News
Clinical Topics
Integrative Care
Global Bulletin
All News
Approval Alert
Media
2 Minute Drill
Around the Practice
Between the Lines
Clinical Consult
Expert Interviews
Face Off
Medical World News
Morning Rounds
OncView
Podcasts
Readout 360
Satellite Sessions
Sponsored Media
Training Academy
Year in Review
Conferences
Publications
All Journals
For Authors
Tumor Board
Events
Frontline Forum
CME/CE
Resources
Contemporary Concepts
Awareness Month
Interactive Tools
Nurse Practitioners/Physician's Assistants
Partners
Sponsored
Subscribe
Print Subscription
eNewsletter

logo
Spotlight
Around the Practice
Between the Lines
Contemporary Concepts
Journal
OncView
Podcasts
Readout 360
2022 ASCO Genitourinary Cancers Symposium Urothelial Cancer Updates
CancerNetwork® Inaugural Face-Off
Contemporary Concepts in Hematologic Oncology
Insights from Experts at Mayo Clinic on Translating Evidence to Clinical Practice
Optimizing Outcomes in Patients with HER2+ Metastatic Breast Cancer
Clinical
Acute Myeloid Leukemia
Brain Cancer
Breast Cancer
Gastrointestinal Cancer
Genitourinary Cancer
Gynecologic Cancer
Hematology
Leukemia
Lung Cancer
Lymphoma
Pediatric Cancers
Skin Cancer
Clinical Topics
Integrative Care
Global Bulletin
All News
Approval Alert
2 Minute Drill
Around the Practice
Between the Lines
Clinical Consult
Expert Interviews
Face Off
Medical World News
Morning Rounds
OncView
Podcasts
Readout 360
Satellite Sessions
Sponsored Media
Training Academy
Year in Review
Conferences
All Journals
For Authors
Tumor Board
Frontline Forum
CME/CE
Contemporary Concepts
Awareness Month
Interactive Tools
Nurse Practitioners/Physician's Assistants
Partners
Sponsored
Print Subscription
eNewsletter
Advertisement
Breast Cancer
| Kidney Cancer
| Leukemia
| Lymphoma
| Multiple Myeloma
| Non-Small Cell Lung Cancer (NSCLC)
| Small Cell Lung Cancer (SCLC)
| Adverse Effects
| Biomarkers
| Bladder Cancer
| Brain Cancer
| Cervical Cancer
| Colorectal Cancer
| Endometrial Cancer
| Esophageal Cancer
| Gastrointestinal Cancer
| Genitourinary Cancers
| Gynecologic Cancers
| Head & Neck Cancer
| Hematology
| Hormone-related Cancers
| Immunotherapy
| Infection
| Liver Cancer
| Lung Cancer
| Mesothelioma
| Neuroendocrine Tumors
| Oncology
| Ovarian Cancer
| Ovarian Cancer Clincal Consult
| Pancreatic Cancer
| Pediatric Cancers
| Prostate Cancer
| Radiation Oncology
| Sarcoma
| Screening
| Skin Cancer & Melanoma
| Surgery
| Thoracic Malignancies
| Thyroid Cancer
View All >>
  • Adverse Effects
  • Biomarkers
  • Bladder Cancer
  • Brain Cancer
  • Breast Cancer
  • Cervical Cancer
  • Colorectal Cancer
  • Endometrial Cancer
  • Esophageal Cancer
  • Gastrointestinal Cancer
  • Genitourinary Cancers
  • Gynecologic Cancers
  • Head & Neck Cancer
  • Hematology
  • Hormone-related Cancers
  • Immunotherapy
  • Infection
  • Kidney Cancer
  • Leukemia
  • Liver Cancer
  • Lung Cancer
  • Lymphoma
  • Mesothelioma
  • Multiple Myeloma
  • Neuroendocrine Tumors
  • Non-Small Cell Lung Cancer (NSCLC)
  • Oncology
  • Ovarian Cancer
  • Ovarian Cancer Clincal Consult
  • Pancreatic Cancer
  • Pediatric Cancers
  • Prostate Cancer
  • Radiation Oncology
  • Sarcoma
  • Screening
  • Skin Cancer & Melanoma
  • Small Cell Lung Cancer (SCLC)
  • Surgery
  • Thoracic Malignancies
  • Thyroid Cancer

