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.

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.

Treatment of Pulmonary Metastases in Children With Stage IV Nephroblastoma With Risk-Based Use of Pulmonary Radiotherapy

2012 ◽  
Vol 30 (28) ◽  
pp. 3533-3539 ◽  
Author(s):  
Arnauld Verschuur ◽  
Harm Van Tinteren ◽  
Norbert Graf ◽  
Christophe Bergeron ◽  
Bengt Sandstedt ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
High Risk ◽  
Pulmonary Metastases ◽  
Stage Iv ◽  
Line Treatment ◽  
Event Free Survival ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Purpose The purpose of this study was to determine the outcome of children with nephroblastoma and pulmonary metastases (PM) treated according to International Society of Pediatric Oncology (SIOP) 93-01 recommendations using pulmonary radiotherapy (RT) in selected patients. Patients and Methods Patients (6 months to 18 years) were treated with preoperative chemotherapy consisting of 6 weeks of vincristine, dactinomycin, and epirubicin or doxorubicin. If pulmonary complete remission (CR) was not obtained, metastasectomy was considered. Patients in CR received three-drug postoperative chemotherapy, whereas patients not in CR were switched to a high-risk (HR) regimen with an assessment at week 11. If CR was not obtained, pulmonary RT was mandatory. Results Two hundred thirty-four of 1,770 patients had PM. Patients with PM were older (P < .001) and had larger tumor volumes compared with nonmetastatic patients (P < .001). Eighty-four percent of patients were in CR postoperatively, with 17% requiring metastasectomy. Thirty-five patients (16%) had multiple inoperable PM and required the HR protocol. Only 14% of patients received pulmonary RT during first-line treatment. For patients with PM, 5-year event-free survival rate was 73% (95% CI, 68% to 79%), and 5-year overall survival (OS) rate was 82% (95% CI, 77% to 88%). Five-year OS was similar for patients with local stage I and II disease (92% and 90%, respectively) but lower for patients with local stage III disease (68%; P < .001). Patients in CR after chemotherapy only and patients in CR after chemotherapy and metastasectomy had a better outcome than patients with multiple unresectable PM (5-year OS, 88%, 92%, and 48%, respectively; P < .001). Conclusion Following the SIOP protocol, pulmonary RT can be omitted for a majority of patients with PM and results in a relatively good outcome.

scholarly journals Real-world systemic therapy treatment patterns for squamous cell carcinoma of the head and neck in Canada

2019 ◽  
Vol 26 (2) ◽  
Author(s):  
K. Byrne ◽  
P. Hallworth ◽  
A. Abbas Tahami Monfared ◽  
A. Moshyk ◽  
J. W. Shaw
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Practice ◽  
Drug Treatment ◽  
Real World ◽  
Treatment Patterns ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Drug ◽  
First Line Treatment

Background In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown.Methods Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May–July 2016 for 6–8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease).Results Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided; 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57–68 years], and 24% were current smokers, with a mean exposure of 26.2 ± 12.7 pack–years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20–146 days). The most common second-line regimen was cetuximab monotherapy (43%); platinum-based regimens were markedly infrequent (13%).Conclusions Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines; cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 526-526 ◽  
Author(s):  
Barbara Eichhorst ◽  
Anna-Maria Fink ◽  
Raymonde Busch ◽  
Elisabeth Lange ◽  
Hubert Köppler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Interim Analysis ◽  
Research Funding ◽  
Response Rate ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

