Investigators identified a specific subgroup of patients with mantle cell lymphoma who were at higher risk by defining a combination of MIPI, Ki-67, and p53/TP53 alternations.
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.
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.
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