SPOTLIGHT -

Around the Practice
| Between the Lines
| Contemporary Concepts
| Journal
| OncView
| Podcasts
| Readout 360
| 2022 ASCO Genitourinary Cancers Symposium Urothelial Cancer Updates
| CancerNetwork® Inaugural Face-Off
| Contemporary Concepts in Hematologic Oncology
| Insights from Experts at Mayo Clinic on Translating Evidence to Clinical Practice
| Optimizing Outcomes in Patients with HER2+ Metastatic Breast Cancer

Response Acheivement With Nivolumab Plus Ipilimumab Combo for Clear Cell RCC Linked With Immune Cell–Related Factirs

Feb 19, 2022
Nichole Tucker
Article
Conference|ASCO Genitourinary Cancers Symposium

Data from the TITAN-RCC trial presented at 2022 ASCO GU showed that certain immune cell–related parameters may be predictive of response to nivolumab/ipilimumab in advanced or metastatic clear cell renal cell carcinoma

Analysis of the phase 2 TITAN-RCC trial (NCT02917772) presented during the 2022 Genitourinary Cancers Symposium identified specific immune cell–related parameters that are associated with efficacy of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the treatment of patients with advanced or metastatic clear cell renal cell carcinoma.1

Results from the study were presented by Marc-Oliver Grimm, MD of Jena University Hospital at the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium and revealed that having 4-1BB or LAG-3-expressing T cells at baseline correlated with response to nivolumab induction. Moreover, nivolumab/ipilimumab boosts were associated with a high proportion of PD-L1-expressing myeloid cells and plasmacytoid dendritic cells (pDC) during boost cycles.

Response to immune checkpoint inhibitors in patients with RCC appears to vary from patient to patient. There is a need in the field to identify key predictors of response to immunotherapy. With consideration that a boost of nivolumab plus ipilimumab improved response compared with nivolumab monotherapy in patients with RCC treated in the TITAN-RCC clinical trial,2 investigators assessed characteristics of blood-circulating immune cell subsets within the study population to identify the markers of response.1

TITAN-RCC included 207 patients with ccRCC whose disease was metastatic or locally advanced according to histologically confirmation. Patients were required to have intermediate or high International Metastatic RCC Database Consortium (IMDC) risk, be either untreated or previously treated with 1 prior tyrosine kinase inhibitor, and have measurable disease per RECIST v1.1, and a Karnofsky performance score ≥70.

Baseline characteristics of the intention-to-treat (ITT) population of 207 patients showed a median patient age of 65 years (range, 20-87), and the population was predominantly male (71%). Fifty-three percent of patients entered the study while in the first-line treatment setting and the remaining 47% were second line. In terms of IMDC risk factors, 18% of the ITT population had a Karnofsky performance score of <80%, 65% had an initial RCC diagnosis < 12 months, and laboratory values including hemoglobin, platelet count, neutrophil, and calcium were adequate. Overall, 70% of the ITT population had intermediate-risk disease, 25% had poor-risk disease, and 4.3% had favorable-risk disease.

Among the 137 patients who received an immunotherapeutic boost during the study, the median age was 64 years (range, 20-86), and the cohort was also 71% male. Forty-eight of the patients were the first line and 52% were second line. IMDC risk factors were adequate and similar o the ITT population. Overall, 74% of the boost group had intermediate-risk disease, 21% had poor-risk disease, and 5.1% has favorable-risk disease.

“Patients received nivolumab induction until week 16 and continued with nivolumab maintenance upon remission. Patients who had stable disease or progressive disease or early progressive disease at week 8 continued up to 4 cycles,” explained Grimm during the presentation. The 4 cycles included immunotherapeutic boosts of nivolumab 3 kg/mg with ipilimumab 1 kg/mg in patients who were stable after 4 cycles. Nivolumab maintenance was then continued in these patients at multiple time point during induction and before each boost cycle.

