Expanding the indication for nivolumab (Opdivo) plus doxorubicin, vinblastine, and dacarbazine (AVD) to include pediatric patients 12 years and older—in addition to adults—represents a key advance in the treatment of classical Hodgkin lymphoma, according to Sharon Castellino, MD, MSc.
“The inclusion of children [and] adolescents in studies advancing novel therapy, when [the disease] biology is similar, needs to always be considered by trial sponsors, so that children with cancer benefit from advances at the same pace as adults,” Castellino said in an interview with OncLive.
On March 20, 2026, the FDA approved nivolumab plus AVD for the treatment of adult and pediatric patients at least 12 years of age with previously untreated, stage III or IV classical Hodgkin lymphoma.1,2 In tandem, the regulatory agency granted traditional approval to nivolumab for the treatment of adult patients with relapsed/refractory Hodgkin lymphoma following autologous hematopoietic stem cell transplant (HSCT) and treatment with brentuximab vedotin (BV; Adcetris), or following 3 or more lines of systemic therapy that include HSCT.1
The frontline approval of nivolumab plus AVD was supported by data from the phase 3 SWOG 1826 trial (NCT03907488), which showed that 6 cycles of nivolumab plus AVD reduced the risk of disease progression or death by 58% compared with 6 cycles of BV plus AVD (HR, 0.42; 95% CI, 0.27-0.67; P < .0001). The median progression-free survival (PFS) was not reached in either arm at a median follow-up of 13.7 months. At a median follow-up of 36.7 months, 1.8% of patients in the nivolumab plus AVD arm had died, and 3.4% of patients in the BV plus AVD arm had died.
In the interview, Castellino broke down the key implications of the FDA’s approval of nivolumab plus AVD, expanded on key data from SWOG 1826 that supported the decision, and explained the importance of the regimen’s category 1 recommendation in the updated NCCN Clinical Practice Guidelines in Oncology for Hodgkin lymphoma and pediatric Hodgkin lymphoma.3,4
Castellino is a professor in the Department of Pediatrics at Emory University School of Medicine and director of the Leukemia and Lymphoma Program, Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, in Georgia.
OncLive: With frontline nivolumab plus AVD now approved by the FDA for patients with untreated classical Hodgkin lymphoma, how do you see this regimen affecting clinical practice?
Castellino: This regimen has now been increasingly adopted by medical oncologists for [adult] patients with advanced-stage disease. In pediatric [oncology], there is increased adoption for patients at least 12 years of age, and [this is] now supported by the NCCN guidelines for pediatric Hodgkin lymphoma.
Nivolumab Plus AVD for Advanced Hodgkin Lymphoma
- The FDA approved nivolumab plus AVD for the treatment for adult and pediatric patients 12 years and older with previously untreated stage III/IV classical Hodgkin lymphoma.
- In the phase 3 SWOG 1826 trial, nivolumab plus AVD cut the risk of progression or death by 58% vs BV plus AVD.
- Castellino highlighted high 3-year survival rates in adolescent patients, reduced radiation use, and easier delivery with fewer clinic visits. She also noted the need for thyroid monitoring and long-term follow-up for immune-related adverse effects.
What is the significance of the efficacy data that supported the approval of nivolumab plus AVD?
The 3-year [PFS rate] of 93% [95% CI, 87%-96%] for adolescent [patients who received nivolumab plus AVD] is incredible.5 This rivals the 3-year efficacy results seen in the phase 3 AHOD1331 trial [NCT02166463], which led to FDA approval of the anti-CD30 antibody-drug conjugate [BV] in [pediatric patients with stage IIB to IVB Hodgkin lymphoma], but with a dramatically lower use of radiation. [The incorporation of nivolumab plus AVD into the treatment paradigm] also changes the field from making therapy decisions based on interim PET imaging.
What is important to note about the safety profile of nivolumab plus AVD? How could past experience help hematologists integrate it into patient care?
The key differences between the study arms relate to the decreased rate of clinically reported peripheral neuropathy in the group that received nivolumab plus AVD vs the group that received BV-AVD. In contrast, there was a higher proportion of patients [treated with nivolumab plus AVD] who developed thyroid dysfunction, which may resolve or require management with thyroid hormone replacement. [Therefore,] monitoring thyroid function early needs to be part of practice with the use of nivolumab plus AVD across the age spectrum. A new consideration and a shift from current practice is that with the planned use of 6 cycles of therapy, there is no dependence on getting a PET scan after 2 cycles to modify therapy.
