TOPLINE:

Early [¹⁸F]fluorodeoxyglucose (FDG) PET-CT assessment after one cycle of brentuximab vedotin-based chemotherapy in advanced‑stage classical Hodgkin lymphoma allowed selective treatment intensification and avoided escalated chemotherapy in most patients, according to a phase 2 trial. Patients with a positive scan who switched to escalated treatment achieved a 2‑year modified progression-free survival (PFS) rate of 91.3%, supporting further exploration of very early response-adapted strategies.

METHODOLOGY:

• The integration of [¹⁸F]FDG PET and PET-response-adapted therapy and the advent of novel agents such as brentuximab vedotin have transformed management of advanced‑stage classical Hodgkin lymphoma. Early interim PET has shown a strong prognostic value and has informed PET‑adapted and intensified regimens.
• Researchers conducted a single-arm, multicenter phase 2 trial involving 150 adults (median age at registration, 32 years) with previously untreated advanced-stage classical Hodgkin lymphoma to evaluate whether very early PET-CT-guided adaptation of brentuximab vedotin-based chemotherapy could identify patients who may benefit from treatment escalation while limiting unnecessary toxicity for others.
• Participants received one cycle of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine, all administered intravenously on days 1 and 15 of a 28-day cycle, followed by a PET-CT scan.
• Patients with a negative scan (60%; Deauville score, 1-3) continued with five additional cycles of the same treatment, whereas those with a positive scan (40%; Deauville score, 4-5) switched to six cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone, along with dexamethasone.
• The primary endpoint was 2-year modified PFS, and secondary endpoints included overall survival and safety. The median follow-up duration was 30.1 months.

TAKEAWAY:

• A total of 16 of 145 evaluable patients (11%) experienced a modified PFS event; the estimated 2-year modified PFS rate was 89.5%. Among patients with a negative PET-CT scan (n = 86) who continued initial treatment, the estimated 2-year rate of modified PFS was 88.3%. Among patients with a positive PET-CT scan (n = 59) who escalated treatment, the estimated 2-year modified PFS rate was 91.3%. The rate of overall survival at 2 years was 100%.
• Baseline levels of serum thymus and activation-regulated chemokine were elevated in 91% of evaluable patients. After one cycle (n = 129), levels normalized in 77% of patients and remained elevated in 23%.
• Positivity of serum thymus and activation-regulated chemokine after one cycle was associated with PET-CT positivity (odds ratio, 2.3; P = .048) and a lower 2‑year rate of modified PFS (73.0% vs 91.5% for positive vs negative patients; P = .0028).
• Among 150 patients, 63% reported adverse events of grades 3-4; the most common were neutropenia (35%), anemia (12%), and peripheral sensory neuropathy (6%), with serious adverse events occurring in 45 patients (30%). No treatment-related deaths were reported. Two patients (1%) discontinued the initial therapy due to toxicity; none discontinued intensified therapy.

IN PRACTICE:

The findings of this study demonstrate that “early PET-guided adaptation of brentuximab vedotin-containing first-line chemotherapy for advanced-stage classical Hodgkin lymphoma yields high activity while sparing most patients from intensive chemotherapy,” the authors wrote, further noting that “the integration of [serum thymus and activation-regulated chemokine] into interim response assessment might enhance risk stratification and guide treatment decisions more precisely.”

SOURCE:

The study, led by Martin Hutchings, PhD, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, was published online in The Lancet Haematology.

LIMITATIONS:

The trial was nonrandomized and single‑arm, which limited causal inference. Patient selection could have introduced bias despite baseline characteristics that resembled those of participants in recent randomized trials. Moreover, any apparent outcome advantages vs historical ECHELON‑1 results for patients aged 18-60 years could not be definitively attributed to the intervention.

DISCLOSURES:

This study was funded by Takeda Oncology. Hutchings disclosed receiving consultancy fees from AbbVie, AstraZeneca, Genmab, Johnson & Johnson, Merck, F. Hoffmann-La Roche, and Takeda; research funding from AbbVie, AstraZeneca, Bristol Myers Squibb, Celgene, Genentech, Genmab, Incyte, Johnson & Johnson, Merck, Novartis, Roche, and Takeda; and honoraria from AbbVie, AstraZeneca, Genmab, and others. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.