scholarly journals Recurrent Gallbladder Carcinoma With pMMR/MSS Achieved a Complete Response Following Camrelizumab Combined With Apatinib: A Case Report

2022 ◽  
Vol 11 ◽  
Author(s):  
Liting Zhong ◽  
Xiaoyu Liu ◽  
Zelei Li ◽  
Xuebing Zhang ◽  
Yuli Wang ◽  
...  
Keyword(s):  
Gallbladder Carcinoma ◽  
Complete Response ◽  
Limited Data ◽  
Effective Treatment Option ◽  
Tumor Mutation Burden ◽  
Angiogenic Therapy ◽  
Mutation Burden ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Durable Complete Response

Gallbladder carcinoma (GBC) with proficient mismatch repair (pMMR)/microsatellite stable (MSS) is associated with limited response to programmed death-1 (PD-1) inhibitor monotherapy. Limited data of PD-1 blockade combined with anti-angiogenic therapy in GBC are reported. One recurrent GBC patient with pMMR/MSS was treated with camrelizumab plus apatinib. After 4 cycles of combination therapy, the patient achieved a durable complete response with manageable toxicity. The next-generation sequencing and immunohistochemistry analysis showed that tumor mutation burden (TMB) was 7.26 mutants/Mb and PD-L1 expression was 10% (tumor proportion score) and 20% (immune proportion score). This case suggests that camrelizumab in combination with apatinib may be an effective treatment option for GBC patients with pMMR/MSS status, who have moderate expression of TMB and PD-L1. Additionally, TMB and PD-L1 expression may serve as potential biomarkers for predicting PD-1 inhibitor response of GBC. Furthermore, this needs to be verified in future studies.

The Immunobiology of Kidney Cancer

2018 ◽  
Vol 36 (36) ◽  
pp. 3547-3552 ◽  
Author(s):  
Charles G. Drake ◽  
Mark N. Stein
Keyword(s):  
Kidney Cancer ◽  
Immune Checkpoint Blockade ◽  
Antiangiogenic Agents ◽  
Tumor Mutation Burden ◽  
Programmed Death Ligand 1 ◽  
T Cell Infiltration ◽  
Mutation Burden ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Tumor Types

Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a worse prognosis. In addition, kidney cancer responds to programmed death-1/programmed death-ligand 1 blockade, despite a relatively low tumor mutation burden. Recent clinical data highlight the efficacy of combined immune checkpoint blockade and demonstrate that combining antiangiogenic agents with programmed death-1/programmed death-ligand 1 blockade has additive activity. Yet an important unanswered question in RCC is the nature of the antigens that are targeted by the immune system when immunotherapy is successful. Ongoing clinical studies are interrogating the multiple suppressive mechanisms in the RCC TME, including metabolic pathways such as those mediated by adenosine and tryptophan as well as cytokine-based therapies. Future regimens are likely to be combinatorial and may eventually be based on a broader understanding of the RCC TME and how it is modulated by both conventional and immune-based therapy.

scholarly journals Hypofractionated Stereotactic Re-Irradiation with Pembrolizumab and Bevacizumab in Patients with Recurrent High Grade Gliomas: Results from a Phase 1 Study

2020 ◽  
Author(s):  
Solmaz Sahebjam ◽  
Peter A Forsyth ◽  
Nam D Tran ◽  
John A Arrington ◽  
Robert Macaulay ◽  
...  
Keyword(s):  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Glioblastoma ◽  
High Grade ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
High Grade Gliomas ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Abstract Background Radiotherapy may synergize with programmed death 1 (PD-1)/PD-1 ligand (PD-L1) blockade. The purpose of this study was to determine the recommended Phase II dose, safety/tolerability, and preliminary efficacy of combining pembrolizumab, an anti-PD-1 monoclonal antibody, with hypofractionated stereotactic irradiation (HFSRT) and bevacizumab in patients with recurrent high grade gliomas (HGGs). Methods Eligible subjects with recurrent glioblastoma or anaplastic astrocytoma were treated with pembrolizumab (100 or 200 mg based on dose level Q3W) concurrently with HFSRT (30 Gy in 5 fractions) and bevacizumab 10 mg/kg Q2W. Results Thirty two patients were enrolled (bevacizumab naïve, n = 24; bevacizumab resistant, n = 8). The most common treatment-related adverse events (TRAEs) were proteinuria (40.6%), fatigue (25%), increased alanine aminotransferase (25%), and hypertension (25%). TRAEs leading to discontinuation occurred in 1 patient who experienced a grade 3 elevation of aspartate aminotransferase. In the bevacizumab naïve cohort, twenty patients (83%) had a complete response (CR) or partial response (PR). The median overall survival (OS) and progression-free survival (PFS) were 13.45 months (95% CI: 9.46-18.46) and 7.92 months (95% CI: 6.31-12.45), respectively. In the bevacizumab resistant cohort, PR was achieved in 5 patients (62%). Median OS was 9.3 months (95% CI: 8.97-18.86) with a median PFS of 6.54 months (95% CI: 5.95-18.86). The majority of patients (20/26 pts; 77%) had tumor-cell/tumor-microenvironment PD-L1 expression <1%. Conclusions The combination of HFSRT with pembrolizumab and bevacizumab in patients with recurrent HGG is generally safe and well tolerated. These findings merit further investigation of HFSRT with immunotherapy in HGGs.

PS02.182: EFFECTIVENESS OF ANTI-PD-1 ANTIBODY MONOTHERAPY FOR THE PRIMARY MALIGNANT MELANOMA OF THE ESOPHAGUS: A CASE REPORT

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 173-174
Author(s):  
Hiroto Muroi ◽  
Masanobu Nakajima
Keyword(s):  
Case Report ◽  
Malignant Melanoma ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Primary Malignant Melanoma ◽  
Innovative Strategies ◽  
First Case ◽  
Positron Emission ◽  
Programmed Death ◽  
Programmed Death 1

Abstract Background Primary malignant melanoma of the esophagus (PMME) is extraordinarily rare with a high prevalence of malignancy and poor prognosis, and a standard therapy remains to be established. Since conventional therapeutic methods have been limited in their effects on treatment outcomes, innovative strategies for treating PMME are being explored, especially molecular targeting strategies. The programmed death 1 (PD-1) protein/programmed death ligand-1(PD-L1) inhibitor nivolumab is a promising agent for various cancers. To our knowledge, this is the first case report of PMME where a complete response was achieved using nivolumab. Methods We report an 80-year-old woman who was diagnosed with PMME with bone metastasis and lymph node metastases. Although dacarbazine combined chemotherapy was performed and continued for six cycles, the primary tumor deteriorated and liver metastases appeared. The patient then received nivolumab monotherapy (2 mg/kg, once every three weeks). Results After three cycles, nivolumab monotherapy for PMME resulted in a complete response as shown by positron emission tomography, computed tomography, and esophagogastroduodenoscopy. Conclusion In our case, nivolumab exerted a curative effect on PMME, thus suggesting that nivolumab can be effective in the treatment of this rare disease. Disclosure All authors have declared no conflicts of interest.

Discrepancies in response and immune-related adverse events (irAE) of anti-PD-1 monotherapy between races and primary sites in patients (pts) with advanced nonacral cutaneous melanoma (NACM).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9530-9530
Author(s):  
Xue Bai ◽  
Alexander Noor Shoushtari ◽  
Allison Betof Warner ◽  
Henry Quach ◽  
Christopher G Cann ◽  
...  
Keyword(s):  
Lower Limb ◽  
Complete Response Rate ◽  
Complete Response ◽  
Primary Site ◽  
Anatomic Site ◽  
Tumor Mutation Burden ◽  
Best Response ◽  
Mutation Burden ◽  
The Us ◽  
Grade 3

