Phase 2 study of pegylated liposomal doxorubicin plus cyclophosphamide, vincristine/vindesine, and prednisone in newly diagnosed PTCL: 8-year results

Abstract

Background: Pegylated liposomal doxorubicin (PLD) is a liposome-encapsulated form of doxorubicin with equivalent efficacy and less cardiotoxicity. This phase 2 study evaluated the efficacy and safety of the PLD-containing CHOP regimen in newly diagnosed patients with aggressive peripheral T-cell lymphomas (PTCL).

Methods: Patients received PLD, cyclophosphamide, vincristine/vindesine, plus prednisone every 3 weeks for up to 6 cycles. The primary endpoint was the objective response rate at the end of treatment (EOT).

Results: From September 2015 to January 2017, 40 patients were treated. At the EOT, objective response was achieved by 82.5% of patients, with 62.5% complete response. As of the cutoff date (September 26, 2023), median progression-free survival (mPFS) and overall survival (mOS) were not reached (NR). The 2-year, 5-year, and 8-year PFS rates were 55.1%, 52.0%, and 52.0%. OS rate was 80.0% at 2 years, 62.5% at 5 years, and 54.3% at 8 years. Patients with progression of disease within 24 months (POD24) had worse prognosis than those without POD24, regarding mOS (41.2 months vs NR), 5-year OS (33.3% vs 94.4%), and 8-year OS (13.3% vs 94.4%). Common grade 3-4 adverse events were neutropenia (87.5%), leukopenia (80.0%), anemia (17.5%), and pneumonitis (17.5%).

Conclusion: This combination had long-term benefits and manageable tolerability, particularly with less cardiotoxicity, for aggressive PTCL, which might provide a favorable benefit-risk balance.

Clinicaltrials.gov identifier: Chinese Clinical Trial Registry, ChiCTR2100054588; IRB Approved: Ethics committee of Fudan University Shanghai Cancer Center (Date 2015.8.31/No. 1508151-13.

Keywords: chemotherapy; first-line treatment; pegylated liposomal doxorubicin; peripheral T-cell lymphomas.

Figure 1.

Kaplan-Meier curves in the overall population. (A) Progression-free survival. PFS analysis was performed by censoring patients who received non-study antitumor therapies prior to progression at the time of starting new antitumor therapies. With 16 disease progression or death occurring, the median PFS was not reached at the data cutoff, with estimated PFS rates of 55.1% (95% CI, 40.5-74.9) at 2 years, and both 52.0% (95% CI, 37.5-72.2) at 5 and 8 years. (B) Overall survival. Based on 18 deaths, the median OS of all patients was not reached due to insufficient events, with 2-year, 5-year, and 8-year OS rates of 80.0% (95% CI, 68.5-93.4), 62.5% (95% CI, 49.2-79.5), and 54.3% (95% CI, 40.7-72.5).

Figure 2.

Kaplan-Meier curves of overall survival according to progression of disease within 24 months (POD24) status. Median OS was longer in non-POD24 patients than in POD24 patients (not reached vs 41.2 months; P < .001).

Figure 3.

The changes of left ventricular ejection fraction (LVEF) over time from baseline to the end of treatment in 39 with post-treatment LVEF results. From baseline to the end of treatment, 30 patients exhibited different degrees of LVEF decline, with a mean LVEF decline of 7.2% (range, 1.0%-19.0%; SD, 4.3%). The LVEF decline of ≥10% was observed in 6 patients (15.0%), of which 2 (5.0%) patients had a resting LVEF of <50%. Thirteen (43.3%) of 30 patients displayed a subsequent recovery of LVEF.