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. 2022 Oct 11;9(11):ofac535.
doi: 10.1093/ofid/ofac535. eCollection 2022 Nov.

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases

Tempe K Chen  1   2 , Jagmohan S Batra  1   2 , David E Michalik  1   2 , Jacqueline Casillas  3   4 , Ramesh Patel  3   4 , Maritza E Ruiz  3   4 , Harneet Hara  3   4 , Bhavita Patel  3   4 , Meena Kadapakkam  3   4 , James Ch'Ng  3   4 , Catherine B Small  5 , Panagiotis Zagaliotis  5   6   7 , Carolyn E Ragsdale  8 , Luis O Leal  8 , Emmanuel Roilides  6 , Thomas J Walsh  5   9
Affiliations

Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases

Tempe K Chen et al. Open Forum Infect Dis. .

Abstract

Background: Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).

Methods: The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single institution were analyzed in a retrospective cohort review. Further, a systematic review of published reports of rhu GM-CSF for IFDs was also conducted.

Results: Among 65 cases, 15 were newly described pediatric patients and 50 were previously published cases of IFDs treated with rhu GM-CSF. Among the newly reported pediatric patients, IFDs were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Rhizopus sp., Lichtheimia sp., and Scedosporium sp). Twelve (80%) were neutropenic at baseline, and 12 (80%) were refractory to antifungal therapy. Among 12 evaluable patients, the overall response rate was 92% (8 [67%] complete responses, 3 [25%] partial responses, and 1 [8%] stable). Treatment is ongoing in the remaining 3 patients. Among 50 published cases (15 Candida spp., 13 Mucorales, 11 Aspergillus spp., 11 other organisms), 20 (40%) had baseline neutropenia and 36 (72%) were refractory to standard therapy before rhu GM-CSF administration. Consistent with responses in the newly reported patients, the overall response rate in the literature review was 82% (40 [80%] complete responses, 1 [2%] partial response, and 9 [18%] no response).

Conclusions: Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory IFDs.

Keywords: antifungal agents; fungal diseases; granulocyte-macrophage colony-stimulating factor; immune modulation; sargramostim.

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Conflict of interest statement

Potential conflicts of interest. C.R. and L.L. are employees of and hold stock options for Partner Therapeutics, Inc. T.W. has received grants for experimental and clinical antimicrobial pharmacology, therapeutics, and diagnostics to his institutions from Allergan, Amplyx, Astellas, Lediant, Medicines Company, Merck, Scynexis, Shionogi, T2 Biosystems, Tetraphase, and Viosera. He has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Karyopharm Therapeutics, Leadiant, Medicines Company, Merck, Methylgene, Partner Therapeutics, Inc., Pfizer, Scynexis, Shionogi, and T2 Biosystems. C.B.S. has received grant support from GlaxoSmithKline, ViiV, Abbott, Merck, Gilead, Chimerix, Shire/Takeda, Schering-Plough, Ablynx, Janssen, Ansun Biopharma, and Karyopharm Therapeutics. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
PRISMA flow diagram of cases systematically reviewed from the published literature. aThese articles were excluded from analysis as the content was judged by the authors to not be relevant to current study based on the article title or abstract. Abbreviations: GM-CSF, granulocyte-macrophage colony-stimulating factor; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
See this image and copyright information in PMC

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