Resource Utilization and Perceptions of Major Molecular Response In Chronic Myeloid Leukemia (CML): Results of a Delphi Panel Study.

With the introduction of tyrosine kinase inhibitors (TKIs), CML treatment and monitoring have undergone significant advances over the last decade. With prolonged survival, it is important to better understand factors that impact therapeutic decisions, particularly when a change in treatment is warranted, and to better understand healthcare resource utilization.

A modified Delphi panel study was conducted, utilizing initial in-depth interviews with 16 CML treating physicians to develop key themes and questions for testing, followed by an on-line survey to capture initial estimates regarding treatment patterns, monitoring and healthcare use. The results were presented and discussed at a live meeting to develop consensus on the estimates provided and complete a second round of surveying. A panel of 7 CML treating physicians, based on their CML treatment experience and pre-established Delphi panel guidelines, from across U.S. was convened. The range and certainty of the estimates provided for resource utilization and treatment approaches were discussed to determine whether the ranges could be narrowed.

The majority of panelists believe that 20% to 30% of patients are not treated in accordance with the current CML treatment guidelines, with ≤50% of patients monitored according to the National Comprehensive Cancer Network guidelines, in part because of the rapidly evolving research. The mean estimated percentage of patients who are switched to a second-generation TKI during the first year is 25% (range, 10–40%) most commonly (mean >75%) because: patient is responding but has not achieved a complete hematologic response (CHR) within 6 months, patient lost CHR (having not achieved complete cytogenetic response [CCyR]), and patient lost CCyR (having not achieved major molecular response [MMR]). Panelists report that community oncologists are more likely to make a treatment switch due to side effects (generally a combination of low-grade adverse events [AEs]) whereas patients treated in the academic setting are primarily switched for efficacy-related concerns. There is no clear time frame in which TKI switching occurs when adverse events (AE) become problematic; the mean percentage of patients reported being switched due to grade 1/2 AEs was equivalent to that of grade 3/4 (30% and 31%, respectively). Six of 7 panelists believe that MMR is a superior monitoring endpoint to CCyR and that there is credible evidence to support that MMR provides superior protection from progression. Panelists believe that molecular monitoring is less intensive and less time consuming, and is a better predictor of progression-free survival. There is considerable variation in when molecular testing via polymerase chain reaction (PCR) is implemented. Once patients have achieved and maintained stable MMR for ≥12 months, 3/7 panelists would monitor patients by reducing the frequency of cytogenetic testing and 3/7 would not use cytogenetic testing. Panelists reported that mutational analysis is not routinely conducted in patients responding to the treatment; however, when performed in the second- and third-line settings, mutational analyses are generally conducted once or twice yearly. Utilization of healthcare resources (nursing and oncologist visits, hospitalization visits, and non-TKI CML treatments) were higher in patients in accelerated phase (AP) and blast crisis (BC) as shown in table and was two to three times higher in non-responders than responders.

CML treatment and monitoring practices may not align well with established CML guidelines; furthermore, management of patients may differ markedly between academic centers and community oncology settings. Monitoring disease burden using PCR is expected to become increasingly important particularly as methods are standardized and new therapies are anticipated to yield deeper responses.

Quintas-Cardama:Novartis: Consultancy; BMS: Consultancy. Flamm:Novartis: Consultancy. Lill:Novartis: Consultancy. Thirman:Novartis: Consultancy, Honoraria. Ravandi:Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Honoraria, Research Funding. Akard:Novartis: Consultancy, Speakers Bureau; Chemgenix: Consultancy; BMS: Speakers Bureau; Millenium: Speakers Bureau; Celgene: Speakers Bureau. Talpaz:Novartis: Consultancy.