Paul Barr, MD: Significance of Treating to Progression

Why is it important to treat to progression in this patient?

It is very important to treat to progression in such a patient. The reason we think this way comes from how the newer BRC signaling agents work compared with chemoimmunotherapy. With chemotherapy, the longer we administer [it] we see diminishing responses over time, and we also see increased toxicity the longer we continue therapy. As a result, when we administer chemoimmunotherapy we typically use 6 cycles or so and then have to stop. Whereas with ibrutinib and idelalisib, and some of the other BCR signaling inhibitors, it does appear that treating to progression is important. When patients become resistant or if therapy is stopped for side effects, we often will see a rapid return of the disease.

Additionally, we don’t see cumulative toxicity similar to what we’ve seen with cytotoxic chemotherapy. A good example of this is in the ibrutinib data. We don’t see cumulative side effects, we see less infections, we see an improvement of IGA over time. So not only do we see better efficacy but less side effects, again suggesting that it is important to continue the agents.

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