KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting.

Longitudinal health-related quality of life in first-line treated patients with chronic lymphocytic leukemia: Results from the Connect CLL Registry.

Health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) is important in guiding treatment decisions. However, the impact of CLL treatment initiation on HRQoL is unclear. We assessed HRQoL using the FACT-Leu and EQ-5D-3L questionnaires in the Connect CLL Registry, a large, US-based, multicenter, prospective observational study of CLL patients enrolled between 2010 and 2014, prior to the introduction of novel therapies.

Determining the Suitability of Registries for Embedding Clinical Trials in the United States: A Project of the Clinical Trials Transformation Initiative.

Background: Patient registries are organized systems that use observational methods to collect uniform data on specified outcomes in a population defined by a particular disease, condition, or exposure. Data collected in registries often coincide with data that could support clinical trials. Integrating clinical trials within registries to create registry-embedded clinical trials offers opportunities to reduce duplicative data collection, identify and recruit patients more efficiently, decrease time to database lock, accelerate time to regulatory decision-making, and reduce clinical trial costs.

The Connect CLL Registry: final analysis of 1494 patients with chronic lymphocytic leukemia across 199 US sites.

Optimal treatment of chronic lymphocytic leukemia (CLL) remains unclear. The Connect CLL Registry, a United States-based multicenter prospective observational cohort study, enrolled 1494 patients between 2010 and 2014 from predominantly community-based settings. Patients were grouped by line of therapy (LOT) at enrollment.

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.

Reasons for initiation of treatment and predictors of response for patients with Rai stage 0/1 chronic lymphocytic leukemia (CLL) receiving first-line therapy: an analysis of the Connect CLL cohort study.

A 'watch-and-wait' strategy is recommended for most patients with early-stage chronic lymphocytic leukemia (CLL) prior to treatment initiation. In the Connect CLL registry, a prospective observational cohort study of 1494 patients treated in 199 US centers, median time to first-line treatment initiation was 3.8, 1.

Prognostic Testing Patterns and Outcomes of Chronic Lymphocytic Leukemia Patients Stratified by Fluorescence In Situ Hybridization/Cytogenetics: A Real-world Clinical Experience in the Connect CLL Registry.

Introduction: Prognostic genetic testing is recommended for patients with chronic lymphocytic leukemia (CLL) to guide clinical management. Specific abnormalities, such as del(17p), del(11q), and unmutated IgHV, can predict the depth and durability of the response to CLL therapy.

Patients And Methods: In the present analysis of the Connect CLL Registry (ClinicalTrials.

Early progression of disease as a predictor of survival in chronic lymphocytic leukemia.

Chemoimmunotherapy for chronic lymphocytic leukemia (CLL) promotes clonal evolution of aggressive clones, which in some patients may lead to early progression of disease (POD). We studied the prognostic value of early POD in a cohort of patients with CLL enrolled between 2010 and 2014 in the Connect CLL Registry. Overall, 829 eligible patients receiving first-line therapy were categorized into 3 groups: early POD (progression <2 years after treatment initiation), late POD (progression ≥2 years after treatment initiation), and no POD as of 1 May 2017.

Azacitidine in Lower-Risk Myelodysplastic Syndromes: A Meta-Analysis of Data from Prospective Studies.

Background: After erythropoiesis-stimulating agent (ESA) failure, lenalidomide and hypomethylating agents are the only remaining treatment options for most patients with lower-risk myelodysplastic syndromes (LR-MDS). Optimal choice of these agents as front-line therapy in non-del(5q) LR-MDS is unclear. Because azacitidine clinical data mainly describe experience in higher-risk MDS, we performed a meta-analysis of patient-level data to evaluate azacitidine in patients with red blood cell (RBC) transfusion-dependent LR-MDS.

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 > 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.

Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group.

We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML.

Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study.

The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment.

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).

Real-world analysis of the Celgene Global Drug Safety database: early discontinuation of lenalidomide in patients with myelodysplastic syndromes due to non-serious rash.

Background: Lenalidomide is approved for treating transfusion-dependent anemia due to lower-risk del(5q) myelodysplastic syndromes (MDS). In clinical trials, rash was common, although severe rash was infrequent. To examine rash in patients with MDS treated with lenalidomide in the real world, the Celgene Global Drug Safety database was analyzed and compared with clinical trials.

Efficacy and safety of long-term treatment with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma.

Data from two randomized pivotal, phase 3 trials evaluating the combination of lenalidomide and dexamethasone in relapsed/refractory multiple myeloma (RRMM) were pooled to characterize the subset of patients who achieved long-term benefit of therapy (progression-free survival ⩾ 3 years). Patients with long-term benefit of therapy (n = 45) had a median duration of treatment of 48.1 months and a response rate of 100%.

Patients with myelodysplastic syndromes treated with azacitidine in clinical practice: the AVIDA registry.

The AVIDA registry evaluated azacitidine usage and effectiveness in unselected patients with myelodysplastic syndromes (MDS) in community practice. Treating physicians made all treatment decisions. Hematologic improvement (HI) and transfusion independence (TI) assessments used International Working Group (IWG) 2000 criteria.

Challenges of phase III trial design for novel treatments in diseases with no standard treatment: the AZA-001 myelodysplasia study model.

For cancers lacking standard treatments, comparing new agents with existing treatments is problematic. Here we discuss the study design from the AZA-001 trial, which compared azacitidine with 3 frequently used conventional care regimens (CCR) for higher-risk myelodysplastic syndromes. Before randomization, physicians preselected the most appropriate of 3 CCR for each patient, after thorough examination.

Association of health-related quality of life with gender in patients with B-cell chronic lymphocytic leukemia.

Purpose: This analysis examined associations between gender and health-related quality of life (HRQOL) in patients with B-cell chronic lymphocytic leukemia (CLL) as they initiate therapy for CLL outside the clinical trial setting.

Methods: Baseline data were collected as part of Connect® CLL Registry, a prospective observational study initiated in community, academic, and government centers. Patient demographics and clinical characteristics were provided by clinicians.