De-escalated Hodgkin's lymphoma treatment only minimally less effective, study says

The New England Journal of Medicine published a study this month that investigated Hodgkin’s lymphoma patients’ survival rates in relation to the chemotherapy based on PET-CT scan results.

The study found that omitting one chemotherapy medication (bleomycin) in subsequent rounds of chemo for Hodgkin’s lymphoma patients with a negative PET-CT after two previous rounds of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy had a very small effect of decreasing the three-year progression-free survival rate compared with patients who went on to receive more ABVD chemotherapy after the negative PET-CT scan. In contrast, the overall survival rate minimally increased.

The bleomycin-omitted treatment is also called AVD. The researchers randomized the distribution of third-round AVD and ABVD treatment among patients who had negative PET-CT scans after two previous ABVD treatments.

Patients who received subsequent rounds of ABVD after a negative PET-CT scan had a progression-free three-year survival rate of almost 86 percent, and an overall three-year survival rate of more than 97 percent. The three-year progression-free and overall survival rate for patients who received subsequent AVD treatment was more than 84 percent and nearly 98 percent, respectively.

The ABVD chemo treatment is already a reduced-risk treatment. Previously, the chemotherapy BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) was used, but was found to cause adverse effects such as long-term fatigue and permanent infertility. In this study, patients who were found to have positive PET-CT scans after two rounds of ABVD (about 16 percent) were then given the BEACOPP treatment. About 75 percent of those patients then went on to have a negative PET-CT scan, with an overall three-year survival rate of about 88 percent.

As the study said, “The intention was to reserve more intensive treatment for patients whose poor prognosis justified the added risk” and to try to de-escalate treatment wherever possible without compromising the efficacy of the treatment.  

The study included 1,203 patients with advanced-stage and newly diagnosed Hodgkin’s lymphoma, studied between August 2008 and December 2012 in several countries including the U.K., Australia and Sweden.

The study's authors said the findings that ABVD and AVD treatments (after an initial round of two ABVD treatments) don’t carry a significant difference in survival rates of the disease could influence treatment decisions. Bleomycin can have adverse respiratory effects; limiting patients’ exposure to the drug could improve health outcomes without compromising the cancer treatment. The patient group who went on to receive ABVD treatment after the negative PET-CT scan were more likely to experience respiratory adverse events.

Based on these results, the study authors said that the 1.6 percentage-point difference in the three-year progression-free survival rate between AVD and ABVD treatments did not necessarily cross the threshold of the specified noninferiority margin.

Still, the reduction in adverse respiratory events coupled with the very small decrease in progression-free survival rate could mean a change in treatment for certain patients in specific circumstances. Or, at the very least, the results could be seen as a mandate for further research into the differences between the two kinds of chemotherapy.