British journal of haematology
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B-cell maturation antigen (BCMA, also termed TNFRSF17) is an attractive therapeutic target due to its restricted expression on normal and malignant plasma cells (PC). GSK2857916 (or J6M0-MMAF) is a BCMA-specific antibody conjugated to the microtubule-disrupting agent monomethyl auristatin F (MMAF) via a protease-resistant linker. To evaluate the clinical potential of this agent, tumour cells from seventy multiple myeloma (MM) patients were assessed for BCMA expression by immunohistochemistry and flow cytometry. ⋯ J6M0-MMAF mediated cytotoxicity of MM cells varied with dose and antigen levels, with clonogenic progenitors killed at lower doses than mature cells. In comparison, J6M0-MMAF killing of primary CD138(+) myeloma cells occurred with slower kinetics. Our observations support BCMA to be a promising therapeutic target in MM for novel therapies such as J6M0-MMAF.
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The combination of fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-Ida) is widely used in relapsed/refractory acute myeloid leukaemia (AML). We retrospectively analysed the results of 259 adult AML patients treated as first salvage with FLAG-Ida or FLAG-Ida plus Gentuzumab-Ozogamicin (FLAGO-Ida) of the Programa Español de Tratamientos en Hematología (PETHEMA) database, developing a prognostic score system of survival in this setting (SALFLAGE score). Overall, 221 patients received FLAG-Ida and 38 FLAGO-Ida; 92 were older than 60 years. ⋯ Using this stratification system, three groups were defined: favourable (26% of patients), intermediate (29%) and poor-risk (45%), with an expected 5-year OS of 52%, 26% and 7%, respectively. The SALFLAGE score discriminated a subset of patients with an acceptable long-term outcome using FLAG-Ida/FLAGO-Ida regimen. The results of this retrospective analysis should be validated in independent external cohorts.
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Nucleoside analogues are highly active in patients with hairy cell leukaemia (HCL); however, patients continue to relapse. This phase II study evaluated the efficacy and safety of cladribine followed by rituximab in patients with untreated HCL (N = 59), relapsed HCL (N = 14) and HCL variant (HCLv, N = 7). Cladribine 5·6 mg/m(2) was given intravenously (IV) daily for 5 d and was followed approximately 1 month later with rituximab 375 mg/m(2) IV weekly for 8 weeks. ⋯ Almost all patients (94%) achieved negative minimal residual disease (MRD) after the treatment. Positive MRD during the follow up did not necessarily result in clinically relevant relapse. Cladribine followed by rituximab is highly effective even in patients with relapsed disease and HCLv, and can achieve durable remission.