scholarly journals KMT2D AND TP53 MUTATIONS PREDICT POOR PFS AND OS IN MANTLE CELL LYMPHOMA RECEIVING HIGH-DOSE THERAPY AND ASCT: THE FONDAZIONE ITALIANA LINFOMI (FIL) MCL0208 PHASE III TRIAL

2017 ◽  
Vol 35 ◽  
pp. 94-95 ◽  
Author(s):  
S. Ferrero ◽  
D. Rossi ◽  
A. Bruscaggin ◽  
A. Evangelista ◽  
A. Di Rocco ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Therapy ◽  
Phase Iii Trial ◽  
Tp53 Mutations ◽  
Dose Therapy ◽  
Mantle Cell

scholarly journals Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma

Cancer ◽  
2005 ◽  
Vol 104 (7) ◽  
pp. 1434-1441 ◽  
Author(s):  
Catherine Thieblemont ◽  
Daciana Antal ◽  
Laurence Lacotte-Thierry ◽  
Vincent Delwail ◽  
Daniel Espinouse ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Mantle Cell

Sequential Chemotherapy Followed by High Dose Therapy and Autologous Stem Cell Rescue for Mantle Cell Lymphoma: Impact of MIB-1 on Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3759-3759
Author(s):  
Andrew D Zelenetz ◽  
Craig Moskowitz ◽  
Jocelyn Maragulia ◽  
Carol S. Portlock ◽  
Julie Teruya-Feldstein
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose ◽  
High Dose Therapy ◽  
Sequential Chemotherapy ◽  
Dose Therapy ◽  
Stem Cell Rescue ◽  
Mantle Cell ◽  
Mib 1

Abstract Introduction: Optimal management of mantle cell lymphoma (MCL) remains undefined. However, recent data support the conclusion that upfront consolidation with high dose therapy with autologous stem cell rescue (HDT/ASCR) can improve the PFS (Dreyling, et al., 2005; Geisler, et al., 2008) and possibly OS (Geisler, et al. 2008). Based on gene expression profiling data, the proliferation signature has emerged as a critical determinant of prognosis in MCL (Rosenwald, et al., 2003). Immunohistochemical assessment of proliferation as estimated by MIB-1 (Ki-67) staining has been shown to predict outcome in patients with MCL treated with chemotherapy or immunochemotherapy. With conventional chemotherapy, the reported MIB-1 staining cutoff associated with poor prognosis reportedly varies from 10–30%. Since 1994 we have treated patients (pts) with MCL with sequential chemotherapy followed by HDT/ASCR. The current analysis is a retrospective review of our treatment program focused on the impact of upfront consolidation with HDT/ASCR on the prognostic significance of proliferation as measured by MIB-1 immunohistochemistry. Methods: Seventy-nine patients underwent upfront consolidation with HDT/ASCR for MCL. Fifty-two patients had evaluation of proliferation by MIB-1 immunohistochemistry. MIB-1 expression was estimated visually and assigned a percentage. Patients were binned into quintiles of MIB-1 expression: 0–20% (n=32, 61.5%); 21–40% (n=5, 9.6%); 41–60% (n=5, 9.6%); 61–80% (n=5, 9.6%); and 81–100% (n=5, 9.6%). Outcomes were analyzed by the method of Kaplan-Meier and comparisons were by log-rank. Results: The EFS and OS at 5 years was 65.1% and 61.4% respectively for the subset of patients with available MIB-1 staining (n=52); the outcomes for the entire group (n=79) did not differ from the subset. Outcomes (PFS, OS) were evaluated by MIB-1 quintile with successive cutoff values of 20%, 40%, 60% and 80%. MIB-1 cutoff values of 40% or less were not predictive of outcome. However, when the cutoff was 60% or 80%, both the PFS and OS were significantly worse for the high proliferation group. Nineteen percent of patients had a proliferation fraction of greater than 60%. For patients with MIB-1 staining of >60% the PFS was 4.2 years and was not reached for the group with staining ≤60% (p=0.004). Similarly, overall survival was significantly different, (p=0.031). Conclusions: These findings suggest that upfront consolidation with HDT/ASCR can partially overcome the adverse impact of proliferation on outcome and the adverse outcomes are seen in a subgroup of approximately 20% of patients with MIB-1 staining of greater than 60%.

