Paper:3782 'Change in Chronic Low-Grade Non-hematologic Adverse Events (AEs) and Quality of Life (QoL) in Adult Patients (pts) with Philadelphia Chromosome–Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Switched From Imatinib (IM) to Nilotinib (NIL)'

Jorge E. Cortes, MD1, Jeffrey H. Lipton, MD, PhD2, Carole B. Miller, MD3*, Sikander Ailawadhi, MD4, Luke Akard, MD5, Javier Pinilla-Ibarz, MD, PhD6*, Felice P. Lin, PharmD7*, Solveig G. Ericson, MD, PhD7 and Michael J. Mauro, MD8

Winning the battle against leukaemia: positive early results in clinical trial for DNA vaccine: News Release from University of Southampton.

There are a number of approaches for selective targeting of leukemic stem cells (LSCs). These include targeting stem-cell properties, such as self-renewal, inducing cycling of quiescent LSCs to sensitize them to conventional agents, employing or inducing immune-based mechanisms, and targeting tumor-specific physiology. Agents such as parthenolide inhibit the ability of leukemic stem cells to respond to oxidative stress and make leukemic stem cells and bulk leukemic cells susceptible to cell death, while normal stem cells remain relatively unharmed by these agents. The major mechanism of action of these small molecules appears to revolve around the aberrant glutathione metabolism pathway found in leukemic cells.

FDA approves Iclusig to treat two rare types of leukemia
Drug approved 3 months ahead of schedule

The U.S. Food and Drug Administration today approved Iclusig (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases.

The researchers report their findings December 9 in a plenary scientific session at the 54th American Society of Hematology Annual Meeting and Exposition in Atlanta.

“This is another tool to fight this disease, but it’s the tool we’ve been waiting for,” said Brian Druker, M.D., director of the OHSU Knight Cancer Institute.

Paper46810

3743 Long-Term Anti-Leukemic Activity of Ponatinib in Patients with Philadelphia Chromosome-Positive Leukemia: Updated Results from an Ongoing Phase 1 Study

Michael W Deininger, MD, PhD1,2, Jorge E. Cortes, MD3, Hagop M. Kantarjian, MD4*, Neil Shah, MD, PhD5, Dale Bixby, MD, PhD6*, Michael J. Mauro, MD7, Ian W. Flinn, MD, PhD8, Thomas O'Hare, PhD1,9, Simin Hu, PhD10*, David J. Dorer10*, Victor M. Rivera, PhD10*, Tim Clackson, PhD10, Christopher D. Turner, MD, FAAP10, Frank G Haluska, MD, PhD10, Brian J. Druker7 and Moshe Talpaz, MD6

'A frequent question now is whether results such as the ones reported here mean that all patients should be treated with a second-generation TKI. Taken at face value, we should always aim in cancer treatment to use our best agent first to have the best chance of rendering our patient free of disease for the longest time, and cured if possible. Our first shot is always our best shot. Nonetheless, one cannot disregard some important facts: (1) most patients do well with imatinib, (2) most patients with resistance to imatinib are still in chronic phase and in generally good condition, and (3) many patients with resistance to imatinib respond to second-generation TKIs. If one adjusts for the sequential use of effective therapy, the current event-free survival is 88% at 7 years compared with the unadjusted rate of 81%.7 However, only 40% to 50% of patients with resistance to imatinib achieve a complete cytogenetic response with second-generation TKIs.8⇓–10 With growing awareness of the relevance of early responses, an argument can be made for using imatinib first and switch patients who are lagging behind early on. This is an attractive approach, but one without data that confirms that patients who fall behind on their response can catch up (in long-term outcome) after such intervention. Then there is the argument of what would we use if we start with a second-generation TKI and the patient develops resistance to it.'.....read full article here:

Challenging Situations in the Management of Leukemias
By John M. Goldman, DM, FRCP, FRCPath, FMedSci, David Marin, MD, FRCP

Managing chronic myeloid leukemia patients intolerant to tyrosine kinase inhibitor therapy


D J DeAngelo


Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

The tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA) has transformed the treatment of patients with chronic myeloid leukemia (CML). Based on positive findings from the International Randomized Study of Interferon Versus STI571 (IRIS) trial,1 published in 2003, imatinib quickly replaced interferon-α as the standard of care. Imatinib has prolonged survival in newly diagnosed patients with chronic-phase (CP) CML; patients from the IRIS study have been followed now for 8 years.2 Their survival rate is 85% overall and 93% when only patients with CML-related deaths and those who have not received stem cell transplant are considered. The more potent BCR–ABL1 TKIs, dasatinib (Sprycel, Bristol-Myers Squibb Company, Princeton, NJ, USA) and nilotinib (Tasigna, Novartis Pharmaceuticals Corporation), were approved by the US Food and Drug Administration (FDA) in 2006 and 2007, respectively, as second-line agents in patients with imatinib resistance or intolerance, and in 2010 both agents received FDA approval for treatment of patients with newly diagnosed CML.