Mogamulizumab (1) – Poteligeo®

• Clinical trials
  • For the benefit assessment of the active ingredient mogamulizumab, the pharmaceutical manufacturer submitted the pivotal, open-label, randomised Phase III trial MAVORIC.

Adult patients with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior course of systemic therapy

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification
• Overall, a non-quantifiable additional benefit of mogamulizumab compared with vorinostat is identified in the treatment of adult patients with MF or SS who have received at least one prior systemic therapy, as the scientific evidence does not permit quantification.
• Consequently, the strength of the evidence for the identified additional benefit is classified as ‘hint’.
• mortality
  • overall survival
  • In the MAVORIC study, overall survival was defined as the time from the day of randomisation to death from any cause, censored on the last date on which the person was known to be alive.
  • There was no statistically significant difference between the treatment arms.
• Morbidity – Progression-free survival (PFS)
  • In the MAVORIC study, PFS was defined as the time from the day of randomisation until documented disease progression in at least one of the compartments potentially affected by MF or SS – namely the skin, blood, lymph nodes and internal organs – or until death from any cause.
  • For the PFS endpoint, there is a statistically significant advantage for treatment with mogamulizumab compared with the control therapy.
  • The assessment of disease progression in the compartments of lymph nodes, internal organs and blood was carried out not on the basis of symptoms, but using imaging procedures and laboratory parameters, in accordance with the operationalisation. Consequently, the assessment of disease progression in these areas is based on asymptomatic findings and is therefore considered not to be directly relevant to patients.
  • Taking the above aspects into account, there are differing views within the G-BA regarding the patient relevance of the PFS endpoint. The overall conclusion regarding the extent of the additional benefit remains unaffected by this.
  • In the overall assessment of the morbidity endpoints, no advantages or disadvantages can be identified for determining the additional benefit of mogamulizumab compared with vorinostat.
• Morbidity – Cutaneous symptoms – Complete response of the skin
  • Complete response of the skin was defined as the complete resolution of all skin symptoms according to mSWAT.
  • Given that the skin symptoms are highly visible, often painful and/or itchy, the endpoint of complete response is considered to be patient-relevant.
  • No statistically significant difference was observed between the treatment arms for these endpoints.
• Morbidity – Cutaneous symptoms – Skin response
  • Skin response was defined as a complete or partial skin response.
  • Given the highly visible, often painful and/or itchy skin symptoms and the associated noticeable burden on the patient, a reduction of ≥ 50% in this indication is generally regarded as a relevant change in skin symptoms and assessed as patient-relevant.
  • For skin response measured using mSWAT, there is a statistically significant advantage for mogamulizumab compared with vorinostat.
  • As previously explained, there are doubts as to whether the mSWAT measurement tool used to assess skin response is sufficiently valid and reliable to reflect the cutaneous burden of disease.
  • For these reasons, the results for this endpoint are considered insufficiently meaningful to be used for determining the additional benefit.
• Morbidity – Cutaneous symptoms – Pruritus NRS
  • Itching was assessed using the Pruritus Numerical Rating Scale (NRS), where a score of 0 corresponded to no itching and a score of 10 to the worst imaginable itching.
  • There are currently no externally validated, anchor-based MIDs available for the assessment of the pruritus NRS.
  • Based on the difference in mean scores compared with Cycle 1, there is no statistically significant difference between the treatment groups.
• Quality of life – ItchyQoL
  • The ItchyQoL is a specific measurement tool for assessing quality of life in pruritus.
  • Based on the difference in mean total scores compared with Cycle 2 and Cycle 1 in the domains ‘Emotion’, ‘Function’ and ‘Symptoms’, there is no statistically significant difference between the treatment groups.
• Side effects – Total adverse events (AEs)
  • Adverse events (AEs) occurred in almost all study participants. The results are presented here for supplementary information only.
• Overall assessment
  • For the assessment of the additional benefit of mogamulizumab in the treatment of adult patients with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic therapy, results are available for the endpoint categories of mortality, morbidity, quality of life and side effects.
  • The analysis of the overall survival endpoint shows no statistically significant difference between the treatment arms.
  • In the overall assessment of the morbidity endpoints, no overall advantages or disadvantages can be identified for determining the additional benefit of mogamulizumab compared with vorinostat.
  • Furthermore, data on health-related quality of life are available for this assessment. For the disease-specific questionnaires ItchyQoL and Skindex-29, as well as for the cancer-agnostic questionnaire FACT-G, there are no relevant differences (standardised mean difference in the form of Hedges’ g) between the treatment groups.
  • With regard to side effects, there is a relevant—though with an extent no greater than minor—advantage of mogamulizumab over vorinostat in terms of severe adverse events (CTCAE grade ≥ 3) and therapy discontinuations due to adverse events.
  • Due to the described limitations in the applicability of the present study to the reality of healthcare provision in Germany, the G-BA considers that there are significant uncertainties in the interpretation of the study results; the extent of these uncertainties is deemed so significant that, despite the relevant advantages regarding side effects, do not, on the whole, permit a quantification of the extent of the additional benefit.

Courtesy translation only, please refer to the German original.