Introduction:

While FMC7, an epitope on CD20, expression is frequently seen in mantle cell lymphoma (MCL), it is also encountered in other CD5+ small B-cell lymphomas such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), lymphoplasmacytic lymphoma (LPL), and mucosa-associated lymphoid tissue (MALT) lymphoma (Garcia et al, 2001) in addition to monoclonal B-cell lymphocytosis (MBL) encountered in our practice. Historically, it has been associated with atypical morphology, enrichment of trisomy 12 and worse clinical outcomes. Frequently these patients (pts) are managed as atypical CLL/SLL. Currently, there is a paucity of data on baseline characteristics, FISH and mutational abnormalities found in small CD5+/FMC7+ lymphoproliferative disorders (LPDs) in comparison to classic CD5+/FMC7- CLL/SLL cases. We sought to compare baseline characteristics between CD5+/FMC7+ LPDs and classic CD5+/FMC7- CLL/SLL pts receiving care at Weill Cornell Medical Center.

Methods:

We performed a single center retrospective analysis of pts sequentially diagnosed with CD5+/FMC7+ LPDs and classic FMC7- CLL/SLL managed between the year 2015-2024. MCL was excluded given clear diagnostic criteria. We compared baseline characteristics including age at diagnosis, sex, diagnosis, white blood cell (WBC) count at diagnosis, hemoglobin (hgb) level at diagnosis, platelet count at diagnosis, rates of del11q. del13q, del17p and trisomy 12, immunoglobulin heavy chain gene (IGHV) mutation status, rates of complex karyotype (CK), and rates of NOTCH1, SF3B1 and TP53 mutations between the CD5+/FMC7+ LPDs and FMC7- classic CLL/SLL pts. We used Pearson's chi-squared test to compare categorical variables and Wilcoxon rank-sum test to compare continuous variables. Kaplan-Meier method was used to estimate the survival probabilities to calculate time-to-first treatment (TTFT) and overall survival (OS).

Results:

A total of 120 classic CLL pts and 314 CD5+/FMC7+ LPD pts were identified. Median age at diagnosis was different between the groups: median of 62.5 years (range 34-87 years) for the CLL/SLL group and 66 years (range 32-94 years) for the CD5+/FMC7+ group, p 0=0.015. There was no difference in sex between groups. The distribution of clinical diagnoses in the CD5+/FMC7+ LPD group was: CLL/SLL (N=200, 63.7%), MBL (N=51, 16.2%), MZL (N=35, 11.1%), CD5+ Small B-Cell Lymphoma (N=13, 4.1%), Waldenström Macroglobulinemia (N=6, 1.9%), IgM MGUS and LPL (each N=3, 1.0%), splenic MZL (N=2, 0.6%), and MALT lymphoma (N=1, 0.3%). There was a difference in median WBC at diagnosis (N=414), with the CLL/SLL group having a higher count at 21.7x10^3/uL vs 11.3x 10^3/uL for CD5+/FMC7+ LPD group (p <0.001). There was no difference in the median hgb or platelet count levels at diagnosis. The CLL/SLL group had a significantly higher rate of del13q vs CD5+/FMC7+ LPD (66.7% vs 39.8%, p <0.001, N=386), as well as a higher rate of del11q (21.4% vs 10.1%, p=0.003, N=384). Out of 383 pts, the CD5+/FMC7+ group had a higher rate of trisomy 12 (21.4% vs 46.6%, p <0.001). In 251 pts, the CLL/SLL group had a higher rate of IGHV unmutated status (61.2% vs 42.5%, p=0.004). There was no difference in rates of CK (N=256), del17p (N=387), TP53 or SF3B1 mutation (N=246 for both), and NOTCH1 (N=247) between the groups. The median TTFT for CD5+/FMC7+ LPD group was 73.2 months, and the median OS was 254.6 months.

Conclusions:We present a large retrospective study comparing baseline characteristics of CD5+/FMC7+ LPDs in comparison to classic CLL/SLL. The CLL/SLL group had a lower age at diagnosis but had a higher WBC at diagnosis and higher rates of del13q, del11q and unmutated IGHV status. The CD5+/FMC7+ LPD group had a higher rate of trisomy 12. There was no difference in rates of CK, TP53, SF3B1 and NOTCH1 mutations between the groups. The difference in WBC at diagnosis are likely skewed by our inclusion of MBL pts in the CD5+/FMC7+ cohort. Previous reports have identified FMC7+ CLL cases to have higher rates of trisomy 12 (Reddy et al, 2012) and our results support these prior findings. Of interest we found higher-risk findings of del11q and unmutated IGHV status in the classic CLL/SLL group, however these results should be interpreted with caution as 183 pts did not have IGHV testing. Overall, baseline characteristics are largely similar between typical CLL/SLL and CD5+/FMC7+ LPDs suggesting that they may respond similarly to current CLL therapies.

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2025
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