ASCO Names CAR T-Cell Therapy as Cancer Advance of the Year

The annual update on oncology treatment highlights the most impactful clinical cancer research and policy developments over the past year in CAR T-cell therapy.

David L. Porter, MD

Saying that the treatment is “poised to transform the outlook for children and adults with certain otherwise incurable cancers,” ASCO has selected CAR T-cell therapy as its Advance of the Year.

ASCO made the announcement today as part of Clinical Cancer Advances 2018: ASCO's Annual Report on Progress Against Cancer. The annual update on oncology treatment highlights the most impactful clinical cancer research and policy developments over the past year.

ASCO President Bruce E. Johnson, MD, said in a press release that the emergence of CAR T-cell therapy is the payoff for decades of investment by the National Institutes of Health, academic medical centers, and the pharma/biotech industry in the basic sciences of immunology, cancer biology, and genetics.

“It is remarkable to see these decades of effort come together to create this whole new type of treatment, as well as other precision medicine approaches that offer hope to people with advanced cancer,” he said. “While we still have work to do to make these treatments accessible to patients everywhere and more tolerable, the successes of CAR T-cell therapy demonstrate the profound impact new treatments could make to markedly extend the lives of people with cancer.”

The FDA approved a pair of CAR T-cell therapies in 2017: tisagenlecleucel (Kymriah) for the treatment of children and young adults aged up to 25 with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL) and axicabtagene ciloleucel (axi-cel; Yescarta) for adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Axi-cel is also indicated for primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed from follicular lymphoma (TFL).

Tisagenlecleucel, developed by the University of Pennsylvania and Novartis, was the first CAR T-cell therapy approved by the FDA.

“The FDA approval of the first CAR T-cell therapy marked a major turning point in the way we approach the treatment of cancer,” David L. Porter, MD, a CAR research team leader and director of Blood and Marrow Transplant in the Abramson Cancer Center at the University of Pennsylvania, said in an email to OncLive.


“The patients who participated in the early clinical trials of this therapy at Penn starting nearly 8 years ago are pioneers, whose stories are now part of medical history. Our experiences developing this therapy and caring for these patients have revolutionized our belief about what is possible in oncology, and galvanized us as we move into adapting CAR T-cell therapies for the treatment of solid tumors,” added Porter.Tisagenlecleucel won approval based on results from the phase II, single-arm, international ELIANA trial of 63 patients who received a single dose of tisagenlecleucel. The overall remission rate was 82.5% (95% CI, 70.9-91.0) in treated patients. Forty patients (63%) had complete remission (CR) and 12 (19%) had complete remission with incomplete hematologic recovery (CRi). All patients who had CR or CRi also had negative minimal residual disease status in the bone marrow.

The estimated relapse-free rate among responders at month 6 was 75.4% (95% CI, 57.2-86.7). The median duration of response was not reached at a median follow-up of 4.8 months.

Eleven patients who had CR or CRi relapsed after tisagenlecleucel prior to data cutoff and before any new cancer therapy. Two other patients relapsed after receiving both tisagenlecleucel and new cancer therapy. Of the 52 patients who had CR or CRi, 29 were still in remission at the last assessment before the data cutoff.

In an update presented at 2017 SOHO Annual Meeting ORR was 83%, including CRs with complete hematologic recovery in 63% of patients and CRs with incomplete recovery in 19%. Additionally, 83% of patients met the secondary endpoint: CR (with or without complete recovery) within 3 months with MRD-negative bone marrow.1

Among all infused patients, the relapse-free survival rate was 75% at 6 months and 64% at 9 and 12 months. Overall survival (OS) was 89% at 6 months and 79% at 9 and 12 months. Median OS was 16.6 months.

ZUMA-1 Trial

In the updated safety results, 48% of patients experienced grade 3/4 cytokine release syndrome (CRS). There were no deaths associated with CRS.The FDA relied on results from the single-arm ZUMA-1 study in approving axi-cel.2 Those with DLBCL had an ORR of 82% and a CR rate of 49%. After 8.7 months of follow-up, the ORR in the DLBCL group was 36%, which included a CR rate of 31%. In the PMBCL/TFL group, the ORR was 83% and the CR rate was 71%. The 8.7-month ORR rate was 67%, with a CR rate of 63%.

In ZUMA-1, patients were enrolled into 2 cohorts consisting of those with DLBCL (n = 77) and those with PMBCL or TFL (n = 24). Axi-cel was administered as a single infusion of modified autologous T cells at a target dose of 2 x 106 CAR-positive T cells/kg.

All patients had chemorefractory disease and had received a median of 3 prior lines of therapy, with 54% refractory to 2 consecutive lines of therapy. Overall, 79% of patients were refractory to their last line of chemotherapy without having received prior autologous stem cell transplant (ASCT) while the remainder had relapsed within 12 months of ASCT.

Thirteen percent of patients experienced CRS and 28% experienced neurologic events. There were 4 fatal events in the study, 3 of which were deemed related to axi-cel, a hemophagocytic lymphohistiocytosis, a cardiac arrest in the setting of CRS and a cerebral edema in the setting of grade 3 CRS with multiorgan failure.

In updated ZUMA-1 findings presented at the 2017 ASH Annual Meeting, axi-cel maintained a CR rate of 40% across the study population, with a median follow-up of 15.4 months. Forty-two percent of patients treated with axi-cel remained progression-free and 56% remained alive. The 18-month progression-free survival rate was 41% and the 18-month OS rate was 52%.


  1. Pulsipher M, Buechner J, Grupp SA, et al. Global registration trial of efficacy and safety of CTL019 in pediatric and young adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): update to the interim analysis. Presented at 2017 SOHO Annual Meeting. Abstract ALL-152.
  2. Locke FL, Neelapu SS, Bartlett NL, et al. Primary results from ZUMA-1: a pivotal trial of axicabtagene ciloleucel (Axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (NHL). Presented at: 2017 AACR Annual Meeting; April 1-5, 2017; Washington, DC. Abstract CT019.
  3. Neelapu SS, Locke FL, Bartlett NL, et al. Long-Term Follow-up ZUMA-1: A Pivotal Trial of Axicabtagene Ciloleucel (Axi-Cel; KTE-C19) in Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL). Presented at: ASH Annual Meeting and Exposition; Dec. 9-12, 2017; Atlanta. Abstract 578.