Outcomes in Hispanic Patients with Philadelphia-Negative and Philadelphia-like Acute Lymphoblastic Leukemia with the Use of Blinatumomab

Abstract

Introduction: In the United States, Hispanics have the highest incidence rate of B-cell acute lymphoblastic leukemia (ALL) amongst all minority groups. Hispanic adults with ALL have the lowest rates of progression-free survival and overall survival. Hispanic adults, for example, have an increased frequency of Philadelphia chromosome (Ph)-like ALL, a sub-type of ALL associated with significantly inferior survival outcomes In the last decade, use of Blinatumomab and other novel targeted immunotherapies were approved for treatment of relapsed or minimal residual disease positive disease (MRD +) B-cell ALL. Pivotal trial showing efficacy of blinatumomab in relapsed or MRD + setting had very limited number of Hispanic patients. Our aim is to evaluate survival outcomes and the efficacy of blinatumomab usage in Hispanic B-ALL including Philadelphia-negative (Ph negative) and Philadelphia-like (Ph-Like) patients treated at LAC-USC (Los Angeles County Hospital-University of Southern California). We report Hispanic B-cell ALL patients treated with blinatumomab outside of clinical trials Method: This is a retrospective review which included adults aged ≥18 years with newly diagnosed Philadelphia negative ALL (2016-2020) treated at the USC/Norris Comprehensive Cancer Centerand the Los Angeles County Hospital (LAC). Primary objectives was to investigate overall survival in Hispanic patients who were treated with blinatumomab. We stratified patient population into Philadelphia negative and Philadelphia-like B-cell ALL and assessed survival separately for blinatumomab administered for minimal residual positivity and for relapse disease. Most of Ph-Like patients were identified with CRLF2 rearrangement per institutional protocol. Results: 67 patients were B cell ALL, which included Ph-negative B cell ALL and Ph-like B cell ALL, 43 and 24 patients respectively. 50.7% were men and median age was 39 years. 38 patients were considered unfavorable risk due to cytogenetics risk factors and 44 patients received peg-asparaginase based induction. 30 (48%) of patients received blinatumomab, 15 in each ph-negative and ph-like group respectively. More patients received blinatumomab for relapsed disease as compared to MRD positive disease, 23 vs. 8 patients respectively. Mean overall survival for our patients was 68 months (SE=3.3). In ph-negative group, when blinatumomab was used for relapsed disease then 3 years survival probability was 0% compared to 91.5% for patients who did not receive blinatumomab (p-value=0.0001). On the other hand, for MRD positive disease, 3 years OS was 91.7% vs. 79.6% for patients who received blinatumomab compared to no blinatumomab (p-value=0.6). For ph-like group, when blinatumomab was used for relapsed disease then 3 years survival probability was 100% compared to 40% for patients who did not receive blinatumomab (p-value=0.2). For MRD positive disease, median OS was not reached for either group (p-value=0.6). Conclusion: Both relapse disease and MRD+ disease are considered poor prognostic indicator. Our study highlights that blinatumomab can decrease survival gap for MRD + disease and relapse disease for ph-like Hispanic patients and decrease survival gap in MRD + ph-negative Hispanic patients when compared to patients who did not need blinatumomab