SP25 | CC486 AS A SAFE AND EFFECTIVE BRIDGE TO TRANSPLANT IN MDS-DEL5Q WITH TRANSFUSION-DEPENDENT ANEMIA FOLLOWING LENALIDOMIDE RELAPSE: A CASE REPORT

Background: Myelodysplastic syndromes (MDS) with isolated deletion of the long arm of chromosome 5 [del(5q)] constitute a distinct lower-risk (LR) subtype, frequently associated with transfusion-dependent anemia and poor response to erythropoiesis-stimulating agents. Lenalidomide is the standard treatment for transfusion-dependent (TD) anemia in these patients; however, responses may be transient, especially in the presence of TP53 mutations. For patients considered ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT), treatment options following lenalidomide failure are limited. Case Report: We describe the case of a 69-year-old woman diagnosed with LR-MDS with isolated del(5q), with TD anemia. She was initially treated with lenalidomide obtaining hematologic improvement-erythroid (HI-E). After 30 cycles, the patient relapsed with severe TD anemia, and TP53 mutation was detected with a variant allele frequency (VAF) < 20%. Due to impaired mobility from orthopedic complications conditioning poor overall fitness, HSCT was not feasible. Based on data from the phase III trial by Garcia-Manero et al (J Clin Oncol. 2021), off-label oral therapy with CC486 (oral azacitidine) was initiated at 300 mg/day for 21 days every 28 days, later reduced to 200 mg due to grade 4 neutropenia. Iron chelation with deferasirox was concurrently administered for secondary hemosiderosis. The patient obtained HI-E from cycle 3 and transfusion independence from cycle 4, with significant improvement in performance status. As the TP53 VAF increased to > 20% during treatment (Figure 1), despite a persistent HI-E, allo-HSCT became a viable option, considering the patient’s improved overall clinical status. After 16 cycles of CC486, the patient underwent successful allo-HSCT from a matched unrelated donor, using a reduced intensity conditioning regimen (treosulfan/fludarabine). The patient had successful neutrophil and platelet engraftment; post-transplant complications included HHV6 reactivation and grade III acute GVHD, which was managed according to current guidelines. Conclusions: This case illustrates the potential of CC486 as a safe and effective bridge to transplant in patients with LR-MDS del(5q) who relapse after lenalidomide and are temporarily ineligible for allo-HSCT. CC486 restored transfusion independence and improved the patient’s clinical status, enabling definitive curative therapy. Further studies are needed to confirm the role of CC486 in LR-MDS.