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Five-Year Follow-up of SWOG S0816: Limitations and Values of a PET-Adapted Approach for Stage III/IV Hodgkin Lymphoma

Deborah M Stephens, Hongli Li, Heiko Schöder, David J. Straus, Craig H. Moskowitz, Michael Leblanc, Lisa M Rimsza, Nancy L Bartlett, Andrew M Evens, Ann S. LaCasce, Paul M. Barr, Michael V Knopp, Eric Hsi, John P Leonard, Brad Kahl, Sonali M Smith and Jonathan W Friedberg

Key Points

  • Nearly 25% of patients with a negative PET2 relapsed, demonstrating limitations of frontline ABVD and low negative predictive value of PET2.

  • In patients with a positive PET2 who received eBEACOPP, PFS was favorable, but was associated with a high rate of second cancers.

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 S0816 (NCT00822120). Patients received 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Patients achieving complete remission (CR) on PET2 (Deauville Score{less than or equal to}3) continued 4 additional cycles of ABVD. Patients not achieving CR on PET2 (Deauville Score>3) were switched to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. We report the 5-year follow-up of S0816. A subset of 336 eligible patients were analyzed (331 had central review of PET2). PET2 was negative in 82% and positive in 18%. For all patients, the estimated 5-year PFS was 74% (95%CI:69%-79%). For patients with PET2-, the 5-year PFS was 76% (95%CI:70-81%). For patients with PET2+, the 5-year PFS was 66% (95% CI:52-76%). For all patients, the estimated 5-year overall survival (OS) was 94% (95%CI:91%-96%). There were 7 (14%) reported cases of second cancers in patients treated with eBEACOPP and 6 (2%) in patients treated with ABVD (P=0.001). The long-term OS of HL patients treated on S0816 remains high. However, nearly 25% of patients with PET2- experienced relapse events, demonstrating limitations of frontline ABVD therapy and in 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

  • Submitted March 21, 2019.
  • Revision received July 19, 2019.
  • Accepted July 3, 2019.