Comprehensive Analysis of Factors Predictive for Time to Transformation and Risk of Transformation in Patients (pts) with Mantle Cell Lymphoma

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.41-42
• Main Authors: Jain, Preetesh, Kanagal-Shamanna, Rashmi, Navsaria, Lucy, Ok, Chi Young, Hill, Holly, Jung, Dayoung, Nogueras González, Graciela M., Lee, Hun Ju, Nair, Ranjit, Ahmed, Sairah, Steiner, Raphael Eric, Tang, Guilin, Li, Shaoying, Patel, Keyur, Thirumurthi, Selvi, Tinsu, Pan, Xu, Guofang, Vega, Francisco, Flowers, Christopher, Wang, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-136978

Introduction: Mantle cell lymphoma commonly presents as classic variant histology, however 10-30% patients (pts) can transform into an aggressive histology (blastoid and/or pleomorphic variants). We have previously reported that genomic profile and clinical outcomes of transformed MCL pts are distinct from classic variant pts who never transformed (CNT) and that transformed pts have poor clinical outcomes. In this study, we analyzed the factors at initial diagnosis which can predict the time to transformation and the risk for transformation in a cohort of 369 pts with MCL. Methods: We analyzed charts from 369 pts with MCL (293 were CNT and 76 were transformed MCL). Statistical analysis was performed from baseline pt characteristics collected from the time of initial diagnosis in CNT group and at the time of initial diagnosis of classic variant MCL who later transformed (t-MCL). Time to transformation (TTT) was calculated from initial diagnosis to the date of transformation in those who transformed and last follow up in those who never transformed. Univariate and multivariate (MVA) logistic regression modeled the risk of transformation. Classification and regression tree (CART) analysis was performed to identify optimal cut off in categorical variables predictive of TTT. Results: Among the 369 pts, the median age was 62 yrs (range 34-90). Ki-67% values were available in 133 pts (36% of total) and median Ki-67% was 25% (range 1-80). Three hundred eight pts (84%) had initial bone marrow involvement and 66 pts (18%) had leukemic phase at diagnosis. The median follow up was 133 months and the median overall survival (OS) was 95 months and 43% were alive at the time of this analysis. Discernible difference were noted in pts who belong to t-MCL group compared to pts in the CNT group, pts in t-MCL group exhibited - higher values of median Ki-67% (30% vs 20% in CNT; p=0.04), higher LDH levels, higher proportions of pts with high risk simplified MIPI risk score, leukemic phase at initial diagnosis, complex karyotype and lower hemoglobin. First line treatments received by both groups were similar. Eleven pts got anti-CD19 CART therapy at some point and 7 pts were t-MCL and 4 were CNT group. The median time to transformation in months for those who transformed was 39 (range 5-240 months) while in CNT it was 51 months (1-257 months). We further identified that incremental Ki-67% was significantly associated with TTT and OS (Figure-1A-B). Using CART analysis we identifi