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

Haematologica ◽  
2019 ◽  
Vol 105 (6) ◽  
pp. 1604-1612 ◽  
Author(s):  
Simone Ferrero ◽  
Davide Rossi ◽  
Andrea Rinaldi ◽  
Alessio Bruscaggin ◽  
Valeria Spina ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Prognostic Biomarkers ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Mantle Cell

Updated Efficacy and Safety, and Exploratory Ki-67 Results For The MCL-001 Study Of Lenalidomide In Mantle Cell Lymphoma Patients Who Relapsed Or Were Refractory To Bortezomib

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3057-3057 ◽  
Author(s):  
Andre Goy ◽  
Michael E. Williams ◽  
Sevgi Kalayoglu Besisik ◽  
Johannes Drach ◽  
Radhakrishnan Ramchandren ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
High Dose ◽  
Efficacy And Safety ◽  
High Dose Therapy ◽  
Ki 67 ◽  
Mantle Cell ◽  
Heavily Pretreated

Abstract Introduction Patients with mantle cell lymphoma (MCL) typically respond to initial therapy and almost inevitably relapse with frequent chemoresistance over time and poor outcome. Multiple phase II studies have established the efficacy and safety of lenalidomide, an immunomodulatory agent with tumoricidal and antiproliferative properties, in relapsed/refractory MCL. The prospective phase II multicenter MCL-001 “EMERGE” study led to FDA approval of lenalidomide for patients with relapsed/refractory MCL after 2 prior treatments, that included bortezomib. The activity of lenalidomide was seen regardless of MIPI, number of prior therapies, prior high dose therapy, bulky disease or high tumor burden. One of the most established prognostic factors in MCL is the proliferation index Ki67 (MIB1), now confirmed both in standard and dose-intensive high-dose therapy strategies. We present here longer follow-up of efficacy and safety from the MCL-001 study in patients relapsed/refractory to bortezomib and the potential relationship between Ki-67 and efficacy outcomes. Methods Patients with heavily pretreated MCL, that included prior bortezomib, received lenalidomide 25 mg/day PO, days 1-21 in 28-day cycles until disease progression or intolerability. Primary study endpoints were overall response rate (ORR) and duration of response (DOR); secondary endpoints included complete response (CR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and safety. Response rates and time-to-event data were analyzed by independent central reviewers per modified IWG criteria and Kaplan-Meier estimates respectively (data cut-off March 20, 2013). Ki-67 was examined as an exploratory endpoint by immunohistochemistry for 81/134 patients (60%) either performed on biopsy samples for 24 patients, or based on the Ki-67 scores reported in local pathology reports for 57 patients. Results Median age for the enrolled intent-to-treat patient population (N=134) was 67 years (range, 43-83; 63% ≥65 years). The median number of previous therapies was 4 (range, 2-10; 78% received ≥3), 93% stage III/IV, and 72% were <6 months from last prior treatment. At a median follow-up of 13.2 months, the ORR was 28% (CR/CRu 8%), with a median DOR of 16.6 months (95% CI, 9.2-26.7; median not reached in patients with CR/CRu) by central review. Median TTR was 2.3 months (95% CI, 1.7-13.1), with a median time to CR/CRu of 4.1 months (95% CI, 1.9-13.2). Median PFS was 4.0 months (95% CI, 3.6-6.9), and median OS was 20.9 months (95% CI, 13.7-24.4). The average dose intensity of lenalidomide was 20 mg/day, for a median duration of 94.5 days (range, 1-1,256). Dose reductions or interruptions due to adverse events (AEs) occurred in 40% and 58% of patients, respectively. Neutropenia (44%), thrombocytopenia (28%), and anemia (11%) were the most common treatment-related grade 3/4 AEs. Ki-67 results were available in 81/134 patients, and efficacy data were categorized using 30% and 50% cut-off thresholds for Ki-67 expression (Table 1). Although patient numbers were limited, the ORR was similar in both lower and higher Ki-67 group, but those with lower Ki-67 levels demonstrated better CR rates, DOR and survival outcomes compared with patients with elevated Ki-67. Conclusions Single-agent lenalidomide in heavily pretreated patients with relapsed/refractory MCL post-bortezomib showed durable long-term efficacy with a consistent safety profile. Consistent with what is reported in the literature, high Ki-67 is associated with poor outcome in our cohort with shorter OS. Though based on retrospective evaluation and subsets of patients, the ORR to lenalidomide was similar in both low and high Ki-67 groups, suggesting lenalidomide can be active in patients expressing high levels of Ki67. Prospective studies are needed to confirm these findings. Disclosures: Goy: Celgene: Consultancy, Research Funding, Speakers Bureau. Off Label Use: This is a phase 2 clinical study of safety and efficacy for lenalidomide in patients with MCL. Williams:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Drach:Celgene: Honoraria. Ramchandren:Celgene: Research Funding. Zhang:Celgene: Employment. Cicero:Celgene: Employment. Fu:Celgene: Employment. Heise:Celgene: Employment, Equity Ownership. Witzig:Celgene: Research Funding.

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