Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program

Hassana El Haddaoui; Rianne Brood; Diba Latifi; Astrid A. Oostvogels; Yarne Klaver; Miranda Moskie; Dana A. Mustafa; Reno Debets; Casper H.J. van Eijck

doi:10.3390/cancers14061377

Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program

Hassana El Haddaoui, Rianne Brood, Diba Latifi, Astrid A. Oostvogels, Yarne Klaver, Miranda Moskie, Dana A. Mustafa, Reno Debets, Casper H.J. van Eijck^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients’ survival via immunomodulation, but the effect is unproven. Methods: In this singlecenter named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progressionfree survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤ 1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.

Original language	English
Article number	1377
Journal	Cancers
Volume	14
Issue number	6
DOIs	https://doi.org/10.3390/cancers14061377
Publication status	Published - 1 Mar 2022

Bibliographical note

Funding Information:
Funding: Rintatolimod (Ampligen®) was provided in this program via MyTomorrows (https://my-tomorrows.com/en (accessed: 02-02-2022)) in collaboration with the manufacturer AIM Immuno-Tech, Ocala, FL, USA (www.aimimmuno.com). This work was financially supported by the Support Casper Foundation (www.supportcasper.nl).

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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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El Haddaoui, H., Brood, R., Latifi, D., Oostvogels, A. A., Klaver, Y., Moskie, M., Mustafa, D. A., Debets, R., & van Eijck, C. H. J. (2022). Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program. Cancers, 14(6), [1377]. https://doi.org/10.3390/cancers14061377

@article{0f8055d3461d4713a2de07348ca1ab65,

title = "Rintatolimod (Ampligen{\textregistered}) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program",

abstract = "Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients{\textquoteright} survival via immunomodulation, but the effect is unproven. Methods: In this singlecenter named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progressionfree survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤ 1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.",

author = "{El Haddaoui}, Hassana and Rianne Brood and Diba Latifi and Oostvogels, {Astrid A.} and Yarne Klaver and Miranda Moskie and Mustafa, {Dana A.} and Reno Debets and {van Eijck}, {Casper H.J.}",

note = "Funding Information: Funding: Rintatolimod (Ampligen{\textregistered}) was provided in this program via MyTomorrows (https://my-tomorrows.com/en (accessed: 02-02-2022)) in collaboration with the manufacturer AIM Immuno-Tech, Ocala, FL, USA (www.aimimmuno.com). This work was financially supported by the Support Casper Foundation (www.supportcasper.nl). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = mar,

day = "1",

doi = "10.3390/cancers14061377",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "6",

}

El Haddaoui, H, Brood, R, Latifi, D , Oostvogels, AA, Klaver, Y, Moskie, M , Mustafa, DA , Debets, R & van Eijck, CHJ 2022, 'Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program', Cancers, vol. 14, no. 6, 1377. https://doi.org/10.3390/cancers14061377

Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program. / El Haddaoui, Hassana; Brood, Rianne; Latifi, Diba et al.
In: Cancers, Vol. 14, No. 6, 1377, 01.03.2022.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX

T2 - A Single-Center Named Patient Program

AU - El Haddaoui, Hassana

AU - Brood, Rianne

AU - Latifi, Diba

AU - Oostvogels, Astrid A.

AU - Klaver, Yarne

AU - Moskie, Miranda

AU - Mustafa, Dana A.

AU - Debets, Reno

AU - van Eijck, Casper H.J.

N1 - Funding Information: Funding: Rintatolimod (Ampligen®) was provided in this program via MyTomorrows (https://my-tomorrows.com/en (accessed: 02-02-2022)) in collaboration with the manufacturer AIM Immuno-Tech, Ocala, FL, USA (www.aimimmuno.com). This work was financially supported by the Support Casper Foundation (www.supportcasper.nl). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/3/1

Y1 - 2022/3/1

N2 - Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients’ survival via immunomodulation, but the effect is unproven. Methods: In this singlecenter named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progressionfree survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤ 1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.

AB - Background: Treatment with the TLR-3 agonist rintatolimod may improve pancreatic cancer patients’ survival via immunomodulation, but the effect is unproven. Methods: In this singlecenter named patient program, patients with locally advanced pancreatic cancer (LAPC) or metastatic disease were treated with rintatolimod (six weeks total, twice per week, with a maximum of 400 mg per infusion). The primary endpoints were the systemic immune-inflammation index (SIII), the neutrophil to lymphocyte ratio (NLR), and the absolute counts of 18 different populations of circulating immune cells as measured by flow cytometry. Secondary endpoints were progressionfree survival (PFS) and overall survival (OS). Subgroup analyses were performed in long-term survivors (>1-year overall survival after starting rintatolimod) and compared to short-term survivors (≤ 1 year). Results: Between January 2017 and February 2019, twenty-seven patients with stable LAPC or metastatic disease were pre-treated with FOLFIRINOX and treated with rintatolimod. Rintatolimod treatment was well-tolerated. The SIII and NLR values were significantly lower in the 11 long-term survivors, versus 16 short-term survivors. The numbers of B-cells were significantly increased in long-term survivors. Numbers of T cells and myeloid cells were not significantly increased after treatment with rintatolimod. Median PFS was 13 months with rintatolimod, versus 8.6 months in a subset of matched controls (n = 27, hazard ratio = 0.52, 95% CI = 0.28–0.90, p = 0.007). The median OS was 19 months with rintatolimod, versus 12.5 months in the matched control (hazard ratio = 0.51, 95% CI = 0.28–0.90, p = 0.016). Conclusions: Treatment with rintatolimod showed a favorable effect on the numbers of peripheral B cells in patients with pancreatic cancer and improved survival in pancreatic cancer, but additional evidence is required.

UR - http://www.scopus.com/inward/record.url?scp=85125895502&partnerID=8YFLogxK

U2 - 10.3390/cancers14061377

DO - 10.3390/cancers14061377

M3 - Article

AN - SCOPUS:85125895502

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 6

M1 - 1377

ER -

El Haddaoui H, Brood R, Latifi D , Oostvogels AA, Klaver Y, Moskie M et al. Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program. Cancers. 2022 Mar 1;14(6):1377. doi: 10.3390/cancers14061377

Rintatolimod (Ampligen®) Enhances Numbers of Peripheral B Cells and Is Associated with Longer Survival in Patients with Locally Advanced and Metastasized Pancreatic Cancer Pre-Treated with FOLFIRINOX: A Single-Center Named Patient Program

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