Abstract Introduction FCR is the current standard first line treatment regimen in advanced CLL (Hallek et al., Lancet, 2010), but is associated with significant side effects. The GCCLSG initiated an international phase III study in order to test the non-inferiority regarding efficacy and potentially better tolerability of BR compared to FCR in first-line therapy of physically fit pts without del(17p). Methods and Patients 688 CLL pts from 158 sites in five countries (Germany, Austria, Switzerland, Denmark and Czech Republic) were screened centrally for immunophenotype, genomic aberrations by FISH, IGHV sequenzing, comorbidity burden and renal function. 564 CLL pts with CIRS score ≤ 6, creatinine clearance > 70 ml/min and without del(17p) were enrolled between October 2008 and June 2011. Pts were randomly assigned to receive 6 courses of either FCR (N= 284; F 25mg/m2 i.v. d1–3, C 250 mg/m2 i.v. d1–3, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days) or BR (N=280; B 90mg/m2 i.v. d1+2, R 375 mg/m2 i.v. d 0 at first cycle and 500 mg/m2 d1 all subsequent courses; q 28 days). The intent-to-treat population consisted of 561 pts, because three patients were excluded due to deferred treatment (1 pt decision, 1 treatment before randomization, 1 misdiagnosis). 22 % were Binet A, 38 % Binet B and 40 % Binet C. The median age was 62 years (yrs) (range 33 to 82), median CIRS score 2 (range 0-6). There were significantly more pts with unmutated IGVH in the BR arm (68%) in comparison to the FCR arm (55%; p=0.003). All other characteristics including median age were well balanced. A mean number of 5.27 courses was given in the FCR arm versus 5.41 courses in the BR arm (p=0.022). 70.6% (FCR) and 80.3% (BR) of pts received 6 courses (p=0.008). Dose was reduced by more than 10% in 27.3% (FCR) and 31.6% (BR) of all courses given (p = 0.012). Results The median observation time was 27.9 months (mo) in all pts alive. While response evaluation was missing in 14 pts, 547 pts (274 FCR; BR 273) were evaluable for response and all 561 pts (282 FCR; 279 BR) for progression-free survival (PFS), event-free survival (EFS) and OS. The overall response rate was identical in both arms with 97.8% (p=1.0). The complete response rate (CRR) (confirmed by central immunhistology) with FCR was 47.4% as compared to 38.1% with BR (p=0.031). MRD data were available at interim analysis from 192 pts (99 FCR; 93 BR) of the first 300pts. 71.7% of pts in the FCR and 66.7% in the BR arms achieved MRD-levels below 10-4 in peripheral blood at final staging (p=0.448). The complete MRD data set will be available by November. PFS was 85.0% at 2 yrs in the FCR arm and 78.2% in the BR arm (p=0.041). EFS was 82.6% at 2 yrs in the FCR arm and 75.7% in the BR arm (p=0.037).There was no difference in OS rate for the FCR vs BR arm (94.2% vs 95.8% at 2 years p=0.593). Hazard Ratio for PFS, EFS and OS was 1.385, 1.375 and 0.842 respectively. PFS was assessed in pts < 65 yrs and ≥ 65 yrs. While there was a significant difference in pts < 65 yrs between both treatment arm (median PFS for BR 36.5 mo vs not reached for FCR; p=0.016), the difference disappeared in elderly pts (not reached vs. 45.6 mo; p=0.757). A multivariate analysis including treatment arm, Binet stage, age, sex, comorbidity, serum TK, serum beta2-microglobulin (Beta2M), del(11q) and IGHV status identified treatment arm, Beta2M, del(11q) and IGHV as independent prognostic factors for PFS and EFS. FCR treated pts had significantly more frequent severe, CTC grade 3 to 5, adverse events during the whole observation period (90.8% vs 78.5%; p<0.001). Especially severe hematotoxicity was more frequent in the FCR arm (90.0% vs 66.9%, p<0.001). The higher rate of severe neutropenia (81.7% vs 56.8%, p<0.001) resulted in a significantly higher rate of severe infections (39.0% vs 25.4%, p=0.001) in the FCR arm, especially in the elderly (FCR: 47.4% vs BR: 26.5%; p=0.002). Treatment related mortality occurred in 3.9% (n=11) in the FCR and 2.1% (n=6) in the BR arm. Conclusion The results of this planned interim analysis show that FCR seems more efficient than BR in the first-line treatment of fit CLL pts with regard to higher CRR, as well as longer PFS and EFS. These advantages might be balanced by a higher rate of severe adverse events, in particular neutropenia and infections, associated with FCR. In light of these results, no firm recommendation of one regimen over the other can be given at the present time regarding the first-line use in CLL pts with good physical fitness. Disclosures: Eichhorst: Roche: Consultancy, Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding. Gregor:Roche: Consultancy, Honoraria, Travel Support Other; Mundipharma: Travel Support, Travel Support Other. Plesner:Mundipharma: Research Funding. Trneny:Roche: Honoraria, Research Funding. Fischer:Roche: Travel grants Other; Mundipharma: Travel grants, Travel grants Other. Kneba:Roche: Consultancy, Research Funding. Wendtner:Roche: Consultancy, Research Funding; Mundipharma: Consultancy, Research Funding. Kreuzer:Roche: Honoraria; Mundipharma: Honoraria. Stilgenbauer:Roche: Consultancy, Research Funding, Travel grants Other; Mundipharma: Consultancy, Research Funding. Böttcher:Roche: Honoraria, Research Funding. Hallek:Janssen: Research Funding; Gilead: Research Funding; Roche: Research Funding.

