October 19, 2022

1:30 pm / 3:00 pm

TITLE: Impact of CAR T-Cell Expansion in the First 28 Days on Clinical Outcomes

TIME: 1:30–3:00 PM

LOCATION: Conference Room X303, Medical School Office Building, 1265 Welch Road, Stanford, CA


Mark P. Hamilton (1)

Matt Frank (1,2)

David Miklos (1,2)

  1. Center for Cancer Cell Therapy, Stanford Cancer Institute
  2. Blood & Marrow Transplantation-Cell Therapy



The Data Studio Workshop brings together a biomedical investigator with a group of experts for an in-depth session to solicit advice about statistical and study design issues that arise while planning or conducting a research project. This week, the investigator(s) will discuss the following project with the group.


Chimeric antigen receptor (CAR) T-cell therapy is a new therapy that is increasingly used as second- and third-line treatment of relapsed and refractory aggressive and indolent lymphoma. CAR T-cells expand rapidly in vivo in the first 14 days post-infusion and then retract. Persistent CAR T-cells can be detected for up to 10 years post-treatment. There is limited preliminary data indicating CAR T-cell expansion is associated with increased CAR-related toxicity such as cytokine release syndrome (CRS) and immune-effector-cell-associated neurotoxicity syndrome (ICANS).  Similarly, there is limited data indicating CAR expansion may be associated with survival response.


Assessment of clinical outcomes associated with CAR T-cell expansion will represent a major advance in understanding clinical CAR T-cell function. We hypothesize that CAR T-cell expansion is associated with clinical endpoints of toxicity and survival response. The first purpose of this project is to understand the impact of CAR T-cell expansion on toxicity and survival outcomes that include: maximal CRS, maximal ICANS, duration of post-treatment neutropenia, and progression free survival.


This study is the largest analysis of clinical CAR T-cell expansion data using commercial products to date. We followed 230 patients treated with axicabtagene ciloleucel (axi-cel) or brexucabtagene autoleucel (brexu-cel) over five years, including 189 patients treated for large B-cell lymphoma (LBCL), 20 patients treated for follicular lymphoma (FL) and 21 patients treated for mantle cell lymphoma (MCL). We used flow cytometric phenotyping of CAR T-cells (CAR-FACS) to define CAR T-cell expansion in blood in the majority of patients. CAR-FACS was performed on days 7 (D7), 14 (D14), 21 (D21), and 28 (D28). At least two CAR expansion measurements were available for 140 LBCL patients, 20 FL patients and 18 MCL patients for a total of 640 measurements. Numerous pre- and post-treatment parameters are assessed for each patient including both categorical and continuous variables. A limited number of variables are shared and interpretable between the LBCL, MCL, and FL histologies.


We hope to build two models of survival after CAR in our LBCL patient population where mature survival data exists (at least six months of follow up). First, we would like to leverage the dataset to perform an unbiased analysis of factors associated with CAR T-cell outcomes. Second, we would like to focus on CAR T-cell expansion metrics on D7 and D14 as a possible early indicator of CAR T-cell expansion failure. This is clinically relevant because CAR patients with poor early expansion and worse expected outcomes could receive second infusions, or move on to an allogeneic CAR T-cell therapy.


  1. What is the best method to assess the impact of CAR T-cell expansion on endpoints of CAR T-cell toxicity?
  2. How should we perform assessment of clinical outcomes associated with progression free survival in a large cohort of CAR T-cell patients using training and validation datasets?
  3. Can CAR T-cell expansion on D7 and D14 be incorporated with other clinical parameters to predict poor outcomes associated with expansion failure?