Approved medical treatments for patients with MDS
| Treatment . | Drug label . | Notes . |
|---|---|---|
| ESAs | EMA: epoetin alfa is indicated for the treatment of symptomatic anemia (Hb concentration of ≤10 g/dL) in adults with low- or intermediate-1-risk primary MDS who have low serum erythropoietin (< 200 mU/mL) | Many patients with MDS-del(5q) have elevated serum erythropoietin levels and are not responsive to ESAs |
| Lenalidomide | FDA: transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities EMA: lenalidomide as monotherapy is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate | Treatment schedule: 10 mg/d on days 1-21, or 5 mg/d on days 1-28 of 28-day cycles Severe neutropenia represents a common adverse event in the early phase of treatment, frequently requiring the administration of granulocyte colony-stimulating factor |
| Luspatercept | FDA: anemia without previous ESA use (ESA-naïve) in adult patients with very low-to intermediate-risk MDS who may require regular red blood cell transfusions EMA: luspatercept is indicated in adults for the treatment of transfusion-dependent anemia due to very low, low, and intermediate-risk MDS | The recommended starting dose of luspatercept is 1 mg/kg once every 3 weeks by subcutaneous injection It must be noted that the clinical trials that led to the approval of luspatercept (MEDALIST71 and COMMANDS72) specifically excluded patients with MDS-del(5q) |
| Imetelstat | FDA: imetelstat is an oligonucleotide telomerase inhibitor indicated for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia requiring ≥4 red blood cell units over 8 weeks who have not responded to, or have lost response to, or are ineligible for, ESAs EMA: imetelstat is indicated as monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low, or intermediate risk MDS without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to, or are ineligible for, erythropoietin-based therapy | The clinical trial that led to the approval of imetelstat (IMerge73) specifically excluded patients with MDS-del(5q) |
| Hypomethylating agents (azacitidine and decitabine) | The agents have been approved with partly different criteria by the FDA and EMA for patients with higher-risk MDS |
| Treatment . | Drug label . | Notes . |
|---|---|---|
| ESAs | EMA: epoetin alfa is indicated for the treatment of symptomatic anemia (Hb concentration of ≤10 g/dL) in adults with low- or intermediate-1-risk primary MDS who have low serum erythropoietin (< 200 mU/mL) | Many patients with MDS-del(5q) have elevated serum erythropoietin levels and are not responsive to ESAs |
| Lenalidomide | FDA: transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities EMA: lenalidomide as monotherapy is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with an isolated deletion 5q cytogenetic abnormality when other therapeutic options are insufficient or inadequate | Treatment schedule: 10 mg/d on days 1-21, or 5 mg/d on days 1-28 of 28-day cycles Severe neutropenia represents a common adverse event in the early phase of treatment, frequently requiring the administration of granulocyte colony-stimulating factor |
| Luspatercept | FDA: anemia without previous ESA use (ESA-naïve) in adult patients with very low-to intermediate-risk MDS who may require regular red blood cell transfusions EMA: luspatercept is indicated in adults for the treatment of transfusion-dependent anemia due to very low, low, and intermediate-risk MDS | The recommended starting dose of luspatercept is 1 mg/kg once every 3 weeks by subcutaneous injection It must be noted that the clinical trials that led to the approval of luspatercept (MEDALIST71 and COMMANDS72) specifically excluded patients with MDS-del(5q) |
| Imetelstat | FDA: imetelstat is an oligonucleotide telomerase inhibitor indicated for the treatment of adult patients with low- to intermediate-1 risk MDS with transfusion-dependent anemia requiring ≥4 red blood cell units over 8 weeks who have not responded to, or have lost response to, or are ineligible for, ESAs EMA: imetelstat is indicated as monotherapy for the treatment of adult patients with transfusion-dependent anemia due to very low, low, or intermediate risk MDS without an isolated deletion 5q cytogenetic (non-del 5q) abnormality and who had an unsatisfactory response to, or are ineligible for, erythropoietin-based therapy | The clinical trial that led to the approval of imetelstat (IMerge73) specifically excluded patients with MDS-del(5q) |
| Hypomethylating agents (azacitidine and decitabine) | The agents have been approved with partly different criteria by the FDA and EMA for patients with higher-risk MDS |
Clinical trials that led to drug approval by EMA or FDA used the IPSS or the IPSS-R for risk stratification. Lenalidomide is the only compound that has been specifically approved for MDS-del(5q), whereas the EMA approval for imetelstat specifically excludes MDS-del(5q).
EMA, European Medicines Agency; ESAs, erythropoiesis stimulating agents; FDA, US Food and Drug Administration; Hb, hemoglobin; IPSS-R, revised IPSS.