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Response-adapted approach fails to impress in first-line treatment of Hodgkin’s lymphoma

Jackey Suen
28 Dec 2018

Response-adapted therapy based on PET scan results following the second cycle of standard first-line treatment is found to have limitations in stage III/IV Hodgkin’s lymphoma.

This finding came from the long-term follow-up of the SWOG S0816 study presented recently at the 60th American Society of Hematology Annual Meeting and Exposition (ASH 2018) in San Diego, California, US. [Stephens DM, et al, ASH 2018, abstract 929]

In the study, 331 patients with newly diagnosed stage III/IV Hodgkin’s lymphoma received two cycles of standard first-line treatment comprising doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD), followed by PET scan assessment (PET2). Patients who achieved a complete remission (CR) on PET2 (PET2-negative; defined as Deauville score ≤3) received four additional cycles of ABVD, while those who did not achieve CR on PET2 (PET2-positive; defined as Deauville score >3) were switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP).

The primary endpoint of 2-year progression-free survival (PFS) rate, analyzed after a median follow-up of 3.3 years and published previously, was 82 percent in the PET2-negative group and 64 percent in the PET2-positive group. Patients in the PET2-positive group had increased short-term toxicity. The investigators suggested that long-term follow-up was needed to confirm the durability of survival advantage and evaluate long-term toxicity. [J Clin Oncol 2016;34:2020-2027]

In the present analysis conducted after a median follow-up of 5.9 years, the 5-year PFS rate was 76 percent in the PET2-negative group vs 66 percent in the PET2-positive group. “Disappointingly, nearly 25 percent of patients in the PET2-negative group had a relapse, suggesting that PET2 negativity was ineffective in identifying patients at risk of relapse. Better biomarkers are needed at diagnosis,” reported investigator Dr Deborah Stephens of the University of Utah, Salt Lake City, Utah, US. “In the PET2-positive group, the PFS rate was higher compared with a historical series. However, a high rate of secondary malignancies was reported [14 percent vs 2 percent in the PET-negative group; p=0.001].”

The 5-year overall survival rate remained high at 94 percent in the overall cohort. Two percent of patients in the PET2-negative group and 8 percent in the PET2-positive group died due to Hodgkin’s lymphoma. Post-therapy grade ≥3 adverse events were uncommon in both groups.

“ABVD has been the standard first-line therapy for stage III/IV Hodgkin’s lymphoma in the US, with a cure rate of approximately 70 percent. eBEACOPP is an alternate therapy with a higher cure rate, but is also associated with higher toxicity,” Stephens explained. “Previously, PET2 response has been shown to predict survival. Therefore, a response-adapted approach may help maximize efficacy and minimize toxicity in first-line treatment of stage III/IV Hodgkin’s lymphoma.”

“Despite historical data suggesting favourable clinical outcomes in PET2-negative patients, nearly 25 percent of these patients in our study experienced relapse, demonstrating limitations of a PET-adapted approach and of standard first-line therapy with ABVD,” she concluded.

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