scholarly journals Treatment patterns and clinical outcomes in patients with metastatic breast cancer treated with palbociclib-based therapies: Real-world data in the Han population

2020 ◽  
Author(s):  
Hongnan Mo ◽  
Fei Ma ◽  
Qing Li ◽  
Pin Zhang ◽  
Peng Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Propensity Score ◽  
Real World ◽  
Metastatic Breast ◽  
Treatment Patterns ◽  
Line Treatment ◽  
First Line ◽  
Han Population ◽  
First Line Treatment

Abstract Background: Palbociclib combined with endocrine therapy has become the standard treatment for estrogen receptor-positive (ER+) metastatic breast cancer. However, little is known about the effectiveness of diverse palbociclib-based regimens other than letrozole and fulvestrant in the real-world clinical setting. This study aimed to reveal the treatment patterns and clinical outcomes in Han patients in routine clinical practice.Methods: The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the China National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially in patients younger than 40 years, in those with bone-only metastasis, for various regimen combinations, and as different treatment lines. Propensity score matching was employed to match patients with or without previous everolimus treatment. Results: A total of 186 patients from 89 cities in 18 provinces in China were enrolled. The median progression-free survival (PFS) was similar among different palbociclib-combined groups (P=0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the exemestane plus palbociclib group, 9.7 months (95% CI 6.3–13.1) in the letrozole plus palbociclib group, 7.8 months (95% CI 5.5–10.2) in the fulvestrant plus palbociclib group, 7.2 months (95% CI 3.2–11.3) in the toremifene plus palbociclib group, and 6.1 months (95% CI 1.2–11.0) in the anastrozole plus palbociclib group. Kaplan-Meier analysis revealed that patients with bone-only metastasis (median PFS: 8.8 vs. 7.8 months; P=0.023) and those who received palbociclib as first-line treatment (median PFS: 14.0 months, 95% CI 11.4–16.6; P<0.001) had prolonged PFS compared with other patients. Patients pretreated with everolimus had significantly worse PFS (3.4 months, 95% CI 0.7–6.1) than those in the everolimus-naïve group (8.8 months, 95% CI 6.6–11.0, P=0.001) in the whole population. After propensity score matching, patients pretreated with everolimus had inferior PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7–7.5, P=0.439). Conclusions: Various palbociclib-based regimens have promising efficacy in real-world settings, even in patients with bone-only metastasis. Palbociclib resistance is more common in patients pretreated with everolimus, and in the settings of subsequent treatment compared with first-line treatment.

