Tandem Meetings Recap: T-Cell Efficacy and Safety Updates in Lymphoma

Hematologic oncologists from around the world convened in Salt Lake City, Utah, to attend the 2026 Tandem Meetings. Therein, presenters shared key data on CAR T-cell therapy use in patients with non-Hodgkin lymphoma (NHL), particularly regarding its impact on cardiovascular (CV) risk, efficacy in the real-world setting and among younger patients, and in CD19-negative groups.

Which CAR T Therapy is Optimized for Cardiovascular Risks?

In an oral presentation of the CARTiAC trial, Mohammad Alhomoud, MBBS, discussed findings from a propensity core-matched analysis comparing the CV safety of lisocabtagene maraleucel (Breyanzi; liso-cel) with axicabtagene ciloleucel (Yescarta; axi-cel) in patients with NHL, wherein the former exhibited a more favorable CV profile.¹

Specifically, the findings showed that among 906 patients treated with CAR T-cell therapies, including 535 who received axi-cel and 176 who received liso-cel, the overall incidence of cardiovascular events (CVEs) was 9% in the total population and 8% vs 4% among the axi-cel and liso-cel groups. Moreover, the unadjusted OR of developing a CVE with liso-cel compared with axi-cel was 0.29 (95% CI, 0.09-0.76; P = .023), and with propensity-score matching, the OR was 0.19 (95% CI, 0.06-0.46; P < .001). The most common CVE with axi-cel vs liso-cel was atrial arrhythmia (36% vs 43%).

Furthermore, between the overall cohort and those who experienced CVEs, the incidence of grade 1 to 2 cytokine release syndrome (CRS) was similar (68% vs 65%), but the incidence of grade 3 or 4 CRS was numerically larger in those who experienced a CVE (8.8% vs 26%). CVEs also correlated with lower overall survival (OS) among patients receiving CAR T-cell therapies, with 12- and 24-month OS rates of 63% (95% CI, 48%-82%) vs 73% (95% CI, 66%-79%) and 47% (95% CI, 30%-75%) vs 61% (95% CI, 54%-69%) between those who did and did not experience CVEs by day 30 of treatment (P <.001).

Patients receiving CAR T cells were selected across 6 international centers and underwent monitoring for CVEs by a cardiologist. After CVEs were captured and adjudicated, propensity score matching was done between products. The primary end point of the study was to compare CV safety across approved CD19 CAR T-cell products in NHL.

Notably, patients in the axi-cel and liso-cel arms had a median age of 62 years (IQR, 52-69) and 73 years (IQR, 65-78), respectively. Most patients were male (62% vs 61%), had a Karnofsky performance score of less than 90 (56% vs 71%), and had large B-cell lymphoma (LBCL; 92% vs 92%).

In each arm, 51% vs 54% had 1 to 2 CV risk factors, and 14% vs 20% had 3 or more. The most common CV risk factors in both arms were hypertension, smoking, and diabetes.

“In this largest multicenter international cohort to date, enriched with real-world patients with preexisting CV risk factors, CD19 CAR T-cell products demonstrate distinct CV safety profiles with respect to incidence, timing, and type,” Alhomoud, a bone marrow transplant and cellular therapist at Memorial Sloan Kettering Cancer Center, concluded.

Ascertaining CAR T Outcomes in Younger Patients in the Real World and Clinical Trials

A separate poster, presented by Irtiza N. Sheikh, DO, explored outcomes among patients with relapsed/refractory LBCL receiving liso-cel in the clinical trial and real-world settings, as well as among patients younger than 50 and those 50 years and older.² Overall, the findings revealed that efficacy outcomes were similar in both settings, and that younger patients experienced a more pronounced efficacy benefit with the CAR T-cell therapy.

Specifically, in the real-world setting among patients younger than 50 years vs the overall population, the objective response rates (ORRs) were 72% (95% CI, 60%-81.5%) vs 81% (95% CI, 79%-84%), with respective complete response (CR) rates of 68% (95% CI, 56%-78%) vs 72% (95% CI, 69%-75%). Moreover, in the clinical trial setting, the respective ORRs were 65% (95% CI, 55%-75%) vs 74% (95% CI, 70%-78%), with CR rates of 49% (95% CI, 38%-60%) vs 55% (95% CI, 50%-59%).

Furthermore, in the real-world setting, the 12-month progression-free survival (PFS) rates among those younger than 50 vs the overall cohort were 58% (95% CI, 45%-69%) vs 52% (95% CI, 49%-55%). In the clinical trial setting, the 18-month PFS rates were 44.5% (95% CI, 34%-55%) vs 40% (95% CI, 35.5%-44%) in the respective groups.

