Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma.
Yasmin M AbazaHagop M KantarjianStefan FaderlElias J JabbourNitin JainDeborah ThomasTapan Mahendra KadiaGautam BorthakurJoseph D KhouryJan BurgerWilliam WierdaSusan O'BrienMarina KonoplevaAlessandra FerrajoliPartow KebriaeiBouthaina DabajaSteven KornblauYesid AlvaradoNaval DaverNaveen PemmarajuPrithviraj BosePhilip ThompsonHind Al AzzawiMary KellyRebecca GarrisPreetesh JainGuillermo Garcia-ManeroJorge CortesFarhad RavandiPublished in: American journal of hematology (2017)
Nelarabine, a water soluble prodrug of 9-β-D-arabinofuranosylguanine (ara-G), is a T-cell specific purine nucleoside analogue. Given its activity in relapsed and refractory T acute lymphoblastic leukemia (T-ALL) and T lymphoblastic lymphoma (T-LBL), we sought to define its role in the frontline treatment of adult patients. Therefore, we conducted a single arm phase 2 study to determine the safety and efficacy of nelarabine in combination with hyper-CVAD in newly diagnosed patients. For induction/consolidation, patients received eight cycles of hyper-CVAD alternating with high-dose methotrexate and cytarabine plus two cycles of nelarabine given at a dose of 650 mg/m2 intravenously daily for 5 days. This was followed by thirty months of POMP maintenance chemotherapy with two additional cycles of nelarabine given instead of cycles 6 and 7 of POMP maintenance. Sixty-seven patients, including 40 with T-ALL and 26 with T-LBL, were enrolled. Complete response rates in both T-ALL and T-LBL were 87% and 100% respectively. Grade 3 to 4 neurotoxic adverse events were reported in 5 patients. There were 21 relapses (31%) including 2 after allogeneic stem cell transplantation. Median duration of follow-up was 42.5 months. The 3-year complete remission duration (CRD) and overall survival (OS) rates were 66% and 65%, respectively. Compared to our historic hyper-CVAD data, there was no survival benefit with the addition of nelarabine. In conclusion, hyper-CVAD plus nelarabine was well tolerated and active in the frontline treatment of adult T-ALL/LBL patients.
Keyphrases
- newly diagnosed
- acute lymphoblastic leukemia
- end stage renal disease
- high dose
- stem cell transplantation
- peritoneal dialysis
- prognostic factors
- acute myeloid leukemia
- low dose
- drug delivery
- rheumatoid arthritis
- young adults
- diffuse large b cell lymphoma
- systemic lupus erythematosus
- electronic health record
- bone marrow
- smoking cessation
- open label
- allogeneic hematopoietic stem cell transplantation
- rectal cancer
- hodgkin lymphoma