Frontline intensive chemotherapy improves outcome in young, high-risk patients with follicular lymphoma: pair-matched analysis from the Czech Lymphoma Study Group Database

2016 ◽  
Vol 58 (3) ◽  
pp. 601-613 ◽  
Author(s):  
Vít Procházka ◽  
Tomáš Papajík ◽  
Andrea Janíková ◽  
David Belada ◽  
Tomáš Kozák ◽  
...  
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Study Group ◽  
Intensive Chemotherapy ◽  
High Risk Patients ◽  
Risk Patients ◽  
Lymphoma Study Group

scholarly journals Follicular lymphoma: are we ready for a risk-adapted approach?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 358-364 ◽  
Author(s):  
Brad S. Kahl
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Randomized Clinical Trials ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Predictive Biomarkers ◽  
Western Hemisphere ◽  
Ongoing Research ◽  
High Risk Patients ◽  
Risk Patients

Abstract Follicular lymphoma is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. The natural history of FL appears to have been favorably impacted by the introduction of rituximab after randomized clinical trials demonstrated that the addition of rituximab to standard chemotherapy induction has improved the overall survival. Yet, the disease is biologically and clinically heterogeneous with wide variations in outcomes for individual patients. The ability to accurately risk-stratify patients and then tailor therapy to the individual is an area of ongoing research. Historically, tumor grade, tumor burden, and the FL international prognostic index (version 1 and version 2) have been used to distinguish low-risk from high-risk patients. Biologic factors such as mutations in key genes can identify patients at high risk for poor outcomes to first-line therapy (mutational status of 7 genes [EZH2, ARID1A, MEF2B, EP300, FOX01, CREBBP, and CARD11] with Follicular Lymphoma International Prognostic Index). More recently, the quality of the response to initial therapy, as measured by either PET imaging or by remission duration, has been show to identify individuals at high risk. However, several unmet needs remain, including a better ability to identify high-risk patients at diagnosis, the development of predictive biomarkers for targeted agents, and strategies to reduce the risk of transformation.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

scholarly journals Rapid-deployment aortic valve replacement in high-risk patients: A case-control study

2021 ◽  
Vol 13 (1) ◽  
pp. 23-27
Author(s):  
Adama Sawadogo ◽  
An Vinh Bui-Duc ◽  
Nicolas D'Ostrevy ◽  
Lionel Camilleri ◽  
Kasra Azarnoush
Keyword(s):  
High Risk ◽  
Aortic Valve ◽  
Aortic Valve Replacement ◽  
Case Control Study ◽  
Case Control ◽  
Study Group ◽  
High Risk Patients ◽  
Risk Patients ◽  
Rapid Deployment ◽  
Control Study

Introduction: Aortic valve stenosis is the most frequent cardiac valve pathology in the western world. In high-risk patients, conventional aortic valve replacement (C-AVR) carries high rates of morbidity and mortality. In the last few years, rapid-deployment valves (RDV) have been developed to reduce the surgical risks. In this work, we aimed to compare the mid-term outcomes of rapid-deployment AVR (RD-AVR) with those of the C-AVR in high-risk patients. Methods: This retrospective case-control study identified 23 high-risk patients who underwent RD-AVR between 12/2015 to 01/2018. The study group was compared with a control group of 46 patients who were retrospectively selected from a database of 687 C-AVR patients from 2016 to 2017 which matched with the study group for age and Euro SCORE II. Results: RD-AVR group presented more cardiovascular risk factors. Euro SCORE II was higher in the RD-AVR group (P=0.06). In the RD-AVR group, we observed significantly higher mean prosthetic size (P<0.001). In-hospital mortality was zero in RD-AVR group versus 2 deaths in C-AVR group. Hospital stay was longer in the RD-AVR group with statistical significance (P=0.03). In the group AVR with associated cardiac procedures, while comparing subgroups RD-AVR versus C-AVR, early mean gradient was lower in the first cited (P=0.02). The overall mean follow-up was 10.9 ± 4.3 months. Conclusion: The RD-AVR technique is reliable and lead to positive outcomes. This procedure provides a much larger size with certainly better flow through the aortic root. It is an alternative to C-AVR in patients recognized to be surgically fragile.

