Single Institution Real Life Experience with Chimeric Antigen Receptor Therapy in Agressive B-Cell Lymphomas

Background

Chimeric Antigen Receptor Therapy (CAR-T)is a cellular-based therapy used to augment immune responses to treat hematologic malignancies (1). It is a novel therapy which involves targeting the CD-19 antigen on B-cells with autologous derived chimeric antigen receptor (CAR) cells (1). As of June 2024, six CAR-T cell therapies have been approved, demonstrating unprecedented efficacy in patients with B-cell malignancies and multiple myeloma (2). Despite this, the utility of CAR-T has been limited for several reasons including associated toxicities and adverse events following CAR-T administration. These primarily include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (3). In addition, other barriers to CAR-T include cost, time from collection to manufacturing, and patient hesitation given novelty. In addition, travel time to authorized (usually academic) treatment centers, absence of caregiver support, and timely patient selection by referring oncologists also poses barriers to access (4). In this case series, we assess real life outcomes, safety and efficacy of administering autologous anti CD19 CAR T cells to patients with advanced CD19+ B-cell malignancies presenting to a single community center.

Patients and Methods

We performed a retrospective analysis of patients treated with CAR-T at our center. Between December 2022 and May 2024, we treated 10 patients with advanced B-cell malignancies. Half were male and half were female. The average age at treatment was 67 and all patients treated were Caucasian. 6 patients had Diffuse Large B-cell Lymphoma (DLBCL), 3 had Follicular lymphoma (FL) transformed to DLBCL and one had Mantle Cell lymphoma (MCL). 5 patients had progressed past 3 lines of therapy and 3 had previously received a stem cell transplant. There were 2 patients who only had 1 prior line of therapy. Response was defined radiographically using Lugano criteria, at 3 months and at 6 months post therapy.

Results

Of 10 patients, 6 had achieved complete response (CR) at <90 days post therapy. One had progressive disease and one had a mixed response. As of July 31, 2024, 5 patients continue to have durable CR with a median of 260 days post CAR-T. 3 patients are in relapse while one patient is deceased. The last patient has not yet received a 3-month PET scan follow up hence their status is unknown.

Acute toxicities including CRS and ICANS were seen. Virtually all patients developed CRS within 1-3 days of infusion which lasted an average of 4.2 days. All patients received Acetaminophen as soon as they developed a fever. Maximum CRS grade peaked at grade 2 for all patients. One patient was an outlier who did not develop CRS until approximately 11 days post infusion (after initial discharge). Coincidentally, this patient never achieved CR at all and was deceased 187 days post CAR-T due to lymphomatous meningitis. 6 out of 10 patients developed ICANS with a maximum grade of 3 and average duration of 3.1 days. The lowest ICE score seen was 3. Half of our cohort was readmitted within 30 days. Reasons for readmission included: CRS symptoms, ICANS symptoms and pain. The median number of days between initial evaluation and apheresis was 28 days, and the median number of days between apheresis and CAR-T infusion was 25 days. Virtually all patients had successful collection of T cells except for 1 who had an initial failed process.

Conclusion

Our single center experience showed an overall response rate of 75% within the first three months following CAR-T. The durable CR rate was 50% at a median of 260 days post CAR-T. Virtually all our patients experienced side effects of CRS or ICANS. However, prompt recognition helped minimize severity. More data is still needed to explore if presenting disease burden, previous number of therapy lines and degree of CRS or ICANS plays any role in duration of response. In addition, pricing of CAR therapy and availability of caregiver support poses an important ethical challenge. In our single center experience, barriers to access may disproportionately impact racialized, marginalized, and low socioeconomic groups, as well as those lacking caregiver support.

No relevant conflicts of interest to declare.