ASH Clinical News ACN_5.4s_March_supplement_web | Page 22

FEATURE Is the Era of Traditional Chemotherapy for Hodgkin Lymphoma Over? Treatment of Hodgkin lymphoma (HL) has been one of the greatest success stories in oncology, with the invention of radiation therapy and combination chemotherapy (like the standard regimen of doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD]), leading to a cure for most patients. However, improved staging techniques and novel drugs are now challenging the role of a standard chemotherapy approach for all patients diagnosed with HL. In an education session at the 2018 ASH Annual Meeting, presenters discussed moving beyond the approach of “ABVD for everyone” with HL. Maximizing Cure, Minimizing Toxicity Recent advances in the staging and treatment of HL have had a “dramatic impact on the outcome of our patients,” presenter Alison Moskowitz, MD, from the lymphoma inpatient unit at Memorial Sloan Kettering Cancer Center in New York, said. “Now, our challenges are deciding how we best select patients for more or less intense therapy, finding the optimal time to use newer agents for HL, and determining the appropriate predic- tors of response and outcome in HL.” In the first presentation, Ranjana Advani, MD, physician leader of the Lymphoma Clinical Care Program at Stanford Medicine in Palo Alto, California, tackled the question of when to escalate or de-escalate therapy. “ABVD has been the gold standard of care, but this was in the CT era, when patients were not staged using a PET-CT,” she said, before outlining alternative approaches that take advantage of more intense upfront therapy. In Europe, for instance, intense chemotherapy with BEACOPP ((bleomycin sulfate, etoposide phosphate, doxorubicin hydrochloride, cyclophosphamide, vincristine sulfate, procarbazine hydrochloride, prednisone) is a standard of care. While it is associated with a progression-free survival (PFS) of more than 80 percent, it also is associated with substantial toxicity (including hematologic events and sterility) 20 Focus on Lymphoid Malignancies that preclude its adoption in the U.S. Concerns about long-term toxicity also are warranted, particularly given the increased risk of secondary cancers observed after BEACOPP treatment. “This is the dilemma of therapy,” Dr. Advani said. “Do you accept a slightly lower cure rate with an ABVD-like regimen, or do you go with the ‘big gun’ of BEACOPP and accept a slightly higher toxicity rate, but with higher efficacy?” To help answer that question, interim PET imaging has emerged as a tool to distinguish “good vs bad” disease, she explained. Recent research evaluating whether patients can safely de-escalate treatment if they achieve PET-negative disease or whether they would have better outcomes with more intense therapy if they have PET-positive disease has shown favorable results. Omitting bleomycin from the ABVD regimen after patients achieve PET negativity also allowed clinicians to minimize the pulmonary toxicity associated with this agent, without affecting clinical efficacy – a chief concern of therapy. Given these results, Dr. Advani said, it seems clear that a “positive PET scan after two cycles of ABVD might warrant a change in treatment regimen, but prognostic factors other than PET might affect outcomes.” For example, patients with stage IV disease or an International Prognostic Score (IPS) between 4