How to Treat Chronic Lymphocytic Leukemia? Data From a Clinical Registry by Office-Based Hematologists in Germany (TLN Registry)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4606-4606
Author(s):  
Wolfgang Knauf ◽  
Wolfgang Abenhardt ◽  
Ali Aldaoud ◽  
Christian Lerchenmüller ◽  
Michaela Koska ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Median Treatment ◽  
First Line Therapy ◽  
Free Interval ◽  
Line Therapy ◽  
Appropriate Treatment

Abstract Abstract 4606 Introduction: The treatment of patients with Chronic Lymphocytic Leukemia (CLL) has changed significantly over the last years. To select an appropriate treatment, multiple factors have to be considered. In particular, the stage of disease, patient’s age, comorbidities and personal preferences, respectively, influence decision making. The clinical tumor registry on lymphoid neoplasms (TLN Registry) conducted by the iOMEDICO AG in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML) was established to collect data on the daily practice treatment of 3000 non-selected patients with lymphoid neoplasms. Here, we present data regarding treatment and sequences of regimes in patients (pts) with CLL treated by office-based hematologists in Germany. Methods: While targeting 500 CLL pts, the registry prospectively collects data on pts characteristics, tumor history, treatment, response rates and sequences of regimes. In addition data on adverse drug reactions and concomitant diseases are documented. CLL pts older than 18 years receiving a first- or second line therapy which has started no longer than 4 weeks before patient enrolment can be recruited into the registry if informed written consent is present. All pts are followed for 5 years. Currently, 116 sites across Germany are participating. Results: The TLN Registry started in May 2009. Currently, 492 pts with CLL have been recruited. The mean age at the start of first line therapy is 69 years. The majority of pts (63%) are male. About 20% of the pts in first line therapy are treated within clinical trials. Median time between diagnosis and start of first line therapy is 22 months (range 0 – 285 months). Most of the pts receive Bendamustine/Rituximab (BR, 34%) or Fludarabin/Cyclophosphamide/Rituximab (FCR, 21%) in first line therapy. Overall, 97% of the first line therapies were successful (91% CR/PR, 6% SD). In particular, 99% of BR (98% CR/PR, 1% SD) and 100% of FCR (98% CR/PR, 2% SD) therapies were successful. Over time, a change in treatment selection becomes apparent. 50% of the pts started first line therapy before October 2009. They mainly received BR (19%), Bendamustine (16%), FCR (16%) or Chlorambucil (15%), respectively. Pts starting first line therapy after October 2009 mainly received BR (43%) or FCR (24%). Bendamustine-containing regimens are more often used as first line therapy in pts older than 75 years as compared to younger ones (62% vs. 42%). Fludarabine-containing regimens are more often used in pts younger than 75 years (37% vs. 6%). Similar to the first line therapy, BR is the most often used second line therapy (52%). About 41% of the pts have completed first line therapy and have not yet started second line therapy. The median treatment-free interval since the end of the first line therapy is 10 months. Data on second line therapy are available in 24% of the pts. The majority of these pts (73%) were recruited at the start of second line therapy. Most of them receive BR as second line therapy after first line therapy either with Chlorambucil (17%) or Bendamustine (13%). The median treatment-free interval between the end of first line therapy and the start of second line therapy is 16 months (range 1 – 49 months). Conclusion: The registry provides an overview on particularities and changes in routine treatment of pts with CLL treated by office-based hematologists in Germany. Implementation of new standards affecting treatment preferences are currently under evaluation. BR and FCR are widely accepted and very effective as first line therapies. Our data indicate that age is an important factor for selecting the appropriate treatment. Further analyses will investigate additional variables influencing the choice of treatment. With more data becoming available the sequences of regimes and their effectiveness can be analyzed. Disclosures: No relevant conflicts of interest to declare.

Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1790-1790
Author(s):  
Petra Obrtlikova ◽  
Anna Jonasova ◽  
Magda Siskova ◽  
Eduard Cmunt ◽  
Adela Berkova ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

Bendamustine and Rituximab for the Treatment of Chronic Lymphocytic Leukemia: The Moffitt Cancer Center Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4620-4620
Author(s):  
Heather Barnes Pound ◽  
Viet Q. Ho ◽  
Celeste M. Bello ◽  
Jennifer L. Cultrera ◽  
Martine Extermann ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Response Rates ◽  
Primary Objective ◽  
Lymphocytic Leukemia ◽  
Cancer Center ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Third Line

Abstract Abstract 4620 Introduction: Although bendamustine is approved for the treatment of chronic lymphocytic leukemia (CLL), the combination of bendamustine and rituximab (BR) is currently under active investigation in the relapsed/refractory setting as well as for front-line use. Emerging data now suggests BR is acceptable for first-line use and indeed is listed in the NCCN Compendia as a first-line option. Herein, we report the results of a single-center retrospective review of BR use in first-, second- and third-line and beyond and its effects on response rate. Methods: We retrospectively reviewed 21 consecutive patients with CLL that received BR at the Moffitt Cancer Center (MCC) between July 2008 and November 2010. Bendamustine was dosed at 70 mg/m2 IV on Days 1 and 2 every 3–4 weeks; rituximab was dosed at 375 mg/m2 IV once with each cycle along with anti-microbial prophylaxis. Data collected included, but was not limited to age, gender, cytogenetic profile, number of previous therapies, Rai stage at time of treatment and response (based on 1996 NCI-WG definition). The primary objective was to assess response rates. The major secondary objective was to assess the effect of cytogenetics on response rates. All analyses were performed using descriptive statistics. Results: Twenty-one patients received treatment with BR; 7 patients received BR as first-line therapy, 7 received BR as second line therapy and the remaining 7 received BR as third-line therapy or beyond. The median age at time of treatment was 66; 12 of 21 patients were male (57%); All Rai Stages were represented, Stage 0 (n=1), Stage 1 (n=4), Stage 2 (n= 3), Stage 3 (n=5), Stage 4 (n=6). 38% of patients were positive for Del11q, 33% for Del13q, 9.5% for Del17p, and 9.5% for mutated IgVH. In previously untreated patients, 6/7 had a documented complete remission (CR) (71.4%) or partial (PR) (14.3%) response; one patient progressed (PD) on therapy. In second-line therapy, all patients had a documented CR (28.6%) or PR (71.4%). In patients treated with BR as 3rd or 4th line therapy, 3 patients had a CR, 2 patients had stable disease (SD), and 2 had PD. Of the 8 patients with Del11q, 37.5% achieved a CR, 4 had PR and 1 had PD. Of the 7 patients with Del13q, 4 achieved CR and 3 had a PR. Both patients with Del17p had PD. Of the 2 patients with mutated IgVH, one patient achieved a PR while the other had PD. Conclusion: Based on these results, the combination of bendamustine and rituximab in patients with CLL is efficacious and well tolerated in patients with both newly diagnosed and relapsed/refractory disease. Disclosures: Off Label Use: Bendamustine and rituximab for CLL. Ho:Genentech: Honoraria; Cephalon: Consultancy. Cultrera:Genentech: Speakers Bureau. Sotomayor:Genentech: Membership on an entity’s Board of Directors or advisory committees. Pinilla-Ibarz:Genentech: Speakers Bureau; Cephalon: Speakers Bureau.

scholarly journals 1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S680-S681
Author(s):  
Carly Heck ◽  
Judith Martin ◽  
Marcia Kurs-Lasky
Keyword(s):  
Drug Allergy ◽  
Health Concern ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Comparison Results ◽  
Significant Difference ◽  
Recommended Therapy

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures

Survival of Patients With Advanced Colorectal Cancer Improves With the Availability of Fluorouracil-Leucovorin, Irinotecan, and Oxaliplatin in the Course of Treatment

2004 ◽  
Vol 22 (7) ◽  
pp. 1209-1214 ◽  
Author(s):  
Axel Grothey ◽  
Daniel Sargent ◽  
Richard M. Goldberg ◽  
Hans-Joachim Schmoll
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Cytotoxic Agents ◽  
Phase Iii ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials

Purpose Fluorouracil (FU)-leucovorin (LV), irinotecan, and oxaliplatin administered alone or in combination have proven effective in the treatment of advanced colorectal cancer (CRC). Combination protocols using FU-LV with either irinotecan or oxaliplatin are currently regarded as standard first-line therapies in this disease. However, the importance of the availability of all three active cytotoxic agents, FU-LV, irinotecan, and oxaliplatin, on overall survival (OS) has not yet been evaluated. Materials and Methods We analyzed data from seven recently published phase III trials in advanced CRC to correlate the percentage of patients receiving second-line therapy and the percentage of patients receiving all three agents with the reported median OS, using a weighted analysis. Results The reported median OS is significantly correlated with the percentage of patients who received all three drugs in the course of their disease (P = .0008) but not with the percentage of patients who received any second-line therapy (P = .19). In addition, the use of combination protocols as first-line therapy was associated with a significant improvement in median survival of 3.5 months (95% CI, 1.27 to 5.73 months; P = .0083). Conclusion Our results support the strategy of making these three active drugs available to all patients with advanced CRC who are candidates for such therapy to maximize OS. In addition, our findings suggest that, with the availability of effective salvage options, OS should no longer be regarded as the most appropriate end point by which to assess the efficacy of a palliative first-line treatment in CRC.

scholarly journals First-line treatment of chronic lymphocytic leukemia with ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab: final analysis of the randomized, phase 3 iLLUMINATE trial

Haematologica ◽  
2022 ◽  
Author(s):  
Carol Moreno ◽  
Richard Greil ◽  
Fatih Demirkan ◽  
Alessandra Tedeschi ◽  
Bertrand Anz ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Final Analysis ◽  
Lymphocytic Leukemia ◽  
Small Lymphocytic Lymphoma ◽  
First Line ◽  
Open Label ◽  
Phase 3 ◽  
First Line Therapy ◽  
Line Therapy ◽  
Open Label Phase

iLLUMINATE is a randomized, open-label phase 3 study of ibrutinib plus obinutuzumab (n=113) versus chlorambucil plus obinutuzumab (n=116) as first-line therapy for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. Eligible patients were aged ≥65 years, or

scholarly journals Impact of Treatment Sequencing on Outcomes and Costs in Relapsed Follicular or Other Low Grade B-Cell Non-Hodgkin Lymphoma - Results of an Evidence-Based Budget Impact Model

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Ali McBride ◽  
Daniel O. Persky
Keyword(s):  
Follicular Lymphoma ◽  
Low Grade ◽  
Second Line ◽  
Treatment Sequence ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Duration Of Response ◽  
Budget Impact Model

