Maintenance TKI therapy 'feasible' for high-risk CML patients after allogeneic HSCT

Jun 15 2016

By Lynda Williams, Senior medwireNews Reporter

Patients with high-risk chronic myeloid leukaemia (CML) who undergo allogeneic haematopoietic stem cell transplantation (HSCT) may benefit from continuing with tyrosine kinase inhibitor (TKI) therapy, US clinicians believe.

"Maintenance TKI therapy post-transplant is feasible and may reduce relapses and improve outcomes following allogeneic HSCT for high-risk [Philadelphia chromosome-positive] leukemia", suggest Hanna Khoury, from Emory University in Atlanta, Georgia, and co-workers.

They describe the outcomes of nine patients with accelerated or blast phase CML who were given post-transplant maintenance TKI therapy between 2004 and 2014. Data are also reported for 17 patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) who were in their first or second complete remission.

The authors explain in Clinical Lymphoma, Myeloma and Leukemia that post-transplant TKI therapy was initiated a median of 100 days after HSCT and the agent chosen on the basis of pre-transplantation TKI response and tolerability, and the presence of the ABL1 domain mutation.

Ten patients were given imatinib and 14 dasatinib, with nilotinib and ponatinib each given to one patient. Treatment lasted for a median of 16 months, with continuous TKI use for at least 1 year achieved by over half (54%) of the patients. A third (31%) of patients, all of whom had been taking dasatinib, discontinued treatment for side effects, such as fluid retention and pleural effusion.

After a median of 3.6 years, 5-year overall survival and recurrence-free survival for the whole patient group were estimated to be 78% and 61%, respectively. And 5-year overall survival for the subgroup of patients with advanced-phase CML or ALL in second remission was 79%.

Two patients experienced haematological relapse during maintenance TKI therapy and one patient molecular relapse. These patients achieved undetectable molecular residual disease with further TKI therapy and chemotherapy, and remained in complete remission for a median of 2.5 years after relapse.

And none of the relapse patients showed ABL1 domain mutations, countering concerns that TKI exposure "may exert selective pressure on specific clonal populations, which would lead to treatment resistant relapses", the authors say.

One patient developed grade III or IV acute graft versus host disease and eight patients severe chronic GVHD. There were no leukaemia-related deaths, but three septic deaths in ALL patients were reported in the first year after transplant and three CML patients died from chronic GVHD or organ failure.

Summarising post-transplantation TKI therapy as being "well tolerated" with "favorable outcomes" and "encouraging" survival, the team concludes: "These preliminary results argue that the role of maintenance post-transplant TKIs in advanced-phase CML deserves further evaluation in prospective trials."

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