New Info from BLOOD & 2009 ASH

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Fine-tuning targeted therapy of CML

by: Neil P. Shah 12/3/09

" In this issue of Blood, Müller and colleagues correlate clinical outcome on

dasatinib with baseline BCR-ABL kinase domain mutation status, providing a

framework for incorporation of BCR-ABL genotype in choosing the optimal

second-line kinase inhibitor therapy in imatinib-resistant patients. This study

should help improve outcomes by personalizing therapy based on the mutations

detected. "

You don't want to miss reading all of this article.

http://bloodjournal.hematologylibrary.org/cgi/content/short/114/24/4914

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The role of B cells in the pathogenesis of graft-versus-host disease.

http://bloodjournal.hematologylibrary.org/cgi/content/short/114/24/4919

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Nilotinib has a higher binding affinity and selectivity for BCR-ABL with respect

to imatinib and is an effective treatment of chronic myeloid leukemia (CML)

after imatinib failure. In a phase 2 study, 73 early chronic-phase, untreated,

Ph+ CML patients, received nilotinib at a dose of 400 mg twice daily. The

primary endpoint was the complete cytogenetic response (CCgR) rate at 1 year.

With a median follow-up of 15 months, the CCgR rate at 1 year was 96%, and the

major

molecular response rate 85%. Responses were rapid, with 78% CCgR and 52% major

molecular response at 3 months. During the first year, the treatment was

interrupted at least once in 38 patients (52%). The mean daily dose ranged

between 600 and 800 mg in 74% of patients, 400 and 599 mg in 18% of patients,

and was less than 400 mg in 8% of patients. Dose interruptions were mainly due

to nonhematologic and biochemical side effects. Myelosuppression was irrelevant.

One patient progressed to blastic crisis after 6 months; one went off-treatment

for lipase increase grade 4 (no pancreatitis). Nilotinib is safe and very active

in early chronic-phase CML. These data support a role for nilotinib for the

frontline treatment of CML. This study was registered at ClinicalTrials.gov as

NCT00481052 [ClinicalTrials.gov] .

http://bloodjournal.hematologylibrary.org/cgi/content/short/114/24/4933

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Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib

against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by

BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited

to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without

BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a

preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib

resistance or suboptimal response.

http://bloodjournal.hematologylibrary.org/cgi/content/short/114/24/4944

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http://ash.confex.com/ash/2009/webprogram/Paper20904.html

http://ash.confex.com/ash/2009/webprogram/Paper18437.html

FYI,

Lottie Duthu