Overall survival benefit from tebentafusp in patients with best response of progressive disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Anthony M. Joshua ◽  
Jean-Francois Baurain ◽  
Sophie Piperno-Neumann ◽  
Paul Nathan ◽  
Jessica Cecile Hassel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Progressive Disease ◽  
Analysis Data ◽  
Cell Receptor ◽  
Kaplan Meier ◽  
Immortal Time Bias ◽  
Best Response ◽  
Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

Association of response to first-line chemotherapy with the efficacy of atezolizumab in patients with metastatic urothelial carcinoma.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 409-409
Author(s):  
Deniz Tural ◽  
Omer Fatih Olmez ◽  
Ahmet Taner Sümbül ◽  
Mehmet Artac ◽  
Nail Ozhan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Clinical Benefit ◽  
Progressive Disease ◽  
Univariate Analysis ◽  
First Line ◽  
Exact Test ◽  
Best Response ◽  
Metastatic Urothelial Carcinoma ◽  
Line Chemotherapy

409 Background: In the current study, we evaluated whether the response first-line chemotherapy could impact atezolizumab benefit in terms of response rate and overall survival in patients with metastatic urothelial carcinoma. Methods: In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. The association between response to first-line chemotherapy and ATZ was assessed using Fisher’s exact test. Overall survival (OS) was estimated by using the Kaplan-Meier method. Univariate analysis was used to identify clinical and laboratory factors that significantly impact OS. Variables were retained for multivariate analysis if they had a statistical relationship with OS (p˂0.1) and then included the final model if p˂0.05. Results: Best response to first-line chemotherapy was complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) in 5(4.8%), 38(36.2%), 16(15.2%), 46(43.8%) patients, respectively. Best response to atezolizumab was CR, PR, SD, PD in 9(8.6%), 22(21%), 23(21,9%), 51(48,5%). Forty (74.1%) of patients who benefited from first-line chemotherapy also benefited from atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with atezolizumab (Fisher’s exact test, p=0.001). Patients with clinical benefit from first-line chemotherapy had a higher OS. The median OS of atezolizumab were 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (log-rank p=0.001). In univariate analysis, Patients with clinical benefit from first-line chemotherapy, liver metastases, baseline creatinine clearance less (GFR)than 60 ml/min, Eastern Cooperative Oncology Group (ECOG) performance status (1 ≥), and hemoglobin levels below 10 mg/dl were all significantly associated with OS. Three of the adverse prognostic factors according to the Bellmunt criteria were independent factor of short survival: liver metastases (Hazard Ratio [HR]= 0.6; 95% CI 0.174-0.60; p=0.04), ECOG PS≥1 (HR= 0.36; 95% CI 0.2-0.66; p=0.001), and Hemoglobin level below 10 mg/dl (HR= 0.36; 95% CI 0.2-0.66; p <0.001). In addition, Patients with clinical benefit from first-line chemotherapy (HR= 0.39; 95% CI 0.24-0.65; p <0.001) maintained a significant association with OS in multivariate analysis. Conclusions: Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factor on OS in patients' use of atezolizumab as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.

Long-Term Disease Control in Patients with Primary Central Nervous System Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3600-3600
Author(s):  
Ingo Schmidt-Wolf ◽  
Hendrik Pels ◽  
Annika Jürgens ◽  
Sabine Rogowski ◽  
Axel Glasmacher ◽  
...  
Keyword(s):  
Overall Survival ◽  
Central Nervous System Lymphoma ◽  
Response Duration ◽  
Complete Response ◽  
High Dose ◽  
Survival Fraction ◽  
Median Response ◽  
Kaplan Meier ◽  
Time To Treatment Failure

