Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 577-577
Author(s):  
Jason Zhu ◽  
Matthew Labriola ◽  
Sachica Cheris ◽  
Xin Liu ◽  
Kathryn Perkinson ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Immune Cell ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Tumor Type ◽  
Cell Assays ◽  
Metastatic Urothelial Carcinoma

577 Background: Immune checkpoint inhibitors (ICIs) are now standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. Four different PD-L1 assays vary in thresholds of PD-L1 positivity dependent on tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, concordance between assays are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We undertook comparisons of Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 patients with mRCC and 18 patients with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better)). Results: The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142). The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between PD-L1 tumor/immune cell assays chosen for comparison in both mRCC and mUC with similar performance characteristics. Although PD-L1 positivity enriches for response to ICIs, many patients respond who are PD-L1 negative. PD-L1 status could be used interchangeably for the majority of cases when selecting treatment in mRCC and mUC.

Concordance between PD-L1 assays for metastatic renal cell carcinoma (mRCC) and metastatic urothelial carcinoma (mUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14259-e14259
Author(s):  
Matthew Labriola ◽  
Jason Zhu ◽  
Sachica Cheris ◽  
Xin Liu ◽  
Kathryn Perkinson ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Standard Of Care ◽  
Predictive Biomarker ◽  
Tumor Type ◽  
Metastatic Urothelial Carcinoma ◽  
Primary Tissue

e14259 Background: Immune checkpoint inhibitors (ICIs) are standard of care for mRCC and mUC patients (pts). PD-L1 status is gaining importance as a predictive biomarker, particularly for cisplatin-ineligible mUC. PD-L1 positivity is defined differently by PD-L1 assay and tumor type, with limited concordance studies. Given real-world limitations in PD-L1 testing, assay concordance studies are needed to distinguish positive (pos)/negative (neg) results and treatment selection. We compared Dako 28–8 and Ventana SP142 assays in mRCC and Dako 22C3 and Ventana SP263 assays in mUC. Methods: 32 pts with mRCC and 18 pts with mUC who had received ICI therapy at Duke Cancer Institute were identified. FFPE archival tumor samples for pts with mRCC were evaluated with Dako 28–8 and Ventana SP142 PD-L1 immunohistochemistry (IHC) assays. For pts with mUC, FFPE archival tumor samples were evaluated with Dako 22C3 and Ventana SP263 PD-L1 IHC assays. Scoring was validated by two pathologists using the scoring system for each assay. PD-L1 status was subsequently correlated to best RECIST response (objective response rate (ORR) defined as stable disease or better). Results: Tissue was obtained from primary tissue in 72% of mRCC cases and in 61% of mUC cases, with remainder from metastatic biopsies. The majority of mRCC cases (29/32, 91%) were concordant between Dako 28-8 and Ventana SP142 assays (8 cases pos and 21 cases neg), with 3 discordant cases (1 case pos for Dako 28-8 but neg for Ventana SP142 and 2 cases neg for Dako 28-8 but pos for Ventana SP142), all from primary tissue. The majority of mUC cases (17/18, 94%) were also concordant between Dako 22C3 and Ventana SP263 assays (2 pos cases and 15 neg cases), with 1 indeterminate Dako 22C3 test on a metastatic biopsy due to background lymph node. In mRCC, the ORR for PD-L1 pos cases was 45% (5/11) versus 33% (8/24) for PD-L1 neg cases. In mUC, the ORR for PD-L1 positive cases was 50% (1/2) versus 31% (5/16) for PD-L1 neg cases. Conclusions: There was strong concordance between the clinically meaningful PD-L1 assays chosen for comparison in both mRCC and mUC. mUC results were limited by low PD-L1 expression in this cohort. Although PD-L1 status does not fully predict for response to ICIs, this suggests that PD-L1 testing could be used interchangeably for the majority of cases when selecting ICI treatment in mRCC and mUC.

