Immune and Pathologic Responses in Patients With Localized Prostate Cancer Who Received Daratumumab (Anti-CD38) or Edicotinib (Csf-1R Inhibitor)

Authors

Bilal A Siddiqui
Brian F Chapin
Sonali Jindal
Fei Duan
Sreyashi Basu
Shalini S Yadav
Ai-Di Gu
Alexsandra B Espejo
Michelle Kinder
Curtis A Pettaway
John F Ward
Rebecca S S Tidwell
Patricia Troncoso
Paul G Corn
Christopher J Logothetis
Roland Knoblauch
Natalie Hutnick
Marco Gottardis
Charles G Drake
Padmanee Sharma
Sumit K Subudhi

Publication Date

3-1-2023

Journal

The Journal for ImmunoTherapy of Cancer

Abstract

BACKGROUND: The prostate tumor microenvironment (TME) is immunosuppressive, with few effector T cells and enrichment of inhibitory immune populations, leading to limited responses to treatments such as immune checkpoint therapies (ICTs). The immune composition of the prostate TME differs across soft tissue and bone, the most common site of treatment-refractory metastasis. Understanding immunosuppressive mechanisms specific to prostate TMEs will enable rational immunotherapy strategies to generate effective antitumor immune responses. Daratumumab (anti-CD38 antibody) and edicotinib (colony-stimulating factor-1 receptor (CSF-1R) inhibitor) may alter the balance within the prostate TME to promote antitumor immune responses.

HYPOTHESIS: Daratumumab or edicotinib will be safe and will alter the immune TME, leading to antitumor responses in localized prostate cancer.

PATIENTS AND METHODS: In this presurgical study, patients with localized prostate cancer received 4 weekly doses of daratumumab or 4 weeks of daily edicotinib prior to radical prostatectomy (RP). Treated and untreated control (Gleason score ≥8 in prostate biopsy) prostatectomy specimens and patient-matched pre- and post-treatment peripheral blood mononuclear cells (PBMCs) and bone marrow samples were evaluated. The primary endpoint was incidence of adverse events (AEs). The secondary endpoint was pathologic complete remission (pCR) rate.

RESULTS: Twenty-five patients were treated (daratumumab, n=15; edicotinib, n=10). All patients underwent RP without delays. Grade 3 treatment-related AEs with daratumumab occurred in 3 patients (12%), and no ≥grade 3 treatment-related AEs occurred with edicotinib. No changes in serum prostate-specific antigen (PSA) levels or pCRs were observed. Daratumumab led to a decreased frequency of CD38

CONCLUSIONS: Daratumumab and edicotinib treatment was safe and well-tolerated in patients with localized prostate cancer but did not induce pCRs. Decreases in CD38

Keywords

Male, Humans, Leukocytes, Mononuclear, Antineoplastic Agents, Antibodies, Monoclonal, Prostatic Neoplasms, Immunosuppressive Agents, Tumor Microenvironment, Prostatic Neoplasms, Immunotherapy, Tumor Microenvironment, Immunomodulation

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Data availability statement

PMID: 36948506