Abstract Objectives: A pilot phase II trial was performed to evaluate response rate, response duration, overall survival, and toxicity in primary central nervous system lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. Patients and Methods: From 09/1995 to 12/2002, 65 patients with PCNSL (median age 62 years) were enrolled into a pilot/phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was combined with intraventricular MTX, prednisolone and ara-C. Primary endpoint was time to treatment failure (TTF), secondary endpoints were response, overall survival, response duration, 5-year-survival fraction and (neuro)toxicity. Results: 34 patients were male, 31 female. Sixty-one of 65 patients were evaluable for response. Of these, 37 (61%) achieved a complete response (CR), 6 (10%) complete response/unconfirmed, and 12 (20%) progressed under therapy. Overall response rate was 71% for all patients and 86% for patients younger than 61 years. Six (9%) out of 65 patients died due to treatment-related complications. Follow-up time is 78 to 151 months in surviving patients (median 100 months). Kaplan Meier estimates for median time to treatment failure (TTF), median overall survival and median response duration are 22 months, 54 months and 37 months, respectively. For patients aged 60 years or older, the respective numbers were 7 months, 34 months and 30 months; in patients younger than 60 years, the Kaplan Meier estimate for TTF is 49 months, median overall survival and median response duration have not yet been reached. The 5-year survival fraction is 72% in patients < 60 years and 24% in older patients. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 19% of the patients. At present, 17/30 (57%) of younger and 4/35 (9%) elderly patients are still alive. Only 5/30 (17%) of younger, but 19/35 (54%) of elderly patients received radiation salvage therapy at relapse. In 2/65 (3%), secondary cancers developed. In the subgroup of patients with long-term survival (n=17/30 under 61 years), 12 had an ongoing response, 1 an isolated CNS relapse (resolved by radiation), 1 an isolated ocular relapse (resolved by ocular radiation) and 3 a pure systemic relapse without CNS involvement (all resolved by systemic chemotherapy). Eleven of these 17 patients could be investigated by comprehensive neuropsychological testing, which revealed normal cognitive function in all of them. Conclusions: Primary chemotherapy based on high-dose MTX and ara-C is highly efficient in PCNSL. A substantial fraction of patients < 60 years can obviously be cured with this regimen.

E4201: Randomized phase II study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with locally advanced, unresectable, pancreatic cancer (LAPC): Quality-of-life (QOL) analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4627-4627
Author(s):  
H. R. Cardenes ◽  
M. Powell ◽  
P. J. Loehrer ◽  
L. I. Wagner ◽  
D. F. Cella ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Subscale Score ◽  
Prior Therapy ◽  
Randomized Phase Ii ◽  
Grade 3 ◽  
Overall Survival Benefit

4627 Background: E4201 compared radiation and gemcitabine (RT+Gem) versus Gem alone in LAPC. The primary endpoint was overall survival; secondary objectives included: objective response rate (RR), progression-free survival (PFS), toxicity and QOL. We previously reported that RT+Gem was associated with improved overall survival compared with Gem alone [median survival time, 11 months and 9.2 months, respectively; p=0.034], without impact in RR or PFS. (ASCO 2008, abstract # 4506). We now report on QOL as measured by the Hep subscale from the FACT-Hepatobiliary [FACT-Hep] between both arms. Methods: Eligible patients had LAPC adenocarcinoma, PS <2, without prior therapy. They were randomized to Arm A: Gem alone (1,000 mg/m2/week x 3, every 4 weeks, 7 cycles), or Arm B: RT (50.4Gy/28 fractions) plus Gem (600 mg/m2/weekly x 6) followed by 5 cycles of Gem alone (1,000 mg/m2/weekly x 3 every 4 wks). The FACT-Hep was administered at baseline (before starting induction), 6 weeks (immediately after completing induction), week 16 (Arm A) or week 15 (Arm B) mid-consolidation, and at 9 months. Results: From April, 2003 to December, 2005, 74 patients were enrolled, 71 were eligible [37 Arm A; 34 Arm B]. Grade ≥3 was reported in 80% and 82.4% in ARM A and B, respectively (p=1.00). Grade IV toxicities, mainly gastrointestinal and hematologic, were more common in ARM B (41.2% vs 5.7%, p=<0.0001). QOL compliance declined over time, most commonly attributable to either patients or staff choosing not to complete or administer the instrument due to declining health (96%, 69%, 60%, and 40% at baseline, week 6, 15/16 weeks and 9 months, respectively). Within Arm B, QoL scores dropped significantly from baseline to 6 weeks. By week 15, QoL scores for patients on Arm B rebounded to levels similar to baseline. Two-sided Wilcoxon rank sum tests failed to suggest differences in median FACT-Hep subscale score between treatment arms at any of the four time-points (alpha = 0.10). Conclusions: RT+Gem is associated with an overall survival benefit without apparent long term adverse impact on QOL when compared with Gem alone. No significant financial relationships to disclose.

