Outcome By Primary Treatment Type and Timing of Progression Among Follicular Lymphoma Patients: A Large, Population-Based Study in Sweden

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 46-47
Author(s):  
Caroline Weibull ◽  
Björn E Wahlin ◽  
Sandra Lockmer ◽  
Gunilla Enblad ◽  
Per-Ola Andersson ◽  
...  
Keyword(s):  
Research Funding ◽  
Primary Treatment ◽  
Population Based ◽  
Line Treatment ◽  
First Line ◽  
Population Based Study ◽  
Line Therapy ◽  
Progression Of Disease ◽  
First Line Treatment ◽  
Time Point

Purpose: Follicular lymphoma (FL) is generally regarded as an indolent malignancy, yet the clinical outcome is highly variable. In recent years, POD24 (progression of disease within 24 months) has emerged as a potential prognostic marker for overall survival (OS) in FL and other non-Hodgkin lymphomas. The association with survival, however, has mostly been studied in selected clinical trial cohorts and among patients treated with R-CHOP. We aimed to investigate OS by timing of progression and type of primary treatment in a population-based setting in Sweden. Methods: We identified all patients diagnosed with FL in stages II-IV and grade 1-3a between 2007 and 2014, using the population-based Swedish lymphoma register. Data were complemented with information on progression, transformation and second-line treatment through medical charts review up to December 31st, 2017. The analysis covered 4 out of 6 health care regions (75% of all patients diagnosed nationally). The patients were categorized according to type of first-line treatment: R-chemo of any type, R-Benda, R-CHOP (including R-CHOEP), or other (including immunotherapy only). Among patients where it was decided to start first-line treatment within 6 months of diagnosis (and where treatment was started within nine months), POD was defined as either lack of response to first-line therapy (stable [SD] or progressive disease [PD]), or initial response and subsequent relapse/progression/transformation as indication for second-line therapy. To quantify the impact of timing of POD on survival, the five-year OS conditional on either being progression-free (PF) or having experienced POD at different time points during follow-up, was estimated using a flexible parametric illness-death model. Results: Among a total of 970 FL patients, median age at diagnosis was 66 years and patients were followed for a median of 6.4 years (range 0-12 years). The 5-year OS was 75% and progression-free survival was 59%. Six hundred (62%) patients had a first-line treatment within nine months of diagnosis and were hence analyzed further, whereas the remaining 370 (38%) patients were classified as wait-and-watch and were not analyzed further. Among the 600 treated patients, 337 (56%) had R-chemo (R-CHOP or alike (n=210), R-Benda (n=97), other (n=30)), and 263 (44%) received non-R-chemo treatment (mainly R-monotherapy, radiotherapy only, or R-lenalidomide). Patients who received R-Benda were on average older than the other groups. Among patients treated with R-chemo, those who stayed progression-free had a 5-year conditional OS above 75% regardless of PF time point. For patients who progressed, the 5-year conditional OS improved as time point of POD was prolonged (Fig 1a, left panel). Early POD (within 12-24 months) was associated with a particularly poor prognosis (5-year conditional OS below 55%). The OS improvement over time of POD was especially pronounced among R-Benda treated patients (Fig 1b, right panel). Among patients receiving non-R-chemo treatments, early POD was associated with a slightly worse 5-year OS but differences between POD and PF patients were less marked (Fig 1a, right panel). Conclusion: This population-based study of Swedish stage II-IV FL patients shows that among immunochemotherapy-treated patients, progression of disease was always associated with worse survival in comparison to progression-free patients regardless of timing of progression. This reduction in survival was more pronounced the earlier the progression (as described by others). Interestingly, among patients selected for milder non-immunochemotherapy-based treatments, progression of disease did not have a strong effect on survival. Disclosures Weibull: Janssen Cilag: Research Funding. Wahlin:Gilead Sciences: Research Funding; Roche: Consultancy, Research Funding. Smedby:Takeda: Research Funding; Janssen: Research Funding; Celgene: Consultancy.

