The ECHELON-2 trialr was a double-blind phase 3 study from 17 countries of untreated peripheral T-cell lymphoma (PTCL) in patients whose lymphoma had at least 10% of cells expressing CD30. Histological subtypes included anaplastic large cell lymphoma (ALCL) ALK-negative, ALCL ALK-positive with an International Prognostic Index (IPI) score of 2 or higher, PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), adult T-cell leukaemia/lymphoma, enteropathy associated lymphoma, and hepatosplenic T-cell lymphoma. There was a 1:1 randomisation to brentuximab vedotin, cyclophosphamide, doxorubicin and prednisolone (BV-CHP) or cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) for 6-8 cycles. A consolidative stem cell transplant (SCT) or radiotherapy could be performed at the end of the chemotherapy at the investigator’s discretion.
452 patients were randomised. 70% had systemic anaplastic large cell lymphoma (sALCL) and the median age was 58 years. The primary endpoint was progression-free survival (PFS).r
Real world data reinforced the superiority of BV-CHP vs. CHOP with a retrospective analysis of 1344 patients with PTCL treated with BV-CHP (n=749) vs. CHOP (n=595).r The most common subtypes were sALCL , PTCL-NOS and AITL. After propensity matching, patients treated with CHOP had a higher likelihood of receiving a second-line therapy during the follow-up period (HR 1.64).r
Efficacy
The median PFS was 62.3 months for BV-CHP and 23.8 months for CHOP (figure 1) giving a 30% reduction in progression events.r Compared with CHOP, BV-CHP significantly reduced the risk of death by 34% (figure 2). After a median follow-up of 47.6 months, the median overall survival (OS) was not reached for either group. The estimated 5-year OS was 70.1% the BV-CHP arm versus 61.0% for the CHOP arm. 5 year follow up data showed that all patients subgroups benefited of the treatment including those with high IPI scores.
Rates of consolidative SCT were higher in the BV-CHP arm than in the CHOP arm (22% vs. 17%) whilst consolidative systemic anticancer therapy was higher in the CHOP cohort; (31% vs. 45%).r Among the 114 patients who achieved CR following BV-CHP, those who underwent a subsequent SCT had a 64% reduction in the risk of a PFS event with the estimated 3-year PFS of 80.4% in patients who underwent SCT compared to 54.9% in those who didn’t, although this analysis was limited by case numbers.r
The study was not powered to compare the efficacy between the histological subtypes but prespecified subgroup analysis was consistent with the overall study result. In the sALCL subgroup the 5-year PFS was 60.6% for BV-CHP and 48.4% for CHOP.r
Figure 1. Progression-free survivalr
© Ann Oncol 2022
Figure 2. Overall survival for the intention-to-treat populationr
© Ann Oncol 2022
Toxicity
Adverse events were similar in each arm.
Table 1. Adverse eventsr
© Lancet 2019