MRD Negativity and Time-Limited Therapy

Ian W. Flinn, MD, PhD:The significance of achieving MRD [minimal residual disease] negativity seems to trump all previous prognostic factors, in the sense that it’s important no matter what your prognostic factors are. Whether you had good prognostic factors or poor prognostic factors, if you achieve MRD negativity, this translates into an improvement in progression-free survival.

I think for many patients, for a long time, the thought of remaining on treatment indefinitely, with the new molecules that we’ve been using, it’s been a challenge that they had the psychological burden of being on therapy as well as the physical and financial burden of having to continue treatments with all the adverse events that, hopefully minimal, but still significant to the patient, that occur with continuing on therapy. So these new approaches, such as what we saw in the MURANO trial with time-limited therapy—so patients remain on [therapy] for a finite period of time and then come off, is very important for patients in terms of their overall well-being. I mean it wasn’t until very recently that we had these therapies where patients stay on it forever, until the therapy stops working. Certainly in the chemoimmunotherapy era, patients got a time-limited therapy and then they came off.

Now we’re seeing, with some of these new therapies such as venetoclax and rituximab and other combination therapies that we—combining many of these small molecules together, these targeted therapies—that we’re getting back to those treatment options of getting patients on for a period of time and then getting off. And it clearly is very important to patients.

Transcript edited for clarity.

A 71-Year-Old Man With CLL

• A 71-year—old man presented with symptoms of persistent fatigue and weight loss
• PMH: Left axillary lymph node, 1.5 cm X 1.5 cm
• PE: Left axillary lymph node, 1.5 cm X 1.5 cm
• Laboratory findings:
  • WBC, 133,000; 85% lymphocytes (ALC, 68,000 cells/mL)
  • Hb; 11.4 g/dL
  • Platelets; 111 X 10⁹/L
  • ANC; 174/mm³
• Molecular testing:
  • Flow cytometry; CD19++, CD5+, CD20+, CD23++, CD38+
  • IgVHmutated
  • FISH, +12
• β2M, 3.0 mg/L
• Diagnosis; chronic lymphocytic leukemia
• BM biopsy; CLL in 88% of cells
• The patient was treated with ibrutinib and achieved a complete remission within 5 months
• 13 months later, the patient reported extreme fatigue; now with 3.0 X 3.0-cm lymph node
• Laboratory findings:
  • Repeat FISH: remained +12
  • WBC, 225 X 10⁹/L
  • HB, 9.6 g/dL
  • Platelets, 103 X 10⁹/L