CD38 Expression As an Additional Prognostic Marker in Mantle Cell Lymphoma

Mantle-cell lymphoma (MCL) is an aggressive B-cell lymphoma characterized by a t(11;14)(q13;q32) occurring in pre-B cells and determining uncontrolled cell proliferation. MCL cell immunophenotype is typically CD19+CD20+CD5+CD22+CD24+CD79a+CD43+FMC7+BCL2+CD10-CD11c-CD23-CD200-BCL6-CyclinD1+SOX11+; however, neoplastic clones could aberrantly express adhesion molecules that can augment tumor aggressiveness.

In this study, we evaluated the prognostic impact in MCL of several surface markers currently used for immunophenotyping in other B-cell lymphomas.

In this retrospective observational real-life study, a total of 46 newly diagnosed MCL patients (M/F, 35/11; mean age, 67 years old; range, 44-87 years) were enrolled from 2000 to 2023 followed at the Hematology Unit, University Hospital of Salerno, Italy. Most patients (n = 41, 89%) had advanced (III-IV) disease, and high MIPI score (94% of subjects). Ki-67, an immunohistochemistry proliferation marker, was increased in 59% (expression >30%) and in 4% was decreased (≤30%). Flow cytometry immunophenotyping was performed on bone marrow and/or peripheral in all subjects using the following antibody panels: CD19, CD20, CD5, CD23, CD10, CD11c, CD43, CD103, CD200, SmIg, CD22, CD79, FMC7, CD27, CD49d, CD38, CD25, CD56, CD16, CD2.

In our cohort, CD38 was frequently absent in MCL patients (positivity in N = 8, 17%; negativity in N = 16, 36%) patients. However, CD38- subjects tended to have a shorter overall survival (OS) compared to those patients with CD38 expression (median OS, 14 months vs not reached, CD38- vs CD38+ patients; P = 0.0591), as well as for progression-free survival (PFS) (median PFS, 26 months vs not reached, CD38- vs CD38+ patients; P = 0.0391), especially in patients aged 65 or older (median OS, 238 months vs 14 months, younger CD38- vs older CD38- MCL patients; P = 0.1252). Moreover, we investigated the impact of CD38 expression in patients that have Ki-67 expression between 30 and 70%. Despite falling in the high-risk MIPI categories because the patients have Ki-67 expression >30%, CD38+ MCL patients showed better clinical outcomes compared to CD38- subjects with Ki-67 expression between 30-70% (median OS, not reached vs 14 months, respectively; P = 0.0055; and median PFS, not reached vs 14 months, respectively; P = 0.0127).

In conclusions, CD38 negativity is frequent in MCL; however, this condition could be associated with worse outcomes, especially in older patients (>65 years old) and in subjects with intermediated Ki-67 expression (30-70%). Therefore, our results indicated that CD38 could be a potential prognostic biomarker in MCL and could be included in current prognostic scoring systems for better risk stratification.

No relevant conflicts of interest to declare.