What question did this study set out to answer?

To identify genetic biomarkers associated with early failure of intensive chemoimmunotherapy and stem cell transplantation in patients with mantle cell lymphoma.

September 19, 2019HaematologicaOpen Access

KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

View Full Paper

Ask AI

Bookmark

Authors

SFSimone FerreroAzienda Ospedaliera Citta' della Salute e della Scienza di Torino DRDavide RossiOspedale di Santo Spirito ARAndrea RinaldiUniversity of Cagliari

Discussion

Member takes

Implication

Randomized trial demonstrates that KMT2D mutations and TP53 disruptions predict early treatment failure in mantle cell lymphoma, indicating the need for novel targeted therapy regimens.

Key Points

To identify genetic biomarkers associated with early failure of intensive chemoimmunotherapy and stem cell transplantation in patients with mantle cell lymphoma.
Performed targeted resequencing and DNA profiling of purified tumor samples from patients enrolled in the prospective FIL-MCL0208 phase 3 randomized clinical trial (NCT02354313).
Evaluated high-dose cytarabine-containing chemoimmunotherapy followed by autologous stem cell transplantation and lenalidomide maintenance.
Integrated KMT2D and TP53 status into the conventional MIPI-c prognostic index to derive a combined MIPI-genetic (MIPI-g) risk model.
KMT2D mutations and TP53 disruption (deletion or mutation) were significantly associated with increased risk of disease progression and death in both univariate and multivariate analyses.
The integrated MIPI-g model improved risk discrimination over MIPI-c alone, defining three distinct risk tiers: low-risk (4-year PFS 72.0%, OS 94.5%), intermediate-risk (4-year PFS 42.2%, OS 65.8%), and high-risk (4-year PFS 11.5%, OS 44.9%).
Patients harboring KMT2D mutations exhibited similarly poor survival outcomes as those with TP53 disruption, demonstrating poor sensitivity to intensified chemotherapy.

Cite This Study

Ferrero et al. (2019) studied this question.

synapsesocial.com/papers/69d8fd5d7e3358c846d17cf5 https://doi.org/10.3324/haematol.2018.214056

View Full Paper

Ask AI

Bookmark

Implication

Randomized trial demonstrates that KMT2D mutations and TP53 disruptions predict early treatment failure in mantle cell lymphoma, indicating the need for novel targeted therapy regimens.

KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

Discussion

Member takes

Implication

Key Points

Cite This Study

KMT2D mutations and TP53 disruptions are poor prognostic biomarkers in mantle cell lymphoma receiving high-dose therapy: a FIL study

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider