Relapsed and Refractory CLL with Javier Pinilla-lbarz, MD, PhD and Paul Barr, MD: Case 1 - Episode 6
What are the principle treatment options in a patient with a 17p deletion?
We’ve learned that deletion of 17p is a poor risk factor in patients with CLL, and it’s fair to say that it’s probably the worst risk factor in that patient population. Deletion of 17p leads to dysfunction of the TP53 gene, leading to impaired production of the P53 protein, which plays an important role in cell cycle production. As a result, [these] patient’s CLL displays features of much more rapid proliferation and impaired response to cytotoxic therapy.
Clinical trials have taught us over the years that responses to chemoimmunotherapy are much more inferior compared with the greater population of CLL patients. For a patient with deletion of 17p, the primary considerations for therapy are some of the newer treatment options―the B-cell receptor (BCR) signaling inhibitors, specifically ibrutinib or idelalisib with rituximab. Additionally, there are some investigational options, such as the Bcl-2 inhibitor venetoclax, [which] appears to be providing nice results in this patient population. Another investigational approach, chimeric antigen receptor T-cell therapy, appears to be providing nice results in heavily pretreated patients, including some with deletion 17p. And we can’t forget for the younger, fitter patient, allogeneic stem cell transplant [may be appropriate] for these patients with poor predictive factors.
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.