Patients who have been diagnosed with higher-risk myelodysplastic syndromes (HRMDS) face a bleak prognosis. However, studies have demonstrated that azacitidine (AZA) can significantly extend the survival rate of treatment-naive patients with HRMDS, surpassing the available standard-of-care options.
IMM01 is a fusion protein that combines a recombinant signal regulatory protein α with IgG1. This fusion protein exerts its antitumor effects by inhibiting the “don’t eat me” signal and activating the “eat me” signal, resulting in a robust antibody-dependent cellular phagocytosis.
This phase 2 study (NCT05140811) was conducted at multiple centers using an open-label approach. It aimed to assess the safety and effectiveness of IMM01 in combination with AZA as the initial treatment for patients with untreated HRMDS. The enrolled patients were adults ≥18 years diagnosed with intermediate- to very high-risk myelodysplastic syndromes, based on the Revised International Prognostic Scoring System (IPSS-R) score of >3.5.
These patients were not eligible for stem cell transplants or intensive chemotherapy. The treatment regimen involved intravenous administration of IMM01 at a dosage of 2.0 mg/kg/week and subcutaneous administration of AZA at 75 mg/m2 on days 1 through 7, within a 28-day cycle.
On the cutoff day, December 22, 2023, 57 patients had been recruited for the study. The median age was 64 (30-83) years, with 71.9% of patients being male and 96.5% having an Eastern Cooperative Oncology Group performance status of ≥1. According to the IPSS-R risk classification, 43.9% were classified as high-risk and 31.6% as very high-risk. At the beginning of the study, the median levels of blood counts were 69 g/L for hemoglobin, 43×109/L for platelets, and 0.8×109/L for neutrophils.
The median follow-up duration was 12.8 months (95% confidence interval [CI], 9.7-15.3). Of the 51 patients evaluated for efficacy, the overall response rate was 64.7%, with a complete remission (CR) rate of 29.4%, marrow complete remission (mCR) with hematologic improvement (HI) at 15.7%, HI alone at 5.9%, and mCR alone at 13.7%. The median time to respond was 1.9 months (95% CI, 1.8-2.8), while the median duration of response was not reached.
The median progression-free survival (PFS) was also not reached, but the estimated 12-month PFS was 54.4% (95% CI, 31.4-72.6). Next-generation sequencing analysis identified common mutations in DNMT3A, ASXL1, U2AF1, and RUNX1. NPM1 mutations significantly correlated with treatment response, particularly in achieving CR.
Among the most common treatment-related adverse events of grade ≥3 that occurred at a rate of ≥10%, leukopenia (78.9%), thrombocytopenia (66.7%), neutropenia (66.7%), lymphopenia (56.1%), anemia (43.9%), infection (15.8%), and pneumonia (10.5%) were observed. The occurrence of grade ≥3 hemolysis was 1.8% without using a low priming dose.
IMM01 and AZA demonstrated excellent tolerability and promising efficacy outcomes in treatment-naïve HRMDS patients.
Source: Yang W, Gao S, Yan X, et al. Latest results of a phase 2 study of IMM01 combined with azacitidine (AZA) as the first-line treatment in adults with higher risk myelodysplastic syndromes (MDS). Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; abstract 6510.
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