Patients With High-Risk Disease Have Lower Chances of Survival From Mantle Cell Lymphoma

Patients with mantle cell lymphoma (MCL) who have high-risk disease (HRD) had significantly lower rates of failure-free survival (FFS) and overall survival (OS) compared to those with low-risk disease (LRD), according to the results of a study published in Leukemia.

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A total of 1183 participants with MCL were enrolled in the MCL Younger and MCL-Elderly trials. Investigators examined the biological risk variables Ki-67 and p53, along with a clinical prognostic tool, the Mantle Cell Lymphoma International Prognostic Index (MIPI), in various combinations to define a group at the highest risk for MCL.

Of the original enrollment population, 684 patients (MCL Younger n = 390, MCL Elderly n = 294) had evaluable data either for Ki-67 or p53. Among these patients, a low-risk assessment from MIPI was more frequent (43% versus 27%), while high-risk MIPI was significantly less frequent (24% versus 44%, p < 0.0001), the researchers found.

Median FFS and OS also align with this trend, being superior in the subgroup with available data (4.4 years versus 3.2 years, p = 0.0066 and 9.6 years versus 6.6 years, p = 0.0013). This significant difference was due to an overrepresentation of patients with available data from the MCL Younger group, which had a better overall outcome.

The investigators sought to examine characteristics involving p53 expression and Ki-67 to determine the population at the highest risk. They found that high p53 expression was linked to an inferior median FFS (1.5 versus 4.6 years; p < 0.0001) and OS (2.8 versus 10.7 years, p < 0.0001) compared to p53 expression ≤ 50%.

In attempting to further narrow their definition, they tested to see whether the combination of Ki-67 ≥ 30% or high p53 expression could define HRD. Their results showed a relatively large high-risk group, with 37% of complete cases and median FFS and OS of 1.8 years versus 6.0 years (HR 2.01, p < 0.0001) and 4.0 years versus 14.4 years (HR 2.57, p < 0.0001) compared to LRD, respectively.

Similar results were seen when testing the impact of high, high-intermediate combined MIPI with Ki-67 (MIPI-c) or high p53 expression on the outcome. The definition included 41% of complete cases and had a median FFS of 1.7 years versus 6.0 years (HR 2.40, p < 0.0001) and median OS of 3.6 years versus 15.4 years (HR 3.24, p < 0.0001), according to the study authors.

Through their testing, the investigators found that the combination of high MIPI-c or high p53 expression defined the smallest group of high-risk patients, and they used this definition—called definition 3—for their further analysis.

Based on definition 3, there were 22% of complete cases that could be assigned to the HRD group (n = 60), whereas 78% (n = 216) had confirmed LRD. At follow up, the median FFS (1.1 years versus 5.6 years; HR 2.97, p < 0.0001) and OS (2.2 years versus 13.2 years; HR 3.69, p < 0.0001) was significantly decreased in the high-risk group compared to the low-risk group, the researchers found.

Five-year and 10-year FFS probabilities were similarly poor for HRD, with 18% versus 51% in the LRD group and 10% versus 37%, respectively. Similarities were observed in the 5- and 10-year OS probabilities, which were 31% versus 72% and 15% versus 59% for HRD versus LRD, respectively, according to the study investigators.

Between the definitions the investigators analyzed, they noted that definition 3 indicated between high- and low-risk patients most clearly, with a 3-fold higher risk of treatment failure and a 3.7-fold higher risk of death for HRD patients.

“These results will allow risk stratification in clinical trials, to hopefully develop innovative therapies especially for the high-risk MCL population which has the greatest medical need,” the study authors concluded.

Reference

Scheubeck G, Jiang L, Hermine O, et al. Clinical outcome of mantle cell lymphoma patients with high-risk disease (high-risk MIPI-c or high p53 expression). Leukemia. 2023. doi: 10.1038/s41375-023-01977-y