Abstract
TP53 alterations detected by chromosome 17p deletion, oncogenic mutation, or p53 protein overexpression portend extremely poor prognosis for patients with mantle cell lymphoma (MCL), despite aggressive upfront therapy including consolidative high-dose therapy autologous stem cell transplant and; more recently, novel agents such as ibrutinib or lenalidomide. We reviewed outcomes of 42 patients with available TP53 status who had received reduced-intensity/non-myeloablative conditioning (RIC/NMA) allogeneic hematopoietic cell transplant (allo-HCT) for MCL at our institution and examined the impact of TP53 alteration and other clinical factors on outcomes.
Nineteen patients had TP53 alterations including 17p deletion (n=3), oncogenic mutation (n=7), and strong p53 protein overexpression by immunohistochemistry (n=9). There were no differences in demographic or clinical characteristics among patients with and without TP53 alterations (Table 1). With a median follow-up for survivors of 23 months (range 4-119), the one-year overall survival (OS) and progression-free survival (PFS) is 87% (95% CI 72-94) and 74% (95% CI 57-85), respectively (Figure 1A). The one-year cumulative incidence of relapse and non-relapse mortality is 16% (95% CI 6-29) and 10% (95% CI 3-22), respectively (Figure 1B). The cumulative incidences of grade II-IV acute GVHD is 38% at 180 days (95% CI 24-53), and of any chronic GVHD is 33% at three-year (95% CI 17-49).
Importantly, there is no statistically significant difference in OS (p=0.582, Figure 1C), and cumulative incidence of relapse (p=0.715, Figure 1D) among patients with and without TP53 alterations. In univariate and multivariate analyses, we find that only Ki67 >30% is a significant predictor of PFS (HR 4.1, 95% CI 1.1-15.5, p=0.024), and that only Karnofsky Performance Status (KPS) <90 is a significant predictor of OS (HR 4.9, 95% CI 1.4-17, p=0.01). This is the first report that RIC/NMA allo-HCT could overcome the negative prognostic impact of TP53 alterations in MCL with relatively low incidence of transplant-related mortality. While requiring prospective evaluation, our data supports the consideration of RIC/NMA allo-HCT for MCL patients with TP53 alterations.
Ho:Invivoscribe, Inc.: Honoraria. Hamlin:Portola: Consultancy. Perales:Novartis: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.