scholarly journals Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2875-2875
Author(s):  
Rudolf A. Benz ◽  
Kornelius Arn ◽  
Martin Andres ◽  
Thomas Pabst ◽  
Urban Novak ◽  
...  
Keyword(s):  
Overall Survival ◽  
Secondary Malignancies ◽  
Hairy Cell ◽  
First Line ◽  
Purine Analogues ◽  
Minor Response ◽  
Kaplan Meier ◽  
Long Term Follow Up

Abstract Introduction : Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment. Materials and Methods : The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively. Results : The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms. Conclusion : Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies. Disclosures Chalandon: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

scholarly journals Incidence of spinal disease and role of spinal radiotherapy in multiple myeloma

2018 ◽  
Vol 25 (6) ◽  
Author(s):  
A. M. Sharma ◽  
M. Sackett ◽  
D. Bueddefeld ◽  
P. Lambert ◽  
A. Dubey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Cord Compression ◽  
Newly Diagnosed ◽  
Spinal Disease ◽  
Kaplan Meier ◽  
Long Term Survivors

Background Spinal disease (spd) in multiple myeloma (mm) can be a major source of morbidity in newly diagnosed patients and long-term survivors. We retrospectively assessed the incidence of spinal disease in patients newly diagnosed with myeloma, its effect on survival, and the possible effect of spinal radiation therapy (rt).Methods Patients diagnosed with mm between 2010 and 2014 were identified through the provincial cancer registry. Plain radiography, computed tomography, and magnetic resonance imaging were reviewed to detect and document the type of spd. Data related to rt and systemic therapy were collected. Kaplan–Meier and time-varying Cox regression models were used to describe overall survival.Results Of 306 identified patients with newly diagnosed mm, 51% had spd, including 17% with lytic disease, 68% with compression fractures, and 15% with spinal cord compression. Of the patients with spd, 61% received spinal rt. Of those patients, 84% received spinal rt within 3 months after their diagnosis. Median dose was 20 Gy. Most patients (89.2%) received chemotherapy, and 22.5% underwent autologous stem-cell transplantation. Only 6 of the patients treated with spinal rt received re-irradiation to the same site. Overall survival was similar for patients with and without spd. On multivariate analysis, spinal rt had no effect on survival.Conclusions In patients newly diagnosed with mm, spd is a common presentation. With current systemic therapy, the presence of spd had no adverse effect on overall survival. The effect of spinal rt on overall survival was nonsignificant.

Post-hoc analysis of long-term outcomes in patients with CR, PR, or SD to pembrolizumab (pembro) or platinum-based chemotherapy (chemo) as 1L therapy for advanced urothelial carcinoma (UC) in KEYNOTE-361.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 435-435
Author(s):  
Yohann Loriot ◽  
Ajjai Shivaram Alva ◽  
Tibor Csőszi ◽  
Mustafa Ozguroglu ◽  
Nobuaki Matsubara ◽  
...  
Keyword(s):  
Phase Iii ◽  
Term Survival ◽  
Landmark Analysis ◽  
Kaplan Meier ◽  
Best Response ◽  
Platinum Based Chemotherapy ◽  
Duration Of Response ◽  
Post Hoc ◽  
To Receive