Relationship between lymphopenia and objective response rate with programmed death-1 (PD-1) inhibitor therapy: A single-center retrospective analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14512-e14512 ◽  
Author(s):  
Mark Yarchoan ◽  
Adam Diehl ◽  
Burles Avner Johnson ◽  
Blake Scott ◽  
Alexander Hopkins ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Treatment Initiation ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Univariate Analysis ◽  
Objective Response ◽  
Additional Patient ◽  
Tumor Type ◽  
The Impact

e14512 Background: Lymphopenia is frequent in advanced cancers, but the impact of absolute lymphocyte count (ALC) on clinical responses with PD-1 immune checkpoint inhibitors is unknown. Methods: We performed a retrospective chart review of adult solid tumor patients treated with a PD-1 inhibitor (nivolumab or pembrolizumab) at Johns Hopkins from 2015-2016. Patients receiving PD-1 inhibitors concurrently with investigational immunotherapies, on unreported clinical trials or for cancers in which the activity of immune checkpoint inhibitors is unclear, or for whom response information is not available, were excluded. Data were collected on patient treatment history, objective response to PD-1 therapy by RECIST 1.1, and ALC at treatment initiation and one and three months after treatment initiation. Results: 172 patients met the inclusion criteria (lung n = 54; melanoma n = 61; kidney n = 25; other tumors n = 32). Lymphopenia (ALC < 1000) was present in 30.2%, 26.7%, and 34.3%, at 0, 1, and 3 months after treatment initiation. In a multiple regression analysis that adjusted for age, sex, ethnicity, tumor type, number of prior therapies, and concurrent ipilimumab usage, lymphopenia at baseline was not predictive of response to an immune checkpoint inhibitor. However, in this same model, lymphopenia at 1 and 3 months after treatment initiation was inversely related to response rate (p < 0.01). Of patients with lymphopenia at baseline, 37 patients (71.2%) had persistent lymphopenia (ALC < 1000 at baseline persisting to month 3) whereas 15 patients (28.8%) had normalized lymphocyte counts by month 3. In a univariate analysis, patients with persistent lymphopenia had decreased response rates as compared to patients who were not lymphopenic at baseline (21.6% vs. 47.5%, p < 0.01). However, patients with lymphopenia at baseline who had normalized lymphocyte counts at month 3 responded similarly as patients who were not lymphopenic at baseline (46.7% vs. 47.5%). Conclusions: Patients on anti–PD-1 therapy with persistent lymphopenia may have a reduced likelihood of responding to these agents. This association requires further validation in additional patient cohorts.

scholarly journals 363 Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A388-A388
Author(s):  
Byoung Chul Cho ◽  
Ki Hyeong Lee ◽  
Ji-Youn Han ◽  
Byoung Yong Shim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Anti Tumor Activity

BackgroundTargeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy.MethodsPatients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1).ResultsBy August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented.ConclusionsThe combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.Trial RegistrationNCT03732274Ethics ApprovalThe study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

Tissue tumor mutational burden (TMB) as a biomarker of efficacy with immune checkpoint inhibitors (ICI) in metastatic gastrointestinal (mGI) cancers.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14559-e14559
Author(s):  
Robert William Lentz ◽  
Tyler Friedrich ◽  
Junxiao Hu ◽  
Alexis Diane Leal ◽  
Sunnie S. Kim ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Continuous Variable ◽  
Tumor Type ◽  
Logistic Regression Models ◽  
Kaplan Meier ◽  
Academic Center