The Outcome of T-Cell Lymphoma Patients Failing First-Line Treatment: Results of a Population Based-Study From the Modena Cancer Registry

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1611-1611 ◽  
Author(s):  
Irene Biasoli ◽  
Marina Cesaretti ◽  
Stefano Luminari ◽  
Monica Bellei ◽  
Alessandra Dondi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Initial Therapy ◽  
Population Based ◽  
Salvage Treatment ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Population Based Study ◽  
First Line Treatment

Abstract Abstract 1611 Introduction: For many T-cell lymphoma (TCL) patients (pts), current treatment strategies are largely ineffective. In particular, pts failing first line therapy are expected to have a dismal outcome but little is known about them. The purpose of this population-based study was to establish the outcome of TCL pts following relapse/progression. Material and methods: All TCL pts diagnosed in the province of Modena, Italy between January 1, 1997 and December 31, 2010 were identified from the archives of the Modena Cancer Registry that covers a population of approximately 600.000 people. Additional data on disease characteristics, treatment modalities, together with response assessments and outcome were actively retrieved and collected. Results: A total of 146 TCL pts were initially identified, and 18 excluded because of missing data; therefore 128 were available for the present analysis. The most common subtypes were Peripheral T-cell lymphoma not otherwise specified in 46 pts (36%), Anaplastic large T-cell lymphoma in 46 patients (36%) Angioimmunoblastic T-cell lymphoma in 15 (12%), and other subtypes in 21 (16%). The male to female ratio (M/F) for the entire population was 1.7 and the median age was 64 years (16–90). A total of 100 (78%) pts received initial treatment within 3 months of their diagnosis: 74 received combination chemotherapy (CT), 9 received radiation therapy (RT) only, 10 underwent surgery and 7 were addressed to high dose therapy and autologous stem cell transplant (ASCT) as part of initial therapy. Among the remaining 28 patients, 24 (19%) died within 3 months of their diagnosis and 4 (3%) received only palliative therapy because of their comorbidities. The majority of pts received anthracyclines (ADM) containing regimens as part of their initial therapy (71/74, 96%). At the end of first line treatment, 59 (59%) pts achieved complete remission (CR), 13 pts partial remission (PR), 8 pts stable disease (SD) and 20 cases had disease progression (PD). Overall, 59 pts presented relapse/progression; 23 (39%) of them died before receiving any salvage treatment, 14 pts received DHAP (7 of whom were subsequently addressed to ASCT), 8 received gemcitabine-containing regimens, 6 received ADM containing regimes and 8 other CT regimens; 2 patients were treated with RT. At a median follow-up for living patients after relapse/progression of 28 months (range 9–111 months), 49 patients died, and the cause of death was found to be lymphoma progression in all of them. The median overall survival (OS) following relapse/progression was 1.9 months. Among the 36 pts that received salvage treatment median OS was not reached for those who received ASCT and was 4.5 months for those who received conventional dose salvage treatment (p=0.003). A Cox regression analysis was performed in order to identify prognostic factors among these 59 pts: age at relapse (≥60 years, HR=2.35, CI95% 1.04–5.28, P=0.038) and advanced stage (HR=3.24, 1.31–7.98) were associated with a higher risk of death and salvage treatment ASCT was associated with a better survival (HR=0.04, IC95% 0.006–0.36). No other clinical characteristic (gender, histology, LDH and performance status) at diagnosis was associated with higher risk of death among relapsing/progressing patients. Conclusion: In the general population, outside clinical trials, the outcome of TCL pts is dramatically poor. First, about 20% of the whole cohort is not able to receive any kind of therapy mainly due to early death; second, the rate of pts failing first line therapy that could not receive any salvage therapy rose to 39%. As a result, progression during initial therapy or relapse after first line treatment entails a very dismal prognosis with less than 2 months of median survival. Only a few patients that could receive ASCT after relapse had promising chances of long lasting remission. Based on the results of this population based study, it is evident that there is urgent need for novel agents to be offered to TCL pts requiring second line treatment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Real-World Treatment Patterns from the HUMANS Study in Multiple Myeloma in Denmark

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5030-5030
Author(s):  
Niels Abildgaard ◽  
Anders Waage ◽  
Markus Hansson ◽  
Pekka Anttila ◽  
Mate Szilcz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Real World ◽  
Treatment Duration ◽  
Research Funding ◽  
Population Based ◽  
Treatment Patterns ◽  
Line Treatment ◽  
First Line ◽  
Real World Evidence ◽  
First Line Treatment