Propensity Score Matching Analysis Comparing Azathioprine Plus Prednisone Vs Prednisone Alone Regimens As First-Line Treatment in Chronic Graft-Versus-Host Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3126-3126
Author(s):  
Jieun Uhm ◽  
Elizabeth Shin ◽  
Fotios V. Michelis ◽  
Auro Viswabandya ◽  
Jeffrey H. Lipton ◽  
...  
Keyword(s):  
Propensity Score ◽  
Survival Benefit ◽  
Research Funding ◽  
Performance Status ◽  
Case Control ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Steroid Sparing ◽  
First Line Treatment

Abstract Background: Azathioprine (AZA) has been used as a steroid sparing agent in allogeneic BMT program at the Princess Margaret Cancer Centre, Toronto, Canada for last two decades especially for cGVHD treatment. A previous clinical trial (Sullivan, Blood 1998) compared prednisone (PRD) alone vs PRD plus AZA for the treatment of extensive chronic GVHD (cGVHD) suggesting that PRD alone showed a better survival than PRD+AZA. However, the NIH consensus criteria (NCC, 2005) for cGVHD and new statistic endpoint to evaluate efficacy of cGVHD, failure free survival (FFS), have been recently introduced and increasingly used. Therefore, we conducted retrospective study attempted to evaluate the efficacy of PRD+AZA regimen compared to PRD alone regimen with respect to failure free survival (FFS) as well as overall survival (OS), non-relapse mortality (NRM)and relapse incidence. In order to adjust for the risk factors which affect the choice of treatment between different treatment options, propensity score matching (PSM) analysis was adopted in the present study. Methods: The patients diagnosed with late onset acute GVHD was excluded. A total of 240 patients were included in the analysis, transplanted at the Princess Margret Cancer Center between 2009 and 2013, diagnosed with cGVHD by NCC, and treated with PRD+AZA (n=98) or PRD alone (n=142) as first line treatment. Failure free survival (FFS), OS, NRM and relapse were compared between the 2 groups. A case-control study was performed with well-balanced pairs of PRD+AZA vs PRD patients. For the PSM analysis, propensity score (PS) was calculated. Clinical variables included in PS calculation were global score (GS) by NCC, subtype of cGVHD (classical vs overlapping), age, gender, duration from HCT to cGVHD initial treatment, performance status (PS), progressive type onset (PTO) of cGVHD, thrombocytopenia (TP) and each organ involvement of cGVHD per skin, gastrointestinal tract, liver, lung and musculoskeletal system. A total of 74 case-control pairs were selected within 0.1 of a difference in propensity score. RESULTS: With a follow-up of 43. 6 months, the 2-year FFS, OS, NRM and relapse incidence was 24.7 %, 75.6 %, 16.6% and 7.7%, respectively. The median FFS was 7.9 months (95% CI, 6.1-9.6 months). PRD+AZA group showed a longer FFS duration compared to PRD group (13.2 vs 5.6 months, p<0.001). In addition, PRD+AZA showed a lower NRM rate than PRD group (10.8% vs 20.6% at 2 years, p=0.008). A trend of lower relapse risk was noted in PRD+AZA over PRD group (2.6%vs 11.0% at 2 years, p=0.074). Within the overall population, imbalanced demographic and disease characteristics were observed between the 2 groups, including longer duration from HCT to cGVHD initial treatment (p<0.001), fewer patients with severe GS by NCC (p<0.001), fewer patients with PTO (p=0.002), fewer with TP (p=0.008) and better performance status (p=0.008) in the PRD+AZA group. After PSM procedure, all clinical variables became well balanced between the 2 groups. The PSM analysis successfully confirmed our previous observation of superior outcomes in PRD+AZA group to those in PRD group. The median FFS duration was significantly longer in PRD+AZA (17.6 months) compared to PRD group (7.4 months, p<0.001). There was a trend of survival benefit in favor of PRD+AZA group (87.4% vs 78.2% at 2 years; p=0.074). There was no significant difference between 2 groups in NRM (p=0.289) and relapse rate at 2 years (p=0.187). Confined to the same NCC GS group, there was a trend of a longer FFS in PRD+AZA compared to PRD group. In the group with moderate grade of cGVHD, a longer FFS duration was noted in PRD+AZA than in PRD alone ( 11.1 vs 7.4 months, p=0.001). Compared to PRD group, PRD+AZA group showed a higher success rate of PRD tapering below 0.5mg/Kg/day by first 6 months (90.5% in PRD+AZA vs 75.8% in PRD group, p=0.018). Conclusion: The present study suggested that 1) addition of AZA in the PRD based regimen for cGVHD treatment could improve FFS in patients with cGVHD requiring systemic immunosuppression, and that 2) AZA did not increase the risk of relapse and may have a survival benefit with rapid reduction of corticosteroid or delay of switch to second line treatment. Thus AZA should be considered as a therapeutic option for steroid sparing agent in frontline cGVHD treatment, PRD based. Disclosures Kim: Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

scholarly journals Treatment Patterns and Clinical Outcomes in Patients with Metastatic Breast Cancer Treated with Palbociclib-Based Therapies: Real-World Data in the Han Population

