What is the comparative efficacy of Chimeric Antigen Receptor T (CAR-T) cell products in treating follicular lymphoma?

From the Guidelines

CAR-T cell therapy is a highly effective treatment for follicular lymphoma, with axicabtagene ciloleucel and tisagenlecleucel demonstrating significant response rates, although the most recent and highest quality study 1 suggests that axicabtagene ciloleucel may have a higher complete response rate of approximately 54% and overall response rate of 82% in relapsed/refractory disease.

Key Points

• Axicabtagene ciloleucel has shown promising efficacy in treating follicular lymphoma, with complete response rates of approximately 54% and overall response rates of 82% in relapsed/refractory disease 1.
• Tisagenlecleucel has also demonstrated significant response rates, although the exact rates are not specified in the provided evidence.
• The high efficacy of CAR-T therapy in follicular lymphoma is attributed to the strong expression of CD19 on malignant B-cells, which these products target.
• Treatment selection should consider potential side effects, including cytokine release syndrome and neurotoxicity, which vary in frequency and severity among products.
• Patient factors, such as disease burden, prior therapies, and comorbidities, should guide product selection, as these may influence both efficacy and safety profiles.

Comparison of CAR-T Products

• Axicabtagene ciloleucel and tisagenlecleucel are both anti-CD19 CAR T-cell therapies FDA-approved for the treatment of adult patients with relapsed/refractory DLBCL, high-grade B-cell lymphomas, and TFL.
• The choice between these products should be based on individual patient factors and the potential side effects associated with each therapy.
• The most recent and highest quality study 1 suggests that axicabtagene ciloleucel may be a preferred option for patients with relapsed/refractory follicular lymphoma, due to its high complete response rate and overall response rate.

From the FDA Drug Label

Of the 90 patients included in the primary efficacy analysis, 40 patients (45%) were treated with bridging therapies. The most commonly used agents (in ≥ 5% of patients) were rituximab (22%), dexamethasone (13%), gemcitabine (12%), prednisone (11%), oxaliplatin (8%), etoposide (8%), and vincristine (6%) Of 98 patients who were enrolled and underwent leukapheresis, 97 patients received infusion with KYMRIAH and one patient without measurable disease did not receive KYMRIAH. There were no manufacturing failures for the 98 enrolled patients Of the 97 patients infused with KYMRIAH, the efficacy evaluable population, as specified in the protocol, included the first 90 patients with measurable disease who received KYMRIAH consecutively and had at least 9 months follow-up from first objective response or discontinued earlier Among the 90 patients with FL included in the efficacy analysis, the median age was 58 years (range, 29 to 73 years), 31% were female, 78% were White, 10% were Asian, and 1% were Black or African American. The median number of prior therapies was 4 (range, 2 to 13), with 24% receiving 2 prior lines, 21% receiving 3 prior lines, and 54% receiving ≥4 prior lines Eighty-seven percent had Stage III-IV disease at study entry, 64% had bulky disease, 36% had a prior autologous HSCT, 79% were refractory to the most recent regimen, and 66% had progression within 24 months of initiating their first anti-CD20 combination therapy (POD24) Efficacy was established on the basis of objective response rate and duration of response (DOR) as determined by an independent review committee (Table 14 and Table 15). The first disease assessment was scheduled to be performed at Month 3 post-infusion; the median time to first response was 2.9 months (range, 0.6 to 6. 0 months). All responders achieved their response (complete response [CR] or partial response [PR]) at the first performed post-infusion disease assessment. Table 14. Response Rates in Patients with Relapsed or Refractory FL ResponsePrimary efficacy populationN = 90All leukapheresed patientsN = 98 Overall response rate (ORR), n (%)(95% CI) 77 (86%)(76.6,92.1)84 (86%)(77.2,92.0) Complete response rate (CRR)a,b, n (%)(95% CI)61 (68%)(57.1,77.

The efficacy of tisagenlecleucel in follicular lymphoma is as follows:

• Overall response rate (ORR): 86% (95% CI: 76.6,92.1)
• Complete response rate (CRR): 68% (95% CI: 57.1,77)
• Median time to first response: 2.9 months (range, 0.6 to 6.0 months) There is no direct comparison of car-t products efficacy in follicular lymphoma in the provided drug labels, as only one product, tisagenlecleucel, is described. 2 2

From the Research

CAR-T Products Efficacy in Follicular Lymphoma

• The efficacy of CAR-T cell products, such as axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel, has been studied in the treatment of follicular lymphoma 3, 4, 5, 6.
• Axicabtagene ciloleucel has shown high rates of durable responses and a manageable toxicity profile in heavily pre-treated patients with relapsed or refractory follicular lymphoma 3.
• Tisagenlecleucel has also demonstrated high overall response rates and complete response rates in patients with relapsed or refractory follicular lymphoma 5.
• A systematic review and meta-analysis of the three CAR-T cell products found that all three products showed promising results in patients with different pathological subtypes and clinical characteristics, with overall response rates of nearly 70% or above and complete response rates of more than 50% 4.
• However, high rates of severe immune effector cell-associated neurotoxicity syndrome and life-threatening cytokine release syndrome were observed in patients undergoing axicabtagene ciloleucel and tisagenlecleucel treatment, respectively 4.

Comparison of Axicabtagene Ciloleucel and Tisagenlecleucel

• A retrospective study compared the safety and efficacy of axicabtagene ciloleucel and tisagenlecleucel in patients with relapsed/refractory large B-cell lymphoma, including follicular lymphoma 7.
• The study found that both products had comparable efficacy, but axicabtagene ciloleucel was associated with more toxicity, including cytokine release syndrome and neurologic events 7.
• The median progression-free survival and overall survival were similar between the two products, with 12-month progression-free survival rates of 41% and 33% for axicabtagene ciloleucel and tisagenlecleucel, respectively 7.

Overall Efficacy of CAR-T Cell Therapy in Follicular Lymphoma

• CAR-T cell therapy has emerged as an efficacious treatment for relapsed or refractory follicular lymphoma, particularly for patients with early relapse and refractory to alkylating agents and anti-CD20 monoclonal antibodies 6.
• The treatment has shown a high rate of durable responses in a high proportion of patients, with overall response rates and complete response rates comparable to those observed in clinical trials 5, 6.