Myelodysplastic Syndromes

Background : Pevonedistat disrupts proteasomal degradation of certain proteins and has shown good tolerability and promising clinical activity in combination with azacitidine.

Method : For the study, 120 patients with HR-MDS, chronic myelomonocytic leukemia or low-blast AML who were naïve to hypomethylating agents were randomized 1:1 to receive pevonedistat 20 mg/m2 intravenously on days 1, 3, and 5 along with azacitidine 75 mg/m2 either by IV or subcutaneously on days 1–5, 8, and 9 (n=58), or azacitidine alone (n=62),in 28-day cycles.

Results : In HR-MDS, pevonedistatand azacitidine led tolonger event-free survival (EFS), and a higher complete remission (CR) rate compared with azacitidine alone.

Background : An ongoing, open-label, dose-escalation, Phase 1b study evaluated the combination of venetoclax and azacitidine in the management of treatmentnaïve HR-MDS.

Method : Treatment-naïve HR-MDS patients aged ≥18 years with IPSS intermediate-2 or high and bone marrow blasts <20% at baseline, and an Eastern Cooperative Oncology Group (ECOG) score ≤2 were enrolled for the study. Venetoclax was administered at a dose of 400 mg or 800 mg for 28 days in a 28-day cycle.Due to intolerance among patients with MDS, the dose was altered to an escalating dose (100 mg, 200 mg, and 400 mg) for 14 days in a 28-day cycle. Azacitidine was administered at 75 mg/m2 subcutaneously or intravenously on days 1–7 of each 28-day cycle.

Results : The combination of venetoclax and azacitidine demonstrated promising efficacy, which included response durability, and a good safety profile for patients with HR-MDS.

Background : Lenalidomide has been shown to play a role in non-transfusion-dependent (TD) patients with del (5q). However, no randomized trial has assessed the tolerance and efficacy of early lenalidomide treatment in this MDS subset.

Method : The Sintra-REV clinical trial is a phase III multicenter study in LR MDS-del (5q) patients who have anemia (Hb<12g/dL), without TD. Patients were randomized to receive lenalidomide (5 mg/day continuously) vs. placebo (2:1 randomization) for two years of treatment and two years of follow-up.

Results :Low-dose lenalidomide (5 mg) in anemic non-TD low-risk MDS del (5q) patients prolongs the time to TD (75.7 months vs. 25.9 months) and improves the overall Hb levels.