Tisa-Cel Shows Durable Efficacy in Pediatric and Young Adult Patients With R/R B-Cell Acute Lymphoblastic Leukemia

Among treated patients, 42% achieved 5-year event free survival.

A 5-plus year follow-up study has demonstrated durable efficacy of tisagenlecleucel (tisa-cel; Kymriah, Novartis) in pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), with 55% of patients still alive after more than 5 years post-treatment and 42% achieving 5-year event-free survival (95%CI, 29-54), according to findings from ELIANA, a phase 2 global multicenter study (NCT02435849) presented at the 2022 European Hematology Association Annual Meeting, June 9-17, 2022, in Vienna, Austria and virtual.1

Of the 79 patients who received tisa-cel, 82% achieved complete remission or complete remission with incomplete hematologic recovery within 3 months post-infusion (95% CI, 72-90). The 5-year relapse-free survival rate for these patients was 44% (95% CI, 31-56) and median relapse-free survival was 43 months. Based on these results, the researchers concluded that tisa-cel could be a potentially curative treatment option for patients with r/r B-ALL.

“These data mark a moment of profound hope for children, young adults and their families with relapsed or refractory B-cell ALL, as relapse after five years is rare,” according to Stephan Grupp, MD, PhD, section chief of the Cellular Therapy and Transplant Section, and inaugural director of the Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy at Children's Hospital of Philadelphia (CHOP), said in a statement.2 “Since the approval of Kymriah nearly five years ago, we have been able to offer a truly game-changing option to patients who previously faced a five-year survival rate of less than 10 percent.”

The ages of patients involved in the study ranged from 3 to 24 years (median, 11). All patients had been pretreated with 1 to 8 prior lines of therapy (median, 3), and 61% of the patients had a history of prior stem cell transplant. The 5-year overall survival rate among all study participants was 55% (95% CI, 43-66). Notably, there was no significant difference observed in any efficacy end point between participants age 18 or older who received tisa-cel versus those younger than 18. The researchers noted that 82% of the patients received IVIG at some point post-infusion.

Commonly reported adverse events occurring more than 1 year post-infusion included infection (20%) and cytopenias (6%). Investigators noted that 14% of patients experienced cytopenias lasting more than 1 year but not more than 5. 

Additionally, the investigators noted that no new or unexpected adverse events were reported during long term follow-up.

“These results strengthen our confidence in CAR-T cell therapies as a truly transformative and paradigm-shifting advance in cancer care, as well as our commitment to continue developing this technology with next-generation platforms,” stated Jeff Legos, executive vice president, global head of oncology & hematology development, at Novartis.2

Additional studies from Novartis’ CAR-T program presented at the 2022 EHA Congress include updates from the first-in-human dose escalation trials with PHE885 in adults with r/r multiple myeloma3,4 and with YTB323 in adults with r/r diffuse large B-cell lymphoma.5

REFERENCES
1. Rives S, Maude SL, Hiramatsu H, et al. Tisagenlecleucelin pediatric and young adult patients (Pts) with relapsed/refractory (R/R) B-Cell acute lymphoblastic leukemia (B-ALL): Final analyses from the ELIANA study. Presented at: 2022 Hybrid Congress of the European Hematology Association (EHA). June 9-12, 2022; Vienna, Austria. Abstract #S112
2. Novartis five-year Kymriah data show durable remission and long-term survival maintained in children and young adults with advanced B-cell ALL. News release. Novartis. June 12, 2022.https://www.novartis.com/news/media-releases/novartis-five-year-kymriah-data-show-durable-remission-and-long-term-survival-maintained-children-and-young-adults-advanced-b-cell-all
3. Sperling AS, Nikiforow S, Derman B, et. al. Phase I study data update of PHE885, a fully human BCMA-directed CAR-T cell therapy manufactured using the T-Charge™ platform for patients with relapsed/refractory (r/r) multiple myeloma (MM). Presented at: 2022 Hybrid Congress of the European Hematology Association (EHA). June 9-12, 2022; Vienna, Austria. Abstract #P1446
4. Munshi, N. et. al. Phase II study of PHE885, a B-cell maturation antigen-directed chimeric antigen receptor t-cell therapy, in adults with relapsed/refractory (r/r) multiple myeloma (MM). Presented at: 2022 Hybrid Congress of the European Hematology Association (EHA). June 9-12, 2022; Vienna, Austria. Abstract #PB1983
5. Dickinson, M. et. al. Phase I study of YTB323, a chimeric antigen receptor (CAR)-T cell therapy manufactured using T-Charge™, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Presented at: 2022 Hybrid Congress of the European Hematology Association (EHA). June 9-12, 2022; Vienna, Austria. Abstract #S212