The Widely Accepted Standard of Care for Early-Stage Hodgkin Lymphoma

Introduction

The widely accepted standard of care for patients with early-stage Hodgkin lymphoma (HL) is the chemotherapy regimen ABVD (doxorubicin hydrochloride [Adriamycin], bleomycin sulfate, vinblastine, dacarbazine) followed by involved-field radiation therapy (IFRT), or 4 cycles of ABVD with or without IFRT, according to Catherine Diefenbach, MD.

Concerns with Late Toxicities

Despite complete remission rates of up to 90%, late toxicities, such as secondary malignancies and cardiovascular events, are key concerns in patients treated for early-stage HL.

Minimizing Unnecessary Toxicities

In order to minimize unnecessary toxicities, new tools are needed to distinguish between early-stage patients with a high cure rate and those who could benefit from switching to another treatment.

Interim PET Scan as a Prognostic Tool

Interim PET scan is a prognostic tool used to identify patients needing de-escalated or escalated therapy.

EORTC/LYSA/FIL H10 Trial

• Examined treatment adaptation based on early PET scan in patients with previously untreated early-stage HL who received 2 cycles of ABVD
• Patients with a negative PET received only ABVD
• Patients with a positive PET received 2 cycles of BEACOPP followed by radiotherapy
• Results showed improved progression-free survival (PFS) for patients with positive PET results
• Overall survival (OS) did not differ between the two groups

RAPID Trial

• Investigated whether radiotherapy could be omitted in the treatment of patients with nonbulky early-stage HL when the interim PET was negative after 3 cycles of ABVD
• Patients with negative PET results received either IFRT or no further treatment
• Patients with positive PET results received 1 additional cycle of ABVD plus radiotherapy
• 3-year PFS was highest for the PET-negative group with no further treatment
• Therapy escalation may improve outcomes for patients with advanced-stage HL with a suboptimal response to therapy

RATHL Study

• Patients with advanced-stage HL received 2 cycles of ABVD followed by chemotherapy and an interim PET scan
• Patient treatment was randomized based on PET results
• Different treatment groups had varying PFS and OS rates
• ABVD group had more severe respiratory adverse events compared to other groups

ECHELON-1 Study

• Patients with previously untreated advanced-stage HL were randomized to receive A+AVD or ABVD
• A+AVD group showed improved overall survival
• A+AVD is now one of the preferred regiments for the primary treatment of advanced-stage HL

SWOG S1826 Trial

• Treatment with the PD-1 inhibitor nivolumab plus AVD was superior to A+AVD in patients with advanced-stage HL
• Early results showed improved 1-year PFS for patients treated with nivolumab plus AVD

The Need for Tailored Therapy

There are currently no biomarkers available to determine the ideal treatment plans for patients with HL.

Conclusion

There are multiple approaches for treating patients with HL, and emerging data from clinical trials has increased the number of treatment options and the complexity of choosing a regimen. The goal should be to maximize cure while minimizing toxicity, and further research is needed to tailor therapy according to risk and biology.