Tafasitamab (2) – Minjuvi®

• Clinical trials
  • To assess the additional benefit of tafasitamab, the pharmaceutical manufacturer submitted data from the randomised, controlled, double-blind Phase III inMIND trial.
  • In the inMIND trial, tafasitamab in combination with lenalidomide and rituximab is compared with the combination of lenalidomide and rituximab.

a) Adults with relapsed or refractory follicular lymphoma, grades 1 to 3a, following one line of systemic therapy

• In summary, the additional benefit of tafasitamab is assessed as follows: a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• mortality
  • In the inMIND study, overall survival is defined as the time from randomisation to death from any cause.
  • For patient group a), there is no statistically significant difference between the treatment arms.
• Morbidity – Progression-free survival (PFS)
  • PFS, as recorded by the study staff, is the primary endpoint of the inMIND trial and is defined as the time from randomisation to the first documented progression of the disease or to death from any cause, whichever occurs first.
  • For patient groups a) and b), there is a statistically significant difference in favour of the tafasitamab combination compared with the control arm.
• Morbidity – Health status (EQ-5D VAS)
  • Health status is assessed in the inMIND study using the visual analogue scale (VAS) of the European Quality of Life Questionnaire 5 Dimensions (EQ-5D).
  • In patient group a), there is no statistically significant difference in health status between the study arms.
• Morbidity – EORTC QLQ-C30 symptom scales
  • In the inMIND study, disease symptoms are assessed using the symptom scales of the cancer-specific Quality of Life Questionnaire – Core Questionnaire developed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30).
  • For patient group a), there are no statistically significant differences between the treatment arms in the symptom scales.
• Quality of life – EORTC QLQ-C30 functional scales
  • In the inMIND study, health-related quality of life is assessed using the functional scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • In patient group a), there is no statistically significant difference between the study arms for any of the individual health-related quality of life scales of the EORTC QLQ-C30.
• Quality of life – FACT-Lym
  • In the inMIND study, health-related quality of life is also assessed using the lymphoma-specific Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) questionnaire.
  • For patient group a), no statistically significant difference was found between the study arms.
• Side effects – serious AEs (SAEs), severe AEs and therapy discontinuations due to AEs
  • With regard to patient group a), the inMIND study revealed no statistically significant differences between the study arms for the endpoints SAE, severe AEs and therapy discontinuations due to AEs.
• Side effects – AEs of particular interest
  • For patient group a), the results for severe AEs (CTCAE grade ≥ 3), which occurred with an incidence of ≥ 5%, indicate significant differences at the Preferred Terms (PT) level for ‘COVID-19 pneumonia’ and ‘pneumonia’, and at the System Organ Class (SOC) ‘Infections and parasitic diseases’, significant differences to the detriment of the tafasitamab combination compared with the control arm.
  • With regard to SAEs occurring at an incidence of ≥ 5 %, there were significant differences to the detriment of the tafasitamab combination compared with the control arm in patient group a) for the PT ‘COVID-19 pneumonia’ and the SOC ‘Infections and parasitic diseases’, there were significant differences to the detriment of the tafasitamab combination compared with the control arm.
  • Overall, no advantage or disadvantage is identified in the ‘side effects’ endpoint category for patient groups a) and b).
• Overall assessment
  • For the overall survival endpoint, there is no statistically significant difference between the treatment arms.
  • In the morbidity endpoint category, there were no statistically significant differences between the treatment arms with regard to health status (EQ-5D VAS) and the symptom scales of the EORTC QLQ-C30.
  • With regard to quality of life, as measured using the functional scales of the EORTC QLQ-C30 and the FACT-Lym, no statistically significant differences were observed between the treatment arms.
  • With regard to the endpoint category ‘side effects’, there were no statistically significant differences between the treatment arms in the overall rates of SAE and severe AE, or in ‘therapy discontinuations due to AE’. In detail, the tafasitamab combination is associated with disadvantages in relation to certain ‘side effects of particular interest’. Overall, neither an advantage nor a disadvantage can be inferred in the ‘side effects’ category.
  • Overall, for tafasitamab in combination with lenalidomide and rituximab compared with lenalidomide and rituximab in patients who have received one line of systemic therapy, a non-quantifiable additional benefit has been identified, as the scientific evidence does not permit quantification.
• Strength of the evidence
  • The randomised, double-blind inMIND trial forms the basis of this benefit assessment.
  • The potential for bias at the study level is assessed as low overall.
  • The risk of bias at endpoint level is classified as low for overall survival.
  • For the endpoints of morbidity and quality of life, the potential for bias is classified as high, as response rates fluctuated over the course of the treatment period and, at the primary data cut-off, not all randomised patients could be analysed according to the ITT principle, but only those who had reached the end of treatment or the safety follow-up point.
  • For side effects, the potential for bias is classified as low.
  • Overall, a hint is provided about the strength of the evidence.

