Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801

Abstract

Nelarabine (506U78) is a soluble pro-drug of 9-␤-D-arabinofuranosylguanine (ara-G), a deoxyguanosine derivative. We treated 26 patients with T-cell acute lymphoblastic leukemia (T-ALL) and 13 with T-cell lymphoblastic lymphoma (T-LBL) with nelarabine. All patients were refractory to at least one multiagent regimen or had relapsed after achieving a complete remission. Nelarabine was administered on an alternate day schedule (days 1, 3, and 5) at 1.5 g/m 2 /day. Cycles were repeated every 22 days. The median age was 34 years (range, 16-66 years); 32 (82%) patients were male. The rate of complete remission was 31% (95% confidence interval [CI], 17%, 48%) and the overall response rate was 41% (95% CI, 26%, 58%). The principal toxicity was grade 3 or 4 neutropenia and thrombocytopenia, occurring in 37% and 26% of patients, respectively. There was only one grade 4 adverse event of the nervous system, which was a reversible depressed level of consciousness. The median disease-free survival (DFS) was 20 weeks (95% CI, 11, 56), and the median overall survival was 20 weeks (95% CI, 13, 36). The 1-year overall survival was 28% (95% CI, 15%, 43%). Nelarabine is well tolerated and has significant antitumor activity in relapsed or refractory T-ALL and T-LBL. (Blood. 2007;109:5136-5142)

Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T‐cell lymphoblastic leukaemia and lymphoma

“…Nelarabine (AraG), a purine nucleoside antimetabolite, was approved in 2005 for treatment of acute T-cell ALL/LL in patients of all ages. An overall response rate of 41% was seen in a study of 26 adult patients with T-cell ALL and 13 patients with T-cell LL (DeAngelo et al, 2007). In a combined adult and paediatric phase 1 study, patients with T-cell ALL had a response rate of 54%; although T-cell LL patients only had a 13% response rate .…”

Minimal residual disease is an important predictive factor of outcome in children with relapsed ‘high-risk’ acute lymphoblastic leukemia

“…On the other hand, a POS first MRD result identified, after just one chemotherapy cycle, a subset of patients who seem not to benefit from further consolidations, including allogeneic HSCT. These patients with extremely severe prognosis could have the indication to experimental treatment strategies on the basis of the use of novel antileukemia agents, such as clofarabine, 42 nelarabine 43 or anti-CD22 monoclonal antibodies, 44 aimed at obtaining a better leukemia control before allogeneic HSCT.…”

Acute Lymphoblastic Leukemia

“…Nelarabine as single agent was also evaluated in adults with relapsed/refractory Tcell ALL or T-cell lymphoblastic leukemia in a phase II study (N = 39; median age, 34 years; range, 16-66 years; median 2 prior regimens; T-cell ALL, n = 26). 63 The CR rate (including CR with incomplete blood count recovery [CRi]) was 31%; an additional 10% of patients experienced a partial remission. The median DFS and OS were both 20 weeks.…”

“…Grade 3 or 4 myelosuppression was common, but only 1 case of grade 4 CNS toxicity (reversible) was observed. 63 Novel monoclonal antibodies are currently under clinical investigation. Inotuzumab ozogamicin is an anti-CD22 antibody-drug conjugate that has shown high CR rates (57%) in a phase II study in patients with relapsed/refractory ALL (N = 49).…”

“…59,60 In addition, nelarabine has been approved for the treatment of relapsed/refractory T-cell lineage ALL. [61][62][63] These agents may be incorporated as part of frontline induction, consolidation, and/or maintenance regimens during the course of initial ALL therapy, and in relapsed/refractory disease settings.…”