Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients with lymphoma on clinical trials. Sara C Rutherford, MD, Weill Cornell Medicine (New York, NY), and colleagues sought to establish whether BMB added value in assessing response or identifying distinct progression free survival (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort of patients with follicular lymphoma (FL).
Dr Rutherford and her team pooled data from seven trials of 580 patients with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002 to 2016. The proportion of patients with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total patients enrolled as the denominator.
They tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, vs the alternative hypothesis that this proportion was < 10%, using 1-sided exact binomial test.
Because confirmatory BMB were not completed in all indicated patients, landmark survival analyses compared PFS/OS of patients with CR on imaging and negative (-) BMB vs patients with CR on imaging without repeat BMB. Patients with CR on imaging were categorized as having (-) repeat BMB or no repeat BMB within 60 days of first CR on imaging. PFS and OS were calculated from time of first CR and estimated using Kaplan-Meier and Cox models adjusting for age, sex, stage, Follicular Lymphoma International Prognostic Index (FLIPI) score, and treatment type (targeted vs chemotherapy plus targeted therapy), and stratified by treatment arm.
Results showed that median age was 55 with 51% male, 96% stage III-IV disease, and 88% grade I-II disease. FLIPI scores were 113 low-, 265 intermediate-, and 199 high-risk. Sixty-seven percent of patients received chemotherapy-based regimens. Baseline BMB was (+) in 321 patients (55%). Only five of 580 patients (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (P < .0001). Of patients with CR on imaging, PFS and OS were not different among patients with (-) BMB vs patients without repeat BMB (PFS: HR = 1.08; 95% CI, 0.61-1.93; P = .783; OS: HR = 0.52; 95% CI, 0.20-1.40; P = .199).
Authors noted that BMB requirements may discourage patient participation in trials and add pain, expense, and time without providing necessary information. Based on their findings, they recommend eliminating BMB for response assessment from FL clinical trials.—Amanda Del Signore
