High-Risk Biology Associated With Worse Failure-Free Survival, OS in MCL

Martin Dreyling, MD

Patients with mantle cell lymphoma (MCL) who have high-risk biology, including blastoid variant, a Ki-67 score of at least 30%, or high p53 expression, had a significantly shorter failure-free and overall survival (OS), according to results of a retrospective trial.¹

Cytology, cell proliferation as determined by Ki-67 expression, and p53 alterations, have been identified as key characteristics of rapidly progressing MCL, independent of the Mantle Cell Lymphoma International Prognostic Index (MIPI) score. However, the investigators sought to determine a biologically based prognostic score that could permit a more risk-based treatment approach for use in future clinical trials.

“As these biological factors seem to dictate the sometimes dismal clinical course of the disease, we recommend to incorporate these factors into routine clinical practice,” lead study author Martin Dreyling, MD, of the Medical Clinic III at the University of Munich in Germany, and coinvestigators, wrote in a poster for the trial, which was presented during the virtual 2020 European Hematology Association Congress.

In the retrospective study, investigators examined patients were treated in the MCL Younger² (n = 613) and MCL Elderly³ (n = 570) trials. Disease was classified as classic or blastic/pleomorphic variant and were analyzed via Ki-67 or p53 immunohistochemistry (IHC). Additionally, patients were classified as having high-risk biology if they had displayed blastoid cytomorphology, had a Ki-67 score of 30% or higher, or had high p53 staining, which indicated that they had a mutated gene status expression.

Standard-risk MCL was defined as patients with classical MCL who had low Ki-67 scores (at lower than 30%) and a p53 IHC expression of 50% or lower.

Results showed that a total 365 out of 1229 study patients with MCL had at least 1 parameter of high-risk disease excluded by determination of all 3 parameters. Moreover, 10% of 651 cases that were analyzed featured a blastoid cytomorphology (n = 65), 30% of 591 cases had a high Ki-67 score (n = 175), and 16% harbored a p53 mutation (n = 54).

The standard-risk cohort showed a significantly prolonged median failure-free survival (FFS) compared with the high-risk group at 6.3 years and 2.2 years, respectively (P <.0001). There was a similar pattern for OS; the median was not reached in the standard-risk group compared with 4.5 years in the high-risk group (P <.0001).

Specifically, in patients with a normal Ki-67 score or p53 expression, the median PFS was 7.2 years compared with 3.6 years for those with normal 30% or higher Ki-67 score and p53 expression (P = .0009). For those with extreme Ki-67 scores 30% or lower/p53 status, the median PFS was 2.4 years compared with 1.6 years for those with extreme Ki-67 scored of 30% or higher/p53 status (P = .92).

The survival differences were consistent in those treated with conventionally dosed chemotherapy, with a median progression-free survival of 3.8 years in the standard-risk and 1.3 years in the high-risk groups, respectively (P = .0001). The median OS here was not reached compared with 2.5 years, respectively (P <.0001).

For patients receiving a cytarabine–containing induction and autologous transplantation, the survival outcomes were similar for PFS (7.5 years vs 3.7 years; P <.0001) in the standard- and high-risk groups, respectively, and also OS (not reached vs 6.5 years; P <.0001).

References

1. Dreyling M, Hoster E, Unterhalf M, et al. Clinical outcome of mantle cell lymphoma patients with high risk biology (high Ki-67, blastic MCL, or high p53 expression). Presented at: 2020 European Hematology Association Congress; June 11-14, 2020; virtual. Abstract EP1163.
2. Hermine O, Hoster E, Walewski J, Bosly A, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016;388(10044):565-575. doi: 10.1016/S0140-6736(16)00739-X
3. Ribrag V, Feugier P, Doorduijn J, et al. MCL‐R2 Elderly: a phase III study of the European MCL Network assessing efficacy of alternating immunochemotherapy (R-CHOP/R-HAD) and a rituximab‐lenalidomide maintenance. Hem Oncol. 2017;35(S2):421. doi: 10.1002/hon.2440_3.