Axi-Cel Shows Activity in Relapsed/Refractory DLBCL Regardless of Chemo Sensitivity

Data from patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene ciloleucel (axi-cel; Yescarta) showed that post-CAR T outcomes may not correlate with responsiveness observed with treatment received immediately prior, according to a presentation given during the 2021 Transplantation & Cellular Therapy Meetings.

At a median follow-up of 5.9 months (range, 0.9-31.1), the overall response rate (ORR) achieved by patients who received the CAR T-cell therapy was 63.3%, with 30% of patients experiencing a complete response (CR). As of the last follow-up, approximately half, or 55%, of all patients maintained a response to treatment, while 31.7% (n = 19) had died. Specifically, 84.2% (n = 16) died due to progressive disease.

At 1 month, response to axi-cel was strongly linked with better overall survival (OS; HR, 11.82; 95% CI, 3.72-37.54; P <.0001) and progression-free survival (PFS; hazard ratio [HR], 6.44; 95% CI, 2.46-16.87; P <.0001). Patient responsiveness to last therapy received before the CAR T-cell therapy was not found to be significantly associated with changes in either OS (P = .66) or PFS (P = .39).

Moreover, investigators did not observe differences in OS (P = .47) or PFS (P = .64) after designating patients into 2 subgroups based on response: those who did respond versus those who did not. Little difference was observed with regard to ORR between responders and non-responders, at 77.3% and 64.7%, respectively. The number of previous lines of therapy, primary refractory disease, histology, MYC/BCL2 status, pre-CAR T bridging therapy, and site of residual disease were not found to be linked with changes in survival.

Although axi-cel has demonstrated efficacy in patients with relapsed/refractory DLBCL, the association of sensitivity to pre-CAR T chemoimmunotherapy with response to the product is not currently known. To this end, investigators launched the single-institution study to compare the outcomes of patients who had chemotherapy-sensitive disease prior to CAR T-cell therapy with those with unresponsive and refractory disease.

The study included patients with DLBCL who consecutively received axi-cel. Positron emission tomography (PET) and computer tomography scans were done prior to treatment with axi-cel, 28 days after infusion, and at the time of the last follow-up. Responses were defined per the Lugano criteria. Both OS and PFS were estimated by using the Kaplan-Meier method, and hazard ratios were estimated using Cox proportional hazard models.

In total, 60 patients with relapsed/refractory disease underwent apheresis for axi-cel, 75.0% (n = 45) of whom had primary DLBCL. The remaining patients had either transformed follicular lymphoma (20.0%; n = 12), primary mediastinal large B-cell lymphoma (3.3%; n = 2), or high-grade B-cell lymphoma (1.7%; n = 1).

The median age of the participants was 62 years, with 36.7% (n = 22) of patients over the age of 65 years, and the majority of population where male (66.7%; n = 40). Additionally, 31.7% (n = 19) of patients received more than 3 prior lines of therapy, and 70.0% (n = 42) received treatment for primary refractory disease. More than half (56.7%; n = 34) of all patients received a bridging therapy prior to undergoing CAR T-cell infusion and 26.7% (n = 16) of patients had previously received a stem cell transplant. Moreover, 35% of patients had received a novel drug prior to CAR T-cell infusion, and 36.7% of patients responded to their last therapy prior to axi-cel.

When evaluating response to the CAR T-cell therapy at PET-1, 30.0% (n = 18) of patients experienced a CR, 33.3% (n = 20) achieved a PR, and 15.0% (n = 9) had disease stability. Fifteen percent (n = 9) of patients experienced progressive disease.

At a median follow-up of 4.78 months (95% CI, 0.96-31.1), the time of the last follow-up, 35.0% of patients (n = 21) had a CR and 20.0% had a partial response (PR; n = 12). Additionally, 3.3% of patients (n = 2) achieved stable disease, while 8.3% (n = 5) experienced progressive disease. At this time, 33.3% (n = 20) of patients were deceased.

Investigators reported an incidence rate of 10% for grade 3/4 cytokine release syndrome (CRS) and 16.7% for grade 3/4 immune effector cell-associated neurotoxicity syndrome. In total, 76.7% of patients (n = 46) experienced CRS with axi-cel, 51.7% (n = 31) experienced central nervous system toxicity, and 48.3% (n = 29) experienced both.

Based on these findings, investigators concluded that these data support the use of CAR T-cell therapy in patients with refractory and unresponsive lymphoma, provided that they are otherwise eligible for treatment.

_Reference:

_{Iovino L, Wu V, Voutsinas J, et al. Non-responsiveness to immediate pre CAR-T treatment does not preclude response to axicabtagene ciloleucel in relapsed and refractory aggressive B cell lymphomas. Poster presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; Virtual. Poster 416.}