INSTITUTIONAL EXPERIENCE WITH RITUXIMAB AS SALVAGE THERAPY IN RELAPSED REFRACTORY B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA
Bernice Oh,Shawn Lee,Frances Yeap,Allen Yeoh
Viva University Childrens Cancer Centre National University Hospital Singapore Viva University Childrens Cancer Centre National University Hospital Singapore
Background : Despite the excellent cure rates for children with B-Lineage Acute Lymphoblastic Leukemia(B-ALL), a significant proportion of children still relapse. In patients with relapsed/refractory B-ALL, Rituximab is a viable option especially if CD20 is present.
Case Presentation Summary : Here we present a series of 3 patients (Age 15-18years) in Singapore who received Rituximab salvage therapy in the relapsed/refractory setting to maximise chances of successful definitive bone marrow transplant or CAR-T cells from 2016 to present. CD20 expression was 72-99% at initiation of Rituximab. Patient1 with p53mutated B-ALL showed only transient response to Blinatumomab. Despite becoming minimal residual disease(MRD) negative by flow cytometry by the second week, MRD became positive again after 4weeks. He then received activated Natural-Killer-cells in combination with Rituximab which brought him into MRD remission and allowed a therapeutic window for Haploidentical Stem Cell Transplant. He remained MRD negative until D+118 when he eventually relapsed again. Patient2 with multiply-relapsed TEL-AML1-B-ALL, similarly showed transient response to Blinatumomab, underwent CD19-directed CAR-T cell therapy overseas and achieved remission. However, due to loss of persistence of CAR-T cells, he relapsed 9months later with progressively worsening MRD up to 7.16% until Rituximab was started and dropping his MRD to 0.1%, although this was also transient as MRD soon began to rise again. However this allowed a window so that he could subsequently undergo CD22-directed CAR-T cell therapy. In Patient3 with IKFZ1deleted B-ALL relapsed 3 years post matched-sibling transplant, we induced MRD remission with Rituximab as his disease progressed on oral maintenance chemotherapy with 6-Mercaptopurine and Methotrexate. He remains well now following CD19-directed CAR-T cell therapy.
Learning Points/Discussion : Rituximab is a feasible salvage immunotherapy option to reduce disease burden prior to definitive cure achieved by transplantation or CAR-T cell therapy, although further studies need to be carried out in the form of clinical trials to fully determine its effectiveness against B-ALL.