Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial

Maio, Michele; Grob, Jean-Jacques; Aamdal, Steinar; Bondarenko, Igor; Robert, Caroline; Thomas, Luc; Garbe, Claus; Chiarion-Sileni, Vanna; Testori, Alessandro; Chen, Tai-Tsang; Tschaika, Marina; Wolchok, Jedd D.

doi:10.1200/jco.2014.56.6018

Cited by 425 publications

(293 citation statements)

References 12 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…Recently, clinical results for immune-mediated therapies for cancers (IMT-C) have shown encouraging results for treatment of cancers such as lung and melanoma. 67 As these therapies generally activate T cells as a primary mechanism against tumor cells, the reduction in T cell diversity in older cancer patients may require unique personal healthcare strategies to consider potential T cell replenishment to maximize effectiveness of IMT-C in older patients. We also correlate tumoral CD4…”

Section: E1051922-6 Volume 4 Issue 12 Oncoimmunologymentioning

confidence: 99%

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality

et al. 2015

View full text Add to dashboard Cite

Keywords: deep sequencing, non-small cell lung cancer, TCR/BCR repertoire, tertiary lymphoid structure Abbreviations: ADC, adenocarcinoma; BCR, B cell receptor; CDR3, complementarity-determining region 3; DC, dendritic cell; Foll-B cell, follicular B cell; IgH, immunoglobulin heavy chain; LCC, large-cell carcinoma; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; NT, non-tumoral distant tissue; P, peripheral blood or draining lymph node; SCC, squamous cell carcinoma; TFH, follicular helper T cell; TRM, tissue resident-memory T cell; TCR, T cell receptor; TLS, tertiary lymphoid structure.T and B cell receptor (TCR and BCR, respectively) Vb or immunoglobulin heavy chain complementarity-determining region 3 sequencing allows monitoring of repertoire changes through recognition, clonal expansion, affinity maturation, and T or B cell activation in response to antigen. TCR and BCR repertoire analysis can advance understanding of antitumor immune responses in the tumor microenvironment. TCR and BCR repertoires of sorted CD4 C , CD8C or CD19 C cells in tumor, non-tumoral distant tissue (NT), and peripheral compartments (blood/draining lymph node [P]) from 47 non-small cell lung cancer (NSCLC) patients (age median D 68 y) were sequenced. The clonotype spectra were assessed among different tissues and correlated with clinical and immunological parameters. In all tissues, CD4C and CD8 C TCR repertoires had greater clonality relative to CD19 C BCR. CD4 C T cells exhibited greater clonality in NT compared to tumor (p D 0.002) and P (p < 0.001), concentrated among older patients (age > 68). Younger patients exhibited greater CD4 C T cell diversity in P compared to older patients (p D 0.05), and greater CD4 C T cell clonality in tumor relative to P (p < 0.001), with fewer shared clonotypes between tumor and P than older patients (p D 0.04). More interestingly, greater CD4C and CD8 C T cell clonality in tumor and P, respectively (both p D 0.05), correlated with high density of tumor-associated tertiary lymphoid structure (TLS) B cells, a biomarker of higher overall survival in NSCLC. Results indicate distinct adaptive immune responses in NSCLC, where peripheral T cell diversity is modulated by age, and tumor T cell clonal expansion is favored by the presence of TLSs in the tumor microenvironment.

show abstract

Section: E1051922-6 Volume 4 Issue 12 Oncoimmunologymentioning

confidence: 99%

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality

et al. 2015

View full text Add to dashboard Cite

show abstract

“…1,2 These agents showed durable clinical benefit and increased OS, 3,4 for patients with advanced melanoma. Since then, the usage of anti-CTLA-4 mAbs (either ipilimumab, IPI or tremelimumab) in several clinical studies or in the context of expanded access programs (EAP) has shown significant increase in OS for MM patients, and promising clinical activity for tumors with other histology.…”

Section: Introductionmentioning

confidence: 99%

Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Maccalli

Giannarelli²,

Capocefalo³

et al. 2015

OncoImmunology

Self Cite

View full text Add to dashboard Cite

Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or ¡2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) D 33.6 mo for ULBP-1 and ¡2) from poor survivors (OS D 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3 C CD4 C CD45RO C BTLA C or Th17 or CD3 C CD4 C 4-1BB C T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.

show abstract

“…However, as novel agents extend patient survival times, it becomes increasingly difficult to conduct long clinical trials in order to measure OS [75,76]. Although the use of ICBs has improved survival in melanoma over standard chemotherapy, with some patients experiencing OS of 3 to 5 years [77,78], when the follow-up is less than 1 year, median OS is usually not reached [22,23,39,43]. Therefore, there is an interest in validating surrogate endpoints that can accurately predict survival benefit in clinical trials of immunotherapy and using these surrogate endpoints for drug approval [75].…”

Section: Endpoints To Assess Clinical Outcomes Associated With Icbsmentioning

confidence: 99%

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

et al. 2018

View full text Add to dashboard Cite

Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival. Immunotherapies function through modulation of the immune system, which can lead to immune-mediated adverse events (imAEs). These include a range of dermatologic, gastrointestinal, endocrine, and hepatic toxicities, as well as other less common inflammatory events. ImAEs are typically low grade and manageable when identified early and treated with appropriate measures. Identifying the right patient for the right therapy will become more important as new immunotherapies and immunotherapy-based combinations are approved and costs of cancer care continue to rise.

show abstract

Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial

Abstract: The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma.

Cited by 425 publications

References 12 publications

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality

Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Contact Info

Product

Resources

About

Five-Year Survival Rates for Treatment-Naive Patients With Advanced Melanoma Who Received Ipilimumab Plus Dacarbazine in a Phase III Trial

Abstract: The additional survival benefit of ipilimumab plus dacarbazine is maintained with twice as many patients alive at 5 years compared with those who initially received placebo plus dacarbazine. These results demonstrate a durable survival benefit with ipilimumab in advanced melanoma.

Cited by 425 publications

References 12 publications

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+T cell receptor repertoire clonality

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4+T cell receptor repertoire clonality

Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Immune Checkpoint Blockade: The New Frontier in Cancer Treatment

Contact Info

Product

Resources

About

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality

A high density of tertiary lymphoid structure B cells in lung tumors is associated with increased CD4⁺T cell receptor repertoire clonality