435 Background: The phase III KEYNOTE-361 study compared efficacy and safety of 1L pembro + chemo or pembro vs chemo in pts with advanced UC. The trial did not meet its primary endpoints of PFS or OS superiority for pembro + chemo vs chemo; formal testing for OS for pembro vs chemo was not performed. We present a post hoc landmark analysis to examine the durability of CR/PR/SD and long-term survival in pts with CR, PR, or SD to pembro vs chemo at week 9 in KEYNOTE-361 (NCT02853305). Methods: Landmark analyses of OS by CR/PR/SD at 9 weeks after randomization in the ITT population were performed. Pts were included if they had a best response of CR/PR/SD per RECIST v1.1 by blinded independent central review at the landmark date of week 9 (first imaging assessment per study protocol). Duration of CR/PR/SD and OS were estimated by the Kaplan-Meier method. No formal comparisons were performed. Results: 307 pts were randomized to receive pembro and 352 pts to receive chemo in the KEYNOTE-361 study. As of Apr 29, 2020, the median (range) time from randomization to data cutoff was 32.5 (22.0-42.4) mo for the pembo arm and 31.4 (22.1-41.6) mo for the chemo arm. In the landmark analysis, fewer pts had CR/PR/SD at week 9 with pembro (n=137 [45%]) than with chemo (n=253 [72%]). Median (range) duration of response for pembro vs chemo was 18.7 (4.4+-35.4+) vs 12.3 (0.0+-29.7+) mo for pts with CR, and 35.0 (1.1-36.1+) vs 6.1 (0.0+-36.3+) mo for pts with PR. Median (range) duration of SD was 4.8 mo (0.0-38.2+) with pembro and 4.6 mo (0.0-16.1+) with chemo. Median OS (95% CI) for pembro vs chemo was not reached (NR) (25.5-NR) vs NR (19.1-NR) for pts with CR; NR (NR-NR) vs 14.8 mo (12.1-21.0) for pts with PR; and 18.5 mo (13.8-28.8) vs 11.1 mo (8.1-14.6) for pts with SD, respectively. Long-term OS rates were higher with pembro vs chemo across all groups (CR/PR/SD) at week 9 (Table). Conclusions: In this post hoc landmark analysis, chemo was associated with more initial responses than pembro, whereas pembro was associated with longer median duration of CR and PR, and generally longer median OS than chemo. Among pts who achieved CR/PR/SD at week 9, the relative OS benefit for pembro vs chemo increased over time. Clinical trial information: NCT02853305. [Table: see text]

Effectiveness of a Strategy to Proceed to Allogeneic Stem Cell Transplantation in All Elderly AML Patients Treated with Intensive Chemotherapy: Only Patients in Complete Remission After First Induction Show Long Term Survival.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3085-3085
Author(s):  
Peter A. Von Dem Borne ◽  
Constantijn J.M. Halkes ◽  
Erik W.A. Marijt ◽  
Sabina Kersting ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Consolidation Chemotherapy ◽  
Early Relapse ◽  
Kaplan Meier ◽  
Elderly Aml ◽  
Treat Population

