Tisagenlecleucel Maintains Efficacy in Real-World Setting

Jason Harris
Published: Saturday, Sep 14, 2019

Marcelo C. Pasquini, MD, MS

Marcelo C. Pasquini, MD, MS

Early results from a prospective postmarketing assessment showed that tisagenlecleucel (Kymriah) induced responses similar to those seen in pivotal trials for children and adolescents with B-cell acute lymphoblastic leukemia (ALL) and adults with diffuse large B-cell lymphoma (DLBCL).

Marcelo C. Pasquini, MD, MS, associate professor of medicine at the Medical College of Wisconsin and senior scientific director of the Center for International Blood and Marrow Transplant Research (CIBMTR) Cellular Therapy Clinical Trials Support, presented findings from the PICTOR study at the 2019 SOHO Annual Meeting.1

“These results, although early, align with the pivotal trials published in the New England Journal of Medicine,” he said.

“This really demonstrates the implementation of a large outcomes database to collect data in a real-world setting of CAR T cells,” Pasquini added. “This is good news for all centers because using this could leverage multiple CAR T-cell products using the same infrastructure and not requiring a different registry for different commercial products.”

As part of a postmarketing regulatory requirement, patients receiving tisagenlecleucel are followed for 15 years. The CIBMTR established a Cellular Therapy Registry to collect that long-term data.

These results include data from 144 patients with ALL and 63 with DLBCL. As of August 1, 2019, 170 patients were evaluable for safety and 162 were evaluable for efficacy, having had at least their first follow-up reported at 3 months after initiation of tisagenlecleucel therapy. The median follow-up was 6 months for patients with ALL and 4.5 months for those with DLBCL. Investigators eventually plan to recruit 2500 total patients.

In the ALL cohort, the complete response (CR) rate was 87%. Of the 58 patients available for minimal residual disease (MRD) assessment, 98% were MRD negative. At 6 months, the duration of response (DOR) was 71%, event-free survival (EFS) was 66%, and overall survival (OS) was 91%.

The median age in the ALL cohort was 13 years (range, 2-25). Most patients (64.6%) were aged ≥10 years.

At the initiation of tisagenlecleucel treatment, 18 (12%) patients were in primary induction failure, 50 (35%) were in morphologic CR, and 76 (53%) had experienced disease relapse.

In the DLBCL cohort, the CR rate was 42% and the partial response rate was 24%.

Nineteen (30%) patients had double/triple hit lymphoma and 18 (28%) had transformed lymphoma. Fifty-one percent of patients were aged ≥65 years. Eighteen (29%) patients had no prior remission, 3 (5%) were in at least their second remission, and 41 (65%) were in relapse. Thirteen (21%) had received prior autologous hematopoietic cell transplant and 45 (71%) had received ≥3 prior lines of therapy.

In the ALL cohort, 58% of patients experienced cytokine release syndrome (CRS). Twenty-nine percent of patients experienced neurotoxicity, 8% of which was grade ≥3. In the DLBCL cohort, 53% of patients experienced CRS and 18% experienced neurotoxicity. Neurotoxicity was grade ≥3 in 4% of these patients.

Overall, 19% of patients required corticosteroids for neurotoxicity, but Pasquini said there have been no deaths due to CRS or neurotoxicity recorded.

In August 2017, the FDA approved tisagenlecleucel for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse, based on results from the ELIANA trial. Updated data for 75 patients from the pivotal trial published in February 2018 in the New England Journal of Medicine showed that at a median follow-up of 13.1 months, tisagenlecleucel induced an objective response rate (ORR) of 81% with a CR rate of 60%. EFS was 73% (95% CI, 60-82) at 6 months and OS was 90% (95% CI, 81-95).2 At 12 months, EFS was 50% (95% CI, 35-64) and OS 76% (95% CI, 63-86).

Based on findings from the JULIET study, the FDA approved tisagenlecleucel in May 2018 for use in adult patients with relapsed/refractory large B-cell lymphoma—including DLBCL not otherwise specified, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma—after 2 or more lines of systemic therapy. In a 26-month update to the pivotal JULIET trial presented earlier at SOHO, the ORR was 54% (95% CI, 43-64) with a CR rate of 40% and a median OS of 10.3 months. The median DOR was not reached.3


  1. Pasquini M, Hu ZH, Zhang Y, et al. Real world experience of tisagenlecleucel chimeric antigen receptor (CAR) T cells targeting CD19 in patients with acute lymphoblastic leukemia (ALL) and diffuse large b cell lymphoma (DLBCL) using the Center for International Blood and Marrow Transplant Research (CIBMTR) Cellular Therapy (CT) Registry. Presented at: the SOHO 2019 Annual Meeting; September 11-14, 2019; Houston, Texas. Abstract CT-298.
  2. Maude SL, Laetsch TW, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378(5):439-448. doi: 10.1056/NEJMoa1709866.
  3. Bachanova V, Westin J, Tam C. Correlative analyses of cytokine release syndrome and neurological events in tisagenlecleucel-treated relapsed/refractory diffuse large B-Cell lymphoma patients. Presented at: the SOHO 2019 Annual Meeting; September 11-14, 2019; Houston, Texas. Abstract ABCL-278.
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