Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia.

Abstract

Tisagenlecleucel therapy has shown promising efficacy for relapsed/refractory (R/R) B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, relapses occur in 30-50% of patients. Determinants for CD19pos versus CD19neg relapses are poorly characterized. We report on 51 patients with R/R BCP-ALL (median age 17 years) infused with tisagenlecleucel after lymphodepletion. Complete remission rate at D28 was 96%. Prior blinatumomab increased the risk of early failure at D28. The 18-month cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 51%, 44%, and 74%, respectively, at a median follow-up of 15.5 months. Factors associated with a high tumor burden (occurrence of cytokine release syndrome) and prior blinatumomab were associated with an increased CIR, and a shorter EFS and OS. Pre-lymphodepletion high disease burden (MRD ≥ 10-2, SHR 10.4, p = 0.03) and detectable MRD at D28 (SHR 7.2, p = 0.006) correlated with an increased risk of CD19neg relapse. Low disease burden (SHR 5.3, p = 0.03) and loss of B-cell aplasia (BCA) (SHR 21.7, p = 0.004) predicted an increased risk of CD19pos relapses. These data highlight the impact of prior therapy on patient outcome. Finally, detectable MRD at D28 and loss of BCA both define patients at high risk of relapse for whom additional interventions are needed.

• Authors: Marie-Emilie Dourthe, Florence Rabian, Karima Yakouben, Florian Chevillon, Aurélie Cabannes-Hamy, Françoise Méchinaud, Audrey Grain, Delphine Chaillou, Ilhem Rahal, Sophie Caillat-Zucman, Emmanuelle Lesprit, Jérôme Naudin, Julie Roupret-Serzec, Nathalie Parquet, Anne Brignier, Valérie Guérin-El Khourouj, Elodie Lainey, Aurélie Caye-Eude, Hélène Cavé, Emmanuelle Clappier, Stéphanie Mathis, Elie Azoulay, Jean Hugues Dalle, Nathalie Dhédin, Isabelle Madelaine, Jérôme Larghero, Nicolas Boissel, André Baruchel
• Journal: Leukemia (Leukemia) Vol. 35 Issue 12 Pg. 3383-3393 (12 2021) ISSN: 1476-5551 [Electronic] England
• PMID: 34002027 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Nature Limited.

Chemical References

• Antigens, CD19
• Antineoplastic Agents, Immunological
• Receptors, Antigen, T-Cell
• tisagenlecleucel

Topics

• Adolescent
• Adult
• Antigens, CD19 (metabolism)
• Antineoplastic Agents, Immunological (therapeutic use)
• B-Lymphocytes (drug effects, pathology)
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Humans
• Infant
• Male
• Neoplasm Recurrence, Local (drug therapy, pathology)
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, pathology)
• Prognosis
• Prospective Studies
• Receptors, Antigen, T-Cell (therapeutic use)
• Survival Rate
• Young Adult