INTERIM RESULTS FROM a PHASE 1/2 STUDY OF BRENTUXIMAB VEDOTIN IN COMBINATION WITH NIVOLUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY HODGKIN LYMPHOMA

Herrera, Alex F.; Moskowitz, Alison J.; Bartlett, Nancy L.; Vose, Julie M.; Ramchandren, Rod; Feldman, Tatyana; LaCasce, Ann S.; Ansell, Stephen M.; Moskowitz, Craig H.; Fenton, Keenan; Ogden, Carol Anne; Taft, David R.; Zhang, Q.; Kato, Kazunobu; Campbell, Mary S.; Advani, Ranjana H.

doi:10.1002/hon.2437_73

Cited by 21 publications

(17 citation statements)

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“…Across lymphoma entities, anti-PD-1 monotherapy showed the greatest efficacy in R/R cHL. [20][21][22][23]76,[107][108][109][110][111][112][113][114][115] In a phase 1 trial of nivolumab, the objective response rate (ORR) was remarkable (87%). 20 In phase 2 trials, nivolumab and pembrolizumab had similar ORRs (68% and 69%) and OS rates (99%) at 6 months, 22,23 leading to accelerated FDA approval in 2016 for nivolumab and in 2017 for pembrolizumab.…”

Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

“…112 High complete response rates (50% to 65%) have been reported for the combination of nivolumab and brentuximab vedotin in patients with R/R HL in 2 phase 1/2 trials. 113,114 Nivolumab and pembrolizumab showed acceptable safety profiles with low rates of discontinuation resulting from adverse events, although close monitoring is warranted, especially for patients with a history of acute graft-versus-host-disease. 119 Serious immune-mediated adverse events included pneumonitis, neutropenia, thrombocytopenia, hepatitis, rash, dyspnea, anemia, colitis, and others.…”

Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

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PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

Xu-Monette

Zhou

Young

2018

Blood

349

306

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Programmed cell death protein 1 (PD-1) blockade targeting the PD-1 immune checkpoint has demonstrated unprecedented clinical efficacy in the treatment of advanced cancers including hematologic malignancies. This article reviews the landscape of PD-1/programmed death-ligand 1 (PD-L1) expression and current PD-1 blockade immunotherapy trials in B-cell lymphomas. Most notably, in relapsed/refractory classical Hodgkin lymphoma, which frequently has increased PD-1 tumor-infiltrating T cells, 9p24.1 genetic alteration, and high PD-L1 expression, anti-PD-1 monotherapy has demonstrated remarkable objective response rates (ORRs) of 65% to 87% and durable disease control in phase 1/2 clinical trials. The median duration of response was 16 months in a phase 2 trial. PD-1 blockade has also shown promise in a phase 1 trial of nivolumab in relapsed/refractory B-cell non-Hodgkin lymphomas, including follicular lymphoma, which often displays abundant PD-1 expression on intratumoral T cells, and diffuse large B-cell lymphoma, which variably expresses PD-1 and PD-L1. In primary mediastinal large B-cell lymphoma, which frequently has 9p24.1 alterations, the ORR was 35% in a phase 2 trial of pembrolizumab. In contrast, the ORR with pembrolizumab was 0% in relapsed chronic lymphocytic leukemia (CLL) and 44% in CLL with Richter transformation in a phase 2 trial. T cells from CLL patients have elevated PD-1 expression; CLL PD-1 T cells can exhibit a pseudo-exhaustion or a replicative senescence phenotype. PD-1 expression was also found in marginal zone lymphoma but not in mantle cell lymphoma, although currently anti-PD-1 clinical trial data are not available. Mechanisms and predictive biomarkers for PD-1 blockade immunotherapy, treatment-related adverse events, hyperprogression, and combination therapies are discussed in the context of B-cell lymphomas.

