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New Scoring System Helps Stratify Mantle Cell Lymphoma Patients

Fuerst, Mark L.

doi: 10.1097/01.COT.0000717752.89616.82
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A novel, simplified scoring system incorporates more pathology parameters to provide a useful prognostic tool in stratifying mantle cell lymphoma patients. This system appears to work well in both young and older patient cohorts.

The North American Mantle Cell Lymphoma Project was initiated in 2013, led by Julie Vose, MD, MBA, Chief of the Oncology/Hematology Division in the Department of Internal Medicine at the University of Nebraska Medical Center (UNMC). So far, a total of 589 mantle cell lymphoma patients from 23 different institutions in North America have been recruited. All of these patients were diagnosed in the home institution and confirmed by a panel of expert hematopathologists at the UNMC.

“The goal of the North American Mantle Cell Lymphoma Project is to evaluate the clinical, biological, and genomic markers that affect the outcome of patients with mantle cell lymphoma,” said Kai Fu, MD, PhD, a hematopathologist working at UNMC.

Study Details

Fu presented an initial report from the consortium at the 2020 ASCO Annual Meeting (Abstract 8035). “We have retrospectively studied the clinical and pathological features of 307 of 421 patients diagnosed with mantle cell lymphoma between January 2000 and December 2012 from 23 institutions across North America,” he noted.

The registry of consortium mantle cell lymphoma patients, median age 63 years, favors males over females (ratio 3.6 to 1). Virtually all of the patients (89%) presented with high and upper stage, stage III or stage IV disease upon diagnosis. More than one-quarter (28%) of the patients presented with these symptoms, and 72 percent of the patients had extranodal involvement.

The median follow-up is 5.2 years, ranging from less than 1 year to more than 18 years. Five-year progression-free survival is 24 percent and 5-year overall survival is 60 percent, reported Fu.

“At the initial step of the study, we did multiple univariate analysis in the entire cohort of mantle cell lymphoma cases and identified multiple risk factors, which were significantly correlated with overall survival in mantle cell lymphoma patients. We further separated our entire cohort into young versus old cohort, with a cutoff of 60 years,” Fu said.

The researchers identified many factors that continue to be significantly correlated with overall survival. Univariate analysis revealed that the following factors were significantly associated with both inferior overall survival and progression-free survival: older age (≥60 years), presence of B symptoms, advanced Ann Arbor stage, elevated LDH, low platelets (≤100K/mL), blastoid/pleomorphic cytology, Ki67 proliferation ≥30 percent, circulating tumor cells, no transplantation (vs. transplantation), and allogeneic (vs. autologous) stem cell transplantation.

In addition, large tumor size (maximal diameter > 3cm), high WBC count, CD5 or CD23 positivity, and a complex karyotype were associated with inferior overall survival. Multivariate Cox regression analysis showed age (≥ 60 years) and high LDH were the two factors predicting clinical outcome.

“However, there are factors only correlated with survival in younger patients or in older patients. Some of these findings may be related to the sample size. We need to confirm of these findings in future studies,” Fu noted.

The MIPI and the MIPI-c score are widely used in mantle cell lymphoma stratification, and the researchers applied these scores in the patient cohorts. “We found MIPI and MIPI-c both work very well,” he said.

Then they separated the patients into young and older patient cohorts. They found the MIPI and the MIPI-c work well in the younger patients, but it fails to stratify patients in the older patient group.

“Therefore, we tried to identify a new, simplified scoring system to incorporate more pathology parameters. We call this new system MIPI-P,” said Fu. “P” stands for pathology, which includes Ann Arbor stage, LDH, cytology, and Ki67. Each accounts for 1 point. The researchers separated the patients into three risk groups—low (0.0), intermediate (1-2), and high risk (3-4).

“Using the MIPI-P system, we successfully stratified patients into three distinct groups in the entire cohort, as well as in younger patients with significant p-value,” stated Fu. “In older patients, however, although we can separate patients into three distinct groups, the p-value is only marginally significant, probably due to the lower number of patients in our low-risk group.”

The researchers further validated this system in an independent cohort of 33 mantle cell lymphoma cases and confirmed that the modified MIPI-P provided robust prognostic predication.

“In this preliminary report from the North American Mantle Cell Lymphoma Consortium, using univariate analysis, we identified multiple risk factors, which correlate with overall survival in mantle cell lymphoma patients,” Fu noted. “In addition, we identified some factors that may have distinct predictive value in young versus older patient cohorts. The clinical and biologic characteristics of mantle cell lymphoma can provide information assisting with the prognosis of patients with mantle cell lymphoma.

“We will continue work on these to identify an ideal scoring system, which will be reported in the future,” he concluded.

Mark L. Fuerst is a contributing writer.

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