Phase I study evaluating brentuximab vedotin and CHP in PTCL

In March 2018, Michelle Fanale from the University of Texas MD Anderson Cancer Center, Houston, TX, and colleagues, published online in Blood, results from the phase I trial that evaluated the use of brentuximab vedotin (BV) and cyclophosphamide, doxorubicin, and prednisone (CHP), in CD30-expressing peripheral T-cell lymphoma (PTCL) patients.

BV is a CD30-directed antibody that has been successfully used as monotherapy across various PTCL subtypes. It is worth mentioning that, a phase III trial comparing frontline BV + CHP to CHOP for PTCL is ongoing (ECHELON-2; NCT01777152). In this study, the 5-year durability of response, overall survival (OS) and peripheral neuropathy occurrence after BV + CHP was summarized in CD30-expressing PTCL patients, who remained in remission with no additional therapy.

Patient characteristics & study design

• N = 26 treatment-naïve patients with CD30-expressing PTCL
• Patient diagnosis:
  • Systemic anaplastic large cell lymphoma (ALCL): n = 19
  • CD30⁺ PTCL: n = 7
• n = 13 patients in remission with no additional therapy
• Dosing (once every 3 weeks):
  • BV: 1.8 mg/kg intravenously (two cycles)
  • CHP: standard CHOP dose intravenously (six cycles)
  • After 6 cycles, patients with objective response (OR) could receive up to 10 cycles of BV monotherapy
  • Median BV cycle administration (range): 13 (3–16)

Key findings

• All patients achieved OR (100%; 24 complete responses [CR], 2 partial responses [PR])
• Median observation time (range): 59.6 (4.6–66.0) months (5 years)
• At 5-year follow-up:
  • Median OS: not reached
  • Estimated 5-year OS: 80% (95% CI, 59–91)
  • 50% of the patients were in remission with no additional therapy and all of then achieved CR (n = 13)
  • Patients remaining in remission had received a median of 16 treatment cycles, as opposed to a median of 10 cycles for the other patients
• Peripheral neuropathy (PN) occurred in 73% (n = 19) of the total patient population and in 92% (n = 12) of patients in remission
• Median time to any grade PN onset (range): 11 (0–34) weeks
• PN treatment resolution or improvement occurred in 95% of the patients (n =18/19) with a median time of 4.2 and 2.6 months, respectively
• Ongoing PN at last follow-up in 53% of the patients (n = 10)

This long-term evaluation of the BV + CHP regimen in PTCL, demonstrated that of the 100% of the patients responding to the treatment initially, 50% stayed in remission without the use of any other cancer treatment, at 5-year follow-up. Moreover, despite PN occurrence in 73% of the patients, this resolved or improved with PN-targeted treatment in 95% of the cases. The authors concluded that the duration of response and favorable safety profile of BV + CHP, makes this regimen comparable to anthracycline-based therapies combined with consolidative stem cell transplants.