scholarly journals Elastography and Metalloproteinases in Patients at High Risk of Preterm Labor

2021 ◽  
Vol 10 (17) ◽  
pp. 3886
Author(s):  
Izabela Dymanowska-Dyjak ◽  
Aleksandra Stupak ◽  
Adrianna Kondracka ◽  
Tomasz Gęca ◽  
Arkadiusz Krzyżanowski ◽  
...  
Keyword(s):  
High Risk ◽  
Preterm Delivery ◽  
Plasma Concentrations ◽  
Cervical Length ◽  
Control Group ◽  
Study Group ◽  
Median Length ◽  
High Risk Patients ◽  
Ultrasound Evaluation ◽  
Risk Patients

Preterm birth (PTB) is the leading cause of perinatal morbidity and mortality. Its etiopathology is multifactorial; therefore, many of the tests contain the assessment of the biochemical factors and ultrasound evaluation of the cervix in patients at risk of preterm delivery. The study aimed at evaluating the socioeconomic data, ultrasound examinations with elastography, plasma concentrations of MMP-8 and MMP-9 metalloproteinases, and vaginal secretions in the control group as well as patients with threatened preterm delivery (high-risk patients). The study included 88 patients hospitalized in the Department of Obstetrics and Pregnancy Pathology, SPSK 1, in Lublin. Patients were qualified to the study group (50) with a transvaginal ultrasonography of cervical length (CL) ≤ 25 mm. The control group (38) were patients with a physiological course of pregnancy with CL > 25 mm. In the study group, the median length of the cervix was 17.49 mm. Elastographic parameters: strain and ratio were 0.20 and 0.83. In the control group, the median length of the cervix was 34.73 mm, while the strain and ratio were 0.20 and 1.23. In the study group, the concentration of MMP-8 in the serum and secretions of the cervix was on average 74.17 and 155.46 ng/mL, but in the control group, it was significantly lower, on average 58.49 and 94.19 ng/mL. The concentration of MMP-9 in both groups was on the same level. Evaluation of the cervical length and measurement of MMP-8 concentration are the methods of predicting preterm delivery in high-risk patients. The use of static elastography did not meet the criteria of a PTB marker.

Frontline Intensive Chemotherapy Brings Survival Benefit In Young, Risky Patients With Follicular Lymphoma: Pair-Matched Analysis From The Czech Lymphoma Study Group (CLSG) Database

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4354-4354
Author(s):  
Vit Prochazka ◽  
Marek Trneny ◽  
Andrea Janikova ◽  
David Belada ◽  
Tomas Kozak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Maintenance Therapy ◽  
Follicular Lymphoma ◽  
Long Term Results ◽  
Study Group ◽  
Intensive Chemotherapy ◽  
Additional Risk ◽  
Lymphoma Study Group ◽  
Risky Patients ◽  
Risk Of Relapse

