Nivolumab Plus Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B‐cell Lymphoma: Extended Follow‐up From the Phase 2 Checkmate 436 Study

Zinzani, P. L.; Santoro, Armando; Gritti, Giuseppe; Brice, Pauline; Barr, Paul M.; Kuruvilla, John; Cunningham, David; Kline, J.; Johnson, Nathalie A.; Mehta‐Shah, Neha; Fanale, Michelle A.; Francis, Stephen; Moskowitz, Alison J.

doi:10.1002/hon.51_2879

Cited by 8 publications

(12 citation statements)

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“…A total of 905 studies were identified by our search strategy; 83 studies were removed after duplication; 757 studies were excluded after reading titles and abstracts; and 43 studies were excluded after full-text review according to inclusion and exclusion criteria. Finally, 22 studies [8–29] were enrolled in the meta-analysis. A flowchart of our study selection process was shown in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…The pooled ORR, CRR, 1-year-OS rate, and 1-year-PFS rate were the main indicators to evaluate the efficacy of PD-1/ PD-L1 inhibitors in treating NHL. A total of 21 studies and 1066 patients [8][9][10][11][12][13][14][15][16][17][18][20][21][22][23][24][25][26][27][28][29] were included in the analysis of ORR and CRR, with the pooled ORR and CRR being 0.43 (95% CI, 0.33-0.54) and 0.21 (95% CI, 0.13-0.31), respectively (Fig. 2A and B).…”

Section: Efficacy Analysismentioning

confidence: 99%

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Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma: A systematic review and meta-analysis of clinical trials

Guan

Zhang

et al. 2022

Medicine

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Background: Immunotherapy with programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) inhibitors has been widely used in the treatment of solid tumors and Hodgkin lymphoma, demonstrating powerful efficacy and good safety. However, there is no systematic review and meta-analysis to fully investigate the efficacy and safety of PD-1/PD-L1 inhibitors in treating non-Hodgkin lymphoma (NHL). Methods: We searched PubMed, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, Wanfang database, and abstracts of conference proceedings of annual meetings up to January 23, 2022, to identify eligible clinical trials. To evaluate the efficacy of PD-1/PD-L1 inhibitors, objective response rate (ORR), complete response rate (CRR), 1-year overall survival rate, and 1-year progression-free survival rate were analyzed. For safety analysis, we calculated rates of any grade and grade ≥3 treatment-related adverse events. Results: Overall 22 studies and 1150 participants were enrolled in this meta-analysis. The pooled ORR, CRR, 1-year overall survival, and 1-year progression-free survival rates were 0.43 (95% confidence interval [CI], 0.33–0.54), 0.21 (95% CI, 0.13–0.31), 0.72 (95% CI, 0.58–0.89), and 0.42 (95% CI, 0.29–0.62), respectively. The ORR and CRR in the combination immunochemotherapy subgroup (0.65 and 0.41) were higher than those in the monotherapy (0.27 and 0.09) and combination chemotherapy (0.39 and 0.19) subgroups. This study was registered with PROSPERO (#CRD 42022316805). Conclusion: Given that there were limited clinical trials and relatively few relevant studies, we conducted this meta-analysis to fully elucidate the efficacy and safety of PD-1/PD-L1 inhibitors in NHL. Our results suggested that PD-1/PD-L1 inhibitors improved outcomes of responses as well as survival rates in NHL patients with tolerable adverse events. More well-designed randomized clinical trials are still needed to further confirm our findings.

