New Orleans, LA—Most hematologists and oncologists do not follow evidence-based recommendations for managing acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), or B-cell lymphomas, according to new survey results presented at ASH 2013 and compiled by inPractice Resources, LLC, Reston, VA, a company that develops interactive educational resources for oncologists.
Among the deficiencies were that approximately 40% of clinicians were not appropriately monitoring treatment response of patients with CML, and 20% of clinicians were inappropriately using cytogenetic testing.
While acknowledging that advances in understanding CML, ALL, and B-cell lymphomas, as well as the emergence of new treatments, have increased the complexity of decision-making in patient care, Kevin L. Obholz, PhD, Editorial Director, Clinical Care Options, LLC, Reston, VA, and colleagues noted that “a significant proportion of US hematology/oncology specialists are not applying optimal care” for these malignancies.
The investigators aimed to identify and quantify professional practice gaps and barriers to optimal care for patients treated at academic and community centers. They recruited 250 physicians and interviewed 27 of them for the initial qualitative exploratory phase of the study. The focus was on the personal, contextual, and behavioral factors that influence a provider’s clinical reasoning process in the diagnosis and treatment of patients.
These interviews were analyzed using thematic analysis, and the findings shaped the subsequent quantitative phase of the study. For this, 121 physicians completed an online survey of multiple-choice questions, differential rating scales, and case vignettes. A group of expert hematologists provided evidence-based responses for comparison.
“A group of 9 core practice gaps were identified through combined analysis of data from the online surveys and in-depth interviews,” the investigators reported.
Treatment Recommendations Often Not Followed
The current treatment guidelines recommend the tyrosine kinase inhibitors (TKIs) imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna) as first-line therapy; dasatinib and nilotinib are second-generation TKIs that have shown superior efficacy and safety over imatinib. Experts suggest that dasatinib and nilotinib are preferred over imatinib, because they are superior to imatinib in achieving early responses and major molecular remissions.
Only 33% of survey participants agreed with evidence-based expert opinion that early molecular responses to TKIs correlate with long-term clinical outcomes for patients with chronic-phase CML. Similarly, only 38% agreed with expert opinion that achieving a major molecular response to TKIs substantially decreases the patient’s risk of disease progression.
The study showed that the less experienced the clinician, the more likely he or she is to disregard the superiority of the second-generation TKIs in achieving these landmarks.
“Notably, study participants did not adequately recognize that early molecular response to TKI therapy is significantly associated with long-term survival outcomes, which could impact clinical decisions for patients with chronic-phase CML,” Dr Obholz and colleagues noted.
Ignorance of Monitoring and Switching Recommendations
There was also a knowledge gap with regard to the appropriate monitoring of response to TKIs. Quantitative polymerase chain reaction (PCR) on peripheral blood is now the recommended approach, and bone marrow cytogenetics analysis is no longer recommended for monitoring.
The guidelines support cytogenetics at 3 months and 12 months if a major molecular response is not achieved, but 1 of 5 clinicians order these expensive, invasive procedures as often as every 2 to 6 months. Although PCR should be used every 3 months to monitor response, only 40% of the clinicians agreed with the guidelines and expert opinion on this issue. Similarly, only 22% of the clinicians agreed with expert opinion regarding the timing and frequency of cytogenetic analysis by bone marrow biopsy to assess responses to first-line TKI treatment for chronic-phase CML.
Overall, there is overuse of bone marrow cytogenetic analysis by community oncologists, and underuse and inappropriate use of PCR, the survey indicated.
In addition, the current guidelines suggest that 3-month response on PCR correlates with outcomes, and that when patients do not achieve a good response by that time point, they should probably be switched to a new drug; however, 40% of the respondents were unsure or would not change therapy at that threshold.
A Missed Opportunity to Enroll Patients in Clinical Trials
Fewer than 30% of the survey respondents knew the mechanisms of action for agents in phase 2 trials, including inotuzumab ozogamicin (27%), blinatumomab (26%), idelalisib (22%), the recently approved obinutuzumab (Gazyva; 20%), and fostamatinib (18%).
Furthermore, when asked to match 9 targeted agents approved for B-cell lymphomas and B-cell ALL to their molecular target, only 20% of the respondents were able to do so.
“This potentially represents missed opportunities to enroll eligible patients on clinical trials,” Dr Obholz said. “There is a clear need for better education of community physicians. Those with more experience and those in academic centers are more likely to agree with expert recommendations. With these relatively rare hematologic diseases, clinicians need expert-led education targeted to them and tools that will help them learn how to make better decisions.”