Impressions of a 73-Year-Old Man With Relapsed CLL

Danielle M. Brander, MD: The case today is a 73-year-old man who presented to his primary care physician for a scheduled annual checkup. He complained of mild fatigue and occasional night sweats. He had a past medical history notable for hypertension, but this was medically controlled.

On physical exam, he was noted to have palpable axillary and right-sided cervical lymphadenopathy. During his clinical work-up, laboratory tests showed his white blood cell count elevated to 48,000, with lymphocytes comprising 72% of that. And, he was within normal limits—3700. His hemoglobin was 9.4 g/dL. His platelets were low—100,000. His LDH was within normal limits—240 U/L. On flow cytometry sent for work-up of the lymphocytosis, he was found to have a CD5, CD23, CD20-positive monoclonal B-cell population consistent with a diagnosis of CLL [chronic lymphocytic leukemia].

He was referred to a hematologist, who did additional work-up of his CLL. A fluorescence in situ hybridization (FISH) test was conducted. The FISH was normal for all CLL probes tested, and also negative for t(11;14). The IGHV mutational status returned as unmutated. He was Rai stage IV, or Binet stage B, and his ECOG performance status was 0.

For frontline therapy, after a discussion of treatment options, he was started on full-dose ibrutinib—420 mg daily. His symptoms improved, and his lymphadenopathy returned. He continued to do well on the drug during routine follow-up. However, after being treated for about 3 years with ibrutinib, he complained again of increasing fatigue and decreased appetite. On physical exam, he had return of palpable lymphadenopathy as well as palpable splenomegaly of approximately 4 cm below his costal margin. On other labs, it was notable that his chronic kidney disease calculated to a creatinine clearance of approximately 56 mL/min.

This case represents what is typical for many patients with CLL. The patient was over age 70 at the time of diagnosis, and like most patients with CLL, there were minimal to no symptoms at the time of diagnosis. In terms of prognosis, we have discovered key biomarkers at the time of diagnosis that can help predict the amount of time patients may have until they require therapy. Increasingly, these biomarkers are important in choosing frontline therapy for patients.

In this case, the patient had a normal FISH for CLL probes that were detected. Normal FISH is considered an intermediate or standard prognosis. However, the patient also had an unmutated IGHV. Approximately half the patients with CLL have unmutated IGHV, and this is considered a less favorable prognosis. As in this case, the patient progressed to requiring treatment.

However, it should be noted that in the past with chemoimmunotherapy, patients with unmutated IGHV also had inferior responses and duration of responses to treatment with chemotherapy. We are not seeing those same differences, mutated versus unmutated, for patients treated in the frontline with the novel agents, such as in this case, ibrutinib.

This is a very important distinction and again highlights the reason and the importance of testing for these biomarkers at the time of diagnosis, or, at minimum, at the time of first treatment.

Transcript edited for clarity.

Case: A 73-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia

Initial Presentation

• A 73-year-old man presented to his PCP for an annual checkup; he complained of mild intermittent fatigue and occasional night sweats
• PMH: hypertension, medically controlled
• PE: palpable axillary and right-sided cervical lymphadenopathy
  
  

Clinical Work-up

• Labs: WBC 48,000, lymphocyte 72%, ANC 3700/mm3, Hb 9.4 g/dL, plt 100 x 109/L, LDH 240 U/L, Beta-2-microglobulin 4.1 mg/L
• FC CD 5+, CD23+, CD20+ monoclonal B-cell population
• FISH: normal for all CLL probe set tested, no evidence t11;14
• IGHV mutational status: unmutated
• Rai stage IV; Binet stage B
• ECOG PS 0

Treatment and Follow-up

• He was started on ibrutinib 420 mg PO qDay; symptoms improved and achieved stable disease resolution of lymphadenopathy
• After about 3 years he complained of increasing fatigue and decreased appetite, on PE return of palpable lymphadenopathy spleen was palpable ~4 cm below costal margin; creatinine clearance 56 mL/min