Should Intensive Chemotherapy Be Required for All Mantle Cell Lymphoma Patients
Authors: Lao Zhen Tang , Khoo Kathleen , Koh Jasmine , Ong Whee Sze , Tang Tiffany , Quek Richard , Tan Leonard , Tan Daryl , Tao Miriam , Tan Soo Yong , Lim Soon Thye , Tay Kevin 
Published: October 2019

Abstract
Abstract 5188

Background:
Mantle cell lymphoma (MCL) has been found to be a heterogenous disease and this has been further validated based on gene expression profiling studies. Due to this heterogeneity, the treatment of MCL is not standardized, with some groups advocating intensive chemotherapy on initial presentation, and those who adopt a wait and see approach initially. In an effort to better prognosticate MCL, several tools or factors such as MIPI score, blastoid subtype, Ki67 and P53 expression have also been used in clinical practice. As such, our study serves to describe the clinicohistopathological and molecular characteristics of MCL patients and elucidate any correlation between mutation status and prognosis.

Methods:
We studied 25 newly diagnosed MCL patients with adequate clinical, immunohistochemical and cytogenetic data treated at our institution between Jan 1998 and June 2010. The histological diagnosis in all cases was centrally reviewed by our hematopathologists. In addition, all patients had fluorescence in situ hybridization (FISH) performed; using breakapart FISH probes targeting CCND1, BCL2, BCL6, MYC, MALT1 and IgH genes.

Results:
The median age of patients was 59 years (43 to 84), with a male preponderance (ratio of 4:1) and nearly all patients presenting with advanced disease (Stage III or IV) except for one patient. Correspondingly, 7 out of 25 patients had high risk disease based on the simplified mantle cell lymphoma international prognostic index (MIPI). The blastoid morphology was exhibited in 4 of the 25 patients (16%). 21 out of 24 patients (88%) were also found to express SOX11, while none of our patients in the study expressed P21. FISH analysis revealed that P53 mutation was found in 4 (19%) of 21 patients, ATM deletion detected in 10 (42%) out of 24 patients, and BCL 6 amplification was detected in 5 (20%) out of 25 patients. Notably, only one patient with double translocation involving c-myc and cyclin D1 was found, the patient also had ATM deletion. The presence of ATM deletion, however, was not significantly associated with p53 mutation or BCL6 amplification in our series. All except for 2 patients received combination chemotherapy, with 18 patients (78%) receiving rituximab based chemotherapy. 8 patients were treated with the intensive combination chemotherapy of HyperCVAD ± rituximab. Of which, 3 patients were treated with HyperCVAD without rituximab followed by autologous stem cell transplant in 2 of the patients. Only the presence of a blastoid morphology (15.6 months vs. 98.7 months; P= 0.004) and high risk MIPI (81.3 months vs. 154.6 months; P = 0.007) score predicted for a worse outcome. Aside from those 2 factors, the presence of P53 mutation, ATM deletion, SOX11 expression, high Ki67, BCL 6 amplification, patients treated with rituximab based chemotherapy and patients who received HyperCVAD chemotherapy did not confer any difference in survival. Interestingly, the survival outcomes in our MCL patients were longer than the reported median survival of 3–4 years in the literature. The median overall survival (OS) of our MCL patients was 98.7 months and a progression free survival (PFS) of 48.9 months, with a median follow-up of 37.3 months.

Conclusion:
The MCL patients in our study appear to have a favourable outcome, with a median OS of 98.7 months. Only the blastoid subtype and high risk MIPI score conferred a worse prognosis. The presence of P53 mutation, high Ki67, SOX11 expression, BCL6 amplification and the use of intensive chemotherapy such as HyperCVAD did not appear to influence survival. In view of the excellent survival, a period of initial observation or the use of less intensive chemotherapy regimen instead of HyperCVAD may be a reasonable approach for MCL patients with non-blastoid subtype or low risk MIPI score.

Disclosures:
No relevant conflicts of interest to declare.