Low Incidence of Opportunistic Infections in CLL Patients Treated with Single Agent Flavopiridol.
Authors: Andritsos Leslie A. , Fischer Beth , Lin Thomas S. , Blum Kristie A. , Jones Jeffrey A. , Moran Mollie E. , Byrd John C. , Grever Michael R. 
Published: October 2019

Abstract
Background: Infections are a major cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL). Standard therapies such as purine nucleoside analogs and alemtuzumab have been associated with a high incidence of opportunistic infections, particularly in heavily pretreated patients. To date no studies have evaluated the incidence of infections in patients receiving flavopiridol.
Study design: Patients with CLL who had relapsed following fludarabine-based therapy were eligible for participation. Treatment consisted of single agent flavopiridol administered as a 30 minute bolus followed by a 4 hour infusion weekly for 4 weeks every six weeks for up to 6 cycles. There were no exclusions for neutropenia if it was attributable to disease. All patients received prophylactic antimicrobials for prevention of HSV/VZV reactivation and P. jerovici infection unless contraindicated. Myeloid growth factors support was not utilized. Patient outcomes were retrospectively analyzed for infectious toxicities.
Results: From April 2004 to August 2006 121 patients received single agent flavopiridol as part of two clinical trials. Of these, 34 patients experienced either a febrile episode or an infectious complication, or both. Twenty-four patients were male, 10 were female. There were 43 total infectious episodes in 34 patients. Of the patients experiencing an infections complication, the median number of prior therapies was 4 (range 1–11). 17 had received a purine nucleoside analog within the previous 12 months and 9 had received alemtuzumab within the previous 12 months. Of total patients treated, 5 (4%) developed pneumonia, 1 (0.8%) developed bacterial sepsis, 10 (8.3%) developed sinusitis or bronchitis, and 3 developed suspected viral respiratory infections. There were 5 (4%) skin/soft tissue infections, 7 (5.8%) catheter-related infections, and 2 (1.7%) urinary tract infections. One patient developed esophagitis and was treated empirically, as an endoscopy was contraindicated due to thrombocytopenia. Two patients were found to have aspergillus species in sputum cultures, and one of these patients had a concurrent pulmonary infiltrate. One patient experienced exacerbation of his genital HSV. No patients experienced CMV reactivation, PCP, EBV, Candida, or Legionella infections. 9 patients (7.4%) had fever of unknown origin, 5 of these in the context of cytokine release syndrome during therapy. Twenty-two episodes were associated with grade 3 or 4 neutropenia. Two patients died during infectious episodes.
Conclusion: Flavopiridol is associated with an acceptable incidence of opportunistic infections when administered as a single agent, even in heavily pretreated patients. Most infections were bacterial in origin and may reflect altered immunity in patients with CLL, as well as therapy-associated myelosuppression. These results compare favorably to previous studies of infections in fludarabine-refractory patients.