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Attendees at ASH 2018
Photo courtesy of ASH

SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.

In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).

These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.

“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.

Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.

Patients and treatment

ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).

Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.

At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.

Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.

Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).

Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.

Efficacy

The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).

At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).

At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).

Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.

Safety

BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.

The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.

Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.

The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:

  • Nausea (46% and 38%)
  • Peripheral sensory neuropathy (45% and 41%)
  • Neutropenia (38% for both)
  • Diarrhea (38% and 20%)
  • Constipation (29% and 30%)
  • Alopecia (26% and 25%)
  • Pyrexia (26% and 19%)
  • Vomiting (26% and 17%)
  • Fatigue (24% and 20%)
  • Anemia (21% and 16%).

This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.

Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.


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