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Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) is a bone marrow disorder with myelodysplastic and myeloproliferative features
.
MDS/MPN-RS-T-related anemia can lead to fatigue, decreased quality of life, and worsened survival, and treatment is aimed at improving the anemia, reducing the risk of thrombotic events, reducing platelets, and/or altering the course of the disease
MDS/MPN-RS-T-related anemia can lead to fatigue, decreased quality of life, and worsened survival, and treatment is aimed at improving the anemia, reducing the risk of thrombotic events, reducing platelets, and/or altering the course of the disease
Rottecept is a first-in-class erythrocyte maturation agent that binds multiple ligands of the transforming growth factor-beta superfamily and enhances advanced erythropoiesis
Of the 229 patients in the MEDALIST study, 23 (10.
0%) had MDS/MPN-RS-T; 14 were randomly assigned to rotercept and 9 were randomized to placebo
.
Baseline characteristics that differed between the two groups included lower median white blood cell counts (4.
9 1A
Figure 1: Baseline characteristics and treatment response of MDS/MPN-RS-T patients in the MEDALIST trial
.
.
Figure 1: Baseline Characteristics
Figure 1: Baseline CharacteristicsThe primary endpoint of the MEDALIST study was RBC transfusion independence (RBC-TI) ≥8 weeks between weeks 1-24
.
Secondary endpoints included: Modified hematologic response - red blood cell (mHI-E; mean hemoglobin increase ≥1.
As of July 2019, there was a significant increase in the proportion of MDS/MPN-RS-T patients randomized to rotecept who achieved an RBC-TI ≥8 weeks between weeks 1-24 (64.
3 vs 22.
2%; P= 0.
028 ); mHI-E (71.
4 vs 11.
1%; P= 0.
006); and clinical benefit (78.
6 vs 33.
3%; P = 0.
034), compared with placebo (Figure 1B)
.
The median time from the onset of clinical benefit to the end of treatment was 94.
P P P
The numbers were higher in patients with low transfusion burden (<4 units/8 weeks) and RBC-TI ≥8 weeks (5/6 [83.
3%] vs 2/4 [ 50.
0%]; P = 0.
285) achieved a significant increase in the proportion of mHI-E from weeks 1-24 (4/6 [66.
7%] vs 0/4 [0.
0%]; P = 0.
046) (Figure 1C)
.
Numerical values were higher in patients with high transfusion burden (≥4 units/8 weeks) randomized to rotacept versus placebo, and RBC-TI ≥8 weeks (4/8 [50.
P P P P P
Figure 2: Treatment Response, Laboratory Parameters and TEAE
Figure 2: Treatment Response, Laboratory Parameters and TEAEFigure 2: Incidence of RBC-TI ≥48 weeks at any time during treatment for all MDS/MPN-RS-T patients and patients with RBC-TI ≥8 weeks at any time during treatment
Figure 2: Incidence of RBC-TI ≥48 weeks at any time during treatment for all MDS/MPN-RS-T patients and patients with RBC-TI ≥8 weeks at any time during treatmentAlthough limited in number, comparisons with data from the entire MEDALIST study population support the value of rotecept in patients with MDS/MPN-RS-T
.
MDS/MPN-RS-T patients achieved a higher rate of RBC-TI ≥8 weeks in weeks 1-24 (64.
After 24 weeks of treatment, mean hemoglobin, white blood cells, and neutrophils increased from baseline in patients randomized to rotercept , while platelet levels remained stable (Figure 2B)
.
Although increases in hemoglobin levels in patients with MDS/MPN-RS-T after 24 weeks were not significantly different between rothecept and placebo, the absolute increases were nominally higher
.
Patients randomized to rotercept versus placebo had significantly higher mean white blood cell counts, but no mean platelet or neutrophil counts
.
At baseline, MDS/MPN-RS-T patients had higher median platelet counts than the MEDALIST overall population, as expected, lower median sEPO, less likely to receive iron chelation therapy, and moderate transfusion burden The numbers were lower, consistent with their higher RBC-TI and mHI-E response rates
.
Elevated from baseline
The most common TEAEs of any grade in the rottercept group were dizziness, nausea, diarrhea, and asthenia (Figure 2B)
.
TEAEs leading to discontinuation occurred in 2 of 14 patients (14.
3%) in the rotercept group and 3 of 9 patients (33.
3%) in the placebo group
.
One patient randomly assigned to rotercept experienced a transient ischemic attack
.
One patient randomized to placebo progressed to AML ( P =0.
202), but not to rotercept
.
Treatment recommendations for patients with MDS/MPN-RS-T include ESA and blood transfusions for anemia, lenalidomide for anemia and decreased platelet levels
.
Recommendations for lenalidomide use in patients with MDS/MPN-RS-T are based on case reports of 12 patients and a retrospective analysis of 167 patients, not clinical trials; ESA use is based on a single retrospective study that The study included 40 MDS/MPN-RS-T patients, of whom 45% achieved an erythroid response (patients with a hemoglobin increase ≥2.
0 g/dL or an RBC-TI ≥8 weeks requiring ≥4 units/8 weeks), whereas the current 71.
4% of the patients in the study received rotecept (refractory or ineligible for ESAs)
.
However, given the different definitions of erythroid responses, such comparisons should be made with caution
.
In conclusion, this subgroup analysis provides the first clinical trial data to support the efficacy of rotercept in patients with MDS/MPN-RS-T
.
Overall, rottercept was found to be effective—significantly reducing transfusion burden and improving mHI-E and leukocyte levels—with a generally well-tolerated safety profile
.
.
Original source:
Komrokji, RS, Platzbecker, U.
, Fenaux, P.
et al.
Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
Leukemia (2022).
https://doi.
org/10.
1038/s41375-022-01521- 4
, Fenaux, P.
et al.
Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
Leukemia (2022).
https://doi.
org/10.
1038/s41375-022-01521- 4 Komrokji, RS, Platzbecker, U.
, Fenaux, P.
et al.
Luspatercept for myelodysplastic syndromes/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.
Leukemia (2022).
https://doi.
org/10.
1038/s41375-022-01521 -4 leave a message here