Monitoring Hodgkin’s lymphoma patients with positron-emission tomography (PET) scans during chemotherapy can help identify those who respond early to a more intense chemotherapy regimen and switch them to a softer, less toxic regimen, helping to avoid adverse side effects while maintaining the same chance of successful treatment, a Phase 3 trial shows.
The study, “PET-adapted treatment for newly diagnosed advanced Hodgkin’s lymphoma (AHL2011): a randomised, multicentre, non-inferiority, phase 3 study,” was published in The Lancet Oncology.
The AVBD chemotherapy regimen — a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine — is widely used to treat Hodgkin’s lymphoma patients.
But studies have shown that the more intense regimen BEACOPP — increased-dose bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone — is better at delaying disease progression or death in these patients.
The problem with BEACOPP is that it not only increases the risk of infertility, it is also characterized by marked blood toxicity, putting patients at higher risk for a second blood cancer.
Thus, researchers aimed to determine whether early BEACOPP responders — identified through PET imaging scans after the second cycle of chemotherapy — could be safely switched to AVBD with similar efficacy.
From May 19, 2011, to April 29, 2014, the AHL2011 Phase 3 trial (NCT01358747) enrolled 823 advanced Hodgkin’s lymphoma patients, median age 30, who had not received any treatment. Participants were randomly assigned standard treatment or treatment guided by PET scans.
Both groups received two cycles of treatment with BEACOPP followed by PET imaging to track disease progression. While the standard-group patients received two further cycles of BEACOPP regardless of their PET results, in the PET-guided group patients who had no remaining signs of cancer were switched to ABVD for the last two cycles. Otherwise, they would receive the remaining two BEACOPP cycles.
Most patients (84%) in the PET-guided group were switched to ABVD after the midway scan. Compared to those on standard treatment, a similar proportion of these patients lived past the five- year mark — 86.2% versus 85.7% — suggesting that the therapeutic effect was preserved.
Notably, there were fewer adverse side effects in the PET-guided group than in the standard group. While almost all patients experienced some toxicities, such as low white blood cell count (over 90% in both groups), patients in the PET-guided group had fewer instances of anemia (28% vs. 69%) and other blood cell-related problems, as well as few infections (11% vs. 22%). Both groups reported the same rate of gastrointestinal disorders (11%).
Furthermore, serious treatment-related events (primarily infections) were reported in 47% of patients in the standard group but in only 28% of the PET-driven group. Six patients in the standard group died because of treatment-related toxicity, as did two in the PET-guided group.
Overall, the investigators determined that PET monitoring could successfully be used to switch early responders to ABVD, lessening toxicity while preserving therapeutic effect.
“PET staging allowed accurate monitoring of treatment in this trial and could be considered as a strategy for the routine management of patients with advanced Hodgkin’s lymphoma,” they stated.