How does the FDA approval of nivolumab plus AVD affect the untreated classical Hodgkin lymphoma treatment paradigm? Are there subsets of patients for whom you may be hesitant to give the combination?
The inclusion of [patients 12 years and older] in this trial is a large win. Historically, there has been a 6- to 10-year gap in the approval of novel therapies for children [compared with adults]. Additionally, the [inclusion of this regimen in] the NCCN guidelines for pediatric Hodgkin lymphoma is a new model.
The study did exclude patients with a known history of underlying autoimmune disease. This needs to be thought about, as this [regimen] is adopted in clinical practice outside of a clinical trial. In addition, [there] is a limitation in the [current] data for extending the use of nivolumab outside of a clinical trial in children under 12 [years of age]. Younger patients with lymphoma may have a higher risk of harboring an inborn error of immunity, which may be clinically silent.
How might the availability of nivolumab plus AVD affect the quality of life of patients with Hodgkin lymphoma?
This regimen is relatively easy to deliver, with decreased clinic visits compared [with] many [previously approved] pediatric and adult regimens for Hodgkin lymphoma. In addition, it can largely be delivered without the use of granulocyte colony-stimulating factor, which is often an additional burden for patients. Importantly for pediatric patients, this represents a large change in the paradigm, as 1.3% [of patients in SWOG 1826] received radiation therapy.5 This compares [with] 53.4% of patients who received radiation therapy with the AHOD1331 regimen, inclusive of BV.6
Are there any remaining questions regarding the use of nivolumab plus AVD in advanced Hodgkin lymphoma?
The late effects of immune checkpoint inhibitor therapy are unknown at this time. In adolescent [patients], with decades of life ahead, we will need to monitor for the unknown risk of late immune-related adverse [effects]. The off-target effect of any cancer therapy has to be anticipated and watched for in children and adolescents over time. The cumulative dose of doxorubicin used in the nivolumab/AVD 6-cycle approach is higher than that used in recent contemporary pediatric trials for high-risk Hodgkin lymphoma, but [it] is offset by the lower [rates of] radiation use.
Looking to the future, are there ongoing trials or studies that you are watching in the Hodgkin lymphoma realm?
We anticipate data from the ongoing Children’s Oncology Group–led [phase 3] AHOD2131 trial [NCT05675410] of nivolumab in combination with BV in patients across the age spectrum with early-stage Hodgkin lymphoma.
In advanced-stage disease, the next step is to identify and use molecular or imaging biomarkers [to determine in] which patients we can de-escalate therapy or which high-risk patients need therapy intensification. In addition, in the rare patients who may relapse after nivolumab plus AVD, we need to understand the reasons for nonresponse and which approaches with other biologically targeted [options] could benefit these patients.
References
- FDA approves nivolumab with chemotherapy for previously untreated Hodgkin lymphoma. FDA. March 20, 2026. Accessed April 17, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-chemotherapy-previously-untreated-hodgkin-lymphoma
- Opdivo. Prescribing information. Bristol Myers Squibb; 2026. Accessed April 17, 2026. https://packageinserts.bms.com/pi/pi_opdivo.pdf
- NCCN. Clinical Practice Guidelines in Oncology. Hodgkin lymphoma, version 1.2026. Accessed April 17, 2026. https://www.nccn.org/professionals/physician_gls/pdf/hodgkins.pdf
- NCCN. Clinical Practice Guidelines in Oncology. Pediatric Hodgkin lymphoma, version 2.2025. Accessed April 17, 2026. https://www.nccn.org/professionals/physician_gls/pdf/ped_hodgkin.pdf
- Castellino SM, Li H, Herrera AF, et al. Three-year follow-up of nivolumab-AVD versus brentuximab vedotin–AVD in adolescents with advanced-stage classic Hodgkin lymphoma on S1826. J Clin Oncol. 2026;44(6):449-454. doi:10.1200/JCO-25-00203
- Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin with chemotherapy in pediatric high-risk Hodgkin’s lymphoma. N Engl J Med. 2022;387(18):1649-1660. doi:10.1056/NEJMoa2206660