Regarding OS, the 12-month rates in the real-world setting were 73% (95% CI, 61%-82%) and 68% (95% CI, 65%-71%) in the younger than 50 and overall populations. The respective 18-month rates were 66% (95% CI, 55%-75%) vs 57% (95% CI, 52%-61%) in the clinical trial setting.

In the real-world setting, CRS events occurred in 58% of the younger population and 51% of the overall population, and neurological events, including immune effector-cell neurotoxicity syndrome (ICANS), occurred in 28% vs 27%. Among those treated in the clinical trial setting, 52% of those younger than 50 and 43% of all patients experienced CRS, and 26% vs 24% experienced neurological events. Most CRS and neurological events were grade 1 or 2 in both settings.

Patients were included on the study of they received liso-cel for relapsed/refractory LBCL in the real world or within a clinical trial setting. Those from clinical trials including TRANSCEND NHL 001(NCT02631044), OUREACH (NCT03744676), TRANSCEND WORLD (NCT03484702), and TRANSFORM (NCT03575351) were included in the cross-trial analysis. In both settings, ORR, CR rates, duration of response (DOR), PFS, and OS were assessed in addition to adverse effects (AEs) of special interest and non–relapsed mortality rates.

“Efficacy outcomes were similar to the overall population in both settings despite some high-risk features being more prevalent in younger populations,” Sheikh, assistant professor in the Department of Pediatrics - Patient Care, Stem Cell Transplantation and Cellular Therapy Section of the Division of Pediatrics at The University of Texas MD Anderson Cancer Center, wrote in the presentation with study coinvestigators. “Responses were deep and durable in younger patients from the real-world and clinical trial settings, with 12-month and 18-month DOR rates of 80% and 61.5%, respectively.”

Does CD19 Status Impact the Efficacy of CD19-Targeted CAR T Therapies?

In another poster, presented by Chen Zhang, MD, MS, FACP, a third-year Hematology/Oncology fellow at Rush MD Anderson Cancer Center, a real-world study explored the activity of an autologous anti-CD19 CAR T-cell therapy among patients with CD19-negative LBCL.³ Findings from within suggest that similar efficacy and a lower incidence of ICANS was observed in the CD19-negative population compared with those with CD19-positive status, supporting its use in both populations.

Efficacy data showed that among those in the CD19-positive (n = 174) and CD19-negative groups (n = 37), the ORR was 60.0% vs 51.7% (P = .41), and the respective CR rates were 51.1% vs 37.9% (P = .20). Furthermore, the 2-year estimates for PFS and OS were 30.1% vs 30.6% (P = .55) and 45.7% vs 44.4% (P = .84).

Additionally, regarding safety, similar rates of CRS (73.0% vs 67.6%; P = .5047) and severe CRS were observed (8.0% vs 5.4%; P = .7435). By contrast, a significantly higher incidence of any-grade ICANS (43.1% vs 21.6%; P = .0151) and severe ICANS (28.7% vs 5.4%; P = .0015) was observed in the CD19-expressing population. Severe cytopenia was numerically higher in the CD19-posiitve group (54.0% vs 40.0%), but it did not reach statistical significance (P = .2437).

The retrospective analysis collected data from the Cell Therapy Consortium on adult patients with LBCL treated with an anti-CD19 CAR T-cell therapy and no prior CD19-targeting therapy. The study explored CD19 pretreatment status on activity and measured ORR, CR rate, OS, PFS, and safety as measured by rates of CRS, ICANS, and cytopenia.

The median patient age in the CD19-positive and CD19-negative groups was 63.0 years and 62.0 years. Most patients were male (65.5% vs 64.9%), received axi-cel (56.9% vs 48.6%), and had diffuse LBCL or high-grade B-cell lymphoma (88.5% vs 97.3%). The median number of prior lines in each arm was 3, and 69.0% vs 73.0% had refractory disease.

“Similar efficacy of anti-CD19 CAR T [cells] was found in CD19-negative LBCL. Our findings support the use of anti-CD19 CAR T-cell therapy in CD19-negative LBCL, as determined by immunohistochemistry [IHC] or flow cytometry,” Zhang wrote in the poster with study coauthors. “Future larger studies with more sensitive CD19 measurement are warranted.”

References

1. Alhomoud M, Al Wahad AA, Brown S, et al. CARTiAC: Comparative cardiovascular safety of CAR T products for non-Hodgkin’s lymphoma – a propensity score–matched international multicenter study. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 17.
2. Sheikh IN, Patel K, Perales MA, et al. Clinical outcomes of lisocabtagene maraleucel (liso-cel) in YOUNGER PATIENTS (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 210.
3. Zhang C, Sun X, Feng L, et al. Activity of autologous Anti-CD19 chimeric antigen receptor T-cell therapy in CD19-negative large B-cell lymphoma: a cell therapy consortium real world experience. Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 514.