Treatment Options for Patients with Relapsed CLL

Nicole Lamanna, MD: Let’s re-discuss this patient who is a young, fit patient who initially received FCR [fludarabine/cyclophosphamide/rituximab] but then relapsed after 3 years. They’re 17p deleted and they’re unmutated. So, now at this time point, you actually have more than one option. Ibrutinib, of course, comes to mind the quickest; that’s approved both in frontline and a relapse. Now that this patient’s relapsed, of course, venetoclax/rituximab is another option. So, certainly, you can give either of these options to this patient. So let’s say we gave the patient ibrutinib; then you would monitor the patient. I have to say this patient is young, so one thing to keep in mind if you have a high-risk individual with CLL [chronic lymphocytic leukemia] … I do not expect that these therapies will last indefinitely on this young patient with a 17p deletion. So transplant is still potentially an option that you need to think about. And, in fact, a person who is young in their 50s who presents with a 17p, I’m actually HLA [human leukocyte antigen] typing them from the get-go.

It is not that I’ve taken many patients to allogeneic stem cell transplant anymore for CLL, again, because most of our patients are older and frailer, and there’s all these other options. And so their life is improved by these novel agents, and they’ll be much older so they’re not getting to transplant anyway. But a young patient, you still have to think that how are you going to strategize therapies for a young patient with high-risk features because you are trying to prolong their life, hopefully the quality of their life as well. But you have to think how to strategize, and so there’s no doubt that even from the initial ibrutinib studies in patients with 17p, that progression-free survival curve does continue to drop off compared to the rest.

Then can you salvage with venetoclax and rituximab? Absolutely, but you’re still going to think at some point they’re going to relapse on that combination as well. And that’s where a transplant might be a very good option for that person. What about CAR [chimeric antigen receptor] T cells? CAR T cells will also be an option for that person as well. And, in fact, for some folks who probably couldn’t go to transplant if they might have been older, if they’re relatively fit, CAR T-cell therapy actually might be an option even before transplant.

So I think that this person has several options that you’re going to consider, and some would argue perhaps to take that person to transplant sooner because they’re young and they’re fit, versus waiting. Others may decide to milk these therapies as long as possible and then take the patient to transplant. And I think obviously we don’t have the right answer. We do know that if you take patients who are transplant-eligible, and they’re fitter, and healthier, they do obviously better if you take them sooner than waiting until they have multiple relapse and lots of disease and are frailer.

I think a strategy could be employed that you’re closely monitoring those patients, whether they be on ibrutinib or on venetoclax, looking for relapse sooner. So you still can take them relatively healthy with very little disease burden, switching the agent, and then taking them to transplant as well. So there’s probably more than one correct answer to the right way to go about this, depending upon the patient’s preferences and their disease characteristics with close monitoring. But you have to realize that patients with high-risk features may eventually, not may, will likely eventually relapse, even with these novel agents.

And so you can buy a couple of years perhaps out of each subsequent novel agent, but that still only puts this patient perhaps in their mid- or late-60s, depending upon when they first started. And so you always have to think about that as well. So, certainly, we have done better with patients with 17p and high-risk features, but you’ve still got to think long term, and certainly I would always think about transplant earlier or at least HLA type them being that she’s in her 50s with a 17p deletion.

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