e14559 Background: While TMB is very dependent on methodology, tissue TMB-H (≥10 mutations/megabase) may predict benefit with ICIs. Pembrolizumab received tissue-agnostic approval for TMB-H unresectable cancers in 2020, but little is known about TMB as a predictive biomarker in mGI cancers. We hypothesized that tissue TMB will correlate with efficacy of ICIs in mGI cancers. Methods: A retrospective chart review identified patients with mGI cancers who received an anti-PD-(L)1 drug and had known TMB at a single academic center from 2012 to 2020. The association of TMB with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was analyzed using the Fisher’s exact and Log-rank tests. Survival curves were generated using the Kaplan-Meier method. Cox proportional hazard and logistic regression models were used to adjust for microsatellite status. Significance was prespecified at 0.05. Results: 83 patients were identified and included. The most common cancer types were colorectal adenocarcinoma (AC, n = 29), esophageal/gastric AC (n = 21) and SCC (n = 4), cholangiocarcinoma (n = 11), anal SCC (n = 7), and pancreas AC (n = 7). Average age was 61, average number of lines of prior systemic therapy for advanced disease was 1.3 (range 0-4), and 37% of patients were treated on a clinical study. All patients received an anti-PD-(L)1 drug; 6%, 2%, and 36% also received ipilimumab, cytotoxic chemotherapy, and other combinations, respectively. Among those with esophageal/gastric cancer, 76% had known PD-L1 CPS (84% ≥1, 63% ≥5, 42% ≥10). TMB was primarily determined by Foundation One CDx (87%). TMB ranged from 0 to 54; n = 22 (27%) were TMB-H (of these, n = 10 were microsatellite instability-high (MSI-H)), and n = 61 were TMB-L ( < 10 mutations/megabase; of these, n = 2 were MSI-H). The prevalence of TMB-H and microsatellite stable (MSS) was 14.4%. TMB-L, compared to TMB-H, was associated with inferior ORR (3.5% vs 55.6%; odds ratio (OR) 0.045; p < 0.001) and PFS (median 12.7 vs 29.3 weeks; hazard ratio (HR) 2.70; p = 0.001), but not OS (HR 1.20; p = 0.60). In patients with MSS disease, TMB-L, compared to TMB-H, was associated with inferior ORR (OR 0.13; p = 0.04) but not PFS (HR 1.76; p = 0.07) or OS (HR 0.89; p = 0.79). In subgroup analyses, ORR was not significantly associated to tumor type in all or MSS patients. TMB as a continuous variable, in patients with MSS disease, was positively correlated with ORR (p = 0.02) and PFS (p = 0.04), but not OS (p = 0.59). Among all patients, PFS and OS data is immature (median follow-up 13 and 31 weeks). Conclusions: In a single center retrospective study of patients with mGI cancers treated with ICIs, TMB-H was associated with improved ORR and PFS compared to TMB-L. In patients with MSS disease, ORR remained significant. PFS and OS data are immature. TMB as a biomarker of efficacy with ICIs in mGI cancers warrants further study to guide clinical use.

scholarly journals Salvage Ipilimumab and Nivolumab in Patients With Metastatic Renal Cell Carcinoma After Prior Immune Checkpoint Inhibitors

2020 ◽  
Vol 38 (27) ◽  
pp. 3088-3094 ◽  
Author(s):  
Anita Gul ◽  
Tyler F. Stewart ◽  
Charlene M. Mantia ◽  
Neil J. Shah ◽  
Emily Stern Gatof ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Rcc

PURPOSE Immune checkpoint inhibitors (ICIs) are standard therapy in metastatic renal cell carcinoma (RCC). The safety and activity of the combination of ipilimumab and nivolumab in patients who have received prior ICI targeting the programmed death 1 (PD-1) pathway remains unknown. We evaluated ipilimumab and nivolumab in patients with metastatic RCC after prior treatment with anti–PD-1 pathway–targeted therapy. PATIENTS AND METHODS Patients with metastatic RCC who received prior anti–PD-1 pathway-targeted therapy and subsequently received ipilimumab and nivolumab were reviewed. Objective response rate and progression-free survival per investigator assessment were recorded. Toxicity of ipilimumab and nivolumab was also assessed. RESULTS Forty-five patients with metastatic RCC were included. All patients (100%) received prior ICIs targeting the PD-1 pathway. The median age was 62 years (range, 21-82 years). At a median follow-up of 12 months, the objective response rate to ipilimumab and nivolumab was 20%. The median progression-free survival while on ipilimumab and nivolumab was 4 months (range, 0.8-19 months). Immune-related adverse events (irAEs) of any grade with ipilimumab and nivolumab were recorded in 29 (64%) of the 45 patients; grade 3 irAEs were recorded in 6 (13%) of the 45 patients. CONCLUSION Ipilimumab and nivolumab demonstrated antitumor activity with acceptable toxicity in patients with metastatic RCC who had prior treatment with checkpoint inhibition.

