Imatinib, Post-Induction SCT Improve Long-term Survival in Ph+ALL

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(ChemotherapyAdvisor) – Adding imatinib to a first-line chemotherapy and stem cell transplantation (SCT) after induction improve long-term survival among patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL), according to a new analysis published in Biology of Blood and Marrow Transplantation.

The results “suggest that allogeneic or autologous SCT still has a place to overcome the poor prognosis of Ph+ ALL in the era of imatinib therapy,” reported a research team led by senior author Xavier Thomas, MD, at the Pitié-Salpêtrière Hospital Hematology Department, in Paris, France.

The new analysis of GRAAPH-2003 outcomes involved a much longer median follow-up period of 46 months for 45 Ph+ ALL patients between the ages of 16 and 59 years. Overall survival (OS) was 80% among patients who received autologous SCT (n=10 patients), 50% (n=24) after allogeneic SCT, compared to 33% (n=9) without transplant, the authors reported.

The findings suggest that “in Ph+ALL patients, the addition of imatinib to a first-line chemotherapy is associated with an improved long-term outcome,” the authors wrote.

SCT after induction-phase therapy further improved outcomes, they emphasized.

“(E)ven when including imatinib during the induction phase, the prognosis of patients can again be improved by intensifying the post-remission phase, through either autologous SCT – especially if a low or negative MRD [marrow minimal residual disease] level is achieved after the induction phase – or allogeneic SCT – especially from a HLA-identical sibling,” they wrote.

For both of these groups, 4-year OS exceeded 75%, they reported.

Philadelphia chromosome is most frequent recurrent cytogenetic abnormality observed in adult patients diagnosed with ALL, the authors noted. Outcomes for these patients were very poor prior to the tyrosine kinase inhibitors (TKI) era, with long-term survival rates reaching “at best 20% in most studies,” they wrote.

Previous studies involving patients with Ph+ ALL had showed that concurrent or alternating imatinib and high-dose chemotherapy significantly improve short-term survival rates, with 23-month OS reaching 75%, the authors wrote. The first analysis of GRAAPH-2003 study data found that the 18-month disease free survival (DFS) and OS were 51% and 65%.


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