49 research outputs found
Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.
BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting.
METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model.
RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006).
CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients.
TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010
Real-world clinical experience in the Connect® chronic lymphocytic leukaemia registry: a prospective cohort study of 1494 patients across 199 US centres.
The clinical course of chronic lymphocytic leukaemia (CLL) is heterogeneous, and treatment options vary considerably. The Connect® CLL registry is a multicentre, prospective observational cohort study that provides a real-world perspective on the management of, and outcomes for, patients with CLL. Between 2010 and 2014, 1494 patients with CLL and that initiated therapy, were enrolled from 199 centres throughout the USA (179 community-, 17 academic-, and 3 government-based centres). Patients were grouped by line of therapy at enrolment (LOT). We describe the clinical and demographic characteristics of, and practice patterns for, patients with CLL enrolled in this treatment registry, providing patient-level observational data that represent real-world experiences in the USA. Fluorescence in situ hybridization (FISH) analyses were performed on 49·3% of patients at enrolment. The most common genetic abnormalities detected by FISH were del(13q) and trisomy 12 (45·7% and 20·8%, respectively). Differences in disease characteristics and comorbidities were observed between patients enrolled in LOT1 and combined LOT2/≥3 cohorts. Important trends observed include the infrequent use of genetic prognostic testing, and differences in patient characteristics for patients receiving chemoimmunotherapy combinations. These data represent experiences of patients with CLL in the USA, which may inform treatment decisions in everyday practice
Impact of post-transplantation maintenance therapy on health-related quality of life in patients with multiple myeloma: data from the Connect® MM Registry
Maintenance therapy after autologous stem cell transplantation (ASCT) is recommended for use in multiple myeloma (MM); however, more data are needed on its impact on health-related quality of life (HRQoL). Presented here is an analysis of HRQoL in a Connect MM registry cohort of patients who received ASCT ± maintenance therapy. The Connect MM Registry is one of the earliest and largest, active, observational, prospective US registry of patients with symptomatic newly diagnosed MM. Patients completed the Functional Assessment of Cancer Therapy-MM (FACT-MM) version 4, EuroQol-5D (EQ-5D) questionnaire, and Brief Pain Inventory (BPI) at study entry and quarterly thereafter until death or study discontinuation. Patients in three groups were analyzed: any maintenance therapy (n = 244), lenalidomide-only maintenance therapy (n = 169), and no maintenance therapy (n = 137); any maintenance and lenalidomide-only maintenance groups were not mutually exclusive. There were no significant differences in change from pre-ASCT baseline between any maintenance (P = 0.60) and lenalidomide-only maintenance (P = 0.72) versus no maintenance for the FACT-MM total score. There were also no significant differences in change from pre-ASCT baseline between any maintenance and lenalidomide-only maintenance versus no maintenance for EQ-5D overall index, BPI, FACT-MM Trial Outcomes Index, and myeloma subscale scores. In all three groups, FACT-MM, EQ-5D Index, and BPI scores improved after ASCT; FACT-MM and BPI scores deteriorated at disease progression. These data suggest that post-ASCT any maintenance or lenalidomide-only maintenance does not negatively impact patients' HRQoL. Additional research is needed to verify these findings
Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis
<p>Abstract</p> <p>Background</p> <p>Sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, is the first in a new class of oral antihyperglycemic agents (AHAs) for the treatment of patients with type 2 diabetes. Type 2 diabetes is a life-long disease requiring chronic treatment and management. Therefore, robust assessment of the long-term safety and tolerability of newer therapeutic agents is of importance. The purpose of this analysis was to assess the safety and tolerability of sitagliptin by pooling 12 large, double-blind, Phase IIb and III studies up to 2 years in duration. Methods: This analysis included 6139 patients with type 2 diabetes receiving either sitagliptin 100 mg/day (N = 3415) or a comparator agent (placebo or an active comparator) (N = 2724; non-exposed group). The 12 studies from which this pooled population was drawn represent the double-blind, randomized, Phase IIB and III studies that included patients treated with the clinical dose of sitagliptin (100 mg/day) for at least 18 weeks up to 2 years and that were available in a single safety database as of November 2007. These 12 studies assessed sitagliptin as monotherapy, initial combination therapy with metformin, or add-on combination therapy with other oral AHAs (metformin, pioglitazone, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone). Patients in the non-exposed group were taking placebo, pioglitazone, metformin, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone. This safety analysis used patient-level data from each study to evaluate clinical and laboratory adverse experiences.</p> <p>Results</p> <p>For clinical adverse experiences, the incidence rates of adverse experiences overall, serious adverse experiences, and discontinuations due to adverse experiences were similar in the sitagliptin and non-exposed groups. The incidence rates of specific adverse experiences were also generally similar in the two groups, with the exception of an increased incidence rate of hypoglycemia observed in the non-exposed group. The incidence rates of drug-related adverse experiences overall and discontinuations due to drug-related adverse experiences were higher in the non-exposed group, primarily due to the increased incidence rate of hypoglycemia in this group. For cardiac- and ischemia-related adverse experiences (including serious events), there were no meaningful between-group differences. No meaningful differences between groups in laboratory adverse experiences, either summary measures or specific adverse experiences, were observed.</p> <p>Conclusion</p> <p>In patients with type 2 diabetes, sitagliptin 100 mg/day was well tolerated in clinical trials up to 2 years in duration.</p
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Effect of Lenalidomide (LEN) Exposure on AML-Free Survival and Overall Survival in LEN-Treated Patients (Pts) with IPSS Low- or Intermediate-1-Risk Myelodysplastic Syndromes (MDS) with Del(5q)
Abstract
Introduction: The efficacy and safety of LEN in red blood cell (RBC) transfusion-dependent pts with International Prognostic Scoring System (IPSS)-defined Low- or Intermediate-1-risk MDS and del(5q) was assessed in 2 large pivotal trials; protocol-defined dose modifications due to adverse events were required in the majority of LEN-treated pts (MDS-003 [List A, et al. N Engl J Med. 2006;355:1456-65] and MDS-004 [Fenaux P, et al. Blood. 2011;118:3765-76]). Previously we have shown that achievement of cytogenetic response (CyR) with LEN is associated with LEN dose and with achieving RBC transfusion-independence and improved acute myeloid leukemia (AML)-free survival. The current analysis evaluates the impact of actual LEN exposure, including induction-type dosing in Cycle 1 and subsequent dose reductions for LEN-associated cytopenias, and CyR on AML-free survival and overall survival (OS) in lower-risk MDS pts with del(5q) treated in the MDS-003 and MDS-004 studies.
Methods: This analysis includes pooled data from pts who were treated with LEN in MDS-003 and MDS-004. Pts received LEN at one of the following starting doses and schedules: 5 mg/day, days 1-28 (MDS-004); 10 mg/day, days 1-21 (MDS-003 and MDS-004); or 10 mg/day, days 1-28 (MDS-003); all given in 28-day cycles. LEN dose reductions related to adverse events (NCI CTCAE v3.0) of grade ≥ 3 (MDS-003) or grade 4 thrombocytopenia or neutropenia (MDS-004) were predefined in the study protocols. Full dose modification guidelines for MDS-004 have been published previously (Fenaux P, et al. Blood. 2011;118:3765-76). Dose interruptions were not considered. AML-free survival and OS were estimated by the Kaplan-Meier method with differences evaluated by the log-rank test. Univariate and multivariable Cox proportional hazards models were used to identify predictive factors for AML-free survival and OS. CyR and LEN dose reduction were analyzed as time-varying covariates.
Results: Among the 286 LEN-treated pts from MDS-003 and MDS-004, median total doses in Cycle 1 were 245, 210, 280, and 140 mg in the 10 mg (MDS-003: 10 mg × 28 days), 10 mg (MDS-003: 10 mg × 21 days), 10 mg (MDS-004: 10 mg × 21 days), and 5 mg (MDS-004: 5 mg × 28 days) treatment groups, respectively. Median total times on LEN were 364, 385, 510, and 273 days, respectively, and median times to first dose reduction were 53, 63, 54, and 63 days across the treatment groups, respectively. AML-free survival and OS were significantly longer in pts who received > 210 mg versus ≤ 210 mg in Cycle 1 of therapy (log-rank P = 0.0005 and P = 0.0002, respectively). In multivariable analyses, higher total LEN dose in Cycle 1, analyzed as a continuous variable, was significantly associated with improved AML-free survival (hazard ratio [HR] 0.97; P = 0.033) and OS (HR 0.97; P = 0.036) (Table). Sensitivity analyses showed total dose in Cycles 1-3 to be significant, but total dose in Cycle 1 was a better predictor. In the same model, the occurrence of LEN dose reduction was significantly associated with improved AML-free survival (HR 0.54; P < 0.001) and OS (HR 0.56; P = 0.001) (Table) and was strongly associated with longer duration on study (P < 0.001).
Conclusions: In this pooled analysis of LEN-treated pts with MDS and del(5q) from the pivotal MDS-003 and MDS-004 trials, the total cumulative LEN dose actually received in Cycle 1 was a significant predictor of AML-free survival and OS; this is likely mediated through clone suppression, evidenced by the association with CyR. Long-term outcomes were significantly improved in LEN-treated pts who had received early cumulative exposure using 10 mg daily and longer duration through dose modifications. These findings support the use of LEN 10 mg as the recommended induction starting dose, and the importance of dose reductions as required to maximize treatment duration and optimize response and survival outcomes in these pts with lower-risk MDS with del(5q).
Disclosures
Sekeres: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Swern:Celgene Corporation: Employment, Equity Ownership. List:Celgene Corporation: Honoraria, Research Funding. Fenaux:Novartis: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding. Sugrue:Celgene Corporation: Employment, Equity Ownership