Risk of Transformation of Follicular Lymphoma to High Grade Lymphoma After Radioimmunotherapy: A Prospective Observational Single Institutional Experience
Authors: Burnette Brian L. , Wiseman Gregory , Habermann Thomas M. , Macon William R , Ansell Stephen M. , Inwards David James , Micallef Ivana N. , Johnston Patrick B. , Ristow Kay M. , Witzig Thomas E. , Nowakowski Grzegorz S. 
Published: October 2019

Abstract
Abstract 1572

Background:
The incidence of histologic transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma has been reported to range from 10–75%. The British Columbia Cancer Agency reported a risk of 3% per year (Al-Tourah AJ, et al J Clin Oncol 2008;26: 5165–5169). The hallmark of HT is the acquisition of new somatic mutations and genomic instability within the malignant clone. DNA damaging agents such as radioimmunotherapy (RIT) may increase the risk of HT by inducing additional DNA damage. The incidence of HT after RIT is unknown. This single institution study analyzes the risk of histologic transformation (HT) in patients with FL after RIT treatment with yttrium-90 ibritumomab tiuxetan.

METHODS:
The Mayo Clinic Lymphoma Data Base were queried for all patients having received a single dose of yttrium-90 ibritumomab tiuxetan for FL. The Mayo Clinic Lymphoma Database includes all consecutive adult patients diagnosed with lymphoma evaluated at Mayo Clinic Rochester. The prospective radioimmunotherapy lymphoma database was also utilized (GAW). The diagnosis of FL was defined by current WHO Classification, and all cases were centrally reviewed. HT was defined as the development of histologically proven diffuse large B cell lymphoma in patients with history of Grade 1 or 2 FL (change to Grade 3A/B FL was not included). Patients having demonstrated evidence of HT prior to RIT were excluded from this analysis.

RESULTS:
119 consecutive patients were included. 64(54%) were male. The median follow-up was 57(range 2–175) months. RIT was administered as treatment for progressive FL in 96.6% of patients. RIT was administered as a consolidation therapy in 4(3.4%) patients. The median number of prior systemic treatments was 2 (range 0–10). The median time from diagnosis to RIT was not different in patients with HT vs. those without HT 44 (10–186) vs. 40 months (range 1–394) (p=0.30), respectively. The median time to HT from RIT was 13 months (range 1–97). Four patients had HT within 3 months of RIT. The median survival after HT was 15 months (range 1–147). The estimated five year risk of transformation from RIT by Kaplan-Meier in patients with fludarabine exposure and those without exposure was 55% and 29% (p=0.0498). 10 year risk from the time of RIT was 64% with fludarabine exposure and 31% without (p=0.0498). The relative risk of HT after RIT in patients previously treated with fludarabine was HR=4.1 (95% CI: 2.0–7.9). The median number of prior therapies in patients with HT vs. patients without HT was 2 (0–6) and 1 (0–10) (P=0.33).

CONCLUSIONS:
To our knowledge, our data is the first to estimate the risk of HT after the use of RIT. The estimated overall risk of HT of 31% at 10 years from diagnosis in patients without fludarabine exposure is similar to that of patients in whom RIT has not been administered. The estimated overall risk of HT of 64% in those patients having received purine analogues appears to be increased. We conclude that RIT appears to not increase the risk of HT in patients who did not receive prior purine analogue therapy. The differences in extent and mechanisms involved in DNA damage induced by radiation vs. purine analogues may play a role in clinical differences in observed rates of HT.

Disclosures:
No relevant conflicts of interest to declare.