Relevance of bone marrow biopsies for response assessment in NCTN follicular lymphoma clinical trials.

Abstract

8038 Background: Bone marrow biopsies (BMB) are performed pre/post therapy to confirm complete response (CR) in patients (pts) with lymphoma on clinical trials. We evaluated 2 prior data sets and concluded that BMB impact response assessment in a minority of pts with follicular lymphoma (FL) (Rutherford BJH 2017; Rutherford ASH abstract 1605, 2018). We sought to establish if BMB add value in assessing response or identify distinct progression free (PFS) or overall survival (OS) outcomes in a large, multicenter, multi-trial cohort. Methods: Data were pooled from 7 trials of 580 pts with untreated FL conducted through the Alliance for Clinical Trials in Oncology and SWOG from 2002-2016. The proportion of pts with positive (+) baseline BMB, CR on imaging after treatment, and (+) repeat BMB was calculated using total pts enrolled as the denominator. We tested against the null hypothesis that the proportion was = 10%, the threshold below which BMB would be considered irrelevant for response assessment, versus (vs) the alternative hypothesis that this proportion was < 10%, using 1-sided exact binomial test. Response criteria were CT-based. Imaging was not used to assess BM involvement. Because confirmatory BMB were not completed in all indicated pts, landmark survival analyses compared PFS/OS of pts with CR on imaging and negative (-) BMB vs pts with CR on imaging without repeat BMB. Pts 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: Median age was 55 with 51% male, 96% stage III-IV, and 88% grade I-II. FLIPI scores were 113 low, 265 intermediate, and 199 high risk. 67% received chemotherapy-based regimens. Baseline BMB was (+) in 321 (55%). Only 5/580 (0.8%) had (+) baseline BMB, CR on imaging, and subsequent (+) BMB (p < 0.0001). Of pts with CR on imaging, PFS and OS were not different among pts with (-) BMB vs pts without repeat BMB (PFS: HR = 1.08, 95%CI 0.61-1.93, p = 0.783; OS: HR = 0.52, 95%CI 0.20-1.40, p = 0.199). Conclusions: BMB requirements may discourage pt participation in trials and add pain, expense and time without providing necessary information. We recommend eliminating BMB for response assessment from FL clinical trials. Clinical trial information: NCT00553501, NCT01145495, NCT01190449, NCT01286272, NCT01829568, NCT00822120, and NCT00770224 .