Brentuximab vedotin + chemo ups EFS in high-risk paediatric Hodgkin lymphoma

The combination of brentuximab vedotin (Bv) and chemotherapy was superior to a standard paediatric dose-intensive chemotherapy regimen in boosting event-free survival (EFS) in paediatric patients with high-risk Hodgkin lymphoma (HL), according to the phase III AHOD1331* trial presented at ASCO 2022.

At a median follow-up of 42.1 months, 3-year EFS was better with Bv and chemotherapy (doxorubicin [also known as adriamycin], vincristine, etoposide, prednisone, and cyclophosphamide; Bv-AVE-PC) than bleomycin-containing chemotherapy with doxorubicin, bleomycin, vincristine, prednisone, and cyclophosphamide (ABVE-PC) at 92.1 percent vs 82.5 percent, respectively (hazard ratio [HR], 0.41; p=0.0002).

This translates to a remarkable 59 percent risk reduction in EFS in favour of the Bv-AVE-PC combination regimen, said study author Dr Sharon Castellino from Emory University School of Medicine and Aflac Cancer and Blood Disorders Center in Atlanta, Georgia, US.

New standard front-line therapy?
Bv is an anti-CD30 antibody-drug conjugate that has been studied in adults with HL, with promising results. However, there have not been any phase III clinical trials of Bv in children and adolescents aged 2–21 years with HL.

“AHOD1331 is the first,” Castellino told her audience at ASCO 2022. “Bv-AVE-PC presents a new standard for front-line therapy in paediatric high-risk HL, including stage IIB with bulk.”

Using data from the Children’s Oncology Group network, Castellino and her team investigated 587 children and young adults (median age 15.6 years) newly diagnosed with high-risk classic HL (stages IIB with bulk, IIIB, IVA, or IVB). [ASCO 2022, abstract 7504]

Participants were randomized to five cycles of either Bv-AVE-PC (experimental arm; n=298) or ABVE-PC (standard arm; n=289) given every 21 days. An interim PET** assessment was performed on either arm after two cycles.

Consolidative radiation therapy (RT) was required for slow responding lesions (defined as a Deauville score of >3) and in the presence of large mediastinal adenopathy.

At baseline, the majority of the participants had stage IVB HL (31.2 percent and 32.2 percent in the Bv-AVE-PC and ABVE-PC arms, respectively), followed by stages IVA (28.2 percent and 28.7 percent, respectively), IIB with bulk (20.8 percent and 20.4 percent), and IIIB (19.8 percent and 18.7 percent).

The median time to the first event was 9.4 months for both regimens, with relapse being the more common event. A lower cumulative incidence of relapse was however observed with Bv-AVE-PC than with ABVE-PC (7.5 percent vs 17.1 percent; p=0.0003).

“[Although] relapse continues at this point … what’s interesting to us, not dissimilar to prior studies including Bv, is how [the relapse] curves separate. The relapse rate plateaus around 2 years in the [Bv-AVE-PC arm, while this plateau was not observed in the ABVE-PC arm],” Castellino noted.

When the analysis was further stratified by stages of HL and presence of B symptoms or bulky disease, Bv-AVE-PC use was associated with a lower 3-year EFS rate among patients with stages IIB with bulk or IIIB (HR, 0.09 and 0.07, respectively) and those with B symptoms (HR, 0.43) or bulky disease (HR, 0.41). However, those with stage IV did not seem to have a statistically significant advantage due to the small number of patients in that group, said Castellino.

The percentage of patients who received RT was almost similar between the Bv-AVE-PC and ABVE-PC arms at 52.7 percent and 55.7 percent, respectively. Castellino said this represents “the lowest percentage of high-risk paediatric patients [with HL] to date who have received RT” as part of their regimen.

Adverse events (AEs) occurred in 73.5 percent of patients in the Bv-AVE-PC arm and 68.2 percent in the ABVE-PC arm, which were expected for a dose-intensive regimen. Fever, neutropenia, sepsis, and CIPN*** were the most common AEs reported in both treatment arms. “[Of note, Bv-AVE-PC] is a well-tolerated regimen,” Castellino said.

*AHOD1331: Brentuximab vedotin and combination chemotherapy in treating children and young adults with stage IIB, IIIB, IVA, or IVB Hodgkin lymphoma

**PET: Positron emission tomography

***CIPN: Chemotherapy-induced peripheral neuropathy