Investigators looked at 198 samples from patients with RCC, 105 of whom were treated in the frontline setting, and 93 of whom were second line. The samples were evaluated using multiparametric flow cytometry for frequency and phenotype of T cell, monocyte, myeloid-derived suppressor cell (MDSC), and dendritic cell (DC) subsets. Further, uni- and multivariable logistic regression modeling was used to look into the association between treatment response and immune parameters.

By flow cytometry, immune response in the Mo, MDSC, CTL, Th, and Treg cells were evaluated. Further, single marker models that were adjusted for age and gender. Data showed that most of the markers investigated had some correlation with immune response except for CD8-positive T cells like TIM-1, VISTA, OX40, CD69, and CD28 compared with PD-1, LAG-3, CTLA-4, and others. In the CD4-positive T-cell category, only VISTA and CD69 were not associated with immune response.

Results for responders to nivolumab induction were split into 3 categories. First, of those with 4-1BB-positive, CD8-positive T cells at baseline, 41 responded to therapy while 106 did not respond (odds ratio [OR] 1.03; 95% CI, 1.01-1.07). Among the patients with 4-1BB-positive, CD4-positive T cells at baseline, there were 43 responders and 106 non-responders (OR, 1.05; 95% CI, 1.02-1.08). In the last category of patients with LAG-3-positive, CD4-positive T cell at baseline, 41 patients had a response to nivolumab induction while 106 did not respond (OR, 1.03; 95% CI, 1.01-1.05).

Looking at CD14-positive monocytes and pDC, at the time of the first boost cycle, patients with CD86-positive cells were most likely to respond to therapy compared with those with CD40-positive cells or PD-L1-positive cells. Also, ICOS positivity did not correlate with response to the nivolumab/ipilimumab boost.

Across the board in CD14-, e-MDSC-, and pDC-expressing cells, PD-L1 expression correlated with non-response to immunotherapy with nivolumab plus ipilimumab boost at cycle 1. Only 4 patients with PD-L1 expression in CD14-positive cells responded compared with 41 nonresponders (OR, 1.22; 95% CI, 1.06-1.58). In patients with PD-L1 expression in e-MDSC, there were 4 responders and 30 nonresponders (OR, 1.44; 95% CI, 1.02-1.41). Finally, in patients who have PD-L1-expressing pDC, there were only 7 responders versus 40 nonresponders (OR, 1.08; 95% CI, 1.01-1.17).

“These immune cell parameters may represent novel predictive biomarkers for the response to nivolumab and or nivolumab/ipilimumab therapy in clear cell RCC,” stated Grimm.

References

  1. Grimm MO, Kesselmeier M, Leucht K, et al. Novel predictive biomarkers of response to immune checkpoint blockade with nivolumab ± ipilimumab in the TITAN-RCC phase 2 trial. J Clin Oncol. 2022;40(6):367-367. doi: 10.1200/JCO.2022.40.6_suppl.367
  2. Grimm MO, Esteban E, Barthelemy P, et al. Efficacy of nivolumab/ipilimumab in patients with initial or late progression with nivolumab: Updated analysis of a tailored approach in advanced renal cell carcinoma (TITAN-RCC).J Clin Oncol. 2021;39(suppl 5): 4576-4576. doi: 10.1200/JCO.2021.39.15_suppl.4576
Related Videos
Expert on kidney cancer
Common adverse effects following treatment with lenvatinib plus pembrolizumab in the phase 3 CLEAR study include diarrhea, hypertension, and fatigue, according to Thomas E. Hutson, DO, PharmD, FACP.
Expert on kidney cancer
Expert on kidney cancer
Experts on RCC
Expert on RCC
Expert on RCC
Expert on RCC
Expert on RCC
Related Content

FDA Grants Priority Review to Belzutifan in Advanced Previously Treated RCC

September 19th 2023

Oncology On-The-Go Podcast: ASCO 2023 Recap

June 19th 2023

LITESPARK-005 Trial Reveals PFS Benefit of Belzutifan in Advanced RCC

August 23rd 2023

Oncology On-The-Go Podcast: SGO 2023 Recap

April 24th 2023

Lenvatinib/Pembrolizumab Elicits Response in Metastatic RCC

July 17th 2023

T-Cell and B-Cell Immune Repertoires Differences Associated With ICI Response in Metastatic RCC

