Intensified ABVD Bests PET-Adapted ABVD as First-Line Therapy for Hodgkin Lymphoma

Intensified doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) can improve outcomes, when compared with PET-adapted ABVD, in patients with previously untreated Hodgkin lymphoma, according to data presented at the International Conference on Malignant Lymphoma 2023.

Dose-dense or dose-intense ABVD (ABVD_DD-DI) improved progression-free survival (PFS) and event-free survival (EFS), when compared to PET-adapted ABVD, in this phase 3 trial.

The trial, FIL-ROUGE (ClinicalTrials.gov Identifier: NCT03159897), included 503 adults with previously untreated Hodgkin lymphoma. The patients’ median age at baseline was 33.6 years, and 54% were men. Patients had stage IIB (21%), stage III (33%), or stage IV (46%) disease. Some patients had mediastinal (24%) or nodal (13%) bulky disease.

Treatment Details

The patients were randomly assigned to receive ABVD_DD-DI (n=251) or PET-adapted ABVD (n=252). Patients in the ABVD_DD-DI arm received 3 cycles of intensified ABVD. They received all 4 drugs on days 1 and 11 of each 3-week cycle, and the doxorubicin dose was escalated to 35 mg/m² (70 mg/m² per cycle). Nonresponders (per PET/CT) received salvage treatment. Responders received an additional cycle of ABVD_DD-DI, followed by 2 cycles of dose-dense ABVD (all 4 drugs on days 1 and 11 but the conventional dose of doxorubicin [25 mg/m²]).

Patients in the PET-adapted treatment arm received 2 cycles of standard ABVD. If they had a negative PET scan, they continued on ABVD for 4 more cycles. If they had a positive PET, patients received escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) or high-dose therapy plus autologous stem cell transplant.

Ten percent of patients in the ABVD_DD-DI arm and 32% in the PET-adapted treatment arm also received radiotherapy (30 Gy).

Efficacy and Safety Results

The primary endpoint was 3-year PFS. The 3-year PFS rate was 87% with ABVD_DD-DI and 73% with PET-adapted treatment (hazard ratio [HR], 0.44; 95% CI, 0.28-0.67; P =.0002).

The 3-year EFS rate (which included cardiopulmonary events) was 81% with ABVD_DD-DI and 67% with PET-adapted treatment (HR, 0.54; 95% CI, 0.37-0.78; P <.001).

The 3-year overall survival rate was 99% in the ABVD_DD-DI arm and 98% in the PET-adapted treatment arm.

After 2 months of treatment, the complete response (CR) rate was similar with ABVD_DD-DI and PET-adapted treatment — 86% and 81%, respectively (P =.15). However, at the end of the trial, the CR rate was higher with ABVD_DD-DI than with PET-adapted treatment — 94% and 85%, respectively (P =.002).

The rate of primary refractory disease was 4% in the ABVD_DD-DI arm and 12% in the PET-adapted treatment arm (P =.006). Early recurrence was seen in 6% and 10% of patients, respectively (P =.09).

The rate of grade 3-4 adverse events (AEs) was 70% in the ABVD_DD-DI arm and 57% in the PET-adapted treatment arm. The rate of serious AEs was 25% and 16%, respectively. There was 1 fatal AE in the PET-adapted treatment arm.

Mid-term and long-term toxicity data are still needed, said study presenter Antonio Pinto, MD, of Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale” in Naples, Italy.

Dr Pinto noted, however, that the results of this trial suggest there may be no need for early PET-adapted therapy and a limited need for radiotherapy in this patient population.

Disclosures: Dr Pinto disclosed relationships with Roche, Incyte, Merck Sharp and Dohme, Servier Affaires Medicales, and Bristol Myers Squibb/Celgene. The other study authors disclosed no relationships.

Reference

Pinto A, Corazzelli G, Evangelista A, et al. Frontline intensified ABVD demonstrates superior efficacy than PET-adapted ABVD in advanced Hodgkin lymphoma: The FIL-ROUGE phase 3 trial by the Fondazione Italiana Linfomi. ICML 2023. June 13-17, 2023. Abstract 4.