Posted: Tuesday, January 30, 2024
Preclinical efforts to identify therapeutic strategies for patients with multiple myeloma and to prevent the progression of asymptomatic smoldering multiple myeloma to full-blown disease have revealed a potential role for microbiota-based strategies, according to a presentation given at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 754). The combination of microbiota-based strategies with immune checkpoint blockade may be beneficial in this population by limiting the expansion of Th17 cells; however, further studies in humans are warranted to determine the clinical benefit of this approach, explained Matteo Bellone, MD, of the IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues.
Mice models were obtained and employed to mimic asymptomatic (Vk*MYC) and aggressive multiple myeloma (t-Vk*MYC). Subjects were treated with Prevotella melaninogenica (a bacterial species found in the normal microbiota of the upper respiratory tract) and/or anti–PD-L1 antibodies. Paraprotein quantification in the blood was performed to monitor disease progression. Bone marrow, gut, and spleen samples were collected and analyzed via flow cytometry. In addition, to determine the relationship between the gut microbiota and induction of Th17 cells, in vitro assays were performed. Subjects were also exposed to imiquimod on the skin, and toxicity to treatment was monitored via skin inflammation, body weight loss, and inflammatory infiltrate into secondary lymphoid organs.
Vk*MYC mice treated with anti–PD-L1 antibodies demonstrated delayed progression to full-blown multiple myeloma. Similarly, the use of P. melaninogenica also led to delayed progression to full-blown multiple myeloma. The combination of both P. melaninogenica and anti–PD-L1 antibodies delayed disease progression even further.
Similar benefits of these therapeutic strategies were also observed in t-Vk*MYC mice. Moreover, the use of imiquimod resulted in psoriasis-like lesions and an increased expression of Th17 cells in the draining lymph nodes and spleen. When anti–PD-L1 antibodies were administered to mice treated with imiquimod, the extent of inflammation induced by treatment worsened.
Disclosure: For full disclosures of the study authors, visit ash.confex.com.