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Section: Resultsmentioning

confidence: 99%

Section: Efficacy Analysismentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma: A systematic review and meta-analysis of clinical trials

Guan

Zhang

et al. 2022

Medicine

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“…One notable exception is pembrolizumab which was approved for R/R primary mediastinal B‐cell lymphoma (PMBL) based on the results of KEYNOTE‐170 which demonstrated an ORR of 41.5% (CR 20.8%), with median PFS and OS of 4.3 and 22.3 months, respectively 34 . Combination of nivolumab with brentuximab demonstrated activity in R/R CD30+ PMBL with an ORR of 73% (CR 37%), median PFS of 22.3 months, and 2‐year OS 76% 35 . No unexpected toxicities were observed in either study.…”

Section: Investigational/novel Therapiesmentioning

confidence: 99%

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

Goldstein

Advani

2023

Hematological Oncology

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Patients with relapsed or refractory (R/R) diffuse large B‐cell lymphoma (DLBCL), ineligible for or relapsing after autologous stem‐cell transplant or chimeric antigen‐receptor T‐cell therapies have poor outcomes. Several novel agents, polatuzumab vedotin, tafasitamab, loncastuximab tesirine, and selinexor, have been approved and offer new opportunities for this difficult to treat population. Studies are evaluating combination of these agents with chemotherapy and other emerging therapies. Additionally, advances in our understanding of DLBCL biology, genetics, and immune microenvironment have allowed for the identification of new therapeutic targets like Ikaros and Aiolos, IRAK4, MALT1, and CD47 with several agents in ongoing clinical trials. In this chapter we review updated data supporting the use of the approved agents and discuss other emerging novel therapies for patients with R/R DLBCL.

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“…Therefore, BV alone is considered inactive in RR PMCBL. Nevertheless, Zinzani et al presented the data of a phase I/II combination trial of BV with nivolumab (immune checkpoint inhibitor) in RR PMBL at ICML 2021 and the results were just the opposite (NCT02581631, CheckMate436) [ 44 ]. Thirty highly pretreated patients were recruited with a median of two prior lines of therapy.…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

“…Treatment-related toxicity of ADCs depends mainly on the cytotoxic payload and its off-target effect. Both BV and PV contain MMAE, which induces mostly neutropenia (up to 58%) and peripheral neuropathy (27–61% in BV; 43–44% in PV) [ 12 , 13 , 14 , 19 , 44 ]. Brentuximab vedotin-induced neuropathy was predominantly graded 1–2 and usually resolved after treatment discontinuation.…”

Section: Class Specific Toxicitymentioning

confidence: 99%

Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders

Mihályová

Hradská

Jelı́nek

et al. 2021

IJMS

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Over the last few years, treatment principles have been changed towards more targeted therapy for many B-cell lymphoma subtypes and in chronic lymphocytic leukemia (CLL). Immunotherapeutic modalities, namely monoclonal antibodies (mAbs), bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cell therapy, commonly use B-cell-associated antigens (CD19, CD20, CD22, and CD79b) as one of their targets. T-cell engagers (TCEs), a subclass of bsAbs, work on a similar mechanism as CAR-T cell therapy without the need of previous T-cell manipulation. Currently, several anti-CD20xCD3 TCEs have demonstrated promising efficacy across different lymphoma subtypes with slightly better outcomes in the indolent subset. Anti-CD19xCD3 TCEs are being developed as well but only blinatumomab has been evaluated in clinical trials yet. The results are not so impressive as those with anti-CD19 CAR-T cell therapy. Antibody-drug conjugates targeting different B-cell antigens (CD30, CD79b, CD19) seem to be effective in combination with mAbs, standard chemoimmunotherapy, or immune checkpoint inhibitors. Further investigation will show whether immunotherapy alone or in combinatory regimens has potential to replace chemotherapeutic agents from the first line treatment.

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Nivolumab Plus Brentuximab Vedotin for Relapsed/Refractory Primary Mediastinal Large B‐cell Lymphoma: Extended Follow‐up From the Phase 2 Checkmate 436 Study

Cited by 8 publications

References 0 publications

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma: A systematic review and meta-analysis of clinical trials

Efficacy and safety of PD-1/PD-L1 immune checkpoint inhibitors in treating non-Hodgkin lymphoma: A systematic review and meta-analysis of clinical trials

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

Promising Immunotherapeutic Modalities for B-Cell Lymphoproliferative Disorders

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