Luspatercept (6) – Reblozyl®

a1) Adults with transfusion-dependent anaemia due to myelodysplastic syndromes (MDS), with very low, low or intermediate risk, who have not previously received erythropoiesis-stimulating agent (ESA)-based therapy and who are suitable for such treatment

• Hint of a minor additional benefit
• In the overall assessment of the available results on patient-relevant endpoints, a minor additional benefit of luspatercept compared with epoetin alfa is identified, based on the advantage observed in the ‘transfusion-free’ endpoint.
• In summary, a minor additional benefit is identified for luspatercept. The certainty of the findings is subject to uncertainty due to the lack of blinding in the study, which is why only a hint of additional benefit is provided.
• Overall, there is a hint of a minor additional benefit for Luspatercept.
• mortality
  • Overall survival is defined as the time from randomisation until death from any cause or until the patient is censored.
  • There is no statistically significant difference between the treatment arms.
  • There is no difference in overall survival between the treatment arms.
• Morbidity – transfusion-free period
  • The endpoint ‘transfusion-free status’ is defined as a period without red blood cell (RBC) concentrate transfusions for a specified duration during the course of the study.
  • Long-term or sustained avoidance of transfusions is a primary therapeutic goal in this therapeutic indication, aiming to control anaemia and anaemia-related symptoms whilst remaining free from RC transfusions.
  • With regard to the analysis of the various periods of transfusion-free status, a period of 24 weeks without transfusions is used as the benchmark to indicate long-term avoidance of transfusions.
  • With regard to the proportion of patients achieving 24 weeks without transfusion, there is a statistically significant advantage for luspatercept compared with epoetin alfa. A 24-week transfusion-free period was observed in 79 patients (54.5%) in the intervention arm and in 55 patients (38.2%) in the control arm (relative risk = 1.41; 95% confidence interval = [1.10; 1.80]; p-value = 0.007; absolute difference = +16.3%).
  • Overall, based on these results regarding 24-week transfusion-free survival, a statistically significant advantage in favour of treatment with luspatercept can be observed with regard to the long-term avoidance of transfusions.
  • With regard to the 24-week transfusion-free survival results on which the assessment is based, an advantage in favour of treatment with luspatercept can be observed in terms of long-term avoidance of transfusions.
• Morbidity – EORTC QLQ-C30 – Symptom scales
  • Disease symptoms were assessed using the symptom scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • There is no statistically significant difference between the study arms with regard to symptoms.
  • In the morbidity endpoint category, the EORTC QLQ-C30 symptom scales show neither an advantage nor a disadvantage of luspatercept.
• Health-related quality of life – EORTC QLQ-C30 – functional scales
  • Health-related quality of life was assessed using the functional scales and the global health status scale (overall assessment) of the cancer-specific EORTC QLQ-C30 questionnaire.
  • For the individual health-related quality of life scales of the EORTC QLQ-C30, there was no statistically significant difference between the study arms.
  • There were no differences between the study arms in terms of health-related quality of life, as measured using the functional scales of the EORTC QLQ-C30 and the FACT-An.
• Health-related quality of life – FACT-An
  • Health-related quality of life was also assessed using the FACT-An (Functional Assessment of Cancer Therapy – Anaemia) questionnaire, which is specifically designed for cancer patients with anaemia and fatigue.
  • No statistically significant differences were found between the study arms.
• Side effects – Total adverse events (AEs)
  • AE occurred in 90.3% of study participants in the luspatercept arm and 81.8% in the epoetin alfa arm. The results are presented here for supplementary information only.
• Side effects – Serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3), therapy discontinuations due to AEs, thromboembolic events (severe AEs)
  • There were no statistically significant differences between the treatment arms for the endpoints SAEs, severe AEs (CTCAE grade ≥ 3), therapy discontinuations due to AEs and thromboembolic events (severe AEs).
• Overall assessment
  • For the assessment of the additional benefit of luspatercept in the treatment of adults with transfusion-dependent anaemia due to myelodysplastic syndromes (MDS) – with very low, low or intermediate risk – who have not previously received erythropoiesis-stimulating agent (ESA)-based therapy and are suitable for such treatment, results are available for the endpoint categories of mortality, morbidity, quality of life and side effects from the COMMANDS study comparing luspatercept with epoetin alfa.
  • There is no statistically significant difference between the treatment arms in terms of overall survival.
  • For the endpoint category of morbidity, results on freedom from transfusion are available. For patients within the therapeutic indication, the long-term or sustained avoidance of transfusions represents a primary treatment goal, through which control of anaemia and anaemia--related symptoms whilst remaining free from red blood cell concentrate transfusions. For the present assessment, a 24-week period without transfusions is regarded as the relevant timeframe for assuming long-term avoidance of transfusions.
  • With regard to the proportion of patients who remained transfusion-free for 24 weeks, there is a statistically significant advantage of luspatercept compared with epoetin alfa.
  • In the symptom-related endpoints (EORTC QLQ-C30), there is overall neither an advantage nor a disadvantage associated with luspatercept.
  • In the endpoints relating to health-related quality of life (EORTC QLQ-C30 and FACT-An), no significant differences were observed between the study arms.
  • With regard to side effects, no overall advantage or disadvantage of luspatercept compared with epoetin alfa was observed.

a2) Adults with transfusion-dependent anaemia due to MDS without ring sideroblasts, with very low, low or intermediate risk, who have not responded satisfactorily to ESA-based therapy or are not suitable for it

• The additional benefit is not proven.
• As no data have been provided for adults with transfusion-dependent anaemia due to MDS without ring sideroblasts, with very low, low or intermediate risk, who have not responded satisfactorily to ESA-based therapy or are unsuitable for it, no data have been provided; therefore, additional benefit for patient group a2) is not proven.

Courtesy translation only, please refer to the German original.