Retrospective analysis of the safety and efficacy of immune checkpoint inhibitors (CPI) among patients (pts) with pre-existing autoimmune disorders (AD) and renal cell carcinoma (RCC) or urothelial carcinoma (UC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4571-4571
Author(s):  
Nieves Martinez Chanza ◽  
Wanling Xie ◽  
Majd Issa ◽  
Hannah Elizabeth Dzimitrowicz ◽  
Abhishek Tripathi ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Clinical Activity ◽  
Systemic Immunosuppression ◽  
Kaplan Meier ◽  
Inflammatory Bowel ◽  
Clinically Significant ◽  
New Onset

4571 Background: RCC and UC pts with clinically significant AD were generally excluded from CPI trials due to potential AD exacerbation. Thus, the safety and clinical activity of CPI in AD pts are not well characterized. Methods: We retrospectively collected data from RCC and UC pts with AD treated with CPI at 9 centers. Adverse events (AEs) were assessed using CTCAEv5 criteria. Objective response rate (ORR) was assessed by RECIST principles. Overall survival (OS) was estimated by Kaplan Meier. Results: Of 103 pts (57 RCC & 46 UC) with a broad spectrum of AD such as psoriasis (22%), thyroiditis (20%), rheumatoid arthritis (13%), polymyalgia rheumatica (8%), inflammatory bowel disease (6%), multiple sclerosis (3%) and lupus (3%), most received CPI as 1st or 2nd line (77% RCC, 93% UC) and anti-PD-1/L1 monotherapy (65% RCC, 98% UC). At CPI start, 36 had clinically active AD (all grade 1-2) and 4(11%) requiring systemic immunosuppression. AD exacerbations occurred in 37% (n = 38); most frequent: arthritis (12% RCC, 24% UC), rash (11% RCC, 9% UC). New onset immune related (ir) AEs occurred in 36% (n = 37); most frequent: colitis (12% RCC, 4% UC), rash (11% RCC, 9% UC), hypothyroid (each 7%), nephritis (7% UC). Table details timing and management. Median followup was 12.5 (1-52) mos for RCC and 14.5 (1-53) mos for UC. Median time on CPI was 6 mos (1-36) RCC and 4 mos (0.5-40) UC. At data cutoff, 39 RCC & 36 UC had discontinued CPI; 16% for toxicity. ORR was 31% for RCC and 35% for UC. 1 yr-OS rate was 74% (95%CI 58-84) for RCC and 60% (95%CI 43-74) for UC. Conclusions: AD exacerbations or new irAEs occurred in 37% and 36% respectively and were generally manageable. Only a minority required CPI cessation due to toxicity. [Table: see text]

scholarly journals Immune-Checkpoint Inhibitors for Metastatic Colorectal Cancer: A Systematic Review of Clinical Outcomes

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4345
Author(s):  
Dmitrii Shek ◽  
Liia Akhuba ◽  
Matteo S. Carlino ◽  
Adnan Nagrial ◽  
Tania Moujaber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Response ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Response Rates ◽  
Durable Response ◽  
Surgical Options

Background. Colorectal cancer (CRC) is the fourth most deadly cancer worldwide. Unfortunately, a quarter of the patients are diagnosed at late stages, when surgical options are limited. Targeted therapies, particularly immune-checkpoint inhibitors (ICIs), are the latest addition and have been studied herein regarding their efficacy outcomes. Methods. Clinical studies were identified through the PubMed, Scopus and Cochrane databases. Any trial that evaluated ICIs in patients with metastatic CRC (mCRC) and reported the objective response rate was deemed eligible. Data analysis was performed by employing the random-effects model in STATA v.17. Results. A total of 461 articles were identified; 13 clinical trials were included, encompassing a total cohort of 1209 patients. Our study determined that a single PD-1/PD-L1 checkpoint blockade provides durable clinical response in mCRC patients with high microsatellite instability (MSI-H). The combinatorial therapy of CTLA-4 + PD-1 inhibitors also showed high response rates in pre-treated MSI-H patients. The single-arm REGONIVO trial reported durable clinical response in patients with microsatellite stable (MSS) status. Conclusions. Our study surmises that PD-1/PD-L1 inhibitors as well as combination therapy with CTLA-4 and PD-1 inhibitors show encouraging response rates in mCRC patients, albeit exclusively in patients with cancer that are of MSI-H status. A single study suggests that nivolumab + regorafenib can reach a durable response rate in MSS patients; however, further studies in larger randomized settings are required.