July 16th 2023

FDA Grants Priority Review to Belzutifan in Advanced Previously Treated RCC

September 19th 2023

Oncology On-The-Go Podcast: ASCO 2023 Recap

June 19th 2023

LITESPARK-005 Trial Reveals PFS Benefit of Belzutifan in Advanced RCC

August 23rd 2023

Oncology On-The-Go Podcast: SGO 2023 Recap

April 24th 2023

Lenvatinib/Pembrolizumab Elicits Response in Metastatic RCC

July 17th 2023

T-Cell and B-Cell Immune Repertoires Differences Associated With ICI Response in Metastatic RCC

July 16th 2023

FDA Grants Priority Review to Belzutifan in Advanced Previously Treated RCC

September 19th 2023

Oncology On-The-Go Podcast: ASCO 2023 Recap

June 19th 2023

LITESPARK-005 Trial Reveals PFS Benefit of Belzutifan in Advanced RCC

August 23rd 2023

Oncology On-The-Go Podcast: SGO 2023 Recap

April 24th 2023

Lenvatinib/Pembrolizumab Elicits Response in Metastatic RCC

July 17th 2023

T-Cell and B-Cell Immune Repertoires Differences Associated With ICI Response in Metastatic RCC

July 16th 2023
Related Content
Advertisement

Data from the phase 3 LITESPARK-005 trial support the supplemental new drug application for belzutifan as a treatment for patients with advanced renal cell carcinoma.

FDA Grants Priority Review to Belzutifan in Advanced Previously Treated RCC

September 19th 2023
Article

Data from the phase 3 LITESPARK-005 trial support the supplemental new drug application for belzutifan as a treatment for patients with advanced renal cell carcinoma.


Experts from University of California, Los Angeles Health and Mayo Clinic discuss key data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in the gynecologic and gastrointestinal cancer spaces and how they may impact patient care.

Oncology On-The-Go Podcast: ASCO 2023 Recap

June 19th 2023
Podcast

Experts from University of California, Los Angeles Health and Mayo Clinic discuss key data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting in the gynecologic and gastrointestinal cancer spaces and how they may impact patient care.


The primary end point of progression-free survival was met in the phase 3 LITESPARK-005 trial investigating belzutifan vs everolimus in patients with renal cell carcinoma.

LITESPARK-005 Trial Reveals PFS Benefit of Belzutifan in Advanced RCC

August 23rd 2023
Article

The primary end point of progression-free survival was met in the phase 3 LITESPARK-005 trial investigating belzutifan vs everolimus in patients with renal cell carcinoma.


Experts from UCLA Health discuss key data presented at The Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer and how they may apply to clinical practice.

Oncology On-The-Go Podcast: SGO 2023 Recap

April 24th 2023
Podcast

Experts from UCLA Health discuss key data presented at The Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer and how they may apply to clinical practice.


Lenvatinib/Pembrolizumab Elicits Response in Metastatic RCC

Lenvatinib/Pembrolizumab Elicits Response in Metastatic RCC

July 17th 2023
Article

Patients with metastatic renal cell carcinoma, and those who have been pretreated with immune checkpoint inhibitors and are naive, saw a benefit with lenvatinib plus pembrolizumab.


T-Cell and B-Cell Immune Repertoires Differences Associated With ICI Response in Metastatic RCC

T-Cell and B-Cell Immune Repertoires Differences Associated With ICI Response in Metastatic RCC

July 16th 2023
Article

Eddy Saad, MD, explained how responses to immune checkpoint inhibitors can be elicited in patients with metastatic renal cell carcinoma.

About
Advertise
CureToday.com
OncLive.com
OncNursingNews.com
TargetedOnc.com
Contact
Terms and Conditions
Privacy
Do Not Sell My Personal Information
Contact Info

2 Clarke Drive
Cranbury, NJ 08512

609-716-7777

© 2023 MJH Life Sciences

All rights reserved.