Abstract Abstract 3085 Introduction Acute myeloid leukemia (AML) in patients over 60 years has a poor prognosis with 2-year survival rates of less than 10%. Intensive chemotherapy improves interim survival but not long term cure rates compared to non-intensive care. Allogeneic stem cell transplantation (alloSCT) has the potential to cure elderly AML patients, but most reported studies refer to selected patient cohorts. We have developed a T cell-depleted reduced intensity conditioning (RIC) regimen and preplanned post alloSCT donor T-cell infusion, inducing only limited GVHD directly after alloSCT (von dem Borne et al. Curr Opin Oncol 2009) making it a suitable regimen for elderly patients. In 2006, we instituted a center policy to perform RIC alloSCT in every newly diagnosed AML and high grade MDS patient >60 years who qualified for induction therapy. We here report feasibility, toxicity, and outcomes of this strategy. Patients and methods From 2006 to 2011, 45 consecutive patients aged 60–79 years (median: 67) with newly diagnosed AML (n=43) or high-risk MDS (IPSS score >1.5) started induction chemotherapy (continuous infusional cytarabine combined with bolus anthracycline with or without etoposide). Patient not achieving complete remission (CR) after induction received a re-induction cycle with high-dose cytarabine with or without amsacrine. Patients in CR after induction or re-induction were to receive one cycle of consolidation chemotherapy, followed by RIC alloSCT in case of continuous CR. Results Six patients (13%) died during first induction. 19 patients (43%) achieved CR after first induction, of which 12 received a RIC alloSCT (27% of intention-to-treat population) after consolidation chemotherapy. Causes why CR patients did not receive alloSCT were good-risk AML (n=1), early relapse after consolidation chemotherapy (n=2), high age (patient had become over 80 years) (n=1), infectious complication (n=1) and patient choice (n=2). 20 patients (45%) failed to achieve a CR after induction chemotherapy. 16 of these patients received the planned re-induction therapy; 10 of these patients achieved a CR, 7 patients received a third chemotherapy course for consolidation, and 4 underwent RIC alloSCT. There were no long-term survivors in this group. 19 patients without CR after 1st induction died from progressive AML.15 AML deaths after 1st induction failure occurred in patients who were treated according to the institutional strategy (6 patients with progressive disease despite additional chemotherapy, 1 relapse prior to start of re-induction, 3 relapses early after consolidation, and 4 relapses after alloSCT). Relapses in patients not adhering to the pre-specified strategy occurred in patients opting to discontinue therapy while in CR (n=3), inability to find a donor (n=1), and complication preventing alloSCT (n=1). One transplanted patient died from GVHD. For the entire intent-to-treat population, the Kaplan-Meier estimate for overall survival at 1 and 2 years after start of treatment is 38% and 19%, respectively. For patients achieving CR after 1st induction and receiving alloSCT, Kaplan-Meier estimate overall survival at 2 years after start of treatment is 50%. The main reasons for dying when adhering to the protocol were early death (13%) and refractory/relapsing malignancy (47%). Only 2 patients (4%) died after 1st induction as a consequence of TRM. Non-TRM reasons for not adhering to the protocol with subsequent death due to AML were patient preference (n=4; 9%) and inability to identify a matched donor (n=1; 2%). Conclusions This single-center comprehensive cohort study shows that 38% of elderly AML patients that are deemed fit for induction chemotherapy can be brought to alloSCT in CR. At diagnosis, this strategy offers a chance of cure for about 20% of patients. Fifty percent of patients achieving CR after 1st induction and receiving alloSCT are alive 2 years after alloSCT. Since none of the patients who failed to achieve a CR after 1st induction survived long-term, the most important aspect to improve this strategy is to strive for higher primary CR rates, including the prevention of early deaths. Alternative strategies, such as combining alloSCT and consolidation chemotherapy into one coherent regimen may especially improve outcome by preventing early relapse and improving patient compliance. Post-induction TRM and lack of a donor were only minor obstacles to this potentially curative approach. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Early and Long-Term Outcomes of Carotid Stenting and Carotid Endarterectomy in Women

2021 ◽  
Vol 8 ◽  
Author(s):  
Edoardo Pasqui ◽  
Gianmarco de Donato ◽  
Giuseppe Alba ◽  
Brenda Brancaccio ◽  
Claudia Panzano ◽  
...  
Keyword(s):  
Overall Survival ◽  
Transient Ischemic Attack ◽  
Carotid Stenting ◽  
Long Term Outcomes ◽  
Carotid Revascularization ◽  
Kaplan Meier ◽  
Cerebral Ischemic ◽  
Ischemic Attack ◽  
Perioperative Risks

