With the use of modern therapy, Hodgkin lymphoma (HL) has become an increasingly curable disease, with a cure rate of more than 85% in patients with early-stage disease and a 5-year survival of more than 95%. Additionally, disease-free survival is greater than 75% among patients with advanced disease. However, multimodal therapy has been associated with serious long-term toxicities, leading the highly favorable prognosis to increased emphasis on decreasing both acute and late toxicities associated with therapy. The advent of newer and effective novel agents also offer alternative approaches to frontline therapy in those with classical Hodgkin lymphoma (cHL), but there is growing controversy regarding the initial treatment of HL. In a new review paper published in Current Oncology Reports, several areas of frontline treatment which have not been adequately addressed in guidelines are discussed.1
Radiation Therapy in Early Unfavorable Disease
Patients with early unfavorable disease still have an excellent prognosis, with more than80% of patients achieving 5-year survival. Radiotherapy has historically been the mainstay of treatment for patients with early-stage disease, and adding chemotherapy to the regimen has not only improved outcomes but allowed for reduced amounts of radiotherapy. Clinical trials have looked at omitting radiotherapy treatment completely for select patients in this category, and some data have shown that early-stage patients treated with as few as 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) have achieved excellent outcomes. In the RAPID-UK trial (ClinicalTrials.gov Identifier: NCT00943423), for example, early-stage asymptomatic patients (without large mediastinal masses) received 3 cycles of ABVD followed by a PET/CT and those who achieved a complete metabolic response were randomly assigned to receive either consolidative radiotherapy or observation. Overall, results were excellent and overall survival was 97% versus 99%, respectively. Unfavorable risk patients comprised 35% of the group who did not receive radiation therapy, but they were not analyzed separately, so definitive conclusions could not be reached for this subgroup. However the authors noted that this study led to widespread adoption of short-course ABVD alone as an option for early-stage patients who achieve a metabolic response.
The most recent data comes from the CALGB 50604 trial (ClinicalTrials.gov Identifier: NCT01132807), in which 58% of those treated (104 patients) were unfavorable risk, these patients received ABVD for 2 cycles followed by an interim PET. Those with negative results received 2 additional cycles and no radiotherapy. Outcomes were similar for patients with favorable unfavorable disease, with a 3-year progression-free survival of 91%.
The authors noted that they “attempt[ed] to enroll early unfavorable patients in clinical trials investigating radiation-free approaches,” and also may incorporate novel agents into the regimen including brentuximab vedotin (BV) or programmed death (PD)-1 inhibition.
“Radiation-free approaches are being utilized increasingly in North America for early unfavorable patients,” said Pamela B. Allen, MD, of the Winship Cancer Institute of Emory University in Atlanta, Georgia. “If attempting to avoid radiation, patients are treated with 6 cycles of chemotherapy [and] PET directed as per the RATHL trial.”