Value of Reducing Wait Times for Chimeric Antigen Receptor T-Cell Treatment: Evidence From Randomized Controlled Trial Data on Tisagenlecleucel for Diffuse Large B-Cell Lymphoma

Value Health. 2022 Aug;25(8):1344-1351. doi: 10.1016/j.jval.2022.02.007. Epub 2022 Mar 24.

Abstract

Objectives: This study aimed to quantify the value of reducing chimeric antigen receptor T-cell (CAR-T) treatment wait times on patients with refractory and relapsed aggressive blood cancer who can newly gain access to treatment or access treatment earlier in their disease course.

Methods: Using data from the JULIET clinical trial, we first identified the number of additional patients with diffuse large B-cell lymphoma that would have been treated with tisagenlecleucel CAR-T therapy if wait times were shortened. For these patients, we estimated mortality benefits using literature estimates of CAR-T effectiveness. Next, among patients who already received CAR-T, we estimated tumor burden progression over time using a linear probability regression model. The primary outcome variable was an indicator for having above-normal lactate dehydrogenase, and we controlled for time, use of bridging therapy, and time-invariant patient characteristics. The regression results, along with literature estimates relating lactate dehydrogenase to CAR-T effectiveness, were used to compute the survival benefits of earlier CAR-T treatment.

Results: Reducing wait times by 2 months increased the number of eligible patients receiving CAR-T by at least 10.7%. For patients already receiving tisagenlecleucel CAR-T, a 2-month reduction in wait times generated a 3.3% increase in survival gains per treated patient. Thus, among patients seeking treatment, the combined treatment efficacy increased by 14%, with approximately one-quarter of survival benefits accruing to existing patients receiving faster treatment.

Conclusions: Delays affected not only access to CAR-T treatments but also treatment effectiveness. Our results highlight the survival benefits of expediting treatment access and may help explain some observed differences in CAR-T effectiveness across countries.

Keywords: access; chimeric antigen receptor T-cell therapies; survival gains; treatment efficacy; wait time.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lactate Dehydrogenases
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Neoplasm Recurrence, Local
  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen* / therapeutic use
  • T-Lymphocytes / pathology
  • Waiting Lists

Substances

  • Receptors, Antigen, T-Cell
  • Receptors, Chimeric Antigen
  • Lactate Dehydrogenases
  • tisagenlecleucel