Mary Kelly

Phase II study of the histone deacetylase inhibitor panobinostat (LBH589) in patients with low or intermediate-1 risk myelodysplastic syndrome†

A phase II non‐randomized single arm trial of oral panobinostat (LBH589) was conducted in patients with low or intermediate‐1 risk myelodysplastic syndrome (MDS). The objective of this study was to determine the clinical efficacy, safety, and tolerability of panobinostat in this patient population. The study would stop early if there was a chance >99% that the average overall response rate was <15%. Thirteen patients were treated: Median age was 70 years (range 47–84), 70% were transfusion dependent, 70% had intermediate‐1 risk MDS. Most patients were diploid but one patient with del(5q), one with trisomy 8, one with complex cytogenetics, and two with deletion of 20q were included. Approximately 40% had previous therapy for MDS. Of the 13 patients, 1 (8%) achieved hematological improvement (HI‐E and HI‐P, duration 3 months) and 6 (46%) had stable disease for a median duration of 6 months (range 1.7–13.6). Treatment was withheld in one patient because of QTc prolongation but no other serious adverse effects were otherwise observed. Panobinostat did not consistently induce histone acetylation as measured with Western blot. This data indicates that panobinostat at the dose and schedule studied here has limited activity in lower risk MDS. Am. J. Hematol., 2012.

The combination of hyper-CVAD plus nelarabine as frontline therapy in adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma: MD Anderson Cancer Center experience

The combination of hyper-CVAD plus nelarabine as frontline therapy in adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma: MD Anderson Cancer Center experience

Hyper-CVAD plus nelarabine in newly diagnosed adult T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma

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.

A Phase I/II Study of Selinexor (SEL) with Sorafenib in Patients (pts) with Relapsed and/or Refractory (R/R) FLT3 Mutated Acute Myeloid Leukemia (AML)

AML-025 A Phase I/II Study of Selinexor (SEL) with Sorafenib in Patients (pts) with Relapsed and/or Refractory (R/R) FLT3 Mutated Acute Myeloid Leukemia (AML) Naval Daver, Rita Assi, Farhad Ravandi, Guillermo Garcia-Manero, Elias Jabbour, Courtney D. DiNardo, Tapan M. Kadia, Jing Ning, Graciela Nogueras-Gonzalez, Sherry Pierce, Dan Gombos, Steven Kornblau, Marina Konopleva, Mary Kelly, Gautam Borthakur, Weiguo Zhang, Jorge Cortes, Hagop Kantarjian, Michael Andreeff Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Ophthalmology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA