Treating Chronic Lymphocytic Leukemia in Elderly Patients - Episode 1

Risk Stratifying a Case of CLL

Matthew S. Davids, MD, MMSc:This is a 76-year-old man who presented with some low-grade temperatures, sweats, and unintentional weight loss of about 10 pounds over the past several months. The patient had recently been hospitalized for pneumonia and presented to the primary care physician with severe fatigue.

This patient is relatively healthy, although does have a history of diet control, diabetes, as well as hypertension. On physical examination, the patient appeared pale and quite fatigued. And the patient was a bit cachectic looking, although the vital signs were normal. The exam was also notable for enlarged bilateral lymphadenopathy, but no evidence of splenomegaly.

The ECOG performance status was 2. The laboratory evaluation was notable for a lymphocytosis with a total white blood cell count of 18 and a hemoglobin of 12, but a normal platelet count of about 300,000. The primary care physician sent peripheral blood flow cytometry, which revealed a population of monoclonal B cells that were positive for CD20, CD5, and CD23, consistent with the diagnosis of chronic lymphocytic leukemia.

The patient was referred to a hematologist and at this time,IGHVstatus as well as the FISH status were not known. The beta 2 microglobulin came back at 2.6. A bone marrow biopsy was performed, which revealed about 50% involvement by this population of monoclonal B cells.

My general impression of this case is that it’s a bit of an unusual presentation for a patient with CLL these days. The reason I say that is that a majority of patients now are actually asymptomatic at the time of diagnosis. Their primary care doctor may notice an elevated lymphocyte count and confirm the diagnosis, but the patient is feeling fine. But we do still see cases like this with patients who are more symptomatic at the time of diagnosis. And typically, these are patients who have higher-risk disease markers. When I hear this type of story, I do think of a patient perhaps who has FISH test that’s more high risk or perhaps anIGHVstatus that’s higher risk. And so, that would be amongst the first tests that I would send. The FISH test, I wouldn’t be surprised if it revealed either deletion 17p, which is the highest risk abnormality for CLL patients, or possibly a deletion 11q, which is more of an intermediate-risk patient.

On theIGHVside, about 50% of patients with CLL will have unmutatedIGHV, which tends to be a more steadily progressive form of the disease. Patients typically do require treatment relatively soon after diagnosis. And at least historically with our chemoimmunotherapy regimens, the durability of response to treatment was shorter for those patients with the unmutatedIGHV.

So, this is a patient who sounds very symptomatic. The laboratory values are not terribly abnormal, but there is significant lymphadenopathy. So, based on this bulk of disease and the symptoms, this is probably a patient who’s going to need therapy very soon.

Transcript edited for clarity.

  • A 76-year-old male presented with symptoms of low-grade fever, (101.1oF) chills, and weight loss. The patient feels severely fatigued and required extensive rest. He was recently hospitalized for pneumonia.
  • PMH: Hypertension controlled on candesartan, diabetes managed with metformin
  • PE: Pallor and is weak-appearing, vital signs WNL, enlarged mobile lymph nodes bilaterally (~2.0 cm), anterior cervical chain, no hepatosplenomegaly
  • PS, ECOG 2
  • Laboratory findings:
    • WBC; 18.5 X 109/L, 65% lymphocytes
    • Lymphocytes; 86.2 X 109/L
    • Hb; 12.2 g/dL
    • Platelets; 305 X 109/L
    • ANC; 120/mm3
  • Flow cytometry; CD5+, CD19+, CD23+, CD38-low,
  • Cytogenetics, IgVH mutation status, unknown
  • β2M, 2.6 mg/L
  • BM biopsy; 50% lymphocytes
  • Diagnosis; chronic lymphocytic leukemia
  • The patient was treated with ibrutinib and achieved a complete response to therapy after 2 months