Abstract 693P
Background
There are multiple first-line treatment options in the management of metastatic renal cell carcinoma (mRCC). In the face of this broad treatment landscape, a reliable predictive biomarker of response to immune checkpoint-based therapy (ICBT) remains a critical unmet need. We sought to evaluate plasma exosome microRNAs (miRNAs) for such a role.
Methods
Eleven miRNAs that are over-expressed in RCC and/or immune-associated were evaluated in 40 patients with mRCC (prior to initiating ICBT) and 30 healthy volunteers. Exosomes were extracted from 500 uL of plasma and used for miRNAs extraction. MiRNAs expression was evaluated by RT-PCR. Cycle threshold values were normalized to miR-30-3b, and the relative quantity of the expression (RQ) was compared to healthy volunteers and calculated using the 2ΔΔCt method. Mann-Whitney U test was used to evaluate the expression of miRNAs between mRCC patients and healthy volunteers and according to response to first line ICBT between responders (defined as radiographic complete response, partial response or stable disease; n=27) v non-responders (defined as radiographically progressive disease; n=13). The cut-off value of significant miRNAs expression was established by Youden’s index.
Results
Higher expression of miRNA-1233-3p (median 1.85 v 0.81, p=0.008) and miR155-3p [miR-155] (3.69 v 0.21, p=0.006) were found in patients compared to healthy volunteers. Amongst patients, miR-155 was expressed at a significantly lower level in responders than non-responders (median 0.61 v 35.29, p=0.042). Disease control rate amongst patients with low expression of miR-155 (RQ ≤ 2.5) was 84.2%, and 52.4% amongst those with high expression (RQ ≥ 2.5) (p=0.032).
Conclusions
Lower expression of miR-155 was associated with better response to ICBT. Functionally, miR-155 is involved in modulation of the tumour microenvironment and diversification of antibody repertoire. Evaluation of miR-155 biological and molecular mechanisms in TME and immune response modulation is currently ongoing.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
This research was supported by the GUMOC Bayer Research Grant Program jointly established by the Genitourinary Medical Oncologists of Canada (GUMOC) and Bayer Canada; Canadian Urological Association Scholarship Foundation (CUASF) and the Canadian Urological Association in collaboration with Kidney Cancer Research Network of Canada (KCRNC.
Disclosure
M. Soleimani: Financial Interests, Personal, Invited Speaker, honorarium: Pfizer Canada; Financial Interests, Institutional, Research Grant: Abbvie Pharmaceuticals; Financial Interests, Institutional, Research Grant: Astellas. D.J. Khalaf: Financial Interests, Personal, Advisory Role, consulting fees: Janssen. B.J. Eigl: Financial Interests, Personal, Other, honorarium: Pfizer Canada; Financial Interests, Personal, Other, honorarium: Janssen; Financial Interests, Personal, Other, honorarium: AstraZeneca; Financial Interests, Personal, Other, honorarium: Merck; Financial Interests, Personal, Other, honorarium: Roche; Financial Interests, Personal, Other, honorarium: Bayer. K.N. Chi: Financial Interests, Personal and Institutional, Research Grant, and personal fees: Janssen; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Astellas; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Sanofi; Financial Interests, Personal and Institutional, Research Grant, and personal fees: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Bayer; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Pfizer; Financial Interests, Personal and Institutional, Research Grant, and personal fees: Roche. C.K. Kollmannsberger: Financial Interests, Personal, Other, honorarium: Pfizer Canada; Financial Interests, Personal, Other, honorarium: Astellas; Financial Interests, Personal, Other, honorarium: Janssen; Financial Interests, Personal, Other, honorarium: Merck; Financial Interests, Personal, Other, honorarium: Ipsen; Financial Interests, Personal, Other, honorarium: Bristol-Meyers Squibb; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Other, honorarium: Eisai. L. Nappi: Financial Interests, Personal, Other, honorarium: Ipsen Biopharmaceuticals Inc; Financial Interests, Personal, Other, honorarium: Bayer Healthcare Pharmaceuticals. All other authors have declared no conflicts of interest.