Physician:

dr-owen

  • Dr. Carolyn Owen, MD, MDres(UK), FRCPC
  • Division of Hematology and Hematological Malignancies, Foothills Medical Centre and Tom Baker Cancer Centre, Calgary, Alberta, Canada

Patient History:

Past history:

  • Myocardial infarction 10 years ago; no cardiac problems since then.
  • Benign prostatic hypertrophy, mild dyslipidemia (not yet treated), and past kidney stones

March 2010:

  • 69-year-old male.
  • Diagnosed with Rai Stage 1 CLL
  • Incidental diagnosis on computed tomography (CT) scan after presentation to emergency department with kidney stone.
  • CT scan showed mild splenomegaly, intra-abdominal and pelvic lymphadenopathy with largest lymph node at 1.5 cm in diameter.
  • Flow cytometry of peripheral blood showed typical chronic lymphocytic leukemia (CLL) morphology (with B-cell count only 6,000 cells/mm3 at the time).
  • Complete blood count (CBC) otherwise normal (hemoglobin 145 g/L, platelets 185 billion/L). Chemistry all normal.
  • Physical exam normal except for small palpable lymph nodes (0.5-1.0cm) in neck and in both groins

→ Managed with watch and wait.

Presentation:

2013:

  • 73 years of age.
  • Disease progression.
  • Obvious splenomegaly and palpable lymph nodes (measured clinically 3–4 cm each axilla and 2–3 cm in the neck bilaterally).
  • Spleen 10 cm below costal margin.
  • Spleen symptomatic (i.e., causing abdominal discomfort).

Laboratory & Clinical Findings:

2013:

  • Platelets 84 billion/L, hemoglobin 128 g/L, lymphocytosis 8 (Rai stage IV CLL needing treatment for symptomatic splenomegaly).
  • All chemistry still normal except lactic acid dehydrogenase 280 U/L (upper limit of normal 235 U/L).
  • Fluorescence in-situ hybridization did not show a 17p deletion (only marker screened).

Treatment:

2013:

  • Discussion with patient who wants intensive therapy (wanting long remission) but very afraid of toxicity, particularly neutropenic infection because patient is very opposed to the idea of admission to hospital.
  • Patient is relatively fit but not appropriate for treatment with fludarabine, cyclophosphamide, and rituximab (FCR) because of advanced age.
  • Treated with bendamustine plus rituximab (BR) at the standard first line dosing for CLL of 90 mg/m2 intravenously (iv) on days 1 and 2 combined with 375 mg/m2 rituximab iv on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses.

Outcome:

  • Clinical CR: All palpable disease resolved, normalized CBC (2 months after final cycle of chemotherapy).
  • Severe neutropenia after cycle 3; received granulocyte colony-stimulating factor (G-CSF), a week delay before cycle 5, and a dose reduction to 70 mg/m2 for cycles 4, 5, and 6.

Management of Adverse Events:

  • Neutropenia (even Grade 4) is still relatively common with BR and because the patient was worried, he was having q2 weekly CBC screening.
  • Given his advanced age, dose reduction and treatment delay were instituted after the neutropenia was noted. This prevented further severe neutropenia and likely prevented infection.
  • Prophylactic Septra® against Pneumocystis jiroveci pneumonia and Valtrex® during treatment and for 6 months after treatment.

Recommendations:

  • BR at a dose of 90 mg/m2 is a good option for potent, effective therapy for older, fit, and likely for younger, less fit, CLL patients.
  • Health care practitioners should take note of the toxicities with BR and be prepared to counsel patients on the risks of neutropenia and infections, and to watch patients carefully to prevent these events from occurring.
  • If a patient is considered more unfit for intensive chemotherapy, consider a starting dose of 70 mg/m2 iv on days 1 and 2 combined with 375 mg/m2 iv rituximab on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses.
  • Prophylactic anti-infectives are strongly recommended for CLL patients

Conclusion:

  • The patient had an excellent response to therapy, but the use of this immunochemotherapy still requires vigilance for toxicity and management of adverse events as they arise.
  • I chose to treat this patient with BR because it is a potent and effective therapy for CLL as demonstrated in the CLL10 study. While FCR was more effective than BR in younger, fit patients, the toxicity was also greater in terms of Grade 3-4 neutropenia and infections. The increase in toxicity with FCR compared to BR negated the benefit of FCR for PFS in patients over 65 years of age.