Abstract: Introduction: In prior studies, only 13-22% of lower-risk (LR) MDS pts and 11-69% of higher-risk (HR) MDS pts received potentially disease-modifying therapy despite the proven benefits of reduced blood transfusions and prolonged survival. Pt age, frailty, and comorbidities are commonly assumed to influence therapy choice; however, this has not been proven and other factors may govern treatment (tx) decisions. To identify factors associated with receiving first-line tx for MDS, health services data from the Connect® MDS/AML Registry, which includes MDS pts treated in US academic, community, and government-based centers, were analyzed. Methods: The Connect MDS/AML Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts with newly diagnosed acute myeloid leukemia (AML) (aged ≥ 55 years) or MDS (aged ≥ 18 years). Local AML and MDS diagnoses are confirmed by an independent central review of all available diagnostic reports. Baseline demographics, disease characteristics, laboratory parameters, and ZIP-code-level per capita income were collected at enrollment on MDS pts from December 2013 to March 2018. Analyses were performed separately for LR-MDS pts, defined as having Low- or Intermediate (Int)-1-risk MDS according to the International Prognostic Scoring System (IPSS), and HR-MDS pts, defined as having Int-2- or High-risk MDS. Uni- and multivariable logistic regression analyses were used to identify factors associated with early use of first-line tx in MDS pts, defined as chemotherapy or biotherapy initiated ≤ 45 days after diagnosis. Univariable testing was performed for each potential predictor; those with an association of P 〈 0.15 were included in multivariable analysis. The final multivariable model was derived using a score-based selection method. Pts receiving first-line tx (regardless of intensity) were compared with a combined group of pts receiving best supportive care (BSC) or no tx. Results: As of March 8, 2018, data from 536 MDS pts (232 HR-MDS and 304 LR-MDS) from 130 institutions (20 academic and 110 community/government) were available for analysis. In the LR-MDS group, median age was 76 years (range 28-95), with 65% male, and 89% white; 19% had private insurance, and the average median ZIP-code-level per capita income was $28,000 ($10,000-$92,000). In the HR-MDS group, median age was 73 years (range 19-94), with 67% male and 86% white; 23% had private insurance, and the average median ZIP-code-level per capita income was $26,000 (range $14,000-$83,000). In LR-MDS pts, univariable predictors of early first-line therapy initiation included baseline transfusion dependency (defined as ≥ 1 transfusion episode in the 8 weeks prior to diagnosis), comorbidities (higher Adult Comorbidity Evaluation 27 [ACE-27] score), having fluorescence in situ hybridization (FISH) or molecular analyses performed, Int-1 IPSS risk score, primary vs secondary MDS, and higher bone marrow (BM) blast percentage. Multivariable logistic regression analysis identified transfusion dependency (P = 0.001), Int-1 IPSS risk score (P = 0.026), BM blast percentage ≥ 5% (P = 0.002), and having both FISH and molecular genetic testing performed at diagnosis (P = 0.022) as factors significantly associated with early initiation of first-line tx (Table 1). Univariable analysis of HR-MDS pts showed insurance status, comorbidities (ACE-27 score ≤ 2), High IPSS risk score, primary vs secondary MDS, having flow cytometry analysis performed, lower baseline frailty, and BM blast percentage as univariable correlates associated with early tx. Multivariable logistic regression analysis identified private insurance coverage (P = 0.031) and BM blast percentage ≥ 10% (P = 0.021) as factors significantly associated with early initiation of first-line tx (Table 2). Conclusions: Early first-line tx in MDS pts was significantly associated with disease severity as indicated by transfusion dependency, higher IPSS risk score, and higher BM blast percentage. However, counter to common assumptions, age, frailty, and comorbidities were not associated with receiving early tx in MDS. Access to care may be an important factor in the tx of MDS pts, as having private health insurance and undergoing genetic testing were also significantly associated with receiving early tx. Additional pt-centered research with prescribing MDS physicians as stakeholders is needed to verify and extend these findings. Disclosures Cogle: Celgene: Other: Steering Committee Member of Connect MDS/AML Registry. Grinblatt:Celgene: Membership on an entity's Board of Directors or advisory committees; Alexion: Speakers Bureau; AbbVie: Consultancy. Komrokji:Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. Savona:Boehringer Ingelheim: Consultancy; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Scott:Celgene: Consultancy, Honoraria, Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees. Louis:Cellmedica: Patents & Royalties; Celgene: Employment. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Steensma:Takeda: Consultancy; Syros: Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees; Onconova: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Kura: Research Funding; Janssen: Consultancy, Research Funding; H3 Biosciences: Research Funding; Celgene: Research Funding; Amphivena: Membership on an entity's Board of Directors or advisory committees; Acceleron: Consultancy.

