Contributions
Abstract: EP678
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Clinical
Background
The current role of hydroxyurea (hydrea) as a treatment modality in chronic myeloid leukemia (CML) is limited. However, many clinicians still use it as a bridging therapy before starting treatment with tyrosine kinase inhibitors (TKI).
Aims
The objectives of this analysis were to evaluate the use of hydrea in clinical practice in the treatment of CML, and assess the benefits of hydrea pre-treatment on achieving early response milestones and disadvantages such as the occurrence of hematotoxicity during subsequent TKI therapy.
Methods
We performed a retrospective analysis on data from a real-world population-based Dutch registry (The PHAROS CML Registry combined with HemoBase) of newly diagnosed chronic phase CML patients between 2008 and April 2013. Patients were stratified based on having received pre-treatment with hydrea. All time-dependent analyses were performed using the cumulative incidence competing risk (CICR) method with death and progression considered as competing events. The start date of first-line TKI treatment was used as time-point zero in the time-dependent analyses.
Results
From a total of 432 evaluable patients, 194 (45%) patients had received hydrea pre-treatment. Hydrea-treated patients had a higher mean leukocyte count and more often reported presence of hyperviscosity symptoms (3 vs 9%, p = 0.009), constitutional symptoms (36 vs 26%, p = 0.049), or symptomatic splenomegaly (26 vs 12%, p < 0.001) at diagnosis. However, the majority of hydrea-treated patients had no symptoms of hyperleukocytosis or splenomegaly (66%). Surprisingly, the hydrea-treated group had a significantly longer interval between diagnosis and start of first-line TKI treatment (22 vs 15 days, p = 0.002). Also, after the start of TKI therapy, hematotoxicity occurred more frequently in hydrea pre-treated patients (23 vs 11%, p < 0.001). There was no benefit observed of hydrea pretreatment for patients achieving a CHR at 1 or 3 months, nor for CCyR and MMR at the ELN-set response milestones during the first year of treatment. The proportion of patients achieving MMR at 12 months was significantly higher in the non-hydrea group (55% vs 43%, p = 0.05), however this difference was no longer significant when correcting for ELTS-score and type of first-line TKI in a cox-regression model.
Conclusion
Hydrea pre-treatment is used in nearly half of newly diagnosed CML patients, including many patients without a high leukemic load and/or symptom burden. We observed a significantly longer delay in starting first-line TKI treatment in hydrea-treated patients. Furthermore, hydrea pre-treatment was associated with a higher rate of hematotoxicity during first line TKI treatment and no apparent benefit in achieving the ELN-defined response milestones. Our data suggest an unneeded pre-treatment use of hydrea when a diagnosis of CML is under consideration and recommend restricting the use of hydrea pre-treatment to patients with clinically significant (symptomatic) hyperleukocytosis or symptomatic splenomegaly. More restrictive use of hydrea may shorten the delay of TKI treatment initiation at diagnosis and help limit hematotoxicity of TKI therapy.
Keyword(s): Chronic myeloid leukemia, Hydroxyurea
Abstract: EP678
Type: E-Poster Presentation
Session title: Chronic myeloid leukemia - Clinical
Background
The current role of hydroxyurea (hydrea) as a treatment modality in chronic myeloid leukemia (CML) is limited. However, many clinicians still use it as a bridging therapy before starting treatment with tyrosine kinase inhibitors (TKI).
Aims
The objectives of this analysis were to evaluate the use of hydrea in clinical practice in the treatment of CML, and assess the benefits of hydrea pre-treatment on achieving early response milestones and disadvantages such as the occurrence of hematotoxicity during subsequent TKI therapy.
Methods
We performed a retrospective analysis on data from a real-world population-based Dutch registry (The PHAROS CML Registry combined with HemoBase) of newly diagnosed chronic phase CML patients between 2008 and April 2013. Patients were stratified based on having received pre-treatment with hydrea. All time-dependent analyses were performed using the cumulative incidence competing risk (CICR) method with death and progression considered as competing events. The start date of first-line TKI treatment was used as time-point zero in the time-dependent analyses.
Results
From a total of 432 evaluable patients, 194 (45%) patients had received hydrea pre-treatment. Hydrea-treated patients had a higher mean leukocyte count and more often reported presence of hyperviscosity symptoms (3 vs 9%, p = 0.009), constitutional symptoms (36 vs 26%, p = 0.049), or symptomatic splenomegaly (26 vs 12%, p < 0.001) at diagnosis. However, the majority of hydrea-treated patients had no symptoms of hyperleukocytosis or splenomegaly (66%). Surprisingly, the hydrea-treated group had a significantly longer interval between diagnosis and start of first-line TKI treatment (22 vs 15 days, p = 0.002). Also, after the start of TKI therapy, hematotoxicity occurred more frequently in hydrea pre-treated patients (23 vs 11%, p < 0.001). There was no benefit observed of hydrea pretreatment for patients achieving a CHR at 1 or 3 months, nor for CCyR and MMR at the ELN-set response milestones during the first year of treatment. The proportion of patients achieving MMR at 12 months was significantly higher in the non-hydrea group (55% vs 43%, p = 0.05), however this difference was no longer significant when correcting for ELTS-score and type of first-line TKI in a cox-regression model.
Conclusion
Hydrea pre-treatment is used in nearly half of newly diagnosed CML patients, including many patients without a high leukemic load and/or symptom burden. We observed a significantly longer delay in starting first-line TKI treatment in hydrea-treated patients. Furthermore, hydrea pre-treatment was associated with a higher rate of hematotoxicity during first line TKI treatment and no apparent benefit in achieving the ELN-defined response milestones. Our data suggest an unneeded pre-treatment use of hydrea when a diagnosis of CML is under consideration and recommend restricting the use of hydrea pre-treatment to patients with clinically significant (symptomatic) hyperleukocytosis or symptomatic splenomegaly. More restrictive use of hydrea may shorten the delay of TKI treatment initiation at diagnosis and help limit hematotoxicity of TKI therapy.
Keyword(s): Chronic myeloid leukemia, Hydroxyurea