Symposium | Optimizing outcomes before and after CAR T-cell therapy in patients with large B-cell lymphoma

During the European Hematology Association (EHA) 2024 Hybrid Congress, the Lymphoma Hub and Multiple Myeloma Hub held a joint satellite symposium entitled: Sequencing immune-based therapies in B-cell malignancies. Here, the Lymphoma Hub is pleased to share a real-world patient case, real-world evidence and experience, and treatment optimization of chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL), presented by Ulrich Jäger, Medical University of Vienna, Vienna, AT.

Listen to the podcast here:

In this presentation, Jäger started by sharing a case study from 2009 of a 50-year-old male with complicating treatment for an underlying myeloproliferative disease (essential thrombocythemia) who later developed diffused LBCL in 2020 and was treated with axicabtagene ciloleucel (axi-cel) in second-line in 2021.^1,2 The patient is still in complete response from lymphoma after 3 years and does not need treatment for his myeloproliferative disorder. Platelet counts are still within the normal range.

Jäger then discussed real-world experiences of CAR T-cell therapy in lymphoma using EBMT registry data (Figure 1) and clinical trials (Table 1), before exploring key considerations when optimizing CAR T-cell therapy outcomes (Figure 2). 

Figure 1. CAR T-cell therapy in the EBMT registry: A) underlying diagnosis and B) academic vs commercial products* 

CAR, chimeric antigen receptor; EBMT, European Society for Blood and Marrow Transplantation.

*Data provided by Sureda A.

Table 1. Efficacy outcomes of CAR T-cells in R/R LBCL*

Axi-cel, axicabtagene ciloleucel; CAR, chimeric antigen receptor; CR, complete response; HSCT, Hematopoietic stem cell transplantation; LBCL, large B-cell lymphoma; liso-cel, lisocabtagene maraleucel; mo, month; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; R/R, relapsed/refractory; tisa-cel, tisagenlecleucel.

* Data from Jacobson CA, et al.³ Crombie JL⁴. Portuguese A⁵, Sehgal A⁶, Houot, R, et al.⁷

^†Included patients who would have been ineligible for the clinical trial;  ^‡ real-world studies;  ^§trials from patients who are ineligible for HSCT.

Figure 2. CAR T-cell therapy optimization 

Watch the presentation to learn more about:

• The safety and efficacy of lisocabtagene maraleucel (liso-cel) and axi-cel in the real world.
• Factors affecting the response to CAR T-cell therapy, such as incidence of cytopenias, inflammatory markers, and differentiated CD3⁺CD27^‑CD28^‑ T cells.
• Key considerations to optimize CAR T-cell therapy outcomes.

Key points

• A considerable proportion of patients with relapsed/refractory (R/R) LBCL treated in real-world settings are ineligible for clinical studies.^3-7
• The 2021 best practice recommendations by the EBMT, JACEI, and EHA for the management of adults and children receiving CAR T-cell therapy suggest early intervention and management strategies of cytokine release syndrome (CRS)⁸:
  • Grade 1 CRS: in the absence of improvement within 3 days and the absence of other differential diagnoses, consider tocilizumab
  • Grade 2–4 CRS: alert local intensive care unit
• Real-world experiences of axi-cel and liso-cel in second-line R/R LBCL showed that liso-cel had⁵:
  • Lower rates of any-grade CRS (88% vs 62%; p < 0.001)
  • Lower rates of any-grade ICANS (56% vs 32%; p = 0.010)
  • Fewer days with fever (median, 5 vs 2 days; p < 0.001)
  • Fewer Grade 3 CRS (2.1% [no Grade 4/5 events] vs 7.4% [2.5% Grade 4 events])
  • Numerically lower severe cytopenias  (93% vs 72%; p = 0.002)
• Barriers listed by patients in preparation for CAR T-cell therapy include access to clinical trials/registries, access to emergency treatment room, waiting time, communication between local hospital and CAR T team, and their mental and physical health.
• Real-world outcomes can be optimized at various steps of CAR T-cell therapy treatment; for example:
  • Precise patient selection criteria play a key role in improving outcomes.
  • Effective bridging ensures low tumor burden at infusion, and lymphodepletion is also associated with improved tumor microenvironment, contributing to better prediction and management of toxicity.
  • Incidence of cytopenias, inflammatory markers, and differentiated CD3⁺CD27^‑CD28^‑ T cells affects the response to CAR T-cell therapy.
  • After CAR T-cell therapy administration, management should include prediction and treatment of hematotoxicity and non-relapse mortalities.
  • Bispecific antibodies showed promising outcomes, with an overall response rate of up to 63%, with CR rates of 39% in the treatment of patients who relapse after CAR T-cell therapies.⁹

This independent educational activity was supported by Bristol Myers Squibb. All content was developed independently by the faculty.