Patient and Physician Preferences for First-Line Treatment of Classical Hodgkin Lymphoma in the United States

Introduction: The standard of care for previously untreated classical Hodgkin lymphoma (HL) in the United States has been combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or with radiotherapy depending on clinical characteristics. Other treatment programs exist, including intensified chemotherapy regimens, and substitution of brentuximab vedotin for bleomycin recently received FDA approval as first-line therapy for advance stage HL. The objective of this study was to understand how specific treatment attributes impact preferences among patients and physicians for choice of first-line treatment of HL.

Methods: An online survey including a discrete choice experiment (DCE) was administered both to oncologists who manage patients with HL and to patients diagnosed within HL within the last two years in the United States. Participants were identified via online research panels. The attributes and levels of the hypothetical treatments presented in the DCE were informed by targeted literature review and physician and patient interviews. For physicians, six attributes were included: two-year overall survival (OS); two-year progression free survival (PFS); risk of side effects requiring hospitalization; risk of peripheral neuropathy (PN); risk of pulmonary toxicity; and patient out-of-pocket cost. The patient DCE included four attributes: OS, PFS, risk of PN and risk of pulmonary toxicity. DCE scenarios were developed using a d-efficient design. Participants reviewed 10 scenarios, and selected their preference between two hypothetical treatments. Patients considered themselves when selecting their preference; physicians considered four different advanced HL patient profiles that differed in age (30 or 65 years), smoking status, and the presence of baseline PN. The DCE data were analyzed using a mixed logit model (MXL). The relative importance of each attribute was calculated by determining the differences between the maximum and minimum coefficients of each attribute. These were then normalized and presented as percentages.

Results: A total of 200 physicians and 141 patients were included in the analysis. Physicians had a mean of 15 years' experience and 71% practiced in a community setting. Patients had a median age of 35 years (range 19 to 69), 60% were male, and 34% were diagnosed with advanced stage HL. In the DCE, the most important attributes to both patients and physicians were OS and PFS. Based on the coefficients from the MXL model, a 1% increase in OS was more important to both groups than a 1% increase in PFS. The coefficients and level ranges for each attribute were used to calculate preference weights (see methods). Based on preference weights, PFS was the most important attribute for patients, followed by OS, risk of pulmonary toxicity, and risk of PN (Table 1). Compared to male patients, there was a trend for female patients to have a lower preference for a 1% decrease in risk of progression (p=0.077). Patients above the median age of 35 years had a significant preference (p=0.048) for a lower risk of pulmonary toxicity, and a trend for a higher preference for a 1% increase in OS (p=0.059) was observed. OS was also marginally more important to patients diagnosed with advanced stage HL versus those diagnosed in earlier stages. For physicians, preferences for treatment attributes differed based on the patient profile presented. PFS outweighed OS for a healthy 35 year-old patient (Table 2), whereas OS had a higher relative preference weight for a 35 year old smoker and older patients. For smokers, physicians ranked pulmonary toxicity as the most important attribute. Among older patients, side effects requiring hospitalization were more important to physicians' preferences than both OS and PFS. There were no major differences in preferences between academic and community oncologists.

Conclusion: Patients are willing to accept treatments with worse short and long-term side effects in exchange for improved OS or PFS. Physicians' treatment preferences are patient-specific, with age and comorbidities impacting both the relative weight of OS and PFS attributes and the importance of pulmonary toxicity and short-term side effects. These results underscore the importance of assessing and sharing patient and physician preferences in creating a treatment plan for the management of newly diagnosed Hodgkin lymphoma.

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