1 Therapeutics, Teva, and Gilead, and is a member of the medical advisory board for Rafael Pharma. S.M.A. received research funding (to his institution for clinical trials) from Seattle Genetics, Bristol-Myers Squibb, Celldex, Regeneron, Trillium, LAM Therapeutics, and Pfizer. N.M.R. received honoraria and research funding from Bristol-Myers Squibb and honoraria from Teva, Gilead, Janssen, and AbbVie. The remaining authors declare no competing financial interests.

© 2020 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Protocol outline with the study schema. ABVD followed by BV. Q3wks, once every 3 weeks.

Figure 2.

PET-based response by Deauville scores. PET-2, after 2 cycles of ABVD; pre-BV, after 2 to 6 cycles of ABVD; post-BV (after BV consolidation).

Figure 3.

Kaplan-Meier estimates of outcomes by PET-based response in patients with limited-stage HL treated with ABVD followed by BV consolidation. (A) Overall survival. (B) Progression-free survival.