Omitting bleomycin from the treatment regimen for Hodgkin lymphoma in patients with negative findings on an interim PET scan led to a lower incidence of pulmonary toxic effects without significantly lowering treatment efficacy; however, the results did fall just short of the specified noninferiority margin.1
Currently, chemotherapy for advanced Hodgkin lymphoma yields cure rates of 70% to 80% with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), according to background information in the article. Escalated therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), with higher-than-standard doses of etoposide, doxorubicin, and cyclophosphamide (escalated BEACOPP) has led to longer progression-free survival and likely higher 5-year survival rates than ABVD among untreated patients. However, short-term and long-term toxicity are increased significantly with escalated BEACOPP. In particular, bleomycin exposure carries a risk of serious pulmonary toxic effects. In addition, most patients with Hodgkin lymphoma are expected to live for many years.
This study sought to use PET-CT imaging to adapt therapy so that patients with a good outlook received de-escalated treatment and those with the highest risk for treatment failure received intensified treatment. The study was funded by Cancer Research UK and international partners in Europe and Australasia.
Interim PET-CT scans were obtained of 1119 patients with advanced Hodgkin lymphoma after 2 cycles of standard chemotherapy. Among these patients, 937 (83.7%) had negative findings (ie, a clear PET scan). Those patients were assigned to 1 of 2 groups: one group continued with chemotherapy, including bleomycin, and the other had chemotherapy without bleomycin. Patients whose PET-CT scans were not clear received more intense chemotherapy treatment.
The patients who stopped receiving bleomycin had the same survival rates as those who continued it; however, they were spared its side effects. The 3-year overall survival rate was 97.6% in patients who did not receive bleomycin vs 97.2% in patients who did receive bleomycin. Patients who received bleomycin had more severe respiratory adverse events.
“The good news is that the majority of people diagnosed with Hodgkin lymphoma can be cured; in this trial, more than 95% of patients are alive after 3 years,” said Professor Peter Johnson, MD, FRCP, MA, Cancer Research UK chief clinician based at the University of Southampton, England, and the study leader. “But we worry about the long-term side effects from the treatments we use. As we’ve done in this trial, personalizing treatment based on how well it works is a major development for patients with Hodgkin lymphoma, and sets a new standard of care.
“Knowing which patients have a more difficult-to-treat form of the disease means we can select those who need stronger chemotherapy, while sparing everyone else the severe side effects, such as infertility. This approach, along with a reduction in the need for radiotherapy, should substantially reduce damage to healthy tissues and the risk of second cancers caused by treatments.”
The authors report no commercial support was provided, and no commercial entity had any role in study design, data accrual, data analysis, or manuscript preparation.
1. Johnson P, Federico M, Kirkwood A, et al. Adapted treatment guided by interim PET-CT scan in advanced Hodgkin’s lymphoma. N Engl J Med. 2016;374(25):2419-2429.