Abstract Background Follicular lymphoma (FL) is a disease with very heterogeneous course ranging from the indolent forms to rapidly progressive cases with poor outcome. Optimal therapy in FL patients with high tumor burden is immunochemotherapy (R-CHOP is the most frequent regimen used), followed by maintenance treatment. Data from randomized prospective studies (PRIMA) showed poorer outcome in those with high risk disease in terms of lower CR rate, higher risk of relapse and lower efficacy of maintenance therapy. Data comparing up-front intensive approach in younger fit patients and R-CHOP are limited. Aim To analyze long term results of intensive treatment protocol (R-sequential chemotherapy) in comparison with age, FLIPI and maintenance delivery matched (R-CHOP) controls. Methods Here we analyzed data of 48 prospectively enrolled FL patients who were treated by sequential (R-SQ) chemotherapy with or without up-front autologous stem cell transplant (ASCT) as a part of stratified risk adapted treatment in one institution. For R-SQ regimen were indicated patients<65 years with INT-FLIPI (with at least 2 additional risk factors: bulk and/or elevated B2M>3mg/L and/or thymidine kinase>15 IU/L) or HIGH-FLIPI patients (irrespective of additional risk factors). R-SQ protocol consists of alternating three cycles of etoposide-doxorubicine regimen (PACEBO), one methotrexate-ifosfamide regimen (IVAM), and one cycle of high dose cytarabine regimen (HAM). Remission was consolidated with 6th cycle of chemotherapy (PACEBO) in INT-FLIPI patients (n=22, 46%) or with ASCT with BEAM-200 conditioning (n=26, 54%) in HIGH-FLIPI patients. Maintenance immunotherapy was applied for historical reasons in 24 patients (50%). Controls were randomly selected from the Czech Lymphoma Study Group (CLSG) database from 626 cases with confirmed FL grade I to IIIa, treated with R-CHOP. Pair matching was performed on 1:3 basis, controls were matched by age, FLIPI and rituximab maintenance application. In the end, we analyzed intensive SQ-group (n=44) and standard control R-CHOP-group (n=144). Maintenance therapy was delivered to 24 patients (50%) in R-SQ group and to 72 patients (50%) in R-CHOP-group (P=1.00). Results Median age of SQ-group was 47.6 years compared to 48.7 years in R-CHOP (P=0.44), FLIPI index was equally distributed: INT-FLIPI (43% vs 43%), HIGH-FLIPI (57% vs 57%, P=1.00). Treatment response quality was higher in SQ-group than in R-CHOP-group: CR/CRu 93.8% vs 70%, PR 6.2% vs 23% and SD/PD 0% vs 8% respectively (P=0.01). During the follow-up, (median 3.5 and 6.1 years in R-CHOP and SQ-group respectively, P<0.01) 10 patients (20.8%) relapsed or progressed in the R-SQ-group, and 41 (29%) in the R-CHOP-group (P=0.01). Only two of 48 patients (4.2%) died in the R-SQ-group, whereas twelve (8.7%) died in the R-CHOP-group (P=0.03). Five-year progression-free survival (PFS) was superior in the R-SQ-group with 78.5% (95% CI 0.66-0.91) survival compared to 53.8% (95% CI 0.43-0.65, P=0.005, HR=0.37) in the R-CHOP-group. Five-year overall survival (OS) was 100% in the R-SQ-group and 91.9% (95% CI 0.86-0.97, P=0.027, HR=0.18) in the R-CHOP group. When analyzing patients who received maintenance therapy, we found no difference in OS (P=0.13), but there was still significant difference in 5-year PFS in favor of the R-SQ-arm (88.4% and 58.2%, P=0.034). Conclusions In risky FL patients, intensive front-line therapy brings about 24% advantage in CR rate, about 25% higher 5-year PFS (reduces risk of relapse/progression by 62%) and about 10% advantage in 5-year OS (reduces risk of death by 82%). Maintenance immunotherapy application overshadows OS but not PFS advantage of intensive chemotherapy. Finally, in younger physically fit risky patients, more intensive induction regimen leads to superior disease control a remission duration compared to standard R-CHOP. Acknowledgment Supported by grants: LF-2013-004, IGA NT12193-5/2011 and PRVOUK-27/LF1/1. We would like to thank to all referring physicians: Jan Pirnos (Ceske Budejovice), Katerina Kubackova (FN Motol), Lucie Barsova (Liberec), Petr Kessler (Pelhrimov), Jitka Jakesova (Pribram), Milan Lysy (Usti n. Labem), Jindra Ciberova (Znojmo), Dagmar Adamova (Opava), Milan Matuska (Ostrava), Martin Brejcha (Novy Jicin). Disclosures: Trneny: Roche: Honoraria, Research Funding.

scholarly journals Multicenter Study of Risk-Adapted Therapy With Dose-Adjusted EPOCH-R in Adults With Untreated Burkitt Lymphoma

2020 ◽  
Vol 38 (22) ◽  
pp. 2519-2529 ◽  
Author(s):  
Mark Roschewski ◽  
Kieron Dunleavy ◽  
Jeremy S. Abramson ◽  
Bayard L. Powell ◽  
Brian K. Link ◽  
...  
Keyword(s):  
High Risk ◽  
Burkitt Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Intensive Chemotherapy ◽  
Hiv Status ◽  
Pediatric Leukemia ◽  
High Risk Patients ◽  
Cns Prophylaxis ◽  
Risk Patients

PURPOSE Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were ≥ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182 ).

