Treatment with a combination of bendamustine and brentuximab vedotin (BBv) was associated with high rates of response and encouraging improvements in survival in patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL), according to study findings published in Blood Advances.
Patients with R/R PTCL have a poor prognosis with a median progression-free survival (PFS) of only approximately three months and a median overall survival (OS) of less than one year, explained study author Gandhi Damaj, MD, of Normandy University in France.
“Salvage therapies are of limited efficacy regardless of the drugs used,” Dr. Damaj added. “The only curative approach is allogeneic hematopoietic cell transplantation [alloHCT] in this setting, but patients must be in response before transplant.”
The retrospective study included 82 BBv-treated patients with noncutaneous R/R PTCL from 21 LYSA centers in France and Belgium. Brentuximab vedotin was administered at the standard dose of 1.8 mg/kg on the first day of each cycle, while bendamustine was administered at 90 mg/m2 on days one and two. Treatment cycles repeated every three weeks.
Overall response rate (ORR) and partial response (PR) rate after BBv were the primary objectives of the study. The researchers also evaluated PFS, OS, duration of response (DOR), impact of transplantation on outcome, and safety.
The median age of the cohort was 60 years, and most patients were male (61%). Approximately 97% of patients had advanced-stage disease, and half of the overall cohort was refractory to prior treatment. The median number of previous treatment regimens was one (range = 1-6).
Patients received a median of four treatment cycles with BBv. The ORR was 68%, including 49% of patients in complete response and 19% of patients in PR. The median DOR was 15.4 months, and nearly a third of patients (31%) experienced a prolonged response that lasted more than one year.
The median PFS in 81 evaluable patients was 8.3 months, while the median OS was 26.3 months. The estimated one-year PFS was 40.7%, and the estimated one-year OS was 63.7%. After a median follow-up of 22 months, a total of 34 patients died from lymphoma progression and one patient died from toxicity while in PR.
A multivariate analysis designed to discover predictive factors for response found that relapse status after the last regimen was associated with response, with an ORR of 83% for relapsed disease versus 53% for refractory disease (p=0.014).
Among the 16 patients who underwent alloHCT, the median PFS was 19.3 months versus 4.8 months for patients who did not undergo transplant (p=0.0005). Additionally, the median OS rates were not reached in patients who underwent transplant versus 12.4 months for those who did not undergo transplant (p=0.0013).
Most patients (59%) experienced grade 3-4 adverse events, which were predominantly hematologic in nature. Treatment doses were reduced in a third of patients, and treatment was stopped early in 11% of patients. Dose reductions were predominantly a result of hematologic toxicities, neurotoxicity, rash, and gastrointestinal toxicity. Hematologic toxicity and neurotoxicity were the primary causes of discontinuation.
“These findings could be practice changing for those patients with CD30-positive [R/R] PTCL in order to obtain high response rate and high PFS and OS,” Dr. Damaj commented.
Limitations of the study included the small sample size, the limited duration of follow-up, and the inclusion of only patients from France and Belgium. Additionally, the increasing use of BV alone as part of first-line therapy could limit the impact of an approach such as the one studied.
Despite this, Dr. Damaj noted that the studied therapeutic combination could be considered the preferred treatment option at relapse, even in patients with PTCL who do not proceed to consolidation with alloHCT.
“Given the high efficacy of this combination in the relapse and refractory setting, it could be very interesting to move forward with this combination in the front-line therapy of patients with PTCL,” Dr. Damaj concluded.
Any conflicts of interest declared by the authors can be found in the original article.
Damaj G, Aubrais R, Bouabdallah K, et al. Salvage therapy with brentuximab-vedotin and bendamustine for patients with R/R PTCL: a retrospective study from the LYSA [published online, 2022 Dec 7]. Blood Adv. doi: 10.1182/bloodadvances.2022008524.