Studie / Anwendung von Ponatinib in Kombination mit einer Chemotherapie schon bekannt, z.Zt. in einer Phase II Studie?
Nachgang ASCO Konferenz 2014:
http://journals.lww.com/oncology-times/ ... th.16.aspx

Combination of ALL Chemotherapy with Ponatinib

In another report at the meeting, a combination of chemotherapy with the tyrosine kinase inhibitor (TKI) ponatinib showed high response rates and indications that it may be an effective treatment for patients with Philadelphia-positive (Ph+) ALL (Abstract 7064).The third-generation TKI ponatinib is a potent BCR-ABL inhibitor, said Susan O'Brien, MD, Professor of Medicine and Chief of the Section of Acute Lymphocytic Leukemia at the University of Texas MD Anderson Cancer Center, who reported the data.“Ponatinib suppresses T315I clones, commonly causing relapse in Ph+ ALL. It has high activity and acceptable single-agent toxicity.”Complete cytogenetic response (CCyR) rates range from 40 to 50 percent in patients who do not respond to use of two or three TKIs and in those with the T315I mutation, she explained. Combinations of ALL chemotherapy and ponatinib are likely to be associated with better response rates, lower relapse rates, and a higher likelihood of eradication of minimal residual leukemia.For the study, she and her colleagues enrolled 37 newly diagnosed Philadelphia-positive ALL patients, median age of 51, into a Phase II study of a combination of hyperCVAD with ponatinib in frontline therapy. The patients received eight cycles of hyperCVAD every 21 days. Ponatinib was given at 45 mg daily for the first 14 days of cycle 1, and then continuously for the subsequent cycles.Patients who had a complete response received maintenance with ponatinib at 45 mg daily with vincristine/prednisone monthly for two years followed by ponatinib indefinitely. Patients received a median of six cycles, and 12 patients are currently receiving maintenance in complete remission. “All patients were in CR after cycle 1,” O'Brien said. “CCyR rates were 94 percent after one cycle and 100 percent after two cycles.”

Virtually all patients (95%) achieved a major molecular response and nearly 75 percent had a complete molecular response (CMR). Similarly, almost all patients (97%) were MRD negative. Eight patients had an autologous stem cell transplant (ASCT) after a median of four courses.Grade 3 or higher toxicities included infections during induction, increased liver function tests, thrombotic events, myocardial infarction, skin rash, and pancreatitis.The results showed that with a median follow-up of 13 months, 31 patients are alive and in complete remission. The one-year progression-free survival rate is an estimated 100 percent and one-year overall survival is 86 percent.At the last follow-up, O'Brien reported, seven patients are alive post-ASCT, and 15 patients on ponatinib are alive. Of the other nine surviving patients, seven were switched to dasatinib, one to imatinib, and one patient is no longer receiving treatment.“Due to the vascular events observed, some patients were switched to alternative TKIs,” she said. In the remaining patients, the ponatinib dose was modified to 30 mg daily during consolidation, with subsequent reduction to 15 mg in patients in CMR.In conclusion, she said, “HyperCVAD with ponatinib is highly effective in patients with Ph+ ALL, with high molecular response rates and durable responses.”Commenting also on this study, Sekeres said, “This large study looked at the newest TKI approved for chronic myeloid leukemia. Now ponatinib is being applied to ALL. It shows a high response rate in patients who don't typically have high responses—in particular, an extremely high CCyR rate.“Ponatinib may represent a new standard in treating these patients. ALL experts need to think more about combining new agents with established therapies.”


Und bei der ASH 2014
https://ash.confex.com/ash/2014/webprog ... 68300.html

2289 Phase II Study of Combination of Hypercvad with Ponatinib in Front Line Therapy of Patients (pts) with Philadelphia Chromosome (Ph) Positive Acute Lymphoblastic Leukemia (ALL)Clinically Relevant Abstract

Und noch ein Link für den Hintergrund zu anderen Kombinationstherapien:
http://www.intechopen.com/books/clinica ... -fact#SEC6
Acute Lymphoblastic Leukemia (ALL) Philadelphia Positive (Ph1) (Incidence Classifications, Prognostic Factor in ALL Principles of ALL Therapy)

By Alicia Enrico and Jorge Milone