In this episode of Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Joshua Brody, MD, the director of the Lymphoma Immunotherapy Program at the Mount Sinai Tisch Cancer Center and a faculty member of the Icahn Genomics Institute in New York, New York.

Their discussion centered on the evolving frontline and relapsed treatment landscape in Hodgkin lymphoma, highlighting the field’s decades-long shift away from intensive chemotherapy and radiation toward better-tolerated, biologically targeted regimens. Drs Park and Brody framed Hodgkin lymphoma as a rare success story in oncology, noting that a once-uniformly fatal disease is now curable in more than 90% of patients, and emphasized that the modern treatment goal has moved from maximizing efficacy at any cost to preserving efficacy and minimize long-term toxicity, particularly given the disease’s young patient population and correspondingly long survivorship horizon.

A major focus of the conversation was the retirement of bleomycin from frontline regimens. Dr Brody explained that bleomycin carried substantial risk of pneumonitis and pulmonary fibrosis without strong single-agent antitumor activity and traced its decline to the phase 3 RATHL trial (NCT00678327), which established that patients with a clean interim PET scan after 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) could safely omit bleomycin from subsequent cycles. He noted that this PET-adapted approach helped set the stage for the 2 trials that have since reshaped frontline advanced-stage therapy: the phase 3 ECHELON-1 trial (NCT01712490), which showed that brentuximab vedotin (Adcetris) plus doxorubicin, vinblastine, and dacarbazine (AVD) outperformed standard ABVD, and the phase 3 SWOG S1826 (NCT03907488) trial, in which nivolumab (Opdivo) plus AVD produced a significantly lower relapse rate than brentuximab vedotin plus AVD, with durable benefit confirmed at the 2025 ASH Annual Meeting. Dr Brody described nivolumab plus AVD as the current standard of care for most patients with advanced-stage disease in the United States, citing both its efficacy and its more favorable toxicity profile relative to brentuximab vedotin, which carries a meaningful risk of peripheral neuropathy.

The discussion then turned to the underlying biology that makes Hodgkin lymphoma so responsive to PD-1 blockade. Dr Brody explained that the malignant Reed-Sternberg cell relies heavily on PD-L1 overexpression, frequently driven by 9p24 amplifications or translocations, to evade T-cell surveillance, leaving the tumor unusually vulnerable once that mechanism is blocked pharmacologically. He noted that this single dominant immune-evasion pathway helps explain why response rates to anti–PD-1 therapy in Hodgkin lymphoma exceed those seen in melanoma and non–small cell lung cancer.

Drs Park and Brody also explored treatment selection in early-stage disease, where Dr Brody noted that multiple regimens now achieve cure rates exceeding 90%, leaving no single clear standard. Options include traditional ABVD with low-dose radiation, radiation-free approaches with intensified chemotherapy, and emerging nivolumab-inclusive regimens, with selection often individualized based on disease location and patient-specific factors, such as the feasibility of giving radiation to sensitive anatomic sites.

On relapsed disease, Dr Brody emphasized that outcomes remain favorable even after treatment failure, with second-line therapy typically incorporating whichever novel agent, anti–PD-1 or brentuximab vedotin, was not used in the frontline setting, often combined with chemotherapy. He noted that some patients achieve durable remission without proceeding to autologous stem cell transplant, though transplant remains an option for appropriate candidates, and flagged older patients as an ongoing unmet need given poorer transplant tolerability in this population.

The conversation concluded with a look at emerging therapies beyond current CD30- and PD-1-targeted approaches, including CD70-directed antibody-drug conjugates and CD30-directed CAR T-cell therapy, both still early in development. Dr Brody highlighted new data presented at the 2026 ASCO Annual Meeting on an investigational PRMT5 inhibitor among heavily pretreated patients. He described the finding as unexpected and among the most promising developments on the horizon for relapsed and refractory disease.

S18 Ep36: Precision Immunotherapy, PET-Adapted Regimens, and Novel Targets Are Redefining Hodgkin Lymphoma Care: With Chandler Park, MD; Joshua Brody, MD

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S18 Ep36: Precision Immunotherapy, PET-Adapted Regimens, and Novel Targets Are Redefining Hodgkin Lymphoma Care: With Chandler Park, MD; Joshua Brody, MD