Abstract: Background: The diagnosis of AML requires an integrated approach of clinical, morphologic, cytogenetic, and molecular assessments. The CONNECT MDS/AML Disease Registry (NCT01688011) is a prospective, longitudinal, multicenter, observational cohort study of patients (pts) in the United States with newly diagnosed AML, MDS, or idiopathic cytopenia of undetermined significance, designed to evaluate diagnostic and treatment (Tx) patterns, clinical and pt-reported outcomes, and correlative data, such as genetic mutations. This investigation was performed to assess how pts with AML are diagnosed at community and academic sites and compare how these diagnostic practices align with WHO 2008 recommendations for AML. Methods: Pt enrollment began in December, 2013 and will continue until ~1500 pts from ~150 US sites are enrolled. Target enrollment for the AML cohort is 400 pts. To best capture the typical distribution of clinical practice settings in which AML pts are treated, ~80% of the sites will be community-based and ~20% will be academic institutions (ie, affiliated with a medical school). Pts aged ≥55 years (yrs) with newly diagnosed AML (excluding acute promyelocytic leukemia) are eligible. All decisions regarding pt care (Tx, testing) are determined by the study clinician, as the disease registry is non-interventional. AML diagnosis is confirmed by independent central review of all available diagnostic test reports, including bone marrow (BM) aspirates and biopsies, cytogenetics, molecular testing, and laboratory results. Diagnostic procedures are recorded in an electronic data capture system. Pt data will be entered quarterly for up to 8 years of follow-up. Results: Between December 12, 2013 and May 19, 2016, 180 AML pts have enrolled in the registry from 73 sites; 125 pts (69%) enrolled at a community site (including 1 governmental site) and 55 pts (31%) enrolled at an academic center. Median age of all pts was 71 yrs (range 55-91), with 72% of pts aged ≥65 yrs (Table 1). Blast percentages were reported in 97% of cases, mainly in BM, although peripheral blood blasts were also assessed for 71% of pts (Table 2). Manual differential blast count was reported for 63% of pts, and flow cytometry and immunohistochemistry were used to determine blast counts for 10% of pts each. Immunophenotyping by flow cytometry was reported for 97% of pts. Erythroid, megakaryocytic, or neutrophilic dysplasia, and presence or absence of Auer rods, ring sideroblasts, or fibrosis were reported for 〈 50% of all pts (Table 2). Conventional karyotyping was performed for 90% of pts and FISH testing was reported for 80% of pts (Table 3). Mutation testing was reported for 85 pts (47%). Conclusions: The ongoing prospective CONNECT MDS/AML registry is uniquely positioned to assess current clinical practice patterns in AML. Flow cytometry and conventional karyotyping were done in most cases; however, manual blast count was missing for 37% of AML pt samples at diagnosis. Instead, ~10% of blasts counts were evaluated by flow cytometry or immunohistochemistry, and ~18% by 'other' means (ie, blast count estimations). Flow cytometry for blast enumeration is discouraged in WHO 2008 recommendations, as it may both under- and overestimate counts. Despite a 90% rate of conventional karyotyping, FISH testing was reported for 80% of pts, suggesting FISH may be used more than is necessary. Mutation testing was reported for approximately one-half of pts, which may reflect a lack of testing, a lag in mutational test reporting, or a combination of both. Diagnostic practices for AML pts enrolled thus far appear to be guided by WHO 2008 recommendations; awareness of updated recommendations may change diagnostic patterns as new AML pts enter the CONNECT MDS/AML registry. Disclosures