Case 2: Switching a Patient to Dasatinib When Imatinib Therapy Fails

PATIENT 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
Physical
  • Spleen was palpable 2 cm below the left costal margin 
Laboratory Test Results
  • 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 phase

TREATMENT
  • Treatment initiated with imatinib 400 mg/day
  • Blood counts monitored weekly until improvement was noted

FOLLOW-UP

  • After 3 months of therapy with imatinib, blood tests showed
  • – WBC: 9700/μL
    – 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
  • 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

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

FOLLOW-UP

  • 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

DISCUSSION

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.

References
:
1. NCCN Clinical Practice Guidelines in Oncology. Chronic myelogenous leukemia, Version I. 2011.
2. SPRYCEL® [package insert]. Princeton, NJ: Bristol-Myers Squibb; June 2009.
Loading links....
You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings

GET FULL LISTINGS OF TREATMENT Regimens and Drug INFORMATION

Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs