A 77-Year-Old Man with Chronic Lymphocytic Leukemia

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Andrew Zelenetz, MD: Hi, I’m Andrew Zelenetz from Memorial Sloan Kettering Cancer Center [in New York], and I’m here to talk to you about a patient with chronic lymphocytic leukemia [CLL]. This is a 77-year-old man who presented to an urgent care center complaining of increasing fatigue with accompanying unexplained fevers and night sweats. This has been going on for several weeks. Over the past 6 months, he lost about 12 pounds without actually trying. His past medical history is significant for hypertension, which is medically well controlled. He has BPH [benign prostatic hyperplasia], and he has some osteoarthritis in the spine and hips, but he’s relatively active and able to do his regular activities. An examination reveals bilateral cervical axillary and right-sided inguinal lymphadenopathy. The CBC [complete blood count] was remarkable for leukocytosis, with a white count of 49,000 and 74% lymphocytes. The absolute neutrophil count was 3.7 per mm3, and hemoglobin was 9.2 g/dL with a platelet count of 90,000 per mm3. His LDH [lactate dehydrogenase] was normal, and beta-2 microglobulin was elevated at 4.1 with normal creatinine. Peripheral blood flow cytometry was performed and demonstrated a CD5-positive, CD23-positive, CD20 dim, and CD19-positive. The monoclonal B-cell population was consistent with the diagnosis of CLL.

Other markers that can be useful are oral 1 and CD200, particularly if there’s some question about whether this could be mantle cell lymphoma, because mantle cell lymphoma is almost never CD200-positive. The additional work-up included IGHV mutation testing, and it was an unmutated IGHV. FISH [fluorescence in situ hybridization] demonstrated deletion 11q but no evidence of deletion 17p. The patient was Rai stage IV—in the shorter version, Rai high risk. He had ECOG performance status of 1. The patient was started on ibrutinib 420 mg oral daily and had rapid improvement in his symptoms and noted pretty rapid regression of peripheral lymph nodes. Three months into treatment, he presented to the urgent care center again complaining of dyspnea, chest pain, some confusion, and anxiety.

He was convinced he was having a heart attack, but evaluation revealed no evidence of a myocardial infarction. However, there was new-onset atrial fibrillation. The patient was given options of medications for the atrial fibrillation and options for his treatment for CLL. The patient chose to discontinue the ibrutinib. The patient was then started on idelalisib, 150 mg oral twice daily in combination with rituximab.

Overall, my impression is that this is a patient with mild comorbidities, who’s relatively fit, who clearly needed a first-line treatment for CLL. He had symptoms, and he had Rai high-risk disease. Based on the CLL-IPI [CLL International Prognostic Index], he would have been in the high-risk category but not in the very high-risk category, because you can’t get there without aberration of TP53. In the work-up, 1 thing I would have done differently is definitely including sequencing of TP53 as part of the evaluation. This doesn’t have to happen when you first meet the patient, but as soon as you’re considering treatment in addition to the FISH sequencing, the TP53 is important because both the p53 deletion and TP53 mutation can happen independently. But they have similar adverse impacts on alcohol, and it’s very important to know.

In terms of first-line treatment, ibrutinib is well supported by the data we have. This is based on a number of clinical trials, including the RESONATE-2 trial as well as both the ECOG and CALGB randomized trials demonstrating superiority, particularly in the IGHV unmutated patients of Ibrutinib over chemotherapy-immunotherapy. Now, a lot of people ask, “Should we add rituximab to ibrutinib in the first-line?” The answer is pretty clear; the answer is no. We have randomized data demonstrating that there’s no additional benefit of adding rituximab because this will further reduce normal B-cell numbers. [Rituximab] creates greater immunosuppression and greater risk for infection but doesn’t improve outcome.

This transcript has been edited for clarity.

Case: A 77-Year-Old Man With Chronic Lymphocytic Leukemia

Initial Presentation

• A 77-year-old man presented to urgent care reporting worsening fatigue accompanied by persistent, unexplained fevers and night sweats over the past few weeks and unintentional 12-lb weight loss over the past 6 months
• PMH: HTN, medically controlled; BPH; OA in spine and hips
• PE: palpable cervical, axillary, and right-sided inguinal lymphadenopathy
   

Clinical Workup

• Labs: WBC 49,000, lymphocyte 74%, ANC 3700/mm3, Hb 9.2 g/dL, PLT 90 x 109/L, LDH 240 U/L, B2M 4.1 mg/L
• FC: CD 5+, CD23+, CD20+ monoclonal B-cell population; confirmed diagnosis of CLL

Hem/Onc Workup

• Mutation testing: IGHV unmutated; FISH: positive for del(11q)
• Rai stage IV; Binet stage C
• ECOG PS 1
   

Treatment

• Started on treatment with ibrutinib 420 mg PO QD; his symptoms improved and he achieved partial response
• 3 months into treatment he returned to urgent care reporting SOB, pain in his chest, confusion, and anxiety; he was convinced he was having a heart attack
  • Work-up revealed treatment-related atrial fibrillation
  • Situation was explained to the patient and he was offered medication and monitoring but preferred to change to a different medication out of concern for this happening again or worsening
  • Labs were repeated
• Treatment was initiated with idelalisib 150 mg PO BID + rituximab