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ASH 2018 | Real-world efficacy and safety outcomes with axi-cel in patients with relapsed/refractory large B-cell lymphoma comparable to the ZUMA-1 clinical trial

Dec 3, 2018

On Saturday 1 stDecember 2018, an oral abstract session took place at the 60 thAmerican Society of Hematology (ASH) Annual Meetingin San Diego, CA. During Session 627(Aggressive lymphoma - results from retrospective/observational studies: outcomes with CD-19 CAR‑T therapy and checkpoint blockade in the real world setting) Abstract 91was presented by Loretta J. Nastoupil, University of Texas MD Anderson Cancer Center, Houston, TX.

The study evaluated the real-world outcomes of patients treated with standard of care axicabtagene ciloleucel (axi-cel) under the commercial Food and Drug Administration (FDA) label. Data from 17 US academic centers were retrospectively analyzed.

All patients leukapheresed as of 31 stAugust 2018 (N = 295), with the intention to manufacture commercial axi-cel, were included in the analysis. Of the 295 patients, 274 patients received conditioning chemotherapy and were infused with axi-cel. Median time from leukapheresis to start of conditioning chemotherapy was 21.5 days. Of the 21/295 patients who were not infused with axi‑cel: 7 patients went on to receive axi-cel therapy on the ZUMA-9 expanded access trial ( NCT03153462) due to non-conforming cell therapy product, 12 patients died secondary to lymphoma, 1 patient had non-measurable disease, and 1 patient experienced infection.

Baseline characteristics

Median age was 60 years (range 21–83) with 96 (33%) patients aged ≥ 65 years old and 65% of patients were male. Performance status (PS) was ECOG 0–1 (81%), ECOG 2 (15%) and ECOG 3–4 (4%). By histology, 68% of patients had diffuse large B-cell lymphoma (DLBCL), 26% had transformed follicular lymphoma (tFL), and 6% had primary mediastinal B-cell lymphoma (PMBCL). Seventy-five percent of patients had received > 3 prior therapies, 35% of patients were primary refractory, 42% of patients were refractory to second line or later, and 33% of patients had relapsed post-autologous stem cell transplant (ASCT).

Bridging therapy between apheresis and infusion was given in 158 (55%) patients, the majority of which consisted of chemotherapy. In total, 43% of patients in this analysis would not have met the eligibility criteria for the ZUMA-1 study at the time of leukapheresis. Common criteria that would have made these patients ineligible for ZUMA-1 included platelets < 75 (n = 13), active deep vein thrombosis/pulmonary embolism (n = 9), prior CD-19 or CAR-T therapy (n = 8), glomerular filtration rate < 60 (n = 8), a history of CNS lymphoma (n = 8), symptomatic pleural effusion (n = 4), left ventricular ejection fraction < 50% (n = 4) and prior allogeneic transplant (n = 2).

Real-world safety results

  • Cytokine release syndrome (CRS; Lee criteria used for grading) occurred in 240/274 (92%) patients, with Grade ≥ 3 CRS experienced by 18 (7%) patients. The median time to CRS onset was 3 days
  • Neurological toxicity (NT) occurred in 181/274 (69%) patients, with Grade ≥ 3 NT experienced by 85 (33%) patients. The median time to onset of NT was 6 days
  • Tocilizumab was administered in 63% of patients and 55% received corticosteroids
  • Grade 5 adverse events (AEs) occurred in 7/274 (3%) patients
  • Treatment-related deaths: 2/274 (1%) patients
  • Deaths due to non-relapse mortality: 7 patients (n = 5 infection; n = 1 hemophagocytic lymphohistiocytosis; n = 1 cerebral edema)
  • Median hospital stay was 14 days with 85 (32%) patients requiring admission to the intensive care unit (ICU).

Real-world efficacy results

  • Median follow-up: 3.9 months
  • Of the 238 patients evaluable at Day 30, overall response rate (ORR) was 80% with 47% complete response (CR)
  • Of the 248 patients evaluable at Day 90, best ORR was 81% with 57% CR
  • 60 (81%) patients with a CR at Day 30 maintained their response at Day 90
  • 22 (37%) patients with a partial response at Day 30 achieved a CR by Day 90
  • The majority of patients who had stable disease at Day 30 experienced disease progression by Day 90 (7/9 patients [78%])
  • Covariates NOTassociated with ongoing CR at Day 90: age, disease histology, lymphoma subtype, double-/triple-hit, high risk International Prognostic Index (IPI), bridging therapy, tocilizumab/steroid use, ICU admission.
  • Covariates associated with ongoing CR at Day 90:
    • Female (39 [72%] patients) vsmale (50 [51%] patients) sex, P= 0.009
    • ECOG 0–1 (82 [62%] patients) vsECOG ≥ 2 (7 [35%] patients), P= 0.024
    • Relapsed (27 [79%] patients) vsprimary refractory/refractory (24 [47%] / 38 [56%] patients), P= 0.011
    • Non-bulky (76 [62%] patients) vsbulky (≥10 cm; 13 [42%] patients), P= 0.040
    • Met eligibility for ZUMA-1 (62 [65%] patients) vsnot (27 [47%] patients), P= 0.037
  • With a median follow-up of 3.9 months, median progression-free survival was 6.18 months (95% CI, 4.57–NA) and 6-month overall survival estimate was 72% (95% CI, 65–80%)


  • This multicenter retrospective study delineated the real-world outcomes of axi-cel CAR T-cell therapy for relapsed/refractory aggressive B-cell lymphoma when used as a standard of care.
  • Although limited by a short follow-up, 30-day responses in the real-world setting were comparable to the best responses observed in the pivotal ZUMA-1 clinical trial
  • Safety appeared comparable to the ZUMA-1 trial despite > 40% of patients failing to meet ZUMA-1 eligibility criteria
  • Univariate analysis identified potential predictors of ongoing CRs at 3 months, however longer follow-up and multivariate analyses are needed
  1. Nastoupil, L.J., et al. Axicabtagene ciloleucel (axi-cel) CD19 chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory large B-cell lymphoma: real-world experience. 01 Dec 2018. Abstract #91. 60th ASH Annual Meeting, San Diego, CA.