b) Adults with relapsed or refractory follicular lymphoma, grade 1 to 3a, following at least two lines of systemic therapy

• In summary, the additional benefit of tafasitamab is assessed as follows: a hint of a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• mortality
  • In the inMIND study, overall survival is defined as the time from randomisation to death from any cause.
  • For patient group b), there is no statistically significant difference between the treatment arms.
• Morbidity – Progression-free survival (PFS)
  • PFS, as recorded by the trial staff, is the primary endpoint of the inMIND trial and is defined as the time from randomisation to the first documented progression of the disease or to death from any cause, whichever occurs first.
  • For both patient groups a) and b), there is a statistically significant difference in favour of the tafasitamab combination compared with the control arm.
• Morbidity – Health status (EQ-5D VAS)
  • Health status is assessed in the inMIND study using the visual analogue scale (VAS) of the European Quality of Life Questionnaire 5 Dimensions (EQ-5D).
  • In patient group b), there is no statistically significant difference in health status between the study arms.
• Morbidity – EORTC QLQ-C30 symptom scales
  • In the inMIND study, disease symptoms are assessed using the symptom scales of the cancer-specific Quality of Life Questionnaire – Core Questionnaire developed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30).
  • For patient group b), there are no statistically significant differences between the treatment arms in the symptom scales.
• Quality of life – EORTC QLQ-C30 functional scales
  • In the inMIND study, health-related quality of life is assessed using the functional scales of the cancer-specific EORTC QLQ-C30 questionnaire.
  • In patient group b), there is no statistically significant difference between the study arms for any of the individual health-related quality of life scales of the EORTC QLQ-C30.
• Quality of life – FACT-Lym
  • In the inMIND study, health-related quality of life is also assessed using the lymphoma-specific Functional Assessment of Cancer Therapy – Lymphoma (FACT-Lym) questionnaire.
  • For patient group b), no statistically significant difference was found between the study arms.
• Side effects – serious AEs (SAEs), severe AEs and therapy discontinuations due to AEs
  • With regard to patient group b), the inMIND study revealed no statistically significant differences between the study arms for the endpoints SAE, severe AEs and therapy discontinuations due to AEs.
• Side effects – AEs of particular interest
  • For patient group b), the results for severe AEs (CTCAE grade ≥ 3) occurring at an incidence of ≥ 5%, there is a significant difference to the detriment of the tafasitamab combination compared with the control arm for the PT ‘febrile neutropenia’.
  • For SAE occurring with an incidence of ≥ 5%, there is a significant difference in patient group b) for the SOC ‘Gastrointestinal disorders’ in favour of the tafasitamab combination compared with the control arm.
  • Overall, no advantage or disadvantage is identified in the ‘side effects’ endpoint category for patient groups a) and b).
• Overall assessment
  • No statistically significant difference was observed between the treatment arms for the endpoint of overall survival.
  • In the morbidity endpoint category, there are no statistically significant differences between the treatment arms with regard to health status (EQ-5D VAS) and the symptom scales of the EORTC QLQ-C30.
  • With regard to quality of life, as measured using the functional scales of the EORTC QLQ-C30 and the FACT-Lym, no statistically significant differences were observed between the treatment arms.
  • With regard to the endpoint category ‘side effects’, there were no statistically significant differences between the treatment arms in the overall rates of SAE and severe AE, or in ‘therapy discontinuations due to AE’. In detail, for individual ‘side effects of particular interest’, the tafasitamab combination showed either a disadvantage or an advantage. Overall, neither an advantage nor a disadvantage can be inferred in the ‘side effects’ category.
  • Overall, for tafasitamab in combination with lenalidomide and rituximab compared with lenalidomide and rituximab in patients who have received at least two lines of systemic therapy, a non-quantifiable additional benefit has been identified, as the scientific evidence does not permit quantification.
• Strength of the evidence
  • The randomised, double-blind inMIND trial forms the basis of this benefit assessment.
  • The potential for bias at the study level is assessed as low overall.
  • The potential for bias at endpoint level is classified as low for overall survival.
  • For the endpoints of morbidity and quality of life, the potential for bias is classified as high, as response rates fluctuated over the course of the treatment period and, at the primary data cut-off, not all randomised patients could be analysed according to the ITT principle, but only those who had reached the end of treatment or the safety follow-up point.
  • For side effects, the potential for bias is classified as low.
  • Overall, a hint is provided about the strength of the evidence.

Courtesy translation only, please refer to the German original.