72P Interleukin-6 Blockade Abrogates Immunotherapy To Xicity And Promotes Tumor Immunity

abstracts

after ICI. Nevertheless, taxane appears to have modest effectiveness in pre-treated patients. We aimed to assess survival outcomes with taxane chemotherapies after ICI exposure and to identify prognostic and predictive factors that may influence response to those regimens.

Methods: In this multicentric retrospective study, we included patients with stage IIIB or higher NSCLC who received subsequently taxane after ICI failure. Primary endpoints were progression-free survival on taxane (Taxane PFS) and overall survival on taxane (Taxane OS). Secondary endpoints were the Taxane PFS to ICI PFS ratio to evaluate the benefit of subsequent taxane and identification of clinical data associated with better survival on taxane.

Results: We included 110 patients, mostly men (71.8 %) with a median age of 63. Patients mostly had stage IVB (65.5%) and adenocarcinoma was the predominant histologic subtype (59.1%). Docetaxel was the taxane chosen in 70% of cases. Median Taxane PFS was 3.6 months (2.7-4.8) and Taxane OS was 7.3 months (6.1-10.3). Only 36.9% of patients had a ratio of Taxane PFS to ICI PFS greater than 1.3 without clinical difference in this subgroup, except for age (60.2 versus 63.9; p¼0,021). Several 6 or above ICI cycles were an independent prognostic factor for better Taxane PFS and OS. Similarly, in the multivariate model, performance status at 2 or higher (PS2) and a 2g/dL loss of hemoglobin between the end of ICI and taxane initiation were associated with poorer Taxane OS. Only PS 2 was associated with a poorer Taxane PFS.

Conclusions: The effectiveness of further treatment with taxane after ICI failure was observed only in a limited subgroup of patients. Factors associated with good health conditions and long exposure to ICI appeared to be predictive of better survival on taxanes.

Legal entity responsible for the study: Institut de cancérologie de l’ouest.

Funding: Has not received any funding.

Disclosure: All authors have declared no conflicts of interest.

Safety and efficacy of salvage radiotherapy after progression to checkpoint inhibitors in recurrent and/or metastatic head and neck cancer

Background: Immune checkpoint inhibitors (ICIs) are approved in the first- and second-line setting of R/M head and neck cancer (HNC), but most patients (pts) eventually progress. A fraction of these pts suffers from oligo progressive disease that may be subjected to local therapies while maintaining IT. We aimed to study de safety and efficacy of radiotherapy (RT) administered to oligo progressive disease (OPD) in pts with R/M HNC under ICIs.

Methods: We searched our electronic database to identify pts with R/M SCCHN receiving ICIs at our center. Objective response rate (ORR) in irradiated lesions (IRL), percentage of change from baseline (PCB) in IRL, overall survival (OS) since 1st line, and safety of RT after ICIs were evaluated.

Results: From January 2016 until August 2021, we identified 71 patients with R/M SCCHN treated with ICIs, 19 of which received RT for OPD during ICI treatment. The median age was 63 (range: 37-77). Tumor location: oral cavity (7/19), oropharynx (1/ 19), larynx (7/19), squamous skin (1/19), nasopharynx (1/19), CUP (1/20). ICI treatment: anti-PD1 (11/19; nivo: 10/11, pembro: 1/11), anti-PDL1 (8/19). A total of 26 areas were irradiated: external hypofractionated palliative RT (ERT: 18/26), SBRT (3/ 26), and SRS (1/26). Type of IRL: lymphadenopathy (n¼10), soft tissue mass (n¼5), the pleural implant (n¼2), primary tumor (n¼4), brain met (n¼1), bone (n¼4). Radical RT in 3/19 pts. Irradiation of > 2 disease areas in 5/19 pts. ORR in 1st IRL among non-bone lesions: 11/16 (69%; 2 CR, 9 PR) with a median PCB among responders of -52% (range: -100% to -31%). ORR in 2nd IRL among non-bone lesions: 3/4 (75%; PCB range: -50% to +9%). All bone IRL showed sclerotic changes compatible with a response. Median OS since 1st line for R/M disease was 24 months (range: 4-48). Safety: 1 pt G3 bleeding after RT to bulky axillary lymphadenopathy, 1 pt G3 oral mucositis (radical RT), 1 pt G2 radiodermatitis, 1 pt G2 oral mucositis (palliative RT).

Conclusions: Palliative RT administered to OPD after IT achieves high ORR in IRL in R/ M HNC. Palliative RT after ICIs appears safe and rapidly improves symptoms at the IRL. These results merit confirmation in larger, prospective studies.

Legal entity responsible for the study: The authors.

Funding: Has not received any funding.

Disclosure: S. Cabezas-Camarero: Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb; Financial Interests, Personal, Expert Testimony: Merck KGA; Financial Interests, Personal, and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, and Institutional, Principal Investigator: GSK. All other authors have declared no conflicts of interest.

Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity

Background: To mitigate immune checkpoint inhibitors (ICIs) induced immune-related adverse events (irAEs), we need a comprehensive understanding of their pathogenesis.

Methods: We profiled gene expression in intestinal, colitis (n¼23), and tumor tissue (n¼22) from ICI-treated cancer patients, with parallel studies in preclinical models, and validated our findings in a review of the clinical cohort (n¼19) treated with interleukin-6 receptor (IL-6R) blockade at MD Anderson Cancer Center.