9530 Background: Ultraviolet (UV)-induced high tumor mutation burden (TMB) of NACM is associated with response to anti-PD-1 monotherapy (aPD-1). Anatomic location of the primary lesion (reflecting UV exposure) and race (reflecting eumelanin level) may serve as surrogates for TMB and be associated with varying response and irAE patterns. Methods: Pts with advanced NACM receiving aPD-1 between 2009-2019 were retrospectively analyzed from 5 institutions in the US, Australia and China. Best response, survival (PFS and OS), and organ/system-specific irAEs were compared by race (Caucasian [C] vs non-Caucasian [NC]) and primary anatomic site. Results: Among 697 patients, 616 were C, 81 were NC. Complete response rate (CRR) was 24.8% (95%CI, 21.4-28.4) and 2.6% (95%CI, 0.3-9.1) and ORR was 54.9% (95%CI, 50.9-58.9) and 15.6% (95%CI, 8.3-25.6) in C and NC, respectively (both P<.001). Median PFS was 16.5 (95%CI, 12.0-23.1) and 5.2 (95%CI, 3.6-7.6) months, median OS was 60.5 (95%CI, 49.9-not reached [NR]) and 29.2 (95%CI, 17.9-NR) months, in C and NC, respectively (P<.001 and =.04). In multivariate analyses, C had significantly higher CRR (OR 13.4, 95%CI 3.1-57.4), ORR (OR 10.6, 95%CI 4.6-24.5), and longer PFS (HR 0.5, 95%CI 0.4-0.7) than NC. Compared to a head primary site, NACM from less UV-exposed regions had significantly lower CRR (upper trunk, OR 0.6, 95%CI 0.4-0.96; lower limb, OR 0.5, 95%CI 0.2-0.9), ORR (lower limb, OR 0.6, 95%CI 0.3-0.9) and poorer PFS (perineum/buttock, HR 2.1, 95%CI 1.2-3.5; lower limb, HR 1.6, 95%CI 1.2-2.2) and OS (perineum/buttock, HR 3.8, 95%CI 2.2-6.8; lower limb, HR 1.7, 95%CI 1.2-2.4). Overall irAE incidence was similar between C and NC but irAE subtypes varied. C had significantly higher incidence of GI (12.2%, 95%CI 9.5-15.3% vs 1.2%, 95%CI, 0.03-6.7%, P=.001), respiratory (10.3%, 95%CI 7.8-13.2% vs 0, P<.001) and grade 3/4 (15.4%, 95%CI 12.4-18.8% vs 6.2%, 95%CI 2.0-13.8%, P=.03) irAEs; and lower incidence of endocrine (13.8%, 95%CI 10.9-17.0% vs 32.1%, 95%CI 22.2-43.4%, P<.001) and liver (4.8%, 95%CI 3.2-7.1% vs 13.6%, 95%CI, 7.0-23.0%, P=.005) irAEs. IrAEs did not vary by primary NACM site. Conclusions: Race and primary site are independently correlated with distinct response and survival outcomes in pts with advanced NACM receiving aPD-1. IrAE subtypes vary by race although overall irAE incidence does not.

Expectations of cure among patients with advanced genitourinary cancer treated with immunotherapy.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 591-591
Author(s):  
Cristiane Decat Bergerot ◽  
Paulo Gustavo Bergerot ◽  
Errol James Philip ◽  
Joann Hsu ◽  
Nazli Dizman ◽  
...  
Keyword(s):  
Well Being ◽  
Complete Response ◽  
Survey Study ◽  
Considerable Proportion ◽  
Clinical Counseling ◽  
Programmed Death ◽  
Medical Oncologists ◽  
Programmed Death 1 ◽  
Line Of Therapy ◽  
Anxiety Depression