scholarly journals Eosinophil Count as Predictive Biomarker of Immune-Related Adverse Events (irAEs) in Immune Checkpoint Inhibitors (ICIs) Therapies in Oncological Patients

Immuno ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 253-263
Author(s):  
Elisa Giommoni ◽  
Roberta Giorgione ◽  
Agnese Paderi ◽  
Elisa Pellegrini ◽  
Elisabetta Gambale ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Eosinophil Count ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Predictive Biomarker ◽  
Response To Treatment ◽  
Analysis Model

Background: To date, no biomarkers are effective in predicting the risk of developing immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). This study aims to evaluate the association between basal absolute eosinophil count (AEC) and irAEs during treatment with ICIs for solid tumors. Methods: We retrospectively evaluated 168 patients with metastatic melanoma (mM), renal cell carcinoma (mRCC), and non-small cell lung cancer (mNSCLC) receiving ICIs at our medical oncology unit. By combining baseline AEC with other clinical factors, we developed a mathematical model for predicting the risk of irAEs, which we validated in an external cohort of patients. Results: Median baseline AEC was 135/µL and patients were stratified into two groups accordingly; patients with high baseline AEC (>135/µL) were more likely to experience toxicity (p = 0.043) and have a better objective response rate (ORR) (p = 0.003). By constructing a covariance analysis model, it emerged that basal AEC correlated with the risk of irAEs (p < 0.01). Finally, we validated the proposed model in an independent cohort of 43 patients. Conclusions: Baseline AEC could be a predictive biomarker of ICI-related toxicity, as well as of response to treatment. The use of a mathematical model able to predict the risk of developing irAEs could be useful for clinicians for monitoring patients receiving ICIs.

scholarly journals Efficacy and side effects of immune checkpoint inhibitors in the treatment of colorectal cancer

2021 ◽  
Vol 14 ◽  
pp. 175628482110020
Author(s):  
Salomon M. Manz ◽  
Marco Losa ◽  
Ralph Fritsch ◽  
Michael Scharl
Keyword(s):  
Mismatch Repair ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Dna Mismatch Repair ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Antitumoral Activity ◽  
Treatment Approaches ◽  
Dna Mismatch

Colorectal cancers (CRCs) remain one of the most common and challenging neoplasia in the Western world. The response rate of immunotherapeutic treatment approaches in a subset of advanced CRCs is remarkable and has sustainably changed treatment regimens. Unfortunately, currently available immunotherapeutics only displayed significant antitumoral activity – in terms of progression free survival (PFS) and objective response rate (ORR) – in microsatellite instability-high (MSI-H)/DNA mismatch repair deficient (dMMR) CRCs. Subsequently, these remarkable results had led to the US Food and Drug Administration’s approval of both immune checkpoint inhibitors (ICIs) pembrolizumab and nivolumab in the treatment of advanced MSI-H/dMMR CRCs. However, in microsatellite stable (MSS)/DNA mismatch repair proficient (pMMR) CRCs, ICIs have clearly failed to meet their expectations and are therefore not considered effective. As the vast majority of CRCs display a molecular MSS/pMMR profile, current treatment approaches endeavor to improve tumor immunogenicity that consecutively leads to increased proinflammatory cytokine levels as well as tumor infiltrating T-cells, which in turn may be targeted by various immunotherapeutic agents. Therefore, ongoing studies are investigating novel synergistic therapy modalities and approaches to overcome a “cold” to “hot” tumor conversion in MSS/pMMR CRCs. In this review, we summarize the efficacy and possible immune-related adverse events as well as novel therapeutic approaches of ICIs in the treatment of MSI-H/dMMR and MSS/pMMR CRCs.

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