Recent Progress in Treatment of Chronic Lymphocytic Leukemia

Nicole Lamanna, MD: For a patient like this who has high-risk features and is young and fit, I think that the CLL [chronic lymphocytic leukemia] progress recently has been remarkable. And previously, when we took a young, fit patient with 17p deletion who relapsed after FCR [fludarabine/cyclophosphamide/rituximab] therapy back in the day, their overall survival was somewhere between 9 and 12 months. This is completely different. This is why drugs like ibrutinib and venetoclax have been approved. When ibrutinib got approved, all of a sudden, folks like this, their PFS [progression-free survival] was better than chemoimmunotherapy ever was for these individuals. And so we’re prolonging the survival of patients with CLL. So it’s a wonderful time for folks because of all the different therapies that have come out, and targeted therapies. And now we’re tweaking them and looking at minimal residual disease, how do we get people off these therapies.

It’s an exciting time for patients because of the availability of all these therapies. It’s an exciting time for individuals like myself who do research in CLL, because we’re really trying to push the field forward and at much quicker paces than in the era of chemoimmunotherapy. Do I think we have a long way to go? I do. Not a bad thing. It will be the next generation of doctors who will hopefully do this. I think what I’m trying to say is that some of these therapies will hold patients for years, which means that for us to then change things in a meaningful time period may take us much longer, which means these therapies are doing right by the patients and prolonging their lives for much longer. And so finding some of these answers may take us a lot longer as investigators.

But I think it’s a wonderful time, and we have lots of different areas to explore with how to combine and sequence these agents. How do we look at immunotherapies and CAR [chimeric antigen receptor] T cells, where do we move that for patients who need treatment? Given the era of all these new agents, where do you place those types of therapies? It’s an exciting time going forward. And I think it should only highlight the fact that with patients who are going on some of these clinical trials, we can’t thank them enough for participating, and the future of CLL is very bright.

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