5-year ECHELON-1 updates show durable benefits of brentuximab vedotin-chemo for cHL

In the 5-year updated results of the phase III ECHELON-1 study presented at EHA 2021, a combination of the CD30-directed ADC* brentuximab vedotin and chemotherapy (CT) continued to show potential for individuals with previously untreated stage III/IV classical Hodgkin lymphoma (cHL).

 

Previously reported ECHELON-1 findings showed that the combination of brentuximab vedotin and a CT regimen consisting of doxorubicin, vinblastine, and dacarbazine (A+AVD) outdid the ABVD regimen comprising doxorubicin, bleomycin, vinblastine, and dacarbazine in terms of progression-free survival (PFS). [N Engl J Med 2018;378:331-344] This effect was sustained up to 4 years of follow-up in the intention-to-treat (ITT) population and across most key subgroups, regardless of disease stage, interim PET scan status, and baseline risk factor score. [Blood 2019;134(suppl 1):4026; Blood 2020;135:735-742]

 

In this study, 1,334 participants were randomized 1:1 to receive ≤6 cycles of IV A+AVD or ABVD on days 1 and 15 of a 28-day cycle. Interim PET scans were performed following cycle 2 (PET2).

 

At a median follow up of 60.9 months, the estimated 5-year PFS per investigator rates remained higher with A+AVD vs ABVD (82 percent and 75 percent), yielding a favourable PFS for A+AVD (hazard ratio [HR], 0.68; p=0.002). Stratification by PET status revealed a similar trend (85 percent vs 79 percent; HR, 0.66; p=0.004 [PET2-negative] and 61 percent vs 46 percent; HR, 0.70; p=0.229 [PET2-positive]). [EHA 2021, abstract S205]

 

“[These findings reflect] robust and durable treatment improvements … with A+AVD vs ABVD … which were independent of disease stage, risk factor score, and PET2 status,” said the researchers.

 

There were similar proportions of participants in the A+AVD and ABVD arms who had complete resolution or improvement of treatment-emergent peripheral neuropathy (PN; 85 percent vs 86 percent). Most ongoing PN cases were of grade 1 severity (17 percent and 14 percent in the respective A+AVD and ABVD arms).

 

Median time to complete resolution of ongoing PN events was longer with A+AVD vs ABVD (34 weeks vs 16 weeks), as was median time to improvement (49 weeks vs 12 weeks).

 

The incidence of secondary malignancies was lower with A+AVD vs ABVD arms (n=19 vs 29).

 

“[N]early all relapses in cHL occur within 5 years of treatment … [Our 5-year results show that] treatment with A+AVD provides sustained PFS benefits and a manageable safety profile,” said the researchers. Moreover, bleomycin exposure was avoided and symptoms of PN either improved or resolved over time. 

 

A subgroup analysis of ECHELON-1 looked into the effects A+AVD among adolescents and young adults (AYAs; n=771), as cHL commonly occurs in this patient subgroup. [EHA 2021, abstract EP769]

 

There was a higher 5-year PFS rate with A+AVD vs ABVD (86.3 percent vs 79.4 percent) after a median follow-up of 60.7 months, leading to a 36-percent reduction in the risk of progression or death with A+AVD (HR, 0.64; p=0.013). “Consistent with the ITT population, AYAs treated with A+AVD vs ABVD had a durable PFS benefit at this significant 5-year milestone,” said the researchers.

 

Despite the higher rate of any-grade PN in the A+AVD vs the ABVD arm (64 percent vs 40 percent), ongoing PN was mostly grade 1 (62 percent) and most events (up to 89 percent) eventually improved or resolved.

 

The rates of secondary malignancies were similarly low in both A+AVD and ABVD arms (n=7 vs 5). Also, there were more subsequent pregnancies reported in the A+AVD vs the ABVD arm (n=44 vs 26). “[These are] outcomes of interest to AYAs,” the researchers noted.

 

Collectively, the findings from both analyses imply that A+AVD is an attractive treatment option for patients, including AYAs, with previously untreated stage III/IV cHL.