2020 ◽  
Author(s):  
Hongnan Mo ◽  
Fei Ma ◽  
Qing Li ◽  
Pin Zhang ◽  
Peng Yuan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Propensity Score ◽  
Real World ◽  
Metastatic Breast ◽  
Treatment Patterns ◽  
Line Treatment ◽  
First Line ◽  
Han Population ◽  
First Line Treatment

Abstract Background: Palbociclib combined with endocrine therapy has become the standard treatment for estrogen receptor-positive (ER+) metastatic breast cancer. However, little is known about the effectiveness of diverse palbociclib-based regimens other than letrozole and fulvestrant in the real-world clinical setting. This study aimed to reveal the treatment patterns and clinical outcomes in Han patients in routine clinical practice. Methods: The clinical data of patients with ER+ metastatic breast cancer treated with palbociclib were collected from the China National Cancer Center database. The efficacy profile of palbociclib in this Han population was evaluated, especially in patients younger than 40 years, in those with bone-only metastasis, for various regimen combinations, and as subsequent systemic therapy. Propensity score matching was employed to match patients with or without previous everolimus treatment. Results: A total of 186 patients from 89 cities in 18 provinces in China were enrolled. Patients older than 40 years (P=0.189), those with metastasis other than bone metastasis (P=0.023), and those who received palbociclib as first-line treatment (P<0.001) had prolonged progression-free survival (PFS) compared with other patients. Median PFS was similar among different palbociclib-combined groups (P=0.566): 10.0 months (95% confidence interval [CI] 3.8–16.1) in the exemestane plus palbociclib group, 9.7 months (95% CI 6.3–13.1) in the letrozole plus palbociclib group, 7.8 months (95% CI 5.5–10.2) in the fulvestrant plus palbociclib group, 7.2 months (95% CI 3.2–11.3) in the toremifene plus palbociclib group, and 6.1 months (95% CI 1.2–11.0) in the anastrozole plus palbociclib group. Patients pretreated with everolimus had significantly worse PFS (3.4 months, 95% CI 0.7–6.1) than those in the everolimus-naïve group (8.8 months, 95% CI 6.6–11.0, P=0.001) in the whole population. After propensity score matching, patients pretreated with everolimus had inferior PFS (4.4 months, 95% CI 0.5–8.2) compared with everolimus-naïve patients (6.1 months, 95% CI 4.7–7.5, P=0.439). Conclusions: Various palbociclib-based regimens have promising efficacy in real-world settings, even in patients with bone-only metastasis. Palbociclib resistance is more common in patients younger than 40 years, in those pretreated with everolimus, and in the settings of subsequent treatment compared with first-line treatment.

Minimal Residual Disease (MRD) Status in FCR-Treated CLL Patients at the End of Treatment Influences Progression Free Survival (PFS), Results of the Ctrial-IE (ICORG) 07-01/ CLL Ireland Study, with Mutational Analysis Providing Additional Insight

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3237-3237
Author(s):  
Niamh Appleby ◽  
Fiona M Quinn ◽  
David O'Brien ◽  
Smyth Liam ◽  
Johanna Kelly ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Research Funding ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Minimal Residual ◽  
First Line Treatment

