Despite treatment advances, prognosis remains poor for adults
with R/R B-cell ALL1,2
Low complete response rates with standard R/R ALL therapies2-4
| Prior treatment history | CR with subsequent therapy |
|---|---|
| Naïve to established immunotherapies* | 35% |
| Post allo-SCT in first-line therapy† | 35% |
| Primary refractory disease (persistent disease) or short duration of first remission†‡ | 31% |
*Data from a 2021 retrospective cohort study of efficacy and safety of treatments considered to be the SOC in adult patients with R/R ALL. The study included three patient-matched historical control cohorts for a SCA-combined population that included patients with and without prior exposure to blinatumomab or inotuzumab ozogamicin. The primary endpoint was the CR/CRi rate of the SCA-1 population (naïve to blinatumomab and inotuzumab ozogamicin).2-4
†Data from a pooled analysis of adult patients with R/R Ph-negative, B-precursor ALL across 11 groups or sites in the United States and Europe. 2210 salvage records were included in total, with 1628 patients in first salvage, 374 patients in second salvage, and 160 patients in third or greater salvage.4
‡Data from a review of 245 patients with ALL treated at the University of Texas MD Anderson Cancer Center who received first salvage therapy following either primary treatment failure following induction or for relapsed ALL <12 months after initial therapy.2
Type of response may help predict outcomes in R/R adult B-cell precursor ALL5,6
10% to 40% of patients with R/R ALL go on to receive allo-SCT5
- In a retrospective analysis of 180 adults who received allo-SCT between 1995-2018 in Germany, 86% achieved a CR one month after allo-SCT and mOS was 23 months at a median study follow-up of 10.2 years7*
- Achieving a CR before allo-SCT is a favorable prognostic factor7
Minimal residual disease is the strongest independent prognostic factor for ALL8
10-year event-free survival rates in a meta-analysis of 13,637 patients in 39 studies9†
in MRD-negative adults
in MRD-positive adults
- Although 90% of adults reach morphologic CR after standard chemotherapy, as many as half have persistent MRD10
There is an urgent need for treatments that can improve outcomes by
delivering higher rates of CR in adult patients with R/R B-cell ALL4,8
*Retrospective analysis performed according to the Declaration of Helsinki and Good Clinical Practice Guidelines as of January 2019 to determine need for additional disease- and patient-related prognostic factors to predict and optimize post-allo-SCT survival. Prognostic factors were investigated in multivariate regression models adjusted for time of allo-SCT administration.7
†Meta-analysis of clinical studies of ALL found at PubMed, MEDLINE, and clinicaltrials.gov was conducted to quantify relationships between event-free survival and overall survival with MRD status. Search and study screening adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis Guidelines. Abstracts, reviews, and studies with fewer than 40 patients or insufficient MRD description were excluded from the analysis.8
ALL=acute lymphoblastic leukemia; allo-SCT=allogeneic stem cell transplant; CR=complete remission; CRi=complete remission with incomplete hematologic recovery; mOS=median overall survival; MRD=minimal residual disease; mRFS=median relapse-free survival; Ph=Philadelphia chromosome; R/R=relapsed or refractory; SCA=synthetic control arm; SOC=standard of care.
References: 1. Gökbuget N, Stanze D, Beck J, et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;120(10):2032-2041. 2. Kantarjian HM, Thomas D, Ravandi F, et al. Defining the course and prognosis of adults with acute lymphocytic leukemia in first salvage after induction failure or short first remission duration. Cancer. 2010;116(24):5568-5574. 3. Shah BD, Ghobadi A, Oluwole OO, et al. Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study. J Hematol Oncol. 2022;15(1):170. 4. Gökbuget N, Dombret H, Ribera JM, et al. International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia. Haematologica. 2016;101(12):1524-1533. 5. Craddock C, Hoelzer D, Komanduri KV. Current status and future clinical directions in the prevention and treatment of relapse following hematopoietic transplantation for acute myeloid and lymphoblastic leukemia. Bone Marrow Transplant. 2019;54(1):6-16. 6. Saygin C, Papadantonakis N, Cassaday RD, et al. Prognostic impact of incomplete hematologic count recovery and minimal residual disease on outcome in adult acute lymphoblastic leukemia at the time of second complete response. Leuk Lymphoma. 2018;59(2):363-371. 7.Greil C, Engelhardt M, Ihorst G, et al. Prognostic factors for survival after allogeneic transplantation in acute lymphoblastic leukemia. Bone Marrow Transplant. 2021;56(4):841-852. doi:10.1038/s41409-020-01101-z 8. Berry DA, Zhou S, Higley H, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: a meta-analysis. JAMA Oncol. 2017;3(7):e170580. doi:10.1001/jamaoncol.2017.0580 9. Abou Dalle I, Jabbour E, Short NJ. Evaluation and management of measurable residual disease in acute lymphoblastic leukemia. Ther Adv Hematol. 2020;11: 2040620720910023. doi:10.1177/2040620720910023 10. Fulcher J, Leung E, Christou G, Bredeson C, Sabloff M. Selecting the optimal targeted therapy for relapsed B-acute lymphoblastic leukemia. Leuk Lymphoma. 2020;61(9):2271-2273. doi:10.1080/10428194.2020.176196