High single-drug activity of nelarabine in relapsed T-lymphoblastic leukemia/lymphoma offers curative option with subsequent stem cell transplantation.

Abstract

Nelarabine, a purine analog with T-cell specific action, has been approved for relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL). This is a report of a single-arm phase 2 study conducted in adults (18-81 years of age) with relapsed/refractory T-ALL/LBL. After 1 or 2 cycles, 45 of 126 evaluable patients (36%) achieved complete remission (CR), 12 partial remission (10%), and 66 (52%) were refractory. One treatment-related death was observed, and 2 patients were withdrawn before evaluation. A total of 80% of the CR patients were transferred to stem cell transplantation (SCT). Overall survival was 24% at 1 year (11% at 6 years). After subsequent SCT in CR, survival was 31% and relapse-free survival 37% at 3 years. Transplantation-related mortality was 11%. Neurologic toxicities of grade I-IV/grade III-IV were observed in 13%/4% of the cycles and 16%/7% of the patients. This largest study so far with nelarabine in adults showed impressive single-drug activity in relapsed T-ALL/T-LBL. The drug was well tolerated, even in heavily pretreated patients. A high proportion of CR patients were transferred to SCT with low mortality but a high relapse rate. Exploration of nelarabine in earlier stages of relapse (eg, increasing minimal residual disease), in front-line therapy, and in combination is warranted.

• Authors: Nicola Gökbuget, Nadezda Basara, Herrad Baurmann, Joachim Beck, Monika Brüggemann, Helmut Diedrich, Björn Güldenzoph, Gernot Hartung, Heinz-August Horst, Andreas Hüttmann, Guido Kobbe, Ralph Naumann, Richard Ratei, Albrecht Reichle, Hubert Serve, Matthias Stelljes, Andreas Viardot, Mohammed Wattad, Dieter Hoelzer
• Journal: Blood (Blood) Vol. 118 Issue 13 Pg. 3504-11 (Sep 29 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21715318 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antineoplastic Agents
• Arabinonucleosides
• Prodrugs
• nelarabine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (therapeutic use)
• Arabinonucleosides (therapeutic use)
• Chemotherapy, Adjuvant
• Female
• Humans
• Leukemia-Lymphoma, Adult T-Cell (drug therapy, pathology)
• Male
• Middle Aged
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, pathology)
• Prodrugs (therapeutic use)
• Recurrence
• Remission Induction
• Stem Cell Transplantation (methods)
• Treatment Outcome
• Young Adult