A nurse-led telephone intervention program was associated with an increased likelihood of maintaining the relative dose intensity (RDI) of frontline immunochemotherapy at 80% or more of planned RDI in adults with chronic lymphocytic leukemia (CLL). This study was published in Annals of Hematology.

The immunochemotherapy regimen of fludarabine/cyclophosphamide/rituximab (FCR) is considered standard frontline therapy for patients with CLL without the deletion 17p/TP53 mutation. Nevertheless, progression-free survival (PFS) and overall survival (OS) benefits of this treatment have been associated with maintenance of adequate FCR dose intensity. Results from previous studies have suggested that patient-related, therapy-related, and physician-related factors can influence adherence to the recommended RDI of FCR.

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The Facing Obstacles to RDI Through a Telephone Intervention Strategy (FORTIS) Study, a phase 3, multicenter, randomized study, was designed to evaluate the impact of an ambulatory patients medical assistance (AMA) program on maintenance of adequate FCR dose intensity in patients with CLL. Specifically, the AMA program involved nurse-led delivery of patient education/empowerment approaches through 1 to 2 programmed telephone calls/week between chemotherapy cycles.

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In the FORTIS Study, 60 (58 evaluable) adult patients with CLL were randomly assigned (1:1) to the AMA program or not. All patients received primary prophylaxis with pegfilgrastim for febrile neutropenia. The primary outcome measure was an evaluation of observed reductions in RDI through comparisons of the planned and prescribed doses of each drug in the FCR regimen, before and after 6 courses of FCR.

Findings included a nonsignificant trend for the AMA program to reduce the risk of the dose intensity going below 80% of planned RDI (RDI less than 80%: 41.4% in non-AMA patients vs 20.7% in AMA patients [P =.09]). Following adjustments for confounding factors previously shown to be predictive of FCR dose reductions, the AMA program was found to significantly reduce the risk of an RDI at less than 80% of planned RDI (odds ratio = 0.22, 95% CI, 0.05-0.84; P =.04). The results of the FORTIS study also confirmed previous findings that an FCR RDI of less than 80% of planned RDI was associated with PFS and OS detriments, although an independent impact of the AMA program on PFS and OS could not be demonstrated.  

In conclusion, the authors wrote that “our randomized study, though a limited number of patients were included, showed how a telephone intervention strategy might support the dose intensity of FCR in CLL frontline. Despite the use of pegfilgrastim that dramatically reduced the risks of grade 3/4 neutropenia and especially febrile neutropenia, prescribers and/or patient support systems are still warranted to maintain full dose delivery of this gold standard therapy.”


Ysebaert L, Larcher M, Compaci G, et al. Oncology nurse phone calls halve the risk of reduced dose intensity of immunochemotherapy: results of the randomized FORTIS study in chronic lymphocytic leukemia [published online February 18, 2019]. Ann Hematol. doi: 10.1007/s00277-019-03631-z