Abstract Fludarabine, cyclophosphamide and rituximab (FCR) therapy results in a complete remission (CR) rate of 72% and a median progression free survival (PFS) of 80 months in non-del (17P) CLL1. Achieving an MRD negative (MRD-ve) CR after completing therapy is an early surrogate marker for overall survival (OS) and PFS2. Specific genetic CLL subtypes determined by fluorescent in-situ hybridisation (FISH) analysis, immunoglobulin mutation IgVH, NOTCH1 and SF3B1 status determine response to chemotherapy3,4. We completed a multi-centre prospective study between 2008 and 2012, with a median follow up of 62.6 months using MRD status to determine length of therapy. Patients who achieved an MRD-veCR after 4 courses of FCR received no further therapy and the remaining patients completed 6 cycles of FCR. MRD status was tracked 6 monthly in patients who became MRD-veuntil MRD was detected. The genetic subtype was also analysed but did not influence treatment. Fifty-two patients {35M;17F, median age 61years (range 37-73)} were enrolled. Forty-six patients completed the MRD assessment after 4 cycles. Eleven patients discontinued assigned FCR therapy for the following reasons: prolonged cytopenia (4); non-compliance (1); autoimmune haemolytic anaemia (2); renal impairment (1); pleural effusion (1); not recorded (2). Eighteen (34.6%) patients achieved an MRD-veCR after 4 cycles and a further11 after 6cycles resulting in 29/52 (55.8%) MRD-veCRs in total. The median PFS was 72.3 months (95% Confidence Interval 61.3-84.1 months) and the median OS has not been reached. Patients who attained an MRD-veversusMRD+vestatus had a prolonged PFS (81.1 vs 46.2 months, p<0.0002). No difference in PFS was observed between patients reaching an MRD-veCR after 4 versus 6 cycles (median PFS81.1 vs 84.1 months,p=0.29). FISH results were available for 48 patients; del(13q) in 16/48 (33%), del(11q) in 15/48 (31%) no abnormality in 12/48 (25%), trisomy 12 in 4 (8%) and other abnormality in 1 patient. The IgVH status was unfavourable in 34/52 (65%), SF3B1 mutations were detected in 5/51 (9.8%) and NOTCH1 mutations in 10/52(19.2%) patients respectively, comparable to published studies of first-line treatment in CLL3,4. The median PFS for patients with good risk IgVH was not reached. Del(11q) did not impact on PFS (median PFS 66.5 vs 78.9 months, p=0.7301). SF3B1 and NOTCH1 mutated patients had a shortened PFS (median PFS 38.4 vs 71.1 months, p=0.038 and median PFS 62.4 vs 82.2 months p=0.0302, respectively). In conclusion abbreviated FCR therapy is effective for patients achieving MRD-veremission after 4 cycles. SF3B1 and NOTCH1 mutated patients had a short PFS and may benefit from alternative first-line treatment. This finding emphasizes the role mutational profiling will play in optimising and personalising therapy in CLL in the future. Reference: Tam C, O'Brien S, WierdaW, et al. “Long-term results of the fludarabine, cyclophosphamide and rituximab regimen as initial therapy of chronic lymphocytic leukemia” Blood 2008 Aug 15;112(4):975-80 Böttcher S, Ritgen M, Fischer K, et al. "Minimal Residual Disease Quantification is an Independent Predictor of Progression-Free and Overall Survival in Chronic Lymphocytic Leukemia: A Multivariate Analysis From the Randomized GCLLSG CLL8 Trial" J Clin Onc 2012 Mar 20; 30(9):980-8. StilgenbauerS,SchnaiterA,PaschkaP, et al. "Gene mutations and treatment outcome in chronic lymphocyticleukemia: results from the CLL8 trial" Blood 2014 May 22;123(21):3247-54 Chiaretti S, Marinelli M, Del Giudice I, et al."NOTCH1, SF3B1, BIRC3 and TP53 mutations in patients with chronic lymphocytic leukaemia undergoing first-line treatment: correlation with biological parameters and response to treatment"LeukLymphoma 2014 Dec; 55(12):2785-92 Figure 1 Patient outcomes by MRD status in ICORG 07-01 Trial Figure 1. Patient outcomes by MRD status in ICORG 07-01 Trial Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Crotty: BMS, Takeda, Novartis, Janssen, Roche: Honoraria. O'Dwyer:Glycomimetics: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding.

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