Case 2: Switching a Patient to Dasatinib When Imatinib Therapy FailsPATIENT PRESENTATION
MP is a 54-year-old white production manager who complained of a 2-month history of increasing fatigue and upper left quadrant discomfort.
PATIENT HISTORY AND DIAGNOSIS
- Spleen was palpable 2 cm below the left costal margin
- WBC: 189,000/μL
- Hemoglobin: 8.4 g/dL
- Platelets: 125,000/μL
- Bone marrow biopsy: hypercellular marrow with leukemic blast cells
- Cytogenetic testing: positive translocation between chromosomes 9 and 22 in 20 of 20 evaluated metaphases
Assessment: Confirmed diagnosis of Ph+ CML in chronic phaseTREATMENT
- Treatment initiated with imatinib 400 mg/day
- Blood counts monitored weekly until improvement was noted
- After 3 months of therapy with imatinib, blood tests showed – WBC: 9700/μL
- After 6 months of treatment, MP's blood counts remained within normal limits, and his spleen was no longer palpable. Bone marrow examination showed the Ph+ chromosome in 4/20 metaphases by standard cytogenic testing, indicating a major partial response (defined as 1% to 34% Ph+ metaphases).1
- At 9 months of treatment, a complete hematologic response was maintained. Molecular testing showed a 1-log10 reduction in the bcr-abl transcripts
- At 12 months, despite a normal blood count, bone marrow testing showed persistent Ph+ chromosomes in 4 of 20 metaphases, indicating no further response. Molecular testing revealed no significant change in bcr-abl fusion transcripts
– Hemoglobin: 12.5 g/dL
– Platelets: 165,000/μL, indicating a complete hematologic response
– MP complained of ankle edema that improved with a decrease in his dietary sodium intake
CHANGE IN THERAPY
- A mutation analysis testing for the emergence of bcr-abl mutations that might indicate a resistance to TKIs was negative. Due to MP's suboptimal response to imatinib, he was switched to dasatinib 100 mg/day after ECG and electrolytes were monitored
- After 6 months of treatment with dasatinib, MP's bone marrow showed a normal male karyotype with no Ph+ cells detected by standard cytogenetics or by fluorescense in situ hybridization
- Molecular testing revealed a major molecular response (>3-log10 reduction)1
- Adverse events included transient anemia, a moderate skin rash treated successfully with topical corticosteroids, and grade 2 pleural effusion. To manage the pleural effusion, dasatinib was discontinued for 2 weeks and diuretics were administered. Dasatinib was restarted when pleural effusion resolved; MP was monitored for recurrence
- After 9 months of treatment with dasatinib, molecular testing revealed no bcr-abl transcripts, indicating a complete molecular response
In general, second-generation TKIs are well tolerated, but adverse events can occur. One of the adverse events observed with dasatinib is pleural effusion.2 Periodic physical examinations should include assessment of breath sounds to detect pleural effusion. If this occurs, dose modification, therapy interruption, or a switch in therapy to nilotinib or imatinib, may be required, depending on severity. Cytopenias, including transient anemias, are evidenced by a drop in blood counts and must be monitored regularly with blood chemistry panels. Routine skin exams well also help check for rash. QT intervals should also be monitored regularly during treatment.2 The goal is to maintain the patient on continuous drug therapy, with minimal interruptions.
Strategies for handling adverse events such as headache and musculoskeletal pain can be discussed with the patient to ensure that those strategies are congruent with the patient's lifestyle.
It may be appropriate to switch the patient to another TKI if treatment is frequently discontinued. It is also important for nurses to be aware that when a patient is switched from one TKI to another, it can be a frightening event for the patient. Patients should be assured that other options are available to achieve treatment milestones and that to achieve the optimal response, multiple treatment trials may be needed.
1. NCCN Clinical Practice Guidelines in Oncology. Chronic myelogenous leukemia, Version I. 2011.
2. SPRYCEL® [package insert]. Princeton, NJ: Bristol-Myers Squibb; June 2009.