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Brentuximab vedotin + CHP doubles PFS over CHOP in CD30+ peripheral T-cell lymphoma

Roshini Claire Anthony
11 Dec 2018
Dr Steven Horwitz

The combination of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) more than doubled progression-free survival (PFS) as well as improved overall survival (OS) in patients with CD30-expressing peripheral T-cell lymphoma compared with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), according to results of the phase III ECHELON-2* trial.

“A+CHP provided clinically meaningful improvement in PFS and OS vs CHOP with a 29 percent reduction in the risk of a progression event and a 34 percent reduction in the risk of death,” said study author Dr Steven Horwitz from the Memorial Sloan Kettering Cancer Center in New York City, New York, US.

“ECHELON-2 [is also the] first prospective trial in peripheral T-cell lymphoma to show OS benefit over CHOP,” he added.

Participants in this international, double-blind study were adults (median age, 58 years) with previously untreated CD30-expressing peripheral T-cell lymphoma who were randomized 1:1 to receive A+CHP (brentuximab vedotin [1.8 mg/kg], cyclophosphamide [750 mg/m2], and doxorubicin [50 mg/m2] on day 1, and prednisone [100 mg on days 1–5]; n=226, 59 percent male) plus placebo or CHOP (cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], and vincristine [1.4 mg/m2] on day 1, and prednisone [100 mg on days 1–5]; n=226, 67 percent male) plus placebo Q3W for 6–8 21-day cycles. Eighty percent of patients had stage 3–4 disease and 72 and 68 percent of A+CHP and CHOP recipients, respectively, had systemic anaplastic large cell lymphoma (sALCL), with 50 and 46 percent, respectively, having ALK-negative sALCL.

After a median follow up of 36.2 months, PFS was more than doubled among A+CHP compared with CHOP recipients (median, 48.2 vs 20.8 months, hazard ratio [HR], 0.71, 95 percent confidence interval [CI], 0.54–0.93; p=0.0110; 3-year PFS, 57 percent vs 44 percent). [ASH 2018, abstract 997; Lancet 2018;doi:10.1016/S0140-6736(18)32984-2]

PFS was also superior among the A+CHP vs CHOP recipients with sALCL (HR, 0.59, 95 percent CI, 0.42–0.84; p=0.0031).

At a median follow up of 42.1 months, A+CHP recipients demonstrated superior OS over CHOP recipients, with 51 compared with 73 deaths (median OS not reached in either group, HR, 0.66, 95 percent CI, 0.46–0.95; p=0.0244).

“For T-cell lymphoma, this has really been unprecedented as we have no studies that show an OS benefit over standard therapies so that’s really a big step forward,” said Horwitz.

The objective response rate was higher in A+CHP vs CHOP recipients (83 percent vs 72 percent; p=0.0032), as was the complete remission rate (68 percent vs 56 percent; p=0.0066).

Adverse event (AE) incidence was comparable between A+CHP and CHOP recipients (99 percent vs 98 percent), specifically grade 3 AEs (66 percent vs 65 percent), serious AEs (39 percent vs 38 percent), and AE-related deaths (3 percent vs 4 percent). Neutropenia was the most frequent grade 3 AE in A+CHP and CHOP recipients (35 percent vs 34 percent) followed by anaemia (13 percent vs 10 percent). Treatment-emergent peripheral neuropathy occurred in 117 and 124 A+CHP and CHOP recipients, respectively, with resolution rates of 50 and 64 percent. At the most recent follow up, 52 and 36 percent of A+CHP and CHOP recipients, respectively, still had peripheral neuropathy.

Eighty-five and 79 percent of A+CHP and CHOP recipients, respectively, discontinued therapy, with disease progression the primary reason among CHOP recipients (12 percent vs 3 percent [A+CHP recipients]). Discontinuation due to AEs was comparable between A+CHP and CHOP recipients (6 percent vs 7 percent).

“Importantly, [the] improvements in survival came without an observed increase in toxicity. A+CHP was well tolerated, with a manageable safety profile compared with CHOP, although the median time to resolution of peripheral neuropathy was longer with A+CHP [17.0 weeks] than with CHOP [11.4 weeks],” said Horwitz and co-authors.

 

Positioning A+CHP in the treatment regimen

CHOP has been the most common first-line treatment in this patient population for decades, with “attempts to improve upon CHOP … largely unsuccessful, said the authors.

“We consider [the ECHELON-2] results to be potentially practice-changing,” they said. “[T]he ECHELON-2 trial … supports the potential for A+CHP to become a new standard of care for many patients with CD30-positive peripheral T-cell lymphoma.”

“This data led to a … US FDA** approval [in November 2018] for brentuximab vedotin in combination with CHP for adults with previously untreated sALCL and other CD30-expressing peripheral T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified,” said Horwitz.

“Regulatory approval is being sought from additional health authorities worldwide for the use of A+CHP in the treatment of patients with previously untreated CD30-positive peripheral T-cell lymphoma,” the authors said.

“The next step is to understand who the true patients are who benefit [from this treatment],” said Horwitz.

 

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Most Read Articles
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Using vadadustat for treating anaemia in patients with chronic kidney disease (CKD) not on dialysis does not come with excess cardiovascular (CV) risk compared with darbepoetin alfa, particularly for those treated to a target Hb range of 10–11 g/dL, according to a prespecified analysis of the PRO2TECT study presented at ASN 2020 Kidney Week.
Audrey Abella, 18 Dec 2020
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