Introduction Current treatment for multiple myeloma (MM), an incurable but treatment sensitive plasma cell cancer, aims to extend time to disease progression, prolong survival and improve quality of life. Nevertheless, epidemiological knowledge regarding MM treatment is mostly derived from randomized controlled trials, which are limited by strict inclusion criteria, study designs that assess drug efficacy in optimal clinical settings, and short follow-up. Current treatment options for MM are associated with complex and varying treatment-related side effect profiles. However, real-world evidence is available only for a limited selection of treatment regimens. Thus, there is a need for studies to further investigate treatment patterns in clinical settings that reflect real-world practice. The Health Outcome and Understanding of Myeloma - a multi-national real-world evidence (HUMANS) study - aimed to characterize patient characteristics, treatment patterns, and outcomes for newly diagnosed patients with MM who received first-line treatment. Here we report first results from the Danish study. Methods This population-based, retrospective, longitudinal, observational study used secondary data from the Danish Cancer Register (DCR) and National Patient Register (NPR) for patients diagnosed with MM. Patients were stratified by autologous stem cell transplantation (ASCT) and pharmacological treatment (bortezomib-based, lenalidomide-based, or other first-line therapy) and characterized using descriptive statistics. To analyse recent treatment patterns and also include patients with long duration before treatment start, eligible patients had first MM diagnosis from 2005-2016 in the NPR and DCR (diagnosis date identified from the DCR), first MM-specific treatment from 2010-2018 in the NPR, no other hematologic cancer records in the NPR and DCR, and no MM treatment before diagnosis. Treatment duration (time between start and end of treatment period, with set grace period of 60 days and assumed treatment supply of 7 and 28 days per treatment event for bortezomib and lenalidomide, respectively) and overall survival (OS) were estimated by Kaplan-Meier method. Results The study population comprised 2,451 patients with MM, of which 887 patients (36%) underwent ASCT. In the non-ASCT population (n=1564), the majority (n=838, 54%) received bortezomib as first-line treatment, 102 patients (7%) received lenalidomide, and for 631 patients (40%), first-line treatment could not be identified (referred to as the other non-ASCT cohort). Mean (standard deviation) age overall at first MM diagnosis was 68 (±11) years, and was 72 (±8), 75 (±9), 77 (±7), and 59 (±8) years in the bortezomib, lenalidomide, other non-ASCT and ASCT cohorts, respectively. A higher number of men (57%) than women were diagnosed with MM. From 2015 onwards, the proportion of patients who received lenalidomide increased, whereas for patients who received other MM specific drugs, the proportion decreased (see Table 1). The median OS (95% confidence interval [CI]) from administration of first-line treatment for the bortezomib and lenalidomide cohorts was 52.9 (46.2-58.2) and 69.3 (54.7-108.4) months, respectively. For the ASCT cohort the median OS was 117.2 (104.2-133.8) months from MM diagnosis. Patients followed a once or twice weekly regimen of bortezomib treatment, i.e. 3/4 or 7 days between treatments (Figure 1). Patients in the bortezomib cohort remained treated with a median bortezomib treatment duration of 4 months (CI 4.04-4.60) and an estimated 10% remained on treatment at 10 months. In the lenalidomide cohort, patients remained treated with a median duration of 7 months (CI 4.67-10.12) and an estimated 10% remained on treatment at 23 months (Figure 2). Conclusion In this study, we present population-based treatment patterns and outcomes for MM in Danish clinical practice. The 4 month median treatment duration of bortezomib was lower than the target treatment suggested by prior clinical trials. The differences in overall survival and treatment duration should be interpreted with caution, as patients in the different cohorts have varying baseline characteristics. Linked data from the DCR and NPR may provide real-world evidence of treatment patterns in clinical practice. Research regarding time to progression in a multiple myeloma real-world setting is warranted. Disclosures Abildgaard: Amgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Szilcz:Parexel International: Employment. Ma:Parexel International: Employment. Ørstavik:Takeda Pharmaceuticals International AG: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Freilich:Parexel International: Employment. Gavini:Takeda Pharmaceuticals International AG: Employment.

Addition of Rituximab to Front-Line-Treatment Highly Improved the Outcome of Elderly Patients with Follicular Lymphoma: a Population Based-Study From the Modena Cancer Registry

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5077-5077
Author(s):  
Stefano Luminari ◽  
Irene Biasoli ◽  
Luigi Marcheselli ◽  
Monica Bellei ◽  
Alessandra Dondi ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Cox Regression ◽  
The Elderly ◽  
Population Based ◽  
Line Treatment ◽  
First Line ◽  
Population Based Study ◽  
Cox Regression Analysis ◽  
Second Period ◽  
First Line Treatment

Abstract Abstract 5077 Background: The benefit of adding Rituximab to combination chemotherapy in Follicular Lymphoma (FL) has been established in several randomized clinical trials (RCT). All of them have shown improvements in response rates, time to progression or overall survival (OS). The aim of the study was to assess the impact of the introduction of Rituximab in the treatment of FL in the general population of elderly patients, usually not included in RCT. Methods: All FL patients diagnosed in the province of Modena, Italy that had been diagnosed between 1997 and 2010 were identified from the archives of the Modena Cancer Registry that covers a population of approximately 600. 000 people. In the studied region Rituximab was available for first line treatment of FL since 2004. Therefore, for study purposes patients were grouped according to the year of diagnosis in 2 study periods (1997–2003, and 2004–2010). Elderly patients were defined using a cut off for age at 60 years. Clinical and treatment characteristics and also OS were compared according to the period of diagnosis and also, regarding the use or not of Rituximab as part of first line treatment. Moreover, a Cox regression analysis was performed to identify clinical factors and treatment characteristics associated with OS. Results: A total of 340 FL patients were identified of whom 177 (52%) were older than 60 years. No difference was found regarding clinical characteristics at diagnosis (age, gender, stage, bulky disease and LDH level) among study periods. Regarding treatment, no difference was found for the first general approach (watch and wait, chemotherapy or radiotherapy) across time. Among 229 patients initially treated with chemotherapy, antracyclines (ADM) or fludarabine (F)-based-regimens were the most frequently used. However, the use of ADM and/or F-based-regimens decreased from 82% (85/104) in the first period to 66% (83/125) in the last period (p=0. 03). Elderly patients (67%; 83/124) received less frequently ADM or F-based-regimens in comparison with younger patients (81%; 85/105) (P<0. 001). In contrast, the use of Rituximab alone or as part of front line treatment remarkably increased from 15% (16/104) in the first period to 94% (118/125) after 2003 (p<0. 001). This increase was also observed among elderly patients (8% (4/49) in the first period and 92% (69/75) in the last period, p<0. 001). After a median follow up of 68 months (range 8 to 176) for living patients, median OS was not reached. In univariate analysis factors associated with inferior OS were older age (>60), period of diagnosis before 2004, no use of Rituximab and abnormal LDH levels. The 5-years OS increased from 73% to 85% moving from first to second study periods (p=0. 008). In the Cox-Regression analysis, age > 60 (HR 11. 27 95%CI 5–25) and abnormal LDH level (HR 2. 7 95%CI 1. 56–4. 8) at diagnosis were identified as independent adverse risk factors. In contrast, the use of Rituximab yielded a protective effect (HR 0. 4 95%CI 0. 23–0. 79). In multivariate analysis period of diagnosis and use of Rituximab were mutually exclusive. Comparing young with elderly patients, only the latter group had a significant improvement in OS across the study periods: among the young, the 5-years OS in the first and second period was 89% and 98%, respectively, p= 0. 07; and among the elderly the 5-years OS in the first and second period was 58% and 72%, respectively p=0. 02. Conclusion: The present population based study showed a remarkable improvement in OS of FL patients after 2003, as a consequence of introduction of Rituximab as part of first line treatment. This improvement was mostly pronounced in the elderly population. Disclosures: No relevant conflicts of interest to declare.

Dismal outcome of t-cell lymphoma patients failing first-line treatment: results of a population-based study from the Modena Cancer Registry

2014 ◽  
Vol 33 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Irene Biasoli ◽  
Marina Cesaretti ◽  
Monica Bellei ◽  
Antonino Maiorana ◽  
Goretta Bonacorsi ◽  
...  
Keyword(s):  
T Cell ◽  
Cancer Registry ◽  
Cell Lymphoma ◽  
Population Based ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Treatment Results ◽  
Population Based Study ◽  
First Line Treatment

scholarly journals First‐line treatment in older patients with Hodgkin lymphoma: a Surveillance, Epidemiology, and End Results (SEER)‐Medicare population‐based study

2020 ◽  
Vol 190 (2) ◽  
pp. 222-235
Author(s):  
Angie Mae Rodday ◽  
Theresa Hahn ◽  
Anita J. Kumar ◽  
Peter K. Lindenauer ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Older Patients ◽  
Population Based ◽  
Line Treatment ◽  
First Line ◽  
Population Based Study ◽  
Medicare Population ◽  
First Line Treatment ◽  
End Results

Activity of Idelalisib in High-Risk Follicular Lymphoma with Early Relapse Following Front Line Immunochemotherapy

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2744-2744 ◽  
Author(s):  
Ajay K Gopal ◽  
Brad S Kahl ◽  
Christopher Flowers ◽  
Peter Martin ◽  
Brian K Link ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Research Funding ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Free Survival ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Follicular lymphoma (FL) is the most common indolent NHL with a heterogenous natural history of disease and a median survival of 8 to 12 y, albeit ranging between 1 to 20 y. Casulo et al. (2015) identified a high-risk FL cohort of patients with progression of disease (POD) at ≤24 months following initiation of immunochemotherapy with R-CHOP. Idelalisib (Zydelig) is a first-in-class, highly selective, oral inhibitor of PI3Kd which is indicated for relapsed FL or SLL following receipt of at least two lines of systemic chemotherapy. Retrospective subgroup analysis of the idelalisib registrational trial NCT01282424 (101-09) of a cohort with early POD following immunochemotherapy was performed to assess possible activity of idelalisib in this population. Methods: A subset of 46 patients enrolled in study 101-09 were identified as having been diagnosed with FL and having received first-line immunochemotherapy, of which 37 experienced early POD, defined as starting second-line treatment within 24 months of initial first-line treatment. For the latter group, descriptive statistics of demographic and baseline characteristics and inter-treatment intervals in months as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) following initiation of immunochemotherapy and idelalisib were calculated. Population: Demographic characteristics of these 37 patients included median (range) age at initiation of idelalisib of 64 (33-84) y and 18 (48.6%) females. Histologic grade at diagnosis included 33 (89.2%) with grades 1 or 2 as well as 4 (10.8%) with grade 3A, while 21 (56.8%) patients had a FLIPI score ≥3. The mean (s.d.) number of prior therapies was 3.4±1.4, with a range of 2 to 8, while first-line therapies included 21 (56.8%) patients who received R-CHOP-based regimens, 7 (18.9%) who received BR, and 5 (13.5%) who received R-CVP. Mean (s.d.) inter-treatment intervals included 12.5±6.1 months between first- and second-line for all patients, 9.7±9.3 months between second- and third-line for all patients, 11.9±12.0 months between third- and fourth-line for 24 (64.9%) patients, and 11.8±7.6 months between fourth- and fifth-line for 15 (40.5%) patients. Median (range) time from first-line therapy to idelalisib initiation was 30.3 (8.9-94.7) months; no patient received idelalisib as second-line therapy. Results: Best responses included 5 (13.5%) patients with CR, 16 (43.2%) with PR, 2 (5.4%) with SD, and 1 (2.7%) with PD; median duration of response for those with CR or PR was 11.8 months (95% CI: 3.8 months, not evaluable). There were 7 (18.9%) deaths and 21 (56.8%) PFS events in this group. Estimated probabilities of survival (s.e.) and progression-free status at 2 y following initiation of idelalisib were 79%±7% and 29%±10%, respectively. Median PFS was 11.1 months (95% CI: 5.5, 19.3 months). Estimated probability of survival (s.e.) at 5 years following initiation of first-line treatment was 79%±8%. Median overall survival from both initiation of first-line immunochemotherapy as well as with idelalisib was not reached during the course of this study. Conclusions: Idelalisib may have significant clinical activity in high-risk and doubly-refractive FL following early relapse status post first-line immunochemotherapy. Given the small size of the studied subset population which may not be representative, further characterization in additional patients is warranted to ensure the generalizability of this finding, including consideration of further investigational protocols featuring targeted therapies employed both as single agents and in combination. Figure 1. Overall Survival From Initiation of First-line Treatment Figure 1. Overall Survival From Initiation of First-line Treatment Figure 2. Overall Survival From Initiation of Idelalisib Figure 2. Overall Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Figure 3. Progression-Free Survival From Initiation of Idelalisib Disclosures Gopal: Gilead, Spectrum, Pfizer, Janssen, Seattle Genetics: Consultancy; Spectrum, Pfizer, BioMarin, Cephalon/Teva, Emergent/Abbott. Gilead, Janssen., Merck, Milennium, Piramal, Seattle Genetics, Giogen Idec, BMS: Research Funding; Millennium, Seattle Genetics, Sanofi-Aventis: Honoraria. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Flowers:Infinity Pharmaceuticals: Research Funding; Genentech: Research Funding; Spectrum: Research Funding; Millennium/Takeda: Research Funding; Seattle Genetics: Consultancy; Spectrum: Research Funding; Pharmacyclics: Research Funding; AbbVie: Research Funding; AbbVie: Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Research Funding; Onyx Pharmaceuticals: Research Funding; Celegene: Other: Unpaid consultant, Research Funding; OptumRx: Consultancy; Gilead Sciences: Research Funding; Janssen: Research Funding; Acerta: Research Funding; Millennium/Takeda: Research Funding; Acerta: Research Funding; Infinity Pharmaceuticals: Research Funding; Janssen: Research Funding; Onyx Pharmaceuticals: Research Funding. Martin:Janssen: Consultancy, Honoraria; Acerta: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Bayer: Consultancy. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Ye:Gilead: Employment. Koh:Gilead: Employment. Abella:Gilead: Employment. Barr:Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Abbvie: Consultancy; Gilead: Consultancy. Salles:Calistoga Pharmaceuticals, Inc.; Celgene Corporation; Genentech, Inc.; Janssen Pharmaceutica Products, L.P.; Roche: Consultancy; Celgene Corporation; Roche and Gilead Sciences: Research Funding; Celgene Corporation; Roche: Speakers Bureau.

First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13020-e13020
Author(s):  
Carla Pires Amaro ◽  
Atul Batra ◽  
Sasha M. Lupichuk
Keyword(s):  
Hormonal Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Population Based ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Hormone Receptor Positive ◽  
Targeted Agent ◽  
First Line Treatment

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.

scholarly journals SYSTEMIC FRONT LINE THERAPY OF FOLLICULAR LYMPHOMA: WHEN, TO WHOM AND HOW

2016 ◽  
Vol 8 ◽  
pp. e2016062 ◽  
Author(s):  
Francesca Pavanello ◽  
Sara Steffanoni ◽  
Michele Ghielmini ◽  
Emanuele Zucca
Keyword(s):  
Monoclonal Antibodies ◽  
Follicular Lymphoma ◽  
Target Therapy ◽  
Single Agent ◽  
New Drugs ◽  
Response To Treatment ◽  
Line Treatment ◽  
First Line ◽  
Line Therapy ◽  
First Line Treatment

The natural history of follicular lymphoma is usually characterized by an indolent course with a high response rate to the first line therapy followed by recurrent relapses, with a time to next treatment becoming shorter after each subsequent treatment line. More than 80% of patients have advanced stage disease at diagnosis. The time of initiation and the nature of the treatment is mainly conditioned by symptoms, tumor burden, lymphoma grading, co-morbidities and patients preference. A number of clinical and biological factors have been determined to be prognostic in this disease, but the majority of them could not show to be predictive of response to treatment, and therefore can’t be used to guide the treatment choice. CD20 expression is the only predictive factor recognized in the treatment of FL and justifies the use of “naked” or “conjugated” anti-CD20 monoclonal antibodies as single agent or in combination with chemo- or targeted therapy. Nevertheless, as this marker is almost universally found in FL, it has little role for the choice of treatment. The outcome of patients with FL improved significantly in the last years, mainly due to the widespread use of rituximab, autologous and allogeneic transplantation in young and fit relapsed patients, the introduction of new drugs and the improvement in diagnostic accuracy and management of side effects. Agents as new monoclonal antibodies, immuno-modulating drugs and target therapy have recently been developed and approved for the relapsed setting, while studies to evaluate their role in first line treatment are still ongoing. Here we report our considerations on first line treatment approach and on the potential factors which could help in the choice of therapy.

scholarly journals Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5571-5571
Author(s):  
Jesus D Gonzalez-Lugo ◽  
Ana Acuna-Villaorduna ◽  
Joshua Heisler ◽  
Niyati Goradia ◽  
Daniel Cole ◽  
...  
Keyword(s):  
Side Effects ◽  
Real World ◽  
Research Funding ◽  
Treatment Patterns ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Treatment Change ◽  
Free Survival ◽  
First Line Treatment

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

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