Background: The role of carotid revascularization in women remains intensely debated because of the lower benefit and higher perioperative risks concerning the male counterpart. Carotid artery endarterectomy (CEA) and stenting (CAS) represent the two most valuable stroke prevention techniques due to large vessel disease. This study investigates the early and late outcomes in female sex in a real-world everyday clinical practice.Methods: Data were retrospectively analyzed from a single-center database prospectively compiled. A total of 234 procedures, both symptomatic and asymptomatic, were identified (98 CEAs and 136 CASs). Perioperative risks of death, cerebral ischemic events, and local complications were analyzed and compared between the two groups. Long-term outcomes were evaluated in overall survival, freedom from ipsilateral stroke/transient ischemic attack, and freedom from restenosis (&gt;50%) and reintervention.Results: Women who underwent CAS and CEA did not differ in perioperative ischemic cerebral events (2.2 vs. 0%, p = 0.26) and death (0.8 vs. 0%, p = 1). Other perioperative and 30-day outcomes were similarly distributed within the two groups. Kaplan–Meier curves between CAS and CEA groups highlighted no statistical differences at 6 years in overall survival (77.4 vs. 77.1%, p = 0.47) of ipsilateral stroke/transient ischemic attack (94.1 vs. 92.9%, p = 0.9). Conversely, significant differences were showed in 6 years freedom from restenosis (93.1 vs. 83.3%, p = 0.03) and reinterventions (97.7 vs. 87.8%, p = 0.015).Conclusion: Our results revealed that both CEA and CAS have acceptable perioperative risk in women. Long-term outcomes highlighted favorable indications for both procedures, especially for CAS, which seemed to be an excellent alternative to CEA in female patients when performed by well-trained operators.

scholarly journals Colonization with Extensively Drug-Resistant Acinetobacter baumannii and Prognosis in Critically Ill Patients: An Observational Cohort Study

2021 ◽  
Author(s):  
Yue Zheng ◽  
Nana Xu ◽  
Jiaojiao Pang ◽  
Hui Han ◽  
Hongna Yang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Resistant ◽  
Overall Survival Rate ◽  
Short Term ◽  
Extensively Drug Resistant ◽  
Kaplan Meier

Abstract BackgroundAcinetobacter baumannii is one of the most frequently isolated opportunistic pathogens in intensive care units (ICUs). Extensively drug-resistant A. baumannii (XDR-AB) strains lack susceptibility to almost all antibiotics and pose a heavy burden on healthcare institutions. In this study, we evaluated the impact of XDR-AB colonization on both the short-term and long-term survival of critically ill patients.MethodsWe prospectively enrolled patients from two adult ICUs in Qilu Hospital of Shandong University from March 2018 through December 2018. Using nasopharyngeal and perirectal swabs, we evaluated the presence of XDR-AB colonization. Participants were followed up for 6 months. The primary endpoints were 28-day and 6-month mortality after ICU admission. The overall survival rate was estimated by the Kaplan-Meier method. We identified risk factors associated with 28-day and 6-month mortality using the logistic regression model and a time-dependent Cox regression model, respectively. ResultsOut of 431 patients, 77 were colonized with XDR-AB. Based on the Kaplan-Meier curve results, the overall survival before 28 days did not differ by colonization status; however, a significantly lower overall survival rate was obtained at 6 months in colonized patients. Univariate and multivariate analysis results confirmed that XDR-AB colonization was not associated with 28-day mortality, but was an independent risk factor of lower overall survival at 6 months (HR = 1.749, 95% CI = 1.174–2.608).ConclusionsXDR-AB colonization has no effect on short-term overall survival, but is associated with lower long-term overall survival in critically ill patients.

Sign in / Sign up

Export Citation Format

Share Document