CHICAGO – Positron emission tomography (PET) performed after two cycles of BEACOPP could help identify a subset of advanced-stage Hodgkin lymphoma patients who can receive de-escalated treatment without compromising disease control, results of a phase 3 randomized trial show.
Five-year progression-free survival (PFS) exceeded 85% not only for patients receiving six cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) but also for patients who were de-escalated to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy based on negative PET results, according to the final analysis of the AHL2011 LYSA study, presented at the annual meeting of the American Society of Clinical Oncology.
“This approach allows us to significantly reduce the treatment-related toxicity in most patients, and provides similar patient outcomes compared to standard BEACOPP escalated treatment,” said Olivier Casasnovas, MD, of the University Hospital Le Bocage and Inserm, Dijon, France.
Previous studies have shown that BEACOPP may improve PFS, compared with ABVD, but is more toxic and associated with a higher risk of infertility and myelodysplasia or acute leukemia. Dr. Casasnovas and his colleagues sought to evaluate whether upfront BEACOPP followed by de-escalation to ABVD, when warranted by negative PET results, would improve outcomes without compromising efficacy.
The AHL2011 LYSA study included 823 patients (median age, 30 years; 63% male) with previously untreated advanced classical Hodgkin lymphoma. All patients received PET at baseline, after cycle two of chemotherapy, and again after cycle four.
Patients were randomized either to six cycles of escalated BEACOPP, or to an experimental arm in which patients started with BEACOPP but were de-escalated to ABVD if PET results were negative after two or four cycles of treatment.
PET results after cycle two were negative for 87% of patients in the experimental arm, so on an intent-to-treat basis, 84% of them received two cycles of BEACOPP and four cycles of ABVD, Dr. Casasnovas reported.
PFS, with a median follow-up of 50.4 months, was not significantly different for the standard versus the experimental arm (hazard ratio, 1.084; 95% confidence interval, 0.73-1.59; P = .68). Five-year PFS was 85.7% in the experimental treatment de-escalation arm, compared with 86.2% in the standard arm.
Overall survival was likewise similar between arms, with 5-year overall survival exceeding 95% in both groups, Dr. Casasnovas said.
Although there was no significant difference overall in the incidence of adverse events, there was significantly less anemia, febrile neutropenia, thrombocytopenia, and sepsis in the PET-driven de-escalation arm. Overall, 27% of patients in the standard chemotherapy arm experienced at least one serious adverse event, compared with 17% in the PET-driven arm (P less than .002).
The incidence of second primary malignancies was numerically lower in the experimental arm (1.2% vs. 2.4%), though that finding did not reach statistical significance.
On multivariate analysis, interim PET positivity after cycle two was associated with increased risk of disease progression for patients in this study (HR, 3.316). Risk of progression was even higher for patients with PET positivity after four cycles (HR, 12.968), identifying a subset of patients with “particularly poor outcome” who could benefit from development of new treatment options, Dr. Casasnovas said.
Dr. Casasnovas reported financial ties to AbbVie, Bristol-Myers Squibb, Celgene, Gilead Sciences, Janssen, Merck, Roche/Genentech, Sanofi, and Takeda.