Risk Stratification for a Patient with CLL

Nicole Lamanna, MD: Let’s talk about a 58-year-old patient with CLL [chronic lymphocytic leukemia] who was initially watched for a short period of time but then developed evidence of progressive disease. The patient is 17p deleted and unmutatedIGVH, developed an elevated white blood cell count and then subsequently anemia, thrombocytopenia, organomegaly. Required treatment, was initially given fludarabine/cyclophosphamide/rituximab, or FCR, had a complete response initially to therapy but progressed only 3 years later, requiring re-treatment.

If you think about this case, it was almost in the era pre-ibrutinib because initially, the patient is young. So, when you think about young, fit patients, fludarabine/cyclophosphamide/rituximab would not be unreasonable. Nowadays, obviously, with the novel therapies, the fact that the patient has a 17p deletion and is unmutated, I would not have given FCR in this case. Ibrutinib or a clinical trial, of course, but ibrutinib or novel-based therapy would be the approach to take. Because, again, due to the high-risk features that the patient has, we know that patients who got FCR and were 17p deleted have a short response duration to therapy. So it’s really inferior therapy. So a patient nowadays, if they were identified as needing treatment and they have a 17p deletion, they would be selected for ibrutinib-based therapy.

In addition, The University of Texas MD Anderson Cancer Center also presented data many years ago that looked at FCR. When it was broken down by their mutational status—theirIGVH—they did not do as well for those individuals who were unmutated as opposed to those who were mutated. So, if you have somebody who has a 17p deletion and/or who is unmutated, you would probably not give them FCR-based therapy. You would put them on ibrutinib or another novel agent—ibrutinib being of course approved for untreated patients with CLL. But, certainly, you could entertain other therapies as they become approved as well.

That is one of the highlights that I think should come out about this case that’s significant. The fact that the patient in 3 years progressed after FCR, again, just shows you the response duration to FCR in a high-risk individual who is unmutated and has a 17p deletion, this goes along with that. The response duration is short to FCR, and a novel agent would have been better.

When a patient with CLL presents, and this is always I think a little bit up for debate, do you test everything? Do you test their cytogenetics and FISH [fluorescence in situ hybridization] and their mutational status up front? What about CT [computed tomography] scans? I think there’s two ways to look at this. I think that many of us who practice CLL routinely and are in academic centers have the ability to test and get many of these tests covered. I think if you’re in the community and the patient doesn’t otherwise need therapy currently, obviously you need to make the diagnosis, so you need to send flow cytometry and confirm that the patient has CLL. If the patient does not have bulky lymphadenopathy on exam nor has a big spleen or liver that you’re concerned about, do you have to CT scan them at initial presentation? No.

If the patient though subsequently needs therapy, then the testing I think has to be done. You have to get cytogenetics and FISH because you want to know does the patient have a 17p or p53, because that will change the type of therapy you’re giving them. And are they unmutated or they’re mutated? Because, if they’re unmutated, again, you’re going to favor not chemoimmunotherapy-based therapy.

So you do need to test the patient prior to initiating therapy at the very least. Whether you test them as soon as they’re diagnosed, I think there’s room because many of these tests, in particular some of these blood tests, can be extremely expensive. And so if that’s problematic for the patient, doing that up front I don’t think is absolutely necessary if it doesn’t change what you’re going to do with the patient at that time.

But prior to starting therapy, yes, because having that discussion of are you going to start ibrutinib-based therapy, obviously there’s much data that was presented at this ASH [American Society of Hematology meeting] that suggests that ibrutinib-based therapy is better regardless. But, for those individuals who you might want to still give chemoimmunotherapy, if they’re favorable patients, mutatedIGVH, that discussion can still be had. But you need to test the patients to know that. So those testings do need to be performed prior to initiating therapy on patients with CLL.

Transcript edited for clarity.

A 58-Year-Old Man With Relapsed CLL

• A 58-year—old man presented with symptoms of fatigue and left upper quadrant fullness
• PMH: cervical lymphadenopathy, ~2.5 cm; spleen, palpable ~6 cm below left costal margin
• PE: vital signs WNL, right cervical lymphadenopathy, spleen palpable 5 cm below costal margin, otherwise well-appearing
• Laboratory findings:
  • WBC, 160,000; 68% lymphocytes (ALC, 112,000 cells/mL)
  • Hb; 9.4 g/dL
  • Platelets; 130 X 10⁹/L
  • ANC; 174/mm³
• Flow cytometry; CD5+, CD19+, CD23+
• Cytogenetics, IgVH unmutated; del 17p
• β2M, 4.0 mg/L
• BM biopsy; diffuse infiltration by CLL
• Diagnosis; chronic lymphocytic leukemia
• The patient was treated with fludarabine, cyclophosphamide, and rituximab and achieved a complete remission

Three years later, on routine follow up

• Laboratory findings:
  • WBC; 93,000; 97% lymphocytes
  • Hb; 10.4 g/dL
  • Platelets; 123 X 10⁹/L
  • ANC; 1,600/mm³(WNL)
  • LDH; 242 U/L
  • Beta-2-microglobulin; 9.1 µg/L