San Diego, CA—In transplant-eligible patients with newly diagnosed, advanced-stage Hodgkin lymphoma, a decision-analytic model showed that chemotherapy with bleomycin, plus etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) maximized life-expectancy and quality-adjusted life expectancy compared with doxorubicin plus bleomycin, vinblastine, and dacarbazine (ABVD) therapy in the first-line setting, reported Abi Vijenthira, MD, Princess Margaret Cancer Centre, University of Toronto, Canada, at the 2016 American Society of Hematology meeting.
The BEACOPP regimen was superior to ABVD, despite increased rates of hematologic toxicity, secondary malignancy, and infertility in patients who receive the BEACOPP regimen.
“In our decision-analysis model, which was robust to sensitivity analyses of key variables, combination therapy of baseline BEACOPP and/or escalated BEACOPP demonstrated longer life expectancy and quality adjusted-life expectancy than ABVD,” said Dr Vijenthira. “The preferred treatment strategy for patients with newly diagnosed, advanced-stage Hodgkin lymphoma is a combination BEACOPP regimen,” she added.
Despite the large number of clinical trials completed in this area, there remains uncertainty regarding the best treatment for advanced-stage Hodgkin lymphoma, Dr Vijenthira said.
“Knowing that there are no differences in overall survival between these regimens, it becomes a risk and benefit question for clinicians,” she explained. “On the one hand, BEACOPP has shown decreased rates of relapse and superior progression-free survival. On the other hand, ABVD has shown less acute and long-term toxicity,” added Dr Vijenthira.
Using a Markov decision-analytic model, Dr Vijenthira and colleagues explored the trade-off that occurs when initial improvements in progression-free survival are offset with increased morbidity and mortality associated with infection, secondary malignancies, and infertility in the BEACOPP-containing treatment strategy.
With baseline estimates and probabilities obtained from a systematic review of the literature, the model simulated the clinical course of a hypothetical cohort of transplantation-eligible patients with newly diagnosed, advanced-stage Hodgkin lymphoma in a 40-year time horizon.
The key variables included response; disease relapse and survival rates comparing ABVD versus BEACOPP; risk for complications, such as infection, infertility, or secondary malignancy with each treatment strategy; and the estimated survival after secondary malignancy. The researchers incorporated therapies for relapsed disease, including autologous stem-cell transplantation and posttransplantation strategies, based on available data. Data on health state utilities were also derived from a review of the literature.
BEACOPP Demonstrates Superior Life Expectancy over ABVD
Based on a 40-year time horizon, BEACOPP maximized life expectancy and quality-adjusted life-years over ABVD.
Sensitivity analyses determined if variation in key variables and probabilities would impact the decision of the model.
“The highest recorded treatment-related mortality for BEACOPP in a randomized controlled trial was 3%,” said Dr Vijenthira. “Even when varied up to 10%, however, no threshold value would make ABVD preferable to BEACOPP in the model.”
A sensitivity analysis of second malignancies yielded a similar result. The highest rate of second malignancy thus far recorded in the literature is 6.7% in 10 years. After varying the rate to 10% and setting the probability of death from second malignancy at 100%, BEACOPP remained the preferred treatment strategy over ABVD.
A range of disease relapse probabilities after ABVD and BEACOPP were also tested in the sensitivity analyses, with BEACOPP consistently superior over ABVD. The model was robust to the entire range of disease relapse values recorded in the literature.
Infertility, with a threshold utility of 0.55, was the only variable that could sway patients toward the ABVD strategy, said Dr Vijenthira.
“Although the lowest value found in the literature was 0.81, this information would be useful for a patient who greatly values fertility. Patients who want to avoid infertility at all costs might prefer ABVD over BEACOPP,” said Dr Vijenthira.
Ultimately, however, the model overwhelmingly supported BEACOPP over ABVD. In a 100,000-trial microsimulation, BEACOPP was the preferred strategy in 88% of cases.
“It’s important to note that we modeled a 40-year time horizon, which is 30 years past what’s available in terms of clinical trial follow up,” said Dr Vijenthira. “Our next step will be to see if the model is properly calibrated by matching absolute values and rates obtained from the model with what’s recorded in the literature,” she added.