Real-World Patient Characteristics and Treatment Patterns in ALL Survivors with Relapsed/Refractory ALL
Authors: Schuler Tammy , Aggarwal Puja , Kotomale Angele , McAllister Lindsay , Klink Andrew , Feinberg Bruce 
Published: December 2024

INTRODUCTION: Approximately 50% of patients (pts) with adult acute lymphoblastic leukemia (ALL) develop relapsed/refractory (R/R) disease. Understanding real-world characteristics and patterns of care for ALL pts prior to R/R diagnosis (R/R ALL) may help with the development of tailored treatment approaches and strategies to improve survival and cure. This study describes real-world patient characteristics and prior treatment history among pts with R/R ALL and factors associated with long-term survival.

METHODS: This is a retrospective, multi-site, medical chart review study using data from medical records of pts with R/R ALL being managed at community oncology clinics in the United States. Physicians in Cardinal Health's Oncology Provider Extended Network (OPEN) identified patients from their practice who met eligibility criteria and abstracted data into an electronic data capture tool from pts with R/R ALL diagnosed 9/2017-3/2022 and &gt; 12 months of follow-up available. Clinical trial participants and T-cell ALL pts were excluded. In this study long-term survivors (LTS) were defined as surviving ≥ 3 years from initial ALL diagnosis to date of death/last date seen by abstracting physicians. Comparisons were conducted using T-tests/chi-square tests and their non-parametric counterparts, across data from LTS and pts who died &lt; 3 years after initial diagnosis.

RESULTS: 24 physicians abstracted chart data from 204 pts (mean: 9 pts/physician). Physician characteristics: 67% community-based, 96% urban/suburban settings, 100% specialized in hematology/oncology with a mean of 15 years (yrs) in practice. Among pt characteristics: median age at initial ALL diagnosis 54 yrs, median age at R/R diagnosis 56 yrs, median time from initial to R/R diagnosis 11 months, 51% male, 73% white, and 51% had commercial insurance. Among treatments received prior to the R/R setting; 66% received “hyper CVAD (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride/adriamycin, dexamethasone, methotrexate, and cytarabine) plus” (“plus” drugs include: imatinib, ponatinib, dasatinib, and rituximab), and 95%, 40%, 11%, and 36% received induction, consolidation, allo-SCT as consolidation, and maintenance therapy respectively. At R/R ALL diagnosis, 28% had primary refractory disease, and 46% had early relapse (≤ 12 months from last treatment completion). Among all patients, 61 (30%) were LTS, 96 (47%) died within 3 years of initial diagnosis, and 47 (23%) were still alive but had &lt; 3-year survival following initial diagnosis at the time of data collection.

Demographic factors favoring LTS included: age at initial (median: 41 vs. 63 yrs, P&lt;.001) and at R/R (median: 43 vs. 64 yrs, P&lt;.001) diagnoses, commercial insurance (70% vs. 36%, P&lt;.001), and residing in the Southern (34% vs. 20%, P=0.026) and Midwest US (25% vs. 15%, P=0.026).

Clinical factors favoring LTS included: time from initial ALL to R/R diagnosis (median: 35 vs. 8 months, P&lt;.001), NCI scores (median: 0.0, IQR: 0-0.1 vs. median: 0.1, IQR: 0-0.5, P= 0.004), obesity (BMI ≥ 25: 46% vs. 69%, P= 0.002), ECOG (0 or 1: 90% vs. 67%, P&lt;.001) and KPS (Score of ≥80: 57% vs. 30%, P=0.002).

Disease biology factors favoring LTS included: Philadelphia chromosome positive ALL subtype (31% vs. 23%), and not having ≥ 1 high-risk cytogenetic abnormality at initial ALL diagnosis (59% vs. 72%).

Treatment related factors favoring LTS included: not receiving “hyper-CVAD plus” (57% vs. 67%, P&lt;.001), receiving consolidation treatment (79% vs. 24%, P&lt;.001), allo-SCT as consolidation (23% vs. 2%, P&lt;.001), maintenance treatments (67% vs. 21%, P&lt;.001), and MRD negative status (71% vs. 28%, P&lt;.001) after completion of frontline therapy.

CONCLUSIONS: This robust real-world study of R/R B-cell ALL affirmed demographic, and clinical, and treatment characteristics that have been previously identified in clinical trials to play a role in LTS in ALL. LTS was more likely among younger pts who achieve MRD, who in turn were more likely to receive allo-SCT consolidation and maintenance therapy. The index period and eligibility requirements of this study limited observations on the impact of newer therapeutics, e.g., CAR T in this population, the earlier use of which in poor prognostic patients may significantly contribute to LTS.