Pomalidomid (3) – Imnovid®

• Clinical trials
  • The pharmaceutical manufacturer has submitted data from the open-label, randomised, controlled Phase III trial MM-007 for the benefit assessment.
  • In this trial, pomalidomide in combination with bortezomib and dexamethasone is compared with bortezomib in combination with dexamethasone.

Adult patients with multiple myeloma who have received at least one prior line of treatment, including lenalidomide

• Additional benefit is not proven for pomalidomide in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior line of treatment, including lenalidomide.
• mortality
  • Overall survival is defined in the MM-007 study as the time from randomisation to death from any cause.
  • By the data cut-off date of 15 September 2018, a total of 242 patients had died, 116 in the intervention arm and 126 in the control arm. The median survival time was 40.5 months in the intervention arm and 30.5 months in the control arm. The time-to-event analysis showed no statistically significant difference (hazard ratio (HR): 0.91; [95% confidence interval (CI): 0.70; 1.18]; p-value 0.476).
  • An additional benefit of pomalidomide in combination with bortezomib and dexamethasone is not proven in the mortality category.
• Morbidity – Progression-free survival (PFS)
  • Progression-free survival is the primary endpoint of the MM-007 study. It is defined as the time from randomisation to the first documented disease progression or death during study treatment or in the PFS follow-up phase.
  • Median PFS was statistically significantly prolonged by 4.83 months in the intervention arm compared with the control arm (median 11.70 vs. 6.87 months; HR: 0.58 [95% CI: 0.47; 0.71]; p < 0.001).
  • The results for the progression-free survival endpoint are therefore not included in this assessment.
• Morbidity – Symptoms
  • In the MM-007 study, patients’ symptoms are assessed using the eight symptom scales of the EORTC-QLQ-C30 questionnaire and the two symptom scales of the EORTC-QLQ-MY20.
  • In the responder analysis for the time to the first clinically relevant deterioration of at least 10 points from baseline, a statistically significant difference between the treatment arms was observed only for the symptom of constipation. This difference indicates a disadvantage of pomalidomide in combination with bortezomib and dexamethasone.
  • An additional benefit of pomalidomide in combination with bortezomib and dexamethasone is not proven in the morbidity category.
• Health-related quality of life
  • In the MM-007 study, health-related quality of life is reported by patients and assessed using the six functional scales of the EORTC-QLQ-C30 questionnaire and the two functional scales of the EORTC-QLQ-MY20 questionnaire.
  • Based on the overall population, the responder analyses for the time to the first clinically relevant deterioration of at least 10 points from baseline show no statistically significant differences between the treatment groups.
  • In summary, an additional benefit of pomalidomide in combination with bortezomib and dexamethasone is not proven in the quality of life category.
• Side effects – Total adverse events (AEs)
  • Almost every patient in both the intervention arm and the control arm experienced an adverse event. The results for the endpoint ‘Total adverse events’ are presented here only as supplementary information.
• Side effects – Serious AEs
  • In the MM-007 study, at the time of the second data cut-off, approximately 61% of patients in the intervention arm and approximately 43% of patients in the comparator arm experienced a serious adverse event (SAE).
  • In the control arm, a SAE occurred, on a median basis, 12.8 months later than in the intervention arm. The time-to-event analysis reveals a statistically significant disadvantage for pomalidomide in combination with bortezomib and dexamethasone.
• Side effects – severe AEs (CTCAE grade ≥ 3)
  • In the MM-007 study, at the time of the second data cut-off, approximately 93% of patients in the intervention arm and approximately 72% of patients in the control arm experienced a severe adverse event (CTCAE grade ≥ 3).
  • In the control arm, a severe AE occurred, on a median basis, 0.9 months later than in the intervention arm. The time-to-event analysis reveals a statistically significant disadvantage for pomalidomide in combination with bortezomib and dexamethasone.
• Overall assessment
  • For the benefit assessment of pomalidomide in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy, including lenalidomide, the MM-007 study provides results on overall survival, morbidity, health-related quality of life and side effects.
  • In the mortality endpoint category, no statistically significant difference was observed between the treatment groups for the endpoint of overall survival. An additional benefit of pomalidomide in combination with bortezomib and dexamethasone is not proven for overall survival.
  • With regard to morbidity (symptoms, assessed using the EORTC-QLQ-C30 and EORTC-QLQ-MY20 questionnaires) there is a statistically significant difference with regard to the symptom of constipation to the detriment of pomalidomide in combination with bortezomib and dexamethasone; however, this does not alter the overall conclusion regarding symptoms in view of the disease in question and the difference in the magnitude of effect. With regard to morbidity, the additional benefit of pomalidomide in combination with bortezomib and dexamethasone is not proven.
  • With regard to health-related quality of life, based on the overall population, there are neither positive nor negative effects of treatment with pomalidomide in combination with bortezomib and dexamethasone.
  • With regard to side effects, there are numerous statistically significant disadvantages associated with pomalidomide in combination with bortezomib and dexamethasone, which are also markedly pronounced in terms of their severity, across the endpoints of serious AEs, severe AEs and specific AEs.
  • The side effects observed are significant for patients and, in individual cases, also serious; however, it is uncertain to what extent they are directly transferable to the German healthcare context.
  • The G-BA concludes that, despite the clear negative effects in the ‘side effects’ endpoint category as indicated by the study results, the finding of ‘less benefit’ cannot be established with the requisite certainty in the overall assessment.
  • In its overall assessment, the G-BA therefore concludes that an additional benefit of pomalidomide in combination with bortezomib and dexamethasone compared with bortezomib in combination with dexamethasone is not proven.

Courtesy translation only, please refer to the German original.