George: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Allakos: Research Funding; Allakos: Research Funding; Blueprint Medicines: Consultancy; Novartis: Consultancy; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy; GLG: Consultancy; Wiley Blackwell: Consultancy; American Registry of Pathology: Patents & Royalties; Wolters Kluwer: Patents & Royalties; UpToDate: Patents & Royalties. Erba:Sunesis: Consultancy; Novartis: Consultancy, Speakers Bureau; Celator: Research Funding; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Juno: Research Funding; Astellas: Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Agios: Research Funding; Pfizer: Consultancy; Gylcomimetics: Other: DSMB; Millennium Pharmaceuticals, Inc.: Research Funding; Celgene: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Daiichi Sankyo: Consultancy. Steensma:Amgen: Consultancy; Ariad: Equity Ownership; Millenium/Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Genoptix: Consultancy. Pollyea:Alexion: Other: advisory board; Ariad: Other: advisory board; Celgene: Other: advisory board, Research Funding; Glycomimetics: Other: DSMB member; Pfizer: Other: advisory board, Research Funding. Abedi:Celgene: Consultancy. Bejar:Genoptix: Consultancy. Grinblatt:Celgene Corporation: Consultancy, Speakers Bureau. Komrokji:Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Revicki:Celgene: Consultancy. Roboz:Cellectis: Research Funding; Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy. Savona:TG Therapeutics: Research Funding; Takeda: Research Funding; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Sunesis: Research Funding; Ariad: Membership on an entity's Board of Directors or advisory committees. Scott:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Thompson:VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Fliss:Celgene Corporation: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Nifenecker:Celgene: Employment, Equity Ownership. Kiselev:Celgene: Employment, Equity Ownership. Sugrue:Celgene Corporation: Employment, Equity Ownership. Foucar:Celgene: Membership on an entity's Board of Directors or advisory committees; ASCP press: Other: Book royalties; Elsevier: Other: Book royalties; Lippincott WW: Other: Book royalties.

Abstract: Early progression of disease within 2 years of initial therapy independently predicts inferior survival in CLL. Early progression of disease is a robust clinical end point and a useful posttreatment risk stratification tool.

Abstract: Diagnostic and molecular genetic testing are key in advancing the treatment of acute myeloid leukemia (AML), yet little is known about testing patterns outside of clinical trials, especially in older patients. We analyzed diagnostic and molecular testing patterns over time in 565 patients aged ≥ 55 years with newly diagnosed AML enrolled in the Connect ® MDS/AML Disease Registry (NCT01688011) in the United States. Diagnostic data were recorded at enrolment and compared with published guidelines. The percentage of bone marrow blasts was reported for 82.1% of patients, and cellularity was the most commonly reported bone marrow morphological feature. Flow cytometry, karyotyping, molecular testing, and fluorescence in situ hybridization were performed in 98.8%, 95.4%, 75.9%, and 75.7% of patients, respectively. Molecular testing was done more frequently at academic than community/government sites (84.3% vs 70.2%; P  〈  .001). Enrolment to the Registry after 2016 was significantly associated with molecular testing at academic sites (odds ratio [OR] 2.59; P  = .023) and at community/government sites (OR 4.85; P  〈  .001) in logistic regression analyses. Better understanding of practice patterns may identify unmet needs and inform institutional protocols regarding the diagnosis of patients with AML.

