Brentuximab Vedotin Plus Gemcitabine Shows Efficacy, Safety in R/R PTCL

Findings from a phase 2 study (NCT03496779) conducted by the Lymphoma Study Association demonstrated that the combination of brentuximab vedotin (Adcetris) with gemcitabine was safe and efficacious in patients with relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL).^1,2

The study met its primary end point, demonstrating a statistically significant response rate.At the end of the induction phase, the overall response rate (ORR) was 46.5% (90% CI, 36.30%–56.89%). The complete response rate (CR) was 19.7% (90% CI, 12.33%–29.10%). The partial response rate was 26.7% (90% CI, 18.29%–36.75%). The stable disease rate was 5.6% (90% CI, 1.95%–12.43%). The progressive disease rate was 38.0% (90% CI, 28.37%–48.46%).

The lower limit of the 90% CI for the ORR (36.3%) was above the prespecified null hypothesis of 35%, confirming a positive result. The best ORR observed at any point was 55%.

The study had a median follow-up of 32.6 months with a median duration of response of 15.8 months (95% CI, 10.4–not reached). The median progression-free survival (PFS) was 4.5 months (95% CI, 3.5–10.0). The median overall survival (OS) was 12.9 months (95% CI, 9.0–29.6).

Safety and Tolerability

The treatment combination was associated with significant but manageable toxicity, primarily hematological. The most common grade ≥ 3 adverse event (AE) was neutropenia in the induction and maintenance phases (54.9% vs 21.4%). Other AEs included anemia (21.1% vs 0%), thrombocytopenia (14.1% vs 0%), infection (14.1% vs 7.1%), and peripheral neuropathy (4.2% vs 14.3%).

Peripheral neuropathy of any grade was reported in 12.6% of patients during induction and 46.4% during maintenance. During the study, 44 deaths were reported; 31 were related to lymphoma progression and 13 to other causes, including concurrent illness or toxicity from subsequent therapy.

Study Design

The study treatment consisted of 2 phases: an induction phase and a maintenance phase for responding patients.

In the induction phase, patients received 4 28-day cycles of gemcitabine (1000 mg/m² IV on day 1 and day 15) plus brentuximab vedotin (1.8 mg/kg IV on day 8).

In the maintenance phase, patients who achieved a complete or partial response after induction received up to 12 cycles of brentuximab vedotin monotherapy (1.8 mg/kg) every 21 days.

Of the total patients, 45 completed the induction phase (63%), 28 patients started the maintenance phase (39%), and 8 patients completed the full treatment (11%). Additionally, 63 patients discontinued treatment prematurely primarily due to lymphoma progression (n = 36) or AEs/death (n = 15). Nine eligible patients were withdrawn to proceed to a transplantation program.

A secondary end point of the study was to analyze parameters associated with the CD30 target. This analysis yielded one of the study's most significant findings.

An inclusion criterion was at least 5% CD30-positive cells. Using a 10% cutoff for analysis (based on the ECHELON-2 trial [NCT01777152]³), there was no correlation found between the percentage of CD30-positive neoplastic cells and treatment efficacy.

Baseline soluble CD30 (sCD30), measured in serum, emerged as a powerful negative prognostic factor. An optimal cutoff of 120 ng/mL was identified.¹

Patients with high sCD30 (>120 ng/mL) had significantly worse outcomes:

• Lower ORR (P =.0004)
• Lower CR rate (P =.0057)
• Shorter PFS (P =.0114)
• Shorter OS (P =.0196)

Patient Characteristics

A total of 71 patients were enrolled and treated between April 2018 and October 2019. The median age was 66 years (range, 20–79), and 66% of patients were male. The majority of patients had advanced disease, with 91.6% having stage III to IV lymphoma.

The primary diagnoses were:

• Follicular helper T-cell lymphomas (TFHL): 47.9%
• Anaplastic large-cell lymphomas (ALCL), ALK-negative: 19.7%
• PTCL, not otherwise specified (PTCL-NOS): 12.7%
• ALCL, ALK-positive: 7.0%
• Other entities: 12.7%

All patients had received CHOP/CHOP-like regimens; 80.3% were on their second line of therapy, and a majority (60.6%) were refractory to their last line of treatment.

Although the study met its primary end point and yielded efficacious results, Tournilhac O et al, authors of the study, acknowledge limitations.

“Despite being in line with our hypothesis, the benefit of combining [brentuximab vedotin] with gemcitabine in comparison with gemcitabine alone remains modest,” noted authors. “This study does not address the comparison of combining gemcitabine with [brentuximab vedotin] compared with [brentuximab vedotin] alone and does not provide statistically backed result for each PTCL entity, a frequent pitfall in PTCL studies.”

REFERENCES

1.Tournilhac O, Bouabdallah K, Lecolant S et al. Brentuximab vedotin addition to gemcitabine in relapsed or refractory peripheral T-cell lymphoma: a LYSA phase 2 study. Published December 10, 2025. Accessed January 5, 2026. Blood Adv (2025) 9 (24): 6292–6304. doi: 10.1182/bloodadvances.2024015787.

2.Study of brentuximab vedotin in patients with R/R PTCL treated with gemcitabine. ClinicalTrials.gov. Updated July 30, 2025. Accessed January 5, 2026. https://clinicaltrials.gov/study/NCT03496779

3.ECHELON-2: A comparison of brentuximab vedotin and CHP with standard-of-care CHOP in the treatment of patients with CD30-positive mature T-cell lymphomas (ECHELON-2). ClinicalTrials.gov. Updated November 30, 2021. Accessed January 6, 2026. https://clinicaltrials.gov/study/NCT01777152