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Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

Section: Pd-l1 Expression and Clinical Roles In B-cell Lymphomasmentioning

confidence: 99%

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

Xu-Monette

Zhou

Young

2018

Blood

349

306

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“…Second, the remaining 97 articles were full-text screened, and 88 articles were excluded because they did not satisfy the eligibility criteria. Finally, 9 studies [28][29][30][31][32][33][34][35][36] were considered eligible and included in the meta-analysis ( Figure 1). e characteristics of eligible studies are summarized in Table 1.…”

Section: Study Selection and Characteristics Of Eligible Referencesmentioning

confidence: 99%

Safety and Efficacy in Relapsed or Refractory Classic Hodgkin’s Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials

Zhang

Chen

Zhao

et al. 2019

BioMed Research International

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Background. Classic Hodgkin’s lymphoma (cHL) is characterized by the unique biology in which rare Hodgkin-Reed-Sternberg cells propagate an immunosuppressive microenvironment. Checkpoint inhibitors that target the interaction of PD-1 immune checkpoint receptors have demonstrated remarkable activities in various cancers, such as cHL. This study aims to evaluate the safety and efficacy of PD-1 inhibitors in treating relapsed or refractory cHL (rrHL). Methods. We searched PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang, Chinese Biological Medical Literature, and Abstracts of Conference proceedings of annual meetings without any language restrictions to limit language bias (up to January 2019) for prospective clinical trials that evaluate PD-1 inhibitors in treating relapsed or refractory cHL. Results. A total of 9 prospective clinical trials with 731 patients were included in the meta-analysis. The pooled risks of all-grade and grade ≥3 adverse events (AEs) were 0.86 (95% CI: 0.66–0.98) and 0.21 (95% CI: 0.17–0.24), respectively. The pooled response, complete response, partial response, and stable disease rates were 0.74 (95% CI: 0.70–0.79), 0.24 (95% CI: 0.18–0.34), 0.48 (95% CI: 0.41–0.55), and 0.15 (95% CI: 0.12–0.17), respectively. The pooled 6-month progression-free survival and 1-year overall survival rates were 0.76 (95% CI: 0.72–0.79) and 0.93 (95% CI: 0.90–0.96), correspondingly. Conclusions. Our meta-analysis suggested that anti-PD1 monoclonal antibodies improve the outcomes of response and survival rates with tolerable AEs in cHL. However, evidence of immune checkpoint inhibitors for patients with cHL remained insufficient. Well-designed randomized controlled trials or at least nonrandomized trials with a control group should be conducted to confirm the findings of this meta-analysis.

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“…Первые сообщения о таких исследованиях были представлены на Европейском и Американском гематологических конгрессах в 2017 г. [42][43][44].…”

Section: клиническая онкогематологияunclassified

PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma

Демина

2018

Клиническая онкогематология

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During the last two decades individualization of programmed treatment combined w ith intensifi ed chemotherapy has proven to be eff ective treatment for the majority of classical Hodgkin's lymphoma (cHL) patients. However, in 10-30 % of cases relapses and resistance to therapy still occur. Further intensifi cation of therapy induces toxicity that leads to decrease in overall survival and quality of life. The standard second-line treatment with high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) allows for the achievement of long-term 5-year progression-free survival only in 50-60 % of patients with relapsed disease and not more than 40-45 % of patients with refractory disease. Approximately 50 % of patients relapse after HDCT and auto-HSCT. The median overall survival of relapsed patients does not exceed 2 years. Allogeneic HSCT improves treatment results to some extent, but is not an optimal strategy in all patients. A search for new treatment options has been ma de to improve eff ectiveness of relapsed and refractory cHL treatment and to reduce toxicity of highly eff ective programs. А new CD30-targeted conjugate brentuximab vedotin was developed to use anti-CD30 monoclonal antibodies against a specifi c marker of tumor Reed-Sternberg cells allowing for the transfer of the highly eff ective antitumor compound of monomethyl auristatin E directly to tumor cells. This drug showed high eff ectiveness, although failed to provide a complete solution to the problem. The development of anti-PD1 antibody nivolumab opened up new opportunities for cHL treatment. This paper reviews literature information on pharmacological data and antitumor mechanisms of the drug as well as the results of signifi cant international randomised studies.

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INTERIM RESULTS FROM a PHASE 1/2 STUDY OF BRENTUXIMAB VEDOTIN IN COMBINATION WITH NIVOLUMAB IN PATIENTS WITH RELAPSED OR REFRACTORY HODGKIN LYMPHOMA

Cited by 21 publications

References 0 publications

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

PD-1 expression and clinical PD-1 blockade in B-cell lymphomas

Safety and Efficacy in Relapsed or Refractory Classic Hodgkin’s Lymphoma Treated with PD-1 Inhibitors: A Meta-Analysis of 9 Prospective Clinical Trials

PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma

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