Frontline Brentuximab Vedotin Added to Chemotherapy Prolongs Survival in Advanced cHL

Data from the phase 3 ECHELON-1 clinical trial (NCT01712490) shows that the combination of brentuximab vedotin (Adcetris) and chemotherapy in patients with advanced classical Hodgkin lymphoma (cHL) resulted in a statistically significant improvement in overall survival (OS), according to a press release by Seagen, Inc.¹

At an approximate 6-year median follow up, patients who received brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A+AVD) as frontline treatment resulted in a 41% reduction in the risk of death (HR, 0.59; 95% CI, 0.396-0.879) in contrast to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) receiving patients.

After further research, the safety profile of the antibody-drug conjugate (ADC) remains consistent with prior studies, and no new safety signals were seen.

“These groundbreaking results are important for patients with advanced classical Hodgkin lymphoma given that an improvement in overall survival has rarely been shown in frontline treatment of this disease,” said Roger Dansey, MD, chief medical officer at Seagen, in the press release. “We look forward to the presentation of the results at an upcoming medical meeting.”

ECHELON-1, which assessed safety and efficacy of the frontline the A+AVD compared to ABVD and had an ECOG performance status of 0 to 2, enrolled 1,334 patients aged 18 years or older with stage III or IV cHL into its open-label, international, randomized, phase 3 trial.2 On days 1 and 15 of each 28-day cycle for up to six cycles, patients received A+AVD or ABVD intravenously depending on their random assignment.³

Those in the A+AVD arm (n = 664) received the ADC 1.2 mg/kg of body weight, doxorubicin at 25 mg/m² of body surface area, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m². Patients in the ABVD arm (n = 670) were given doxorubicin at 25 mg/m², bleomycin at 10 U/m2, vinblastine at 6 mg/m2, and dacarbazine at 375 mg/m².

The noted primary endpoint for the trial was modified progression-free survival (PFS), and OS as the key secondary endpoint of the trial.

At the median follow up, data from the 5-year progression-free survival estimated to be 82.2% (95% CI, 79.0%-85.0%) with A+AVD v s 75.3% (95% CI, 71.7%-78.5%) with ABVD (HR, 0.68; 95% CI, 0.53-0.87; P = .0017) within the intent-to-treat population.

Additionally, the 5-year PFS for each investigator proved to be generally higher in these patients no matter their age, PET-2 status, International Prognostic score (IPS), risk group, and disease stage. The PET-2-positive patients PFS was 60·6% (95% CI 45.0-73.1) with A+AVD compared to 45.9% (32.7-58.2) with ABVD (HR, 0.70; 95% CI 0.39-1.26; P =.23).

The ADC makes it so that the antibody can direct the drug to a target on lymphoma cells known as CD30. Prior to the ADC being approved for adult patients with previously untreated stage III and IV cHL, the FDA approved it for use in combination with chemotherapy in March 2018.⁴

The decision made it available to treat cHL after relapse, cHL after stem cell transplant when a patient is at a high risk of relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after failure of other treatment, and primary cutaneous ALCL after failure of other treatment.

Based on these findings, it was concluded that A+AVD should be preferred over ABVD for patients who have previously untreated stage III or IV cHL.

_REFERENCES:

_{1. ADCETRIS combination significantly improves overall survival in newly diagnosed patients with advanced Hodgkin lymphoma. News release. Seagen Inc.; February 3, 2022. Accessed February 3, 2022. https://bit.ly/3ojej4U}

_{2. Straus DJ, Dlugosz-Danecka M, Connors JM, et al. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021;8(6):e410-e421. doi:10.1016/S2352-3026(21)00102-2}

_{3. Straus DJ, Długosz-Danecka M, Alekseev S, et al. Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood. 2020;135(10):735-742. doi:10.1182/blood.2019003127}

_{4. FDA expands approval of Adcetris for first-line treatment of stage III or IV classical Hodgkin lymphoma in combination with chemotherapy. News release. FDA; March 20, 2018. Accessed February 3, 2022. https://bit.ly/3gjUOEC}