The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1504-1508 ◽  
Author(s):  
Christian Buske ◽  
Eva Hoster ◽  
Martin Dreyling ◽  
Joerg Hasford ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
High Risk ◽  
Follicular Lymphoma ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Intermediate Risk ◽  
Advanced Stage ◽  
Front Line ◽  
High Risk Patients ◽  
Risk Patients

The Follicular Lymphoma International Prognostic Index (FLIPI) was developed to predict prognosis of patients with follicular lymphoma (FL). However, it was based on different protocols, none of which included rituximab. The current analysis aimed at evaluating the predictive value of the FLIPI for treatment outcome in 362 patients with advanced-stage FL treated front-line with rituximab/CHOP in a prospective trial of the German Low Grade Lymphoma Study Group. According to the FLIPI, 14% of the patients were classified as low-risk, 41% as intermediate-risk, and 45% as high-risk patients. With a 2-year time to treatment failure (TTF) of 67%, high-risk patients had a significantly shorter TTF as compared with low- or intermediate-risk patients (2-year TTF of 92% and 90%, respectively; P < .001). Our data demonstrate that the FLIPI is able to identify high-risk patients with advanced-stage FL after first-line treatment with rituximab/chemotherapy.

Decision Criteria for the Futility of Intensive Chemotherapy in Older Patients with Acute Myeloid Leukemia (AML).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2861-2861 ◽  
Author(s):  
Hervé Dombret ◽  
Jean-Valère Malfuson ◽  
Anne Etienne ◽  
Pascal Turlure ◽  
Thierry de Revel ◽  
...  
Keyword(s):  
High Risk ◽  
Intensive Chemotherapy ◽  
Decision Criteria ◽  
Short Term ◽  
High Risk Patients ◽  
Short Term Mortality ◽  
Comorbidity Scores ◽  
Risk Patients ◽  
Comorbidity Index ◽  
Artery Disease

Abstract Aims and methods. We have recently reported results of intensive chemotherapy in 416 patients with AML aged 65 years or more (median, 72 years) treated in the ALFA-9803 trial (Gardin et al., Blood 2007). We show here the impact of pretreatment characteristics on short-term mortality in these patients (32% at 6 months in the whole population). A first objective was to evaluate the prognostic value of the Charlson Comorbidity Index (CCI) and Sorror Hematopoietic Cell Transplantation Comorbidity Index (HCTCI), but the main objective was to screen the most frequent characteristics individually or in combination, including comorbidities, for their sensitivity in short-term mortality prediction. The aim was to propose decision criteria to advice against the intensive approach in high-risk patients, defined here by the presence of at least one characteristic associated with a probability of death at 6 months of 50% or more. Value of comorbidity scores. Both comorbidity scores correlated pretty well (CCI 0/1/2 = 353/57/6; HCTCI 0/1/2/3+ = 268/85/42/21; P<0.001), but only HCTCI was predictive of mortality (P<0.001). Other independent factors were age, PS, and cytogenetics. As all these patients were previously selected as suitable for intensive chemotherapy, only four HCTCI comorbidities were, however, relatively frequent (prevalence ≥ 5%): coronary artery disease (10%), arrhythmia (8%), infection (8%), and diabetes (7%). Impact on mortality was only due to the demarcation of very few high-risk patients (N=21) limiting the clinical interest of HCTCI in treatment decision making. Of note, HCTCI did not correlate with advanced age or PS in this patient population. Definition of decision criteria. Further analysis of the predictive value of each characteristic or combination identified three decision criteria, each being predictive of 6-month mortality ≥ 50% (Table 1): high-risk cytogenetics, pre-treatment documented infection, and PS ≥ 2 if age ≥ 75 years. Taken together, these 3 criteria, which were validated in an independent set of 123 patients, allowed to demarcate 94 high-risk patients (23%) with a probability of death at 6 months of 57%, as compared to 26% in the remaining patients (P<0.001, by log-rank test). We propose thus to add these criteria to usual eligibilty criteria in order to better define the population of older AML patients who will draw a significant benefit from intensive chemotherapy. Table 1. Short-term mortality associated with most frequent Characteristic. Characteristic Prevalence Median OS (mo) 6-month mortality High-risk cytogenetics 12% 4.8 64% Documented infection 8% 4.7 63% PS≥2 and age≥75 years 7% 2.9 54% PS≥2 27% 7.0 47% Age≥75 years 20% 7.9 42% Coronary artery disease 10% 6.8 43% Diabetes 7% 14.2 41% Arrhythmia 8% 14.6 31% Post–MDS AML 15% 10.6 29%

