Brentuximab Vedotin and Chemotherapy Effective in Peripheral T-cell Lymphoma

By David Douglas

December 17, 2018

NEW YORK (Reuters Health) - Brentuximab vedotin (Adcetris, Seattle Genetics) in combination with chemotherapy is significantly more effective than chemotherapy alone in patients with CD30-positive peripheral T-cell lymphomas, according to the multinational phase 3 ECHELON-2 trial.

"Peripheral T cell lymphomas (PTCL) are aggressive forms of systemic non-Hodgkin lymphomas that we commonly treat with combinations of chemotherapy with curative intent," said Dr. Steven Horwitz of Memorial Sloan Kettering Cancer Center, in New York City.

"ECHELON-2 showed that by adding a targeted therapy, brentuximab vedotin, to frontline chemotherapy in people with CD30-expressing PTCL, you can greatly improve outcomes," he told Reuters Health by email.

The findings were published online December 4 in The Lancet to coincide with a presentation at the American Society of Hematology annual meeting in San Diego, California.

Dr. Horwitz and colleagues randomly assigned 452 patients with previously untreated CD30-positive PTCL to treatment with brentuximab vedotin, cyclophosphamide, doxorubicin and prednisone (A+CHP) or to chemotherapy alone using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

The patients received 21-day cycles of either regimen. A total of six or eight were given at the investigators' discretion.

In the combination group, median progression-free survival was 48.2 months significantly greater than the 20.8 month in the CHOP group (hazard ratio, 0.71;P=0.01).

Rates of adverse events were similar between groups. Febrile neutropenia was seen in 18% of combination patients and 15% of the CHOP group, and peripheral neuropathy in 52% and 55%, respectively.

There were fatal adverse events in seven combination patients (3%) and nine in the CHOP group (4%).

Overall, say the researchers, treatment with the combination "led to a 29% reduction in the risk of a progression-free survival event and a 34% lower risk of death, with a 77% probability of survival at 36 months."

"This," concluded Dr. Horwitz, "is the first study to show an improvement in overall survival compared to a standardly used chemotherapy regimen, CHOP. Given the significant benefit, this is immediately practice changing for patients eligible for this approach."

Dr. Vincent T. DeVita Jr. of Yale School of Public Health, in New Haven, Connecticut, who studies lymphoma, told Reuters Health by email, "It's the most promising data I've seen in CD30-positive T cell lymphomas."

He noted that the study follows a recent report showing the efficacy of substitution of brentuximab vedotin for bleomycin in treatment of Hodgkin lymphoma.

However, added Dr. DeVita, "In the ECHELON-2 study, this was done with no increase in toxicity except for a slightly increased time to recovery from peripheral neuropathy. I think the authors are correct in stating this study supports A+CHP as the new standard of care for this troublesome subset of non-Hodgkin lymphoma."

The study was funded by Seattle Genetics, Millennium Pharmaceuticals Inc, a subsidiary of Takeda Pharmacuetical and the National Institutes of Health. Dr. Horwitz and several coauthors reported financial ties to Seattle Genetics.


Lancet 2018.