See the published version of this preprint at Journal of Translational Medicine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
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Research
Giulia Pomati
Sapienza University of Rome: Universita degli Studi di Roma La Sapienza
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6715-5443
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities.
Methods: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival.
Results: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37-2.09, p<0.0001; median OS, 4 months vs. 35months, HR 1.60, 95 % CI 1.26-2.02, p <0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden.
Discussion: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well.
Conclusions: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.
Keywords
Immunotherapy, opioids, opioid receptors, prognostic factor, predictive factor, early progression
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CURRENT STATUS: Published
View the published article at Journal of Translational Medicine.
Version 1
Posted 08 Feb, 2021
Community comments: 1
Review #2 received
Received 11 Feb, 2021
Editorial decision: Minor revision
On 11 Feb, 2021
Review #1 received
Received 05 Feb, 2021
Reviewer #2 agreed
On 30 Jan, 2021
Editor assigned
On 28 Jan, 2021
Reviewers invited
Invitations sent on 28 Jan, 2021
Reviewer #1 agreed
On 28 Jan, 2021
Editor invited
On 28 Jan, 2021
Submission checks complete
On 28 Jan, 2021
First submitted
On 27 Jan, 2021
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HTML Views: ...
Subject Areas
Translational Medicine
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See the published version of this preprint at Journal of Translational Medicine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Giulia Pomati
Sapienza University of Rome: Universita degli Studi di Roma La Sapienza
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6715-5443
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Journal of Translational Medicine.
Version 1
Posted 08 Feb, 2021
Community comments: 1
Review #2 received
Received 11 Feb, 2021
Editorial decision: Minor revision
On 11 Feb, 2021
Review #1 received
Received 05 Feb, 2021
Reviewer #2 agreed
On 30 Jan, 2021
Editor assigned
On 28 Jan, 2021
Reviewers invited
Invitations sent on 28 Jan, 2021
Reviewer #1 agreed
On 28 Jan, 2021
Editor invited
On 28 Jan, 2021
Submission checks complete
On 28 Jan, 2021
First submitted
On 27 Jan, 2021
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Translational Medicine
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Journal of Translational Medicine.
Background: The response to immunotherapy can be impaired by several factors including external intervention such as drug interactions with immune system. We aimed to examine the immunomodulatory action of opioids, since immune cells express opioid receptors able to negatively influence their activities.
Methods: This observational, multicenter, retrospective study, recruited patients with different metastatic solid tumors, who have received immunotherapy between September 2014 and September 2019. Immunotherapy was administered according to the standard schedule approved for each primary tumor and line of treatment. The concomitant intake of antibiotics, antifungals, corticosteroids and opioids were evaluated in all included patients. The relationship between tumor response to immunotherapy and the oncological outcomes were evaluated. A multivariate Cox-proportional hazard model was used to identify independent prognostic factors for survival.
Results: One hundred ninety-three patients were recruited. Overall, progression-free survival (PFS) and overall survival (OS) were significantly shorter in those patients taking opioids than in those who didn’t (median PFS, 3 months vs. 19 months, HR 1.70, 95% CI 1.37-2.09, p<0.0001; median OS, 4 months vs. 35months, HR 1.60, 95 % CI 1.26-2.02, p <0.0001). In addition, PFS and OS were significantly impaired in those patients taking corticosteroids, antibiotics or antifungals, in those patients with an ECOG PS ≥1 and in patients with a high tumor burden. Using the multivariate analyses, opioids and ECOG PS were independent prognostic factors for PFS, whereas only ECOG PS resulted to be an independent prognostic factor for OS, with trend toward significance for opioids as well as tumor burden.
Discussion: Our study suggests that the concomitant administration of drugs as well as some clinical features could negatively predict the outcomes of cancer patients receiving immunotherapy. In particular, opioids use during immunotherapy is associated with early progression, potentially representing a predictive factor for PFS and negatively influencing OS as well.
Conclusions: A possible negative drug interaction able to impair the immune response to anti-PD-1/PD-L1 agents has been highlighted. Our findings suggest the need to further explore the impact of opioids on immune system modulation and their role in restoring the response to immunotherapy treatment, thereby improving patients' outcomes.
Figure 1
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