Follicular Lymphoma Therapy Based on Biological Insights and Novel Concepts

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-7-SCI-7
Author(s):  
Sonali M. Smith
Keyword(s):  
High Risk ◽  
Follicular Lymphoma ◽  
Unmet Needs ◽  
The United States ◽  
Sales Force ◽  
New Drugs ◽  
Early Relapse ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Impact

The majority of patients with follicular lymphoma experience a protracted course with survival estimates measured in decades. However, there are several critical unmet needs, including pre-emptive identification of high-risk patients, management of early relapse, and treatment of patients with multiply relapsed or rituximab-refractory disease. While exact numbers are not known, approximately 15-20% of patients will have early relapse and the bulk of patients will become rituximab-refractory with time; since there are 30,000 newly diagnosed patients with follicular lymphoma annually in The United States, this constitutes a substantial cancer and societal burden. Unfortunately, the overall possibility for widespread cure remains elusive. Clinical prognostic tools including the FLIPI and FLIPI-2 are difficult to apply at an individual level, and, to date, there are no prospectively validated biologic tools capable of identifying the highest risk groups. The M7-FLIPI, which integrates seven gene mutations (EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, CARD11) with performance status and the FLIPI, is prognostic in patients receiving chemoimmunotherapy, and merits further study. There are currently no pathobiologic predictors of outcome in patients treated with monoclonal antibodies or non-cytotoxic therapies. While prognostication in treatment-naïve patients remains elusive, there are now several time-to-event based observations following initial therapy that define a high-risk subset of patients with inferior survival; these include CR30 and EFS24 which will be further described. As discussed by the previous speakers, a provocative emerging theme is that many somatic mutations and epigenetic and genetic changes occur relatively early in the evolution of the disease and could potentially shape the subsequent clinical course. The possibility that early progression (as defined by EFS24, for example) is directly related to these events affords the exciting prospect of identifying high-risk patients before they receive standard treatment; furthermore, if confirmed, these aberrations are ripe targets for new agents. Moving from prognostication to prediction of response to individual agents or regimens is badly needed in this disease, particularly since there are a plethora of new drugs and new targets being identified. An important and poorly understood component of FL biology that is likely to impact clinical behavior is the tumor microenvironment. The non-malignant milieu of follicular lymphoma is comprised of several cell types, and their composition and interaction with the malignant compartment probably evolves with the disease course. The relationship between the microenvironment and the malignant cell is also a valid target, with both immunomodulatory agents and immunotherapy drugs actively being tested. Overall, the incorporation of biologic insights into treatment of follicular lymphoma will drive the next generation of clinical investigations and move to limit the impact of unmet needs in this disease. Disclosures Smith: Amgen: Other: Educational lecture to sales force; TGTX: Consultancy; Portola: Consultancy; Juno: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Genentech: Consultancy, Other: on a DSMB for two trials ; Pharmacyclics: Consultancy; Gilead: Consultancy.

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