A PET-adapted treatment strategy that combines nivolumab with intensive chemotherapy produced early metabolic responses in patients with newly diagnosed, advanced-stage classical Hodgkin lymphoma (HL), interim results from a small study showed.

All of the 35 patients who completed treatment had a complete metabolic response by the end of therapy, with 83% having achieved this result after two cycles of induction therapy.

“The depth and kinetics of early metabolic and anatomic response in our cohort were broadly comparable with what we had previously observed with intensive chemotherapy without a checkpoint inhibitor,” Hunan Julhakyan, MD, PhD, the study’s lead investigator, told Medscape Medical News. “This suggests that adding nivolumab to an intensive induction backbone does not necessarily compromise the interpretability of early PET, although this observation needs confirmation in larger studies.”

Mobil Akhmedov, MD, PhD, one of the study authors, presented the findings at the Society of Hematologic Oncology (SOHO) 2026 meeting.

Two trials have reshaped frontline treatment of advanced-stage classical HL. SWOG S1826, compared the immune checkpoint inhibitor nivolumab plus AVD chemotherapy (doxorubicin, vinblastine, and dacarbazine) against brentuximab vedotin plus AVD. It showed that adding nivolumab improved progression-free survival and caused lower toxicity than brentuximab vedotin, establishing nivolumab-AVD as a new frontline standard. The German Hodgkin Study Group’s HD21 trial tested BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) against escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), the prior standard for higher-risk disease. BrECADD produced comparable efficacy with less treatment-related toxicity, establishing it as a better-tolerated alternative to escalated BEACOPP.

But there remains a question of “whether PET/CT can still guide treatment in the immune checkpoint inhibitor era, considering that a proportion of patients will have false-positive PET scans either at interim assessment or at the end of treatment due to inflammatory uptake or pseudoprogression,” Akhmedov, of the National Medical Research Radiological Center, Moscow, Russia, said.

The new prospective, single-center study enrolled 43 previously untreated patients with advanced-stage HL between October 2024 and April 2026. Median age was 29 years; 56% had bulky mediastinal disease, 52% had B symptoms, and 14% had an International Prognostic Score ≥ 3. Three patients had well-controlled autoimmune disease at baseline.

Patients received nivolumab 40 mg every 2 weeks plus EACOPD-14, a modified BEACOPP-14 regimen that omits bleomycin and substitutes dacarbazine for procarbazine, for two induction cycles. After PET2 assessment, patients with a complete metabolic response received two cycles of nivolumab-AVD consolidation followed by nivolumab maintenance, and those with a partial response continued nivolumab-EACOPD-14 for up to six cycles. No patient received radiotherapy.

The remaining 17% who did not achieve complete metabolic response after two induction cycles had a partial metabolic response (all with a Deauville score of 4). In every case, the residual uptake was confined to mediastinal lesions. No relapses or progression events have occurred at a median follow-up of 9.1 months.

Tycel Phillips, MD, who was not involved in the study, and Akhmedov agreed that longer follow-up is needed to confirm the durability of disease control with the approach used in the trial.

Phillips, of the Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope in Duarte, California, added that he would want to see progression-free survival data after 12 months, then 24 months to get a better estimate on the durability of the regimen.

The safety profile was consistent with prior experience with this regimen. Grade 3-4 neutropenia occurred in 17% of patients, febrile neutropenia in 10%, and grade 3 immune-related adverse events in 8%; no grade 3 infections were reported, and none of the three patients with preexisting autoimmune disease had a flare during treatment.

Julhakyan, who works at the National Medical Research Center for Hematology and the Russian University of Medicine in Moscow, cautioned that the subgroup of patients with preexisting autoimmune disease was too small to draw conclusions about the safety of the regimen in this subgroup but said stable, well-controlled autoimmune disease “should not necessarily be an automatic exclusion from checkpoint inhibitor trials.”

For now, Phillips said he would not rely on interim PET scans in HL, given the lack of long-term predictability of most PET-directed regimens in HL and the challenges of interpreting PET results in patients treated with immunotherapy.

“I’m much more optimistic about utilization of ctDNA to help determine de-escalation and long-term response in HL,” he added.

Julhakyan and Akhmedov reported no financial disclosures. Phillips reported financial relationships with AbbVie, ADC Therapeutics, AstraZeneca, Bayer, BeiGene (Beijing), Bristol Myers Squibb, Caribou Biosciences, Genmab, Genentech, Gilead Sciences, Lilly, Incyte Corporation, Janssen Pharmacyclics, Pfizer, Merck, Seagen, Xencor, SOBI, and Epizyme.

Christos Evangelou, PhD, is a freelance medical writer.