Introduction: The choice of initial therapy in follicular lymphoma can be a key determinant in future therapy, as irreversible toxicities with first line regimens can impact the patient's ability to tolerate future treatment. Minimizing drug exposure will result in less frequent occurrence of significant adverse events and associated treatment costs. In the era of COVID-19 pandemic, there is additional benefit to minimizing the number of patient visits and hospital admissions. Limited information exists related to the outcomes and associated costs of existing treatment sequences. Additionally, treatment administration at different types of clinical sites results in varied reimbursement models, making informed evaluation of clinical and financial evidence challenging. Methods: The current study applies a budget impact model methodology in order to describe the associated impact of treatment selection and sequencing on outcomes and costs in the treatment of relapsed or refractory low-grade follicular lymphoma in first line therapy followed by Consolidation and also in first line therapy to second line therapy. Key model inputs included: Number of treatment cycles, number of days a treatment was received, duration of response (DOR), rate of side effects and associated costs, and total treatment costs, including drugs, medical treatment, laboratory testing and adverse event costs. Treatment outcomes were based on the published literature that summarized the overall response rate, median DOR, and toxicity. Treatment regimen costs were evaluated based on payer pricing, Wholesale Acquisition Cost (WAC), Average Selling Price (ASP) and Average Wholesale Price (AWP) and modified to adjust for weight-based dosing and negotiate payer reimbursement rates. Associated medical costs for medical treatment and supportive care were estimated using current Medicare fee schedule rates. Included were seven options for first line therapy of follicular lymphoma from 2020 NCCN Guidelines - (Bendamustine + rituximab (BR); Bendamustine + Obinutuzumab (OB); CHOP rituximab (RCHOP); CHOP + Obinutuzumab (OCHOP); CVP+ rituximab (RCVP); CVP + Obinutuzumab (OCVP); Lenalidomide + rituximab (R2)), followed by three for Consolidation (Rituximab maintenance (RM); Obinutuzumab maintenance (O); Radioimmunotherapy (RIT with 90 Y-ibritumomab tiuxetan (Y90-IT, Zevalin)) and three Second Line therapy options (RIT; Lenalidomide only; Lenalidomide + Obinutuzumab (LO)). Results: The treatment sequence of first line BR followed by Consolidation with RIT Y90 (Zevalin) had the longest predicted DOR (2586 days). The associated treatment sequence costs were $212,485 for BR followed by Y90-IT, compared with $233, 388 for BR followed by rituximab maintenance, which had a predicted DOR of 2478 days. The predicted DOR for treatment sequences starting with OCHOP, OCVP and RCHOP and followed by RIT with Y90-IT was approximately 1000 days less than BR followed by Y90-IT for a cost difference of $4,421, $12,914 and $25,826, respectively. The treatment sequence of first line BR followed by Second Line RIT Y90-IT had the second longest predicted DOR of 2586 days at costs of $212,485, compared to 2778 days for BR followed by LO, at a total sequence costs of $796,695. Conclusion: The use of Y90-IT in Consolidation or Second Line treatment demonstrated desired patient outcomes at one of the lowest cost profiles. Additionally, Y90-IT administration can be completed in only two clinic visits, reducing patient travel and contact, improving safety in an era of COVID-19 precautionary measures and reducing cost. Figure 1. Duration of Response and Total Sequence Costs for Twelve First Line to Consolidation and First Line to Second Line Treatment Regimens. Disclosures McBride: Merck: Speakers Bureau; Coherus BioSciences: Consultancy, Speakers Bureau; Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy.

scholarly journals Protocol of the EFFORT study: a prospective study of FOLFIRI plus aflibercept as second-line treatment after progression on FOLFOXIRI plus bevacizumab or during maintenance treatment in patients with unresectable/metastatic colorectal cancer

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Hironaga Satake ◽  
Koji Ando ◽  
Eiji Oki ◽  
Mototsugu Shimokawa ◽  
Akitaka Makiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Background FOLFOXIRI plus bevacizumab is used as a first-line therapy for patients with unresectable or metastatic colorectal cancer. However, there are no clear recommendations for second-line therapy after FOLFOXIRI plus bevacizumab combination. Here, we describe our planning for the EFFORT study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Methods EFFORT is an open-label, multicenter, single arm phase II study to evaluate whether a FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for mCRC. Patients with unresectable or metastatic colorectal cancer who received FOLFOXIRI plus bevacizumab as a first-line therapy will receive aflibercept and FOLFIRI (aflibercept 4 mg/kg, irinotecan 150 mg/m2 IV over 90 min, with levofolinate 200 mg/m2 IV over 2 h, followed by fluorouracil 400 mg/m2 bolus and fluorouracil 2400 mg/m2 continuous infusion over 46 h) every 2 weeks on day 1 of each cycle. The primary endpoint is progression-free survival (PFS). To achieve 80% power to show a significant response benefit with a one-sided alpha level of 0.10, assuming a threshold progression-free survival of 3 months and an expected value of at least 5.4 months, we estimated that 32 patients are necessary. Secondary endpoints include overall survival, overall response rate, safety, and exploratory biomarker analysis for differentiating anti-VEGF drug in 2nd-line chemotherapy for unresectable or metastatic colorectal cancer. Discussion This is the first study to investigate whether FOLFIRI plus aflibercept has efficacy following FOLFOXIRI plus bevacizumab for unresectable or metastatic colorectal cancer. Switching to a different type of anti-VEGF drug in second-line therapy after FOLFOXIRI plus bevacizumab appears to be an attractive treatment strategy when considering survival benefit. It is expected that this phase II study will prove the efficacy of this strategy and that a biomarker for drug selection will be discovered. Trial registration Japan Registry of Clinical Trials jRCTs071190003. Registered April 18, 2019.

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