Paul Barr, MD: Additional Chemo-Immunotherapy

Would you consider additional chemo-immunotherapy in this patient?

I would not consider additional chemoimmunotherapy in this patient [because of] the results we’ve observed over the years for patients with deletion 17p. We’ve observed that patients [who] receive probably our most potent chemo regimen, FCR, have a markedly inferior progression-free survival (PFS) compared to the more general CLL patient population. In the German CLL8 study, the median PFS for all patients was 4 to 5 years. But for the deletion 17p patients we saw a median PFS of about 11 months.

Similarly, after bendamustine/rituximab, for patients receiving this regimen first-line, the median PFS was only about 8 months or so. So some would look at this patient and suggest that the results were somewhat better than average at a 2-year time to progression. Nonetheless, to repeat a similar strategy likely would result in a very short time to progression. So for this patient I would not consider another course of chemoimmunotherapy.

Case 1: Relapsed and Refractory CLL

Robert is a 63-year-old retired civil engineer from Houston, Texas. His medical history is notable for mild hypertension and for an acute appendicitis and appendectomy in 2010. He presented to his PCP in September 2012 with symptoms of intermittent fatigue and abdominal discomfort.

On physical examination, Robert showed moderate splenomegaly (12 cm), lymphadenopathy, and CBC showed elevated WBC count of 98 x 109/L, with 80% lymphocytes, and anemia (Hb 11 g/dL).

He was referred to an oncologist for further evaluation and was subsequently diagnosed with (CLL); peripheral blood flow cytometry showed mature B lymphocytes CD5+/CD23+.

Interphase cytogenetic analysis showed 17p13.1 deletion

He was initiated on chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) in October 2012

After 5 cycles he displayed a complete response, with disappearance of palpable disease, normalization of blood counts, and no evidence of disease on bone marrow biopsy and CT scans.

In January 2015, he presented to his oncologist with symptoms of worsening fatigue and abdominal distension.

• On relapse he shows bulky disease 5.5 cm; Hb 12 g/dL, platelets 120,000 cells/mm3, lymphocytes 39,000/mm3, and beta 2 microglobulin of 4.1 mg/L
• His ECOG performance status at the time of recurrence was 1, and liver and kidney function were within normal limits