February 2014, Vol 3, No 1
Hematologists Often Ignore Treatment and Monitoring Recommendations
Most hematologists and oncologists do not follow evidence-based recommendations for managing acute or chronic myeloid leukemia (AML, CML) or B-cell lymphomas, according to survey results compiled by inPractice Resources LLC, a company that develops interactive educational resources for oncologists.
Among the deficiencies: approximately 40% of clinicians were not appropriately monitoring treatment response in CML, and 20% were inappropriately using cytogenetic testing.
While acknowledging that advances in understanding CML, AML, and B-cell lymphomas and the emergence of new treatments have increased the complexity of decision making in patient care, Kevin Obholz, PhD, editorial director for inPractice Resources, noted, “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 both academic and community centers. To do so, they recruited 250 physicians and interviewed 27 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 diagnosis and treatment.
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 authors reported.
Treatment Recommendations Often Not Followed
The current treatment guidelines recommend the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib as first-line therapy; dasatinib and nilotinib are second-generation agents that have shown superior efficacy and safety over imatinib. Experts suggest these are preferred over imatinib, since they are superior in achieving early responses and major molecular remissions.
Only 33% of 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 less experienced the clinician, the more likely he or she was to disregard the superiority of the second-generation TKIs in achieving these landmarks, the study found.
“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,” Obholz said.
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, while bone marrow cytogenetics 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 in 5 clinicians order these expensive, invasive procedures as often as every 2 to 6 months. PCR should be used every 3 months to monitor response, but only 40% agreed with the guidelines and expert opinion on this issue. Similarly, only 22% of the clinicians agreed with expert opinion regarding timing and frequency of cytogenetic analysis by bone marrow biopsy to assess responses to first-line TKI treatment for chronic phase CML.
Therefore, there is overuse of bone marrow cytogenetic analysis by community oncologists and underuse and inappropriate use of PCR, the survey indicated.
In addition, current guidelines suggest that 3-month response on PCR correlates with outcomes, and that if patients do not achieve a good response by this time point they should probably be switched to a new drug, yet 40% of respondents were unsure or would not change therapy at that threshold.
Ignorance of Novel Agents
Fewer than 30% knew the mechanisms of action for agents in phase 2 trials, including inotuzumab ozogamicin (27%), blinatumomab (26%), idelalisib (22%), obinutuzumab (20%), and fostamatinib (18%).
Furthermore, when asked to match 9 targeted agents approved for B-cell lymphomas and B-cell acute lymphoblastic leukemia to their molecular target, only 20% of respondents were able to do so.
“This potentially represents missed opportunities to enroll eligible patients on clinical trials,” 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.”
Those frustrated with low long-term remission rates in adult acute lymphocytic leukemia (ALL) can find hope in the superior outcomes associated with treatment for pediatric ALL. Overall survival with therapy reaches 85% in children but lags at 45% in adults. Targeting specific pathways and adding novel agents to standard therapy [ Read More ]
A planned interim analysis of a phase 3 study shows that idelalisib, a first-in-class selective oral kinase inhibitor, when combined with rituximab is superior to rituximab alone on the end point of progression-free survival (PFS) in patients with heavily pretreated chronic lymphocytic leukemia (CLL). The 24-week data from the randomized, [ Read More ]