By Rob Dillard
June 2, 2023
A proof-of-concept study indicates the combined use of ruxolitinib and magrolimab is effective in the treatment of myelofibrosis (MF). The results were presented at the 2023 American Society of Clinical Oncology Annual Meeting.
“In solid tumors, calreticulin (CALR) overexpression produces a prophagocytic signal and is counteracted by concomitant expression of antiphagocytic CD47, reflecting an apoptosis versus survival mechanism. We have previously found that CD47, not CALR, is overexpressed on the membrane of patients with [myeloproliferative neoplasms]. Anti-CD47 magrolimab is currently being evaluated in clinical trials in [acute myelogenous leukemia and myelodysplastic syndromes] but has yet to be tested, either in monotherapy or in combination, in MF,” the researchers noted.
In this study, lead researcher Ciro Roberto Rinaldi and colleagues collated mononuclear cells from the bone marrow of 6 patients with MF and 2 controls. Cell expression of CALR and CD47 was measured by flow cytometry before and after incubation with ruxolitinib alone and in combination with magrolimab.
According to the results, CD47 membrane expression was 57% in untreated MF cells versus 12% in the control samples, while CALR membrane expression was observed at almost 52% in untreated MF cells compared with 12.5% in the control samples. Following incubation with ruxolitinib, MF CD34+ cell survival decreased to 98.2%, and after incubation with magrolimab alone, MF CD34+ cells showed no changes in survival. Notably, the analysis showed a significant membrane overexpression of CALR was observed in MF CD34+ cells when incubated with ruxolitinib and magrolimab (74.1%) versus ruxolitinib alone (52.6%), magrolimab alone (53.4%), and in untreated (51.8%).
“In vitro, treatment with ruxolitinib or ruxolitinib plus magrolimab slightly reduces the overall cell survival rate in CD34+ MF samples compared with no significant changes in single-agent magrolimab. However, the combination of ruxolitinib and magrolimab significantly increases CALR membrane expression compared with [ruxolitinib] or magrolimab alone, signaling a much stronger prophagocytic message in MF cells compared with controls,” the researchers concluded. They added that these findings “support the rationale of combining ruxolitinib with magrolimab in the next clinical trial stage in myelofibrosis.”
Source: Rinaldi C, Boasman K, Simmonds M. Effects of ruxolitinib and magrolimab on calreticulin in myelofibrosis CD34+ cells in vitro: proof of concept for combination therapy. Abstract #7064. Published for the 2023 ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois.