Clinical Summary:

• Design/Population: This single-arm study evaluated a sequential treatment approach in 20 patients with very-high-risk myelodysplastic syndromes, using weekly cytarabine induction followed by azacitidine plus continuous lenalidomide. 
• Key Outcomes: All patients achieved either a complete or partial response after induction, with additional complete responses emerging during subsequent therapy. Long-term progression-free and overall survival outcomes were encouraging, while grade 3/4 neutropenia occurred primarily during induction.
• Clinical Relevance: These findings suggest that this sequential regimen may provide a treatment approach in resource-limited settings. However, the small study population and absence of comparator limit conclusions regarding efficacy. 

Sequential cytarabine induction followed by azacitidine plus lenalidomide demonstrated clinical activity in patients with very-high-risk myelodysplastic syndromes (MDS), suggesting a potential treatment strategy for resource-limited settings.

These results were presented by Maher Salamoon, MD, Al Bairouni University Cancer Center, Damascus, Syrian Arab Republic, at the Society of Hematologic Oncology (SOHO) Annual Meeting in Houston, Texas.

This study enrolled 20 patients with very-high-risk MDS according to the International Prognostic Scoring System. Most patients had blast percentages ranging from 12% to 20%, chromosomal abnormalities, and generalized cytopenias, with histology ranging between refractory anemia with excess blasts-1 and refractory anemia with excess blasts-2.

Patients received 3g of induction cytarabine once weekly for 8 consecutive weeks. This was followed by 75 mg/m² of once daily azacitidine for 5 consecutive days of each 28-day cycle in combination with continuous 10 mg/day of lenalidomide. 

Treatment continued among patients who demonstrated a response with acceptable toxicity. Bone marrow aspiration was performed after following completion of induction and every 3 months thereafter.

At the end of induction, 5 of 20 patients achieved a complete response, corresponding to a complete response rate of 25%. The remaining 15 patients achieved a partial response. Three months after initiation of the second treatment block, 3 additional patients achieved a complete response, increasing the complete response rate to 40%.

At 4 years, progression-free survival was 46%, while overall survival was 62%. 

Grade 3/4 neutropenia was reported in 15% of patients and occurred predominantly during induction treatment. The rate of intensive care admission following neutropenia was 8%. The investigators noted that patients maintained a good quality of life following induction.

The findings suggest that an induction chemotherapy approach followed by hypomethylating therapy and an immunomodulatory agent may provide clinical activity in patients with very-high-risk MDS where access to other treatment options is constrained.

However, the study included only 20 patients and did not include a comparator arm, limiting the ability to determine the relative efficacy or safety of the regimen against other treatment strategies.

Source:

Salamoon M. Treatment of higher-risk myelodysplastic syndrome with high-dose chemotherapy followed by lenalidomide and azacitidine: A 4-year survival update. Presented at the 2026 SOHO Annual Meeting; September 9-12, 2026; Houston, Texas. Abstract MDS-635.