Bone Marrow Biopsies Do Not Add Value in Follicular Lymphoma Clinical Trials
Sarah C. Rutherford, MD, discussed how findings from her research could impact the current guidelines for follicular lymphoma.
Bone marrow biopsies add little impact to response assessment for patients with follicular lymphoma who are treated on clinical trials and are ultimately not useful. Therefore, they are recommended to be eliminated from clinical trial requirements, according to research reported in the Journal of Clinical Oncology.
According to Sarah C. Rutherford, MD, et al, bone marrow biopsies are performed prior to and after therapy to confirm patients with lymphoma’s complete response (CR) on clinical trials. However, experts wonder whether bone marrow biopsies add value in assessing response, predicting progression-free survival (PFS), or determining overall survival (OS) outcomes in patients with follicular lymphoma.
Because of this, investigators, including Rutherford, assistant professor of medicine in the Division of Hematology/Oncology at Weill Cornell Medicine, examined data pooled from 7 trials of 580 patients with previously untreated follicular lymphoma. Participants were identified through the Alliance for Clinical Trials in Oncology and SWOG Cancer Research Network and each trial completed enrollment between 2008 to 2016.
When examining the findings, only 5 of the 580 patients (0.9%) had positive baseline bone marrow biopsies, CR on imaging, and subsequent positive bone marrow biopsies (P < .0001). This concluded bone marrow biopsies to be irrelevant to response in 99% of patients.
Additionally, a sensitivity analysis of 385 FL subjects treated on an ECOG study was included, and only 5 of these patients (1.3%) had bone marrow biopsies which affected response assessment. Of the 187 patients with CR on imaging, neither the PFS or OS rates were significantly different between those with negative bone marrow biopsies to confirm CR (n = 47) vs those without repeat bone marrow biopsies (n = 140; PFS adjusted HR 1.10; 95% CI, 0.62-1.94; P = .686; OS: HR, 0.59; 95% CI, 0.23-1.53; P = .276).
Based on these findings, the investigators recommend eliminating bone marrow biopsies from clinical trial requirements, except in cases where it may change management, including confirmation of limited stage and assessment of cytopenias. Ultimately, excluding bone marrow biopsies would result in reduced costs, patient discomfort, resource utilization, and has the potential to remove a barrier that currently exists in trial enrollment.
In an interview with Targeted OncologyTM, Rutherford discussed how the findings from this research could impact the current guidelines for follicular lymphoma.
TARGETED ONCOLOGY: Can you discuss the current guidelines for follicular lymphoma. What do they recommend in terms of bone marrow biopsies?
Rutherford: There is a difference in terms of clinical trials vs clinical practice for requirements of bone marrow biopsies. For clinical trials, the majority recommend bone marrow biopsy and aspirate at those baseline and then to confirm a complete response on imaging of patients that have gotten to that status in clinical practice. While they're often not done because it frequently doesn't impact our treatment decision making, there is some variety in terms of recommendations and guidelines.
The NCCN guideline does recommend bone marrow biopsies to be done in patients who have localized disease or for those who have decrease in blood counts that might be reflective of lymphoma, but they do leave it as an option for patients who are likely going to be monitored without treatment that they don't have to undergo bone marrow biopsies at baseline. That is in contrast with the EHA in Europe, which does recommend that patients with follicular lymphoma do undergo bone marrow biopsy and aspirate when they are initially diagnosed.
Before your study, what did you and your co investigators hypothesize about baseline bone marrow biopsies and its relationship response and survival? Can you discuss the trials used for your pooled analysis?
My co investigators and I hypothesized that bone marrow biopsies impact response assessment in a very minority of patients who are undergoing treatment on clinical trials for diagnosis of follicular lymphoma.
We looked at a number of studies in patients with untreated follicular lymphoma, undergoing their first treatment through the National Clinical Trials Network, the NCTN, and we had a number of studies that were conducted through the Alliance for clinical trials and also the SWOG Research Network. We also investigated a couple of trials from ECOG, the Eastern Cooperative Oncology Group, and those were used in basically a separate analysis, because of some differences in terms of timing of imaging.
How are bone marrow biopsies utilized in these studies?
All of these studies require donor biopsies to be done at baseline and in those patients complete response on imaging, a second bone marrow biopsy was required to be done in order to confirm that complete response. As we expected, we found that only a very minority of patients had a subsequent bone marrow biopsy that impacted their response assessment. We found that a number of patients didn't undergo bone marrow biopsy as mandated by the clinical trial for various reasons, which wasn't really the focus of our study.
But we were able to do an assessment looking at both progression-free survival and overall survival in patients who had a negative bone marrow biopsy that was a confirmatory late response for the versus those who did not undergo a clinical trial response specimen didn't undergo the second bone marrow biopsy. We found that there was no difference, which was notable to us. It indicated that it is very unlikely that these bone marrow biopsies are useful, essentially, in the clinical trial setting for follicular lymphoma.
Can you discuss your findings?
As far as symptoms, we had 2 major findings. First, there was a very small percentage of patients whose response assessment was impacted by the bone marrow biopsy. We conclude from that, that bone marrow biopsies are not useful to the majority of patients who undergo treatment for follicular lymphoma in clinical trials.
Second, we did find that there were a number of patients who actually did not undergo the confirmatory bone marrow biopsy that was required in a clinical trial setting. There are likely various reasons for that, such as patient preference not to undergo a procedure, we didn't really focus on that as part of our study. What we did is we looked at the progression-free and overall survival of patients who had a negative confirmatory bone marrow biopsy vs those who did not undergo the procedure, and we found that there was no difference. That helped solidify our recommendations that bone marrow biopsies should not be a part of clinical trial requirements for follicular lymphoma.
What changes would you recommend to current guidelines based on your findings?
I think most guidelines can now reflect that bone marrow biopsies do not need to be done in the majority of patients with follicular lymphoma. I do think there are still some instances, including the setting of limited stage disease, in which one would still consider doing a bone marrow biopsy, but I think that in the vast majority of patients, there is not a utility to do bone marrow biopsies for follicular lymphoma at this time.
How do you think such a change would impact providers and their patients?
The primary reason for doing this study in the first place was to try to make clinical trial requirements more friendly to patients. I am particularly focused on the patient experience I've had, for example, my dad had lymphoma and I feel strongly that we should minimize procedures and other studies to make it easier for patients to join a clinical trial. I think that this would certainly make some patients more likely even to go on clinical trials, which often provide them with options for therapy that may not be available, and maybe better than the standard of care treatments that are available to them.
This goes along with a number of initiatives, including through the American Society of Clinical Oncology, in which there are efforts to try to make clinical care and research more friendly for patients.