Results: We identified a higher expression of IL-6, neutrophil, and chemotactic markers in colitis than in the normal colon, suggesting the IL-6eTh17 pathway as a potential mediator of irAEs. Genes upregulated in colitis were not upregulated in responding tumors, suggesting potential mechanistic differences between autoimmunity and antitumor immunity. In B16.BL6 and CT26 models, IL-6 inhibition led to improved tumor control with a higher density of CD4/CD8 effector T-cells and reduced Th17/ macrophages and myeloid cells. In the autoimmune encephalomyelitis (EAE) model with tumor, IL-6 blockade + ICIs enhanced tumor rejection and mitigated EAE symptoms vs ICI alone. These findings were supported by our clinical cohort of 19 melanoma pts who received IL-6R blockade for ICI-induced arthritis. Of note, 17 pts (89%) failed to respond to initial immunosuppressants. Median time from arthritis onset till IL-6R blockade was 3.9 mos, leading to arthritis improvement in 89%. The median clinical disease activity index (CDAI) score was 28 at IL-6R blockade initiation indicating high arthritis disease activity. Use of IL-6R blockade led to achieving remission/low arthritis disease activity; median CDAI score dropped to 2 within 3.4 mos of therapy. Median CRP levels at IL-6R blockade initiation was 55.2 mg/L and dropped to 1.4 mg/L within 4 wks of therapy. Of 17 evaluable pts by RECIST 1.1, ORR to ICI before initiation of IL- 6R blockade was 58.8% and was 70.6% after therapy (P ¼ 0.16). Median OS was not reached.

Conclusions: Our data suggest that IL-6R blockade could be an effective therapy for irAEs management without dampening ICI efficiency. A phase II trial (NCT04940299) with longitudinal blood, tumor, and inflamed tissue biopsies is currently ongoing to validate these findings and better study the immunobiology of irAEs.

Cistanche is a type of fungus that has been used in traditional Chinese medicine for centuries. It is made from the dried stems and stalks of the fungus, which grows in tropical and subtropical regions of Asia. It is commonly used to improve immunity, relieve fatigue, and treat colds and other infections.

Research has shown that cistanche can increase the production of antibodies, which can help the body fight off foreign invaders such as viruses and bacteria. It has been found to increase the number and activity of T cells, a type of white blood cell that is responsible for helping the body to recognize and fight off harmful invaders.

In addition, studies have shown that cistanche can reduce the severity of colds, flu, and other viral infections. It has been found to decrease the amount of time it takes for the body to recover from viral or bacterial infections. cistanche can also reduce the duration of fever caused by certain viruses, as well as decrease the risk of developing secondary infections.

Furthermore, cistanche is known to have anti-inflammatory properties, which can reduce inflammation associated with certain diseases. Studies have also shown that dendrobium can help improve the effectiveness of certain antibiotics.

Overall, research suggests that cistanche can be a useful treatment for improving immunity and fighting off various infections. It can help improve the body’s natural defenses, reduce the severity and duration of illnesses, and may even reduce the risk of developing secondary infections.

Click on Cistanche Tubulosa To Enhance Immunity

Ask for more:david.deng@wecistanche.com

Legal entity responsible for the study: The authors. 

Funding: The University of Texas MD Anderson Cancer Center. 

Disclosure: All authors have declared no conflicts of interest.

Characteristics and outcomes of emergency presentations due to immune-mediated toxicities

Background: The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the patient characteristics and outcomes of emergency presentations due to immune-mediated (IO) toxicity are less well known.

Methods: We reviewed all emergency presentations in patients treated with ICI at a single center between May 2018 and February 2020. The aims were to describe and quantify patient and treatment characteristics, toxicity type, and outcomes for IO toxicity.

Results: 1399 patients were treated with ICI and there were 597 emergency presentations in 370 patients. IO toxicity accounted for 191/597 (32%) of presentations. The median age was 64 years, the most common tumor types were melanoma (53%) and lung (22%) and the most common ICIs received were ipilimumab + nivolumab (42%), pembrolizumab (21%) and nivolumab (20%). Previous grade 2 IO toxicity was experienced in 75/191 (39%) of patients and 46/75 (61%) presented with the same IO toxicity. The most common diagnoses were colitis (38%), hepatitis (15%), and pneumonitis (14%) and 32/191 (17%) of patients had more than one IO toxicity. Patients with pneumonitis had a longer median duration of stay of 8 days compared to 4 days for colitis and hepatitis (p¼0.098). Five of 9 (56%) patients admitted to the Critical Care Unit had pneumonitis. Six patients died of toxicity within 30 days of presentation - 5 pneumonitides, and 1 cerebral vasculitis. The 30-day mortality rate of patients with pneumonitis was 19% (5/26). The majority, 180/191 (94%) received steroids and 52/180 (29%) required second-line immunosuppression. Patients with colitis had the highest proportion requiring third or fourth-line immunosuppression.

Conclusions

The majority of patients with emergency presentations due to immune-mediated toxicity were being treated with combination immunotherapy for improving immunity.

Ask for more:david.deng@wecistanche.com