Better Outcomes Observed With CAR T-Cell Therapy in Younger Patients With R/R DLBCL

Chimeric antigen receptor (CAR) T-cell therapy lead to poor overall survival (OS) outcomes it patients who were 75 years or older with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) compared with patients aged 70 to 74 years, but progression-free survival was comparable between the 2 groups, according to results from a real-world analysis.

The primary objective of this study was to evaluate the efficacy and safety of CAR T cells in patients with relapsed/refractory DLBCL who are 70 years old or older. The retrospective analysis enrolled patients who were treated with either axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) at 5 academic medical centers in the United States. Patients were divided to 2 groups by age, including those aged 70 to 74 years old and those who were 75 years or older.

For this analysis, investigators collected baseline patient demographics, tumor characteristics, and CAR-T infusion data, then calculated the cumulative illness rating score (CIRS) and the hematopoietic cell transplantation-specific comorbidity index (HCT-CI).

The median PFS was among patients between the ages of 70 and 74 was 12 months compared with 9.4 months in those who were 75 years of age or older. The difference was P = 0.22, which was not significant. PFS was improved with the use of axi-cel in patients with transformed lymphomas (HR, 0.07; P<.001). LDH above the upper limit of normal prior to infusion was associated with a worse PFS (HR, 6.5; P<.001), and this group also was associated with a worse OS (HR, 7.4; P =.001).

The median OS was not reached in the 70 to 74 age group and was 7.8 months for the 75 year or older group, showing a difference of P = 0.049.

In the analysis, CIRS scores of 6 or greater, (OR, 3.92; P =.002), as well as axi-cel (OR, 44.9; P =.006) were associated with grade 3/4 cytokine release syndrome (CRS). Patients 75 years or older were also associated with grade 3/4 CRS (OR, 6.1; P =.003), as well as CIRS of 6 or greater (OR, 3.92; P =.04) and the use of axi-cel as treatment (OR, 44.9; P <.0001).

A worse OS was observed among those who were aged 75 years or older, but investigators did not see a difference in PFS among these patients compared to the younger group in the analysis.

Overall, higher CIRS appeared predictive of more grade 3/4 CIRS and ICANS, according to this analysis. LDH above the upper limit of normal prior to CAR T-cell infusion appeared to be associated with a worse PFS and OS in these patients.

In the younger group, the ECOG performance status was 0 in 10 patients (21.3%), 1 in 33 patients (70.2 %) or 2 or greater in 4 patients (8.5%), while the status in the older age group was 0 in 6 patients (21.4%), 1 in 18 patients (64.3%), and 2 or greater in 4 patients (14.3%). Seventeen patients (36.3%) in the younger age group had transformed from indolent lymphoma compared with 9 patients (30%) in the older age group. The cell of origin in the younger versus older age groups was GCB in 25 (53/2%) versus 15 (50.0%), ABC in 16 (34.0%) versus 11 (36.7%), and unknown in 6 (12.8%) versus 4 (13.3%), respectively.

Nine patients in the younger group (19.1%) were double- or triple-hit versus 3 patients (10%) in patients 75 years or older. The median number of prior lines was 2 (range, 2-9) in the younger group and 3 (range, 2-6) in the older group, and 11 patients (23.4%) between the ages of 70 and 74 years had received prior autologous stem cell transplant versus 2 patients (6.7%) in the older group. Fourteen patients (29.8%) had a bridging therapy in the younger group versus 15 patients (50.0%) in the older group and the median number of days between T cell collection and infusion was 28 days (range, 22-52) in the younger group versus 33 days (range, 22-63) in the older group. Forty patients (85.1%) received axi-cel and 7 patients (14.9%) received tisa-cel in the younger arm, compared with 21 patients (70.0%) and 9 (30.0%) in the older arm, respectively.

CAR T-cell therapy has revolutionized the treatment landscape for patients with relapsed/refractory DLBCL, according to the study authors. The 2 CAR T-cell agents in this real-word study were approved by the FDA based on the ZUMA-1 study (axi-cel) and the JULIET study (tis-cel). CAR T cells have now become the standard of care for patients with relapsed/refractory DLBCL.

On criticism regarding CAR T-cell therapy is that much is unknown about it’s efficacy and toxicity in patients who are over the age of 70. To some extent, question were answered with this real-world data.

Reference

Fitzgerald L, Kittai A, Nastoupil LJ, et al. Real-world outcomes of elderly patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) treated with chimeric antigen receptor T-cell (CAR-T) therapy. J Clin Oncol 38: 2020 (suppl; abstr 8039). doi: 10.1200/JCO.2020.38.15_suppl.8039