Although escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), or BEACOPPesc, has been shown to be superior to ABVD chemotherapy in controlling disease in patients with advanced-stage Hodgkin lymphoma, it is also associated with higher toxicity, including immediate hematologic toxicity and an increased risk of secondary myelodysplasia or leukemia and infertility.
Given these risks, identifying patients with HL who respond early to BEACOPPesc would allow physicians to begin a strategy of de-escalating treatment intensity – hopefully without impairing the disease control.
In a study presented last month at the ASH annual meeting, Olivier Casanovas, MD, from the Hematology Department at Hôpital Le Bocage in Dijon, France, and colleagues reported the results of a positron emission testing (PET)-driven treatment strategy for identifying Hodgkin lymphoma patients who could safely de-escalate BEACOPPesc and switch to ABVD therapy. They found that PET imaging performed early in the treatment course can be safely used to guide subsequent treatment modifications.
In addition to further confirming the prognostic value of interim PET imaging, “this approach allows us to significantly reduce treatment-related immediate toxicity in most patients and provides a similar outcome compared with standard BEACOPPesc treatment,” Dr. Casanovas said during his presentation of the results.
In this phase III trial, which included patients with high-risk (meaning stage IIB or Ann Arbor stage III-IV) Hodgkin lymphoma, Dr. Casanovas and investigators compared a PET-driven treatment strategy with a standard treatment regimen. All patients received two cycles of BEACOPPesc, then underwent PET imaging. In the PET arm (401 patients), patients who were PET-positive received four additional cycles of BEACOPPesc; if PET-negative, patients instead received four cycles of ABVD. In the standard treatment arm (381 patients), patients received six cycles of BEACOPPesc regardless of PET status.
Patient characteristics were “well-balanced” in both arms, the authors noted. The median age among patients was 30 years (range = 16-60 years), and the majority (60%) had stage IV Hodgkin lymphoma.
After two cycles of BEACOPPesc, rates of PET-positive status were similar between both groups: 48 patients (12%) in the standard treatment arm and 49 patients (13%) in the experimental arm. These 49 patients continued with four additional cycles of BEACOPPesc, while the remaining patients in the experimental arm switched to four cycles of ABVD.
Use of the response-adapted strategy did not significantly alter two-year progression-free survival rates (PFS; the study’s primary endpoint), Dr. Casanovas reported. After a median follow-up of 16.3 months (range = 0.1-37.4 months), the estimated two-year PFS in both arms were similar: 91.6 percent in the standard arm and 88.3 percent in the PET-driven arm (p=0.79).
PET-positive status, however, was associated with significant differences in two-year PFS compared with PET-negative patients in the entire study population (72.9% vs. 92.8%, respectively; p<0.0001), as well as in both randomization arms (75.1% vs. 94% in the standard treatment arms and 70.8% vs. 91.6% in the PET arms, respectively; p<0.0001 for both). PET status and treatment strategy, though, were not associated with differences in overall survival.
The PET-driven treatment strategy leading to a switch in therapy to ABVD also appeared to be safer than continuing with four additional cycles of BEACOPPesc. Rates of grade ≥3 toxicities were significantly higher in the standard treatment arm than in the experimental arm, with the most commonly reported toxicities being:
- anemia (11% vs. 2%, respectively)
- leukopenia (85% vs. 72%)
- thrombocytopenia (44% vs. 13%)
- febrile neutropenia (6% vs. 3%)
- sepsis (7% vs. 4%)
Overall, 108 patients (24%) who remained on BEACOPP experienced serious adverse events (AEs) related to their treatment, including four deaths. Among the patients who switched to ABVD, however, 50 patients (15%) experienced serious AEs, including one death (p<0.002). Most of the AEs in the experimental arm (67%) occurred prior to de-escalation, the authors noted.
“PET positivity after two cycles of BEACOPPesc is related to a higher risk of disease progression,” Dr. Casanovas said, adding that PET performed after four cycles of chemotherapy identifies a subset of patients whose disease has a particularly poor outcome. “These results should encourage the development of new treatment options in patients with PET-positive, advanced-stage Hodgkin lymphoma.”
Casasnovas O, Brice P, Bouabdallah E, et al. Randomized phase III study comparing an early PET driven treatment de-escalation to a not PET-monitored strategy in patients with advanced stages Hodgkin lymphoma: interim analysis of the AHL2011 Lysa Study. Abstract #577. Presented at the 2015 ASH Annual Meeting, December 7, 2015; Orlando, Florida.