Lisocabtagen maraleucel (2) – Breyanzi®

• Clinical trials
  • In the ongoing, open-label Phase III TRANSFORM trial, Liso-Cel is being compared with induction therapy using R-GDP, R-ICE or R-DHAP, followed by high-dose therapy (HDT) with autologous stem cell transplantation (autoSCT).

a) Adults with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and grade 3b follicular lymphoma (FL3B), who are eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion

• On balance, the G-BA concludes that, primarily due to the clearly positive effect in terms of preventing the failure of curative treatment, Liso-Cel is indicated for the treatment of patients with DLBCL, HGBCL, PMBCL and FL3B who are eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion, Liso-Cel offers considerable additional benefit compared with induction chemotherapy with R-GDP, R-ICE or R-DHAP followed by high-dose therapy with autologous stem cell transplantation.
• The certainty of evidence for the observed additional benefit is therefore classified as ‘hint ’.
• mortality
  • Overall survival was defined as the time from randomisation to death from any cause. No statistically significant difference was observed between the treatment arms.
  • There is an effect modification for the characteristic of age (< 65 years vs. ≥ 65 years). For patients < 65 years, there is a statistically significant difference in favour of Liso-Cel, whereas no statistically significant difference is observed for patients ≥ 65 years.
• Morbidity – Failure of the curative treatment approach
  • To illustrate the failure of the curative treatment approach, the event-free survival (EFS) endpoint from the TRANSFORM study is used as an approximation.
  • There is a statistically significant difference in favour of Liso-Cel in both operationalisations. However, there are differences in the extent of the effect between the event rate and EFS operationalisations, with a greater effect observed in the event time analysis.
  • Taking both operationalisations into account, the advantage in terms of the failure of the curative therapeutic approach is assessed overall as a significant improvement for the patient group in question.
• Morbidity – Symptoms
  • The pharmaceutical manufacturer presents in the dossier analyses of symptoms recorded using the symptom scales of the EORTC-QLQ-C30 questionnaire and the FACT-LymS questionnaire; however, it does not use these analyses to derive the additional benefit.
  • The reasons for the missing values cannot be clearly deduced from the study documents and the information in the dossier.
  • Consequently, there are no suitable data available on symptoms as a whole.
• Morbidity – Health status
  • Health status was assessed in the TRANSFORM study using the Visual Analogue Scale (VAS) of the EQ-5D.
  • As the response rates were already below 70% at the start of the study, no suitable data are available for the health status endpoint.
• Health-related quality of life
  • Quality of life was assessed in the TRANSFORM study using the functional scales of the EORTC-QLQ-C30 questionnaire.
  • As the response rates were already < 70 % at the start of the study, no suitable data are available for quality of life.
• Side effects
  • In the TRANSFORM study, adverse events were monitored for up to 90 days following infusion of Liso-Cel or the last dose of chemoimmunotherapy, or until the start of subsequent antineoplastic therapy, whichever occurred first.
  • There was no statistically significant difference between the study arms in the overall rate of serious AEs (SAEs) and severe AEs with a CTCAE grade of ≥ 3.
  • There was no statistically significant difference between the study arms for the endpoint of discontinuation due to AEs.
  • With regard to specific AEs, there was a statistically significant benefit of Liso- for the endpoints of diarrhoea, mucositis, gastrointestinal disorders (SAE), acute kidney injury (SAE), general disorders and administration site conditions (severe AEs with a CTCAE grade ≥ 3; including PT mucositis) as well as febrile neutropenia and thrombocytopenia (each a severe AE with a CTCAE grade ≥ 3), Liso-Cel showed a statistically significant advantage.
  • For the specific AEs ‘decreased neutrophil count’, ‘neutropenia’ and ‘lymphopenia’ (each a severe AE with a CTCAE grade ≥ 3) as well as cytokine release syndrome (including serious cytokine release syndrome), Liso-Cel showed a statistically significant disadvantage.
  • For the endpoints of neurological toxicity (including severe neurological toxicity) and severe infections, there are no statistically significant differences between the treatment arms.
• Overall assessment
  • No statistically significant difference was observed between the treatment arms for overall survival.
  • In the morbidity endpoint category, a statistically significant difference in favour of Liso-Cel was observed for the endpoint ‘failure of curative treatment’, which is regarded as a marked improvement. With regard to symptoms (assessed using the EORTC-QLQ-C30 and FACT-LymS) and health status (assessed using the EQ-5D-VAS), no suitable data are available due to an excessively high proportion of missing values. This also applies to the data on health-related quality of life (assessed using the EORTC-QLQ-C30).
  • With regard to side effects, there are no statistically significant differences for serious side effects, severe side effects or the endpoint of discontinuation due to side effects. In detail, both advantages and disadvantages of Liso-Cel are evident for specific side effects, although the advantages outweigh the disadvantages.

b1) Adults with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL) and grade 3b follicular lymphoma (FL3B) who are not eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion

• An additional benefit is not proven.

b2) Adults with primary mediastinal large B-cell lymphoma (PMBCL) who are not eligible for high-dose therapy and who relapse or are refractory to first-line therapy within 12 months of its completion

• An additional benefit is not proven.

Courtesy translation only, please refer to the German original.