591 Background: Over the past 15 years, considerable progress has been made in systemic therapy options for genitourinary (GU) cancers. In diseases such as metastatic renal cell carcinoma (RCC) and urothelial cancer (UC), immunotherapeutic strategies such as programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition have elicited durable responses, albeit in a minority of patients. We examined expectations for clinical outcome with immunotherapy among patients with advanced GU cancers. Methods: A survey study was conducted in patients with advanced GU cancers initiating PD-1/PD-L1 inhibitors from October 2017 to September 2018. Patients were screened prior to initiation of immunotherapy for their expectation of cure (divided into 4 quartiles), symptoms of anxiety and depression (PROMIS-A and PROMIS-D), and quality of life (QOL; FACT-G). For purposes of the survey, cure was equated to a durable complete response. Differences in frequency of anxiety, depression and QOL were compared amongst subsets of patients divided by expectation of cure. Results: Among 60 patients, median age was 67, 72% were male and 81% were married. Types of cancer included RCC (69%), UC (19%) and prostate cancer (12%). The majority were in the 1st or 2nd line of therapy (40% and 31%, respectively). Despite extensive counseling from GU medical oncologists, 23% of patients thought that cure was “very likely”, defined as in the range of 76-100%. Approximately 70% of patients estimated cure in the range of 0-25%, in line with clinical counseling. These patients had higher rates of anxiety (P = 0.01), depression (P = 0.002) and poorer QOL (P = 0.003) compared to patients who felt cure was very likely. Conclusions: A considerable proportion of patients with advanced GU malignancies harbor unrealistic expectations around the potential benefit of immunotherapy. Although a first instinct may be to remedy these expectations, it is important to bear in mind that these patients had better emotional well-being and QOL. We will validate these findings and assess these parameters longitudinally in an upcoming SWOG trial for patients with mRCC receiving upfront immunotherapy.

A durable complete response to immunotherapy in a patient with metastatic alveolar soft part sarcoma

2020 ◽  
Vol 106 (6) ◽  
pp. NP9-NP13
Author(s):  
Anna Mariuk-Jarema ◽  
Hanna Koseła-Paterczyk ◽  
Paweł Rogala ◽  
Anna Klimczak ◽  
Michał Wągrodzki ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Soft Part ◽  
Death Receptor ◽  
Complete Response ◽  
Treatment Method ◽  
Therapeutic Benefit ◽  
Alveolar Soft Part Sarcoma ◽  
Programmed Death ◽  
Durable Complete Response

Background: Recent years have brought the dynamic development of a new method of cancer treatment: immunotherapy. Monoclonal antibodies blocking the programmed death receptor 1 (PD-1) are now widely used in the treatment of several malignancies: melanoma, lung, head and neck cancer, among others. The therapeutic benefit of immunotherapy in soft tissue sarcoma (STS) has not yet been proven. The exception is results obtained in the treatment of a rare STS subtype alveolar soft part sarcoma (ASPS). Case report: We describe a case of a man with a diagnosis of metastatic ASPS in whom the use of immunotherapy with nivolumab resulted in excellent long-term clinical benefit and a pathologically confirmed complete response. Conclusion: There are strong indications that immunotherapy may become the next important treatment method of ASPS.

scholarly journals The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses

2021 ◽  
Vol 11 ◽  
Author(s):  
Guanglin Cui
Keyword(s):  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Immune Cell ◽  
Basic Research ◽  
Final Analysis ◽  
Therapeutic Outcomes ◽  
Mutation Burden ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cell Densities

Current clinical studies showed distinct therapeutic outcomes, in which CRC patients with mismatch repair-deficient (dMMR)/microsatellite instability high (MSI-H) seem to be relatively more “sensitive” in response to anti-programmed death-1 receptor (PD-1)/programmed death-1 receptor ligand 1 (PD-L1) therapy than those with mismatch repair-proficient (pMMR)/microsatellite instability-low (MSI-L). The mechanisms by which the same PD-1/PD-L1 blockades lead to two distinct therapeutic responses in CRC patients with different MSI statuses remain poorly understood and become a topic of great interest in both basic research and clinical practice. In this review of the potential mechanisms for the distinct response to PD-1/PD-L1 blockades between dMMR/MSI-H CRCs and pMMR/MSI-L CRCs, relevant references were electronically searched and collected from databases PubMed, MEDLINE, and Google scholar. Sixty-eight articles with full text and 10 articles by reference-cross search were included for final analysis after eligibility selection according to the guidelines of PRISMA. Analysis revealed that multiple factors e.g. tumor mutation burden, immune cell densities and types in the tumor microenvironment, expression levels of PD-1/PD-L1 and cytokines are potential determinants of such distinct response to PD-1/PD-L1 blockades in CRC patients with different MSI statuses which might help clinicians to select candidates for anti-PD-1/PD-L1 therapy and improve therapeutic response in patients with CRC.

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