Five-year follow-up of SWOG S0816: limitations and values of a PET-adapted approach with stage III/IV Hodgkin lymphoma

Abstract

Patients with advanced-stage Hodgkin lymphoma (HL) demonstrated excellent 2-year progression-free survival (PFS) after receiving positron emission tomography (PET)-adapted therapy on SWOG S0816. Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete response (CR) on PET scan following cycle 2 of ABVD (PET2) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. After a median follow-up of 5.9 years, a subset of 331 eligible patients with central review of PET2 was analyzed. PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS and OS was 74% (95% confidence interval [CI], 69%-79%) and 94% (95% CI, 91%-96%), respectively. For PET2- and PET2+ patients, the 5-year PFS was 76% (95% CI, 70%-81%) and 66% (95% CI, 52%-76%), respectively. Seven (14%) and 6 (2%) patients reported second cancers after treatment with eBEACOPP and ABVD, respectively (P = .001). Long-term OS of HL patients treated on S0816 remains high. Nearly 25% of PET2- patients experienced relapse events, demonstrating limitations ABVD therapy and of the negative predictive value of PET2. In PET2+ patients who received eBEACOPP, PFS was favorable, but was associated with a high rate of second malignancies compared with historical controls. Our results emphasize the importance of long-term follow-up, and the need for more efficacious and less toxic therapeutic approaches for advanced-stage HL patients. This trial was registered at www.clinicaltrials.gov as #NCT00822120.

Conflict of interest statement

Conflict-of-interest disclosure: D.M.S. has received research funding from Acerta, Gilead, Karyopharm and honoraria from Genentech. H.S. has served as a consultant for Allero Therapeutics. D.J.S. has received research funding from and serves as a consultant for Seattle Genetics. L.M.R. holds a patent through NanoString. N.L.B. has received research funding from Gilead, Kite, Seattle Genetics, Affimed, Bristol-Myers Squibb, Celgene, Forty Seven, Genentech, Immune Design, Janssen, Merck, Millennium, and Pharmacyclics, and serves as a consultant for Pfizer and Acerta. A.M.E. serves as a consultant for and has received honoraria from Seattle Genetics, Bayer, Verastem, and Pharmacyclics. A.S.L. serves as a consultant for Seattle Genetics and Bristol-Myers Squibb. P.M.B. serves as a consultant for AbbVie. E.D.H. serves as a consultant for Celgene, Seattle Genetics, and Jazz and has received research funding from AbbVie and Eli Lilly. J.P.L. serves as a consultant for Celgene, Juno, Bristol-Myers Squibb, Sutro, Gilead, Genentech, Pfizer, Bayer, Biotest, United Therapeutics, Karyopharm, ADC Therapeutics, MEI Pharma, AstraZeneca, and Novartis. B.S.K. serves as a consultant for Genentech, Celgene, Acerta, AstraZeneca, Juno, CTI, ADC Therapeutics, AbbVie, Gilead, and Seattle Genetics. S.M.S. serves as a consultant for Bristol-Myers Squibb, Humanigen, and Seattle Genetics and has received research funding from Forty Seven and Sanofi. J.W.F. has received honoraria from Bayer. The remaining authors declare no competing financial interests.

© 2019 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Flowchart for analyzed HL patients treated on protocol S0816.

Figure 2.

Survival of 336 HIV−patients on SWOG S0816. PFS (A) and OS (B). Conf. Int., confidence interval.

Figure 3.

PFS and OS of 331 HIV−patients treated on SWOG S0816. (A) PFS for patients with PET2+; (B) PFS for patients with PET2−; (C) OS for patients with PET2+; and (D) OS for patients with PET2−.