Dataset Information

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma.

ABSTRACT: Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Despite good responses to standard of care frontline chemoimmunotherapy, the prognosis of relapsed/refractory (R/R) patients remains obscured by the possible inadequate responses to salvage therapy, eligibility for autologous transplantation, age and comorbidities. Polatuzumab vedotin is an antibody-drug conjugate formed by a CD79b antibody conjugated to the highly cytotoxic agent monomethyl auristatin E by means of a cleavable linker. Following significant clinical efficacy in R/R DLBCL, polatuzumab vedotin was granted accelerated Food and Drug Administration (FDA) approval in combination with bendamustine plus rituximab for patients who have failed at least two prior therapies. Other clinical studies involving polatuzumab vedotin in combination with other therapy regimens are also under evaluation for previously untreated DLBCL patients. In this article, we review the different phases from the preclinical development of polatuzumab vedotin to studies leading to its first approval, and highlight the potential future roles of this molecule in the treatment landscape of DLBCL.

SUBMITTER: Assi R

PROVIDER: S-EPMC8432323 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma.

Assi Rita R Masri Nohad N Dalle Iman Abou IA El-Cheikh Jean J Ghanem Hady H Bazarbachi Ali A

Clinical hematology international 20210313 1

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Despite good responses to standard of care frontline chemoimmunotherapy, the prognosis of relapsed/refractory (R/R) patients remains obscured by the possible inadequate responses to salvage therapy, eligibility for autologous transplantation, age and comorbidities. Polatuzumab vedotin is an antibody-drug conjugate formed by a CD79b antibody conjugated to the highly cytotoxic agent monomethyl auristatin ...[more]

PMID: 34595463

Similar Datasets

Project description:BackgroundDiffuse large B-cell lymphoma (DLBCL) is typically treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.MethodsWe conducted a double-blind, placebo-controlled, international phase 3 trial to evaluate a modified regimen of R-CHOP (pola-R-CHP), in which vincristine was replaced with polatuzumab vedotin, as compared with standard R-CHOP, in patients with previously untreated intermediate-risk or high-risk DLBCL. Patients 18 to 80 years of age were randomly assigned in a 1:1 ratio to receive six cycles of either pola-R-CHP or R-CHOP, plus two cycles of rituximab alone. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival and safety.ResultsOverall, 879 patients underwent randomization: 440 were assigned to the pola-R-CHP group and 439 to the R-CHOP group. After a median follow-up of 28.2 months, the percentage of patients surviving without progression was significantly higher in the pola-R-CHP group than in the R-CHOP group (76.7% [95% confidence interval (CI), 72.7 to 80.8] vs. 70.2% [95% CI, 65.8 to 74.6] at 2 years; stratified hazard ratio for progression, relapse, or death, 0.73 by Cox regression; 95% CI, 0.57 to 0.95; P = 0.02). Overall survival at 2 years did not differ significantly between the groups (88.7% [95% CI, 85.7 to 91.6] in the pola-R-CHP group and 88.6% [95% CI, 85.6 to 91.6] in the R-CHOP group; hazard ratio for death, 0.94; 95% CI, 0.65 to 1.37; P = 0.75). The safety profile was similar in the two groups.ConclusionsAmong patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP. (Funded by F. Hoffmann-La Roche/Genentech; POLARIX ClinicalTrials.gov number, NCT03274492.).

Project description:In patients with treatment-naive diffuse large B-cell lymphoma (DLBCL), the POLARIX study (A Study Comparing the Efficacy and Safety of Polatuzumab Vedotin With Rituximab-Cyclophosphamide, Doxorubicin, and Prednisone [R-CHP] Versus Rituximab-Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone [R-CHOP] in Participants With Diffuse Large B-Cell Lymphoma) reported a 6.5% improvement in the 2-year progression-free survival (PFS), with no difference in overall survival (OS) or safety using polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) compared with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). We evaluated the cost-effectiveness of pola-R-CHP for DLBCL. We modeled a hypothetical cohort of US adults (mean age, 65 years) with treatment-naive DLBCL by developing a Markov model (lifetime horizon) to model the cost-effectiveness of pola-R-CHP and R-CHOP using a range of plausible long-term outcomes. Progression rates and OS were estimated from POLARIX. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $150 000 per quality-adjusted life-year (QALY). Assuming a 5-year PFS of 69.6% with pola-R-CHP and 62.7% with R-CHOP, pola-R-CHP was cost-effective at a WTP of $150 000 (incremental cost-effectiveness ratio, $84 308/QALY). pola-R-CHP was no longer cost-effective if its 5-year PFS was 66.1% or lower. One-way sensitivity analysis revealed that pola-R-CHP is cost-effective up to a cost of $276 312 at a WTP of $150 000. pola-R-CHP was the cost-effective strategy in 56.6% of the 10 000 Monte Carlo iterations at a WTP of $150 000. If the absolute benefit in PFS is maintained over time, pola-R-CHP is cost-effective compared with R-CHOP at a WTP of $150 000/QALY. However, its cost-effectiveness is highly dependent on its long-term outcomes and costs of chimeric antigen receptor T-cell therapy. Routine usage of pola-R-CHP would add significantly to health care expenditures. Price reductions or identification of subgroups that have maximal benefit would improve cost-effectiveness.

Dataset Information

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma.

Publications

Polatuzumab Vedotin: Current Role and Future Applications in the Treatment of Patients with Diffuse Large B-Cell Lymphoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets