First-line treatment and survival of newly diagnosed primary plasma cell leukemia patients in the Netherlands: a population-based study, 1989-2018

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.

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

Blood ◽

10.1182/blood-2020-140228 ◽

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.

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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 ◽

10.1182/blood.v120.21.5077.5077 ◽

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.

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Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: A population-based analysis of the Austrian cooperative study group

Pediatric Blood & Cancer ◽

10.1002/pbc.20121 ◽

2004 ◽

Vol 44 (1) ◽

pp. 70-76 ◽

Cited By ~ 50

Author(s):

Andishe Attarbaschi ◽

Michael Dworzak ◽

Manuel Steiner ◽

Christian Urban ◽

Franz-Martin Fink ◽

...

Keyword(s):

Population Based ◽

Study Group ◽

Line Treatment ◽

Cooperative Study ◽

Cell Leukemia ◽

First Line ◽

Cooperative Study Group ◽

Non Hodgkin Lymphoma ◽

B Cell Leukemia ◽

First Line Treatment

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

Hematological Oncology ◽

10.1002/hon.2144 ◽

2014 ◽

Vol 33 (3) ◽

pp. 147-151 ◽

Cited By ~ 4

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

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

British Journal of Haematology ◽

10.1111/bjh.16525 ◽

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

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Current Treatment Approaches to Newly Diagnosed Multiple Myeloma

Oncology Research and Treatment ◽

10.1159/000520504 ◽

2021 ◽

Vol 44 (12) ◽

pp. 690-699

Author(s):

Susanne Ghandili ◽

Katja C. Weisel ◽

Carsten Bokemeyer ◽

Lisa Beatrice Leypoldt

Keyword(s):

Multiple Myeloma ◽

Monoclonal Antibody ◽

Plasma Cell ◽

Cell Clone ◽

Unmet Need ◽

Continuous Treatment ◽

High Dose ◽

Line Treatment ◽

First Line ◽

First Line Treatment

Background: Multiple myeloma is a so far incurable malignant plasma cell disorder. During the past 2 decades, treatment paradigms substantially changed when novel drugs were introduced initially in treatment of relapsed disease and subsequently also in first-line treatment. Summary: Up to now, first-line treatment differs between patients initially classified as transplant eligible and those who are considered as nontransplant eligible. Transplant-eligible patients receive a primary proteasome inhibitor (PI)-based induction which is being combined with an immunomodulating agent and a CD38-directed monoclonal antibody followed by high-dose melphalan therapy and autologous stem cell transplantation with subsequent maintenance treatment with lenalidomide. Patients who are considered as nontransplant eligible receive upfront treatment preferentially with a continuous combination treatment either with a CD38-directed monoclonal antibody in combination with the immunomodulating agent lenalidomide or a lenalidomide-PI combination followed by lenalidomide maintenance. Key Messages: Primary goal of the initiated treatment is to induce a rapid and deep remission which ideally leads to an eradication of the residual plasma cell clone in sense of a minimal residual disease negativity. Achievement of long-term remission with limited toxicity despite continuous treatment strategies and maintenance or improvement of life-quality is key. Despite successful treatment options, specific difficult-to-treat subgroups, especially patients with high-risk myeloma remain with inferior prognosis and a clear unmet need for novel therapeutic strategies. Future concepts will evaluate cellular treatments and other innovative immunotherapies in first-line treatment in curative intention.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13020 ◽

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.

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