Novel agents in relapsed/refractory diffuse large B‐cell lymphoma

Goldstein, Jack; Advani, Ranjana H.

doi:10.1002/hon.3143

Cited by 5 publications

(2 citation statements)

References 104 publications

(142 reference statements)

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“…After the introduction of rituximab, which showed improved results for DLBCL, a ceiling effect of first‐line rituximab‐based immunochemotherapy has been observed over the last decade, 6–29 until the emergence of polatuzumab vedotin. Currently, two antibody drug conjugates (polatuzumab vedotin and loncastuximab tesirine) have been approved for previously untreated or relapsed/refractory DLBCL 44–46 . The pilot study from the POLARIX trial demonstrated 2‐year EFS and PFS benefits of pola‐R‐CHP compared with R‐CHOP in patients with intermediate‐ and high‐risk DLBCL 32 .…”

Section: Discussionmentioning

confidence: 99%

“…Currently, two antibody drug conjugates (polatuzumab vedotin and loncastuximab tesirine) have been approved for previously untreated or relapsed/refractory DLBCL. 44 , 45 , 46 The pilot study from the POLARIX trial demonstrated 2‐year EFS and PFS benefits of pola‐R‐CHP compared with R‐CHOP in patients with intermediate‐ and high‐risk DLBCL. 32 The potent therapeutic efficacy of pola‐R‐CHP might be attributed to the characteristics of the highly specific targeting ability and potent killing effect of polatuzumab vedotin.…”

Section: Discussionmentioning

confidence: 99%

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Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival

Zhang,

Liu,

Zhong

et al. 2024

Cancer Medicine

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This study aimed to predict the 5‐year overall survival (OS) benefit of pola‐R‐CHP versus R‐CHOP in the POLARIX trial based on the 2‐year event‐free survival (EFS) and progression‐free survival (PFS) rates in diffuse large B‐cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the trial‐level. Correlation analysis was performed between 2‐year PFS or EFS and 5‐year OS rates at the treatment arm‐level. Linear regression models were used to calculate the 5‐year OS of pola‐R‐CHP and R‐CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial‐ level. Two‐year EFS (r = 0.918) or 2‐year PFS (r = 0.865) correlated linearly with 5‐year OS. Linear regression analysis between 2‐year EFS/PFS and 5‐year OS gave estimated 5‐year OS rates between pola‐R‐CHP and R‐CHOP of 6.4% and 6.3%, respectively. Two‐year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola‐R‐CHP regimen is expected to improve 5‐year OS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival

Zhang,

Liu,

Zhong

et al. 2024

Cancer Medicine

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Novel IRAK4 Inhibitors for Treating Asthma, COPD, Cancer, Autoinflammatory Diseases, and Autoimmune Diseases

Sabnis

2023

ACS Med. Chem. Lett.

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Targeting CD19-positive lymphomas with the antibody-drug conjugate (ADC) loncastuximab tesirine: preclinical evidence as single agent and as combinatorial approach

Tarantelli,

Wald,

Munz

et al. 2023

Preprint

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Purpose. Antibody-drug conjugates (ADCs) represent one of the most successful therapeutic approaches introduced in clinical practice in the last years. Loncastuximab tesirine (ADCT-402) is a CD19 targeting ADC, in which the antibody is conjugated through a protease cleavable dipeptide linker to a pyrrolobenzodiazepine (PBD) dimer warhead (SG3199). Based on the results of a phase 2 study, loncastuximab tesirine was recently approved for adult patients with relapsed/refractory large B-cell lymphoma. Experimental Design. We assessed the activity of loncastuximab tesirine in in vitro and in vivo models of lymphomas, correlated its activity with CD19 expression levels and identified combination partners providing synergy with loncastuximab tesirine. Results. Loncastuximab tesirine was tested across 60 lymphoma cell lines. Loncastuximab tesirine has strong cytotoxic activity in B-cell lymphoma cell lines and the in vitro activity is correlated with CD19 expression level and with intrinsic sensitivity of cell lines to the warhead of the ADC. Loncastuximab tesirine was more potent than other anti-CD19 ADCs (coltuximab ravtansine, huB4-DGN462), albeit the pattern of activity across cell lines was correlated. Loncastuximab tesirine activity also largely correlated with cell line sensitivity to R-CHOP. Combinatorial in vitro and in vivo experiments identified the benefit of adding loncastuximab tesirine to other agents, especially BCL2 and PI3K inhibitors. Conclusions. Our data support the further development of loncastuximab tesirine as single agent and in combination for patients affected by mature B-cell neoplasms. The results also highlight the importance of CD19 expression, and the existence of lymphoma populations characterized by resistance to multiple therapies.

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Novel agents in relapsed/refractory diffuse large B‐cell lymphoma

Cited by 5 publications

References 104 publications

Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival

Prediction of 5‐year overall survival of diffuse large B‐cell lymphoma on the pola‐R‐CHP regimen based on 2‐year event‐free survival and progression‐free survival

Novel IRAK4 Inhibitors for Treating Asthma, COPD, Cancer, Autoinflammatory Diseases, and Autoimmune Diseases

Targeting CD19-positive lymphomas with the antibody-drug conjugate (ADC) loncastuximab tesirine: preclinical evidence as single agent and as combinatorial approach

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