Abstract: The presence of ring sideroblasts (RS) and mutation of the SF3B1 gene are diagnostic of lower‐risk (LR) myelodysplastic syndromes (MDS) and are correlated with favorable outcomes. However, information on testing and reporting in community‐based clinical settings is scarce. This study from the Connect ® MDS/AML Disease Registry aimed to compare the frequency of RS and SF3B1 reporting for patients with LR‐MDS, before and after publication of the 2016 World Health Organization (WHO) MDS classification criteria. Methods Ring sideroblasts assessment and molecular testing data were collected from patients with LR‐MDS at enrollment in the Registry. Patients enrolled between December 2013 and the data cutoff of March 2020 were included in this analysis. Results Among 489 patients with LR‐MDS, 434 (88.8%) underwent RS assessment; 190 were assessed prior to the 2016 WHO guidelines (Cohort A), and 244 after (Cohort B). In Cohort A, 87 (45.8%) patients had RS identified; 29 (33.3%) patients had RS  〈  15%, none of whom underwent molecular testing for SF3B1 . In Cohort B, 96 (39.3%) patients had RS identified; 31 (32.3%) patients had  〈  15% RS, with 13 undergoing molecular testing of which 10 were assessed for SF3B1 . Conclusions In the Connect ® MDS/AML Registry, only 32% of patients with 〈 15% RS underwent SF3B1 testing after the publication of the WHO 2016 classification criteria. There was no change in RS assessment frequency before and after publication, despite the potential impact on diagnostic subtyping and therapy selection, suggesting an unmet need for education to increase testing rates for SF3B1 mutations.

Abstract: 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. With a median follow-up of 46.6 months (range, 0-63.0 months), median overall survival (OS) was not reached in LOT1, 63.0 months (95% confidence interval [CI], 46.0-63.0 months) in LOT2, and 38.0 months (95% CI, 33.0-47.0 months) in LOT≥3. Bendamustine and rituximab (BR; 33.5%); fludarabine, cyclophosphamide, and rituximab (FCR; 21.4%); and rituximab monotherapy (18.5%) were the most common regimens across LOTs. Median event-free survival (EFS) was similar in patients treated with BR (59.0 months) and FCR (55.0 months) in LOT1; median OS was not reached. In multivariable analysis, BR or FCR vs other treatments in LOT1 was associated with improved EFS (hazard ratio [HR] , 0.60; P & lt; .0001) and OS (0.67; P = .0162). Using the Kaplan-Meier product limit, ibrutinib vs other treatments improved OS in LOT2 (HR, 0.279; P = .009), LOT3 (0.441; P = .011), and LOT≥4 (0.578; P = .043). Prognostic modeling of death at 2 years postenrollment identified 3 risk groups: low (mortality rate, 6.2%), medium (14.5%), and high (27.4%). The most frequent adverse events across LOTs were pneumonia (11.6%) and febrile neutropenia (6.2%). These data suggest that advantages of LOT1 FCR over BR seen in clinical trials may not translate to community practice, whereas receiving novel LOT2 agents improved outcomes. This trial was registered at www.clinicaltrials.gov as NCT01081015.

Abstract: The erythropoietic effects of lenalidomide are cytokine dependent, suggesting that the erythroid hematologic improvement (HI-E) rate may be augmented by combined treatment (CT) with recombinant human erythropoietin (rhu-EPO) in myelodysplastic syndrome (MDS). In the present study, we explored the benefits of CT and the relationship between lenalidomide pharmacokinetics and hematologic toxicity in transfusion-dependent patients with low- to intermediate-1–risk MDS who failed prior rhu-EPO. In stage I, patients received 10 or 15 mg/d of lenalidomide monotherapy. At week 16, erythroid nonresponders (NRs) were eligible for CT with rhu-EPO 40 000 U/wk. Among 39 patients, HI-E response rate to monotherapy was 86% (6 of 7) in del(5q) and 25% (8 of 32) in non-del(5q) patients (10 mg, 17.7%; 15 mg, 33.3%). Twenty-three patients proceeded to CT, with 6 (26.0%) achieving HI-E. In 19 non-del(5q) patients, 4 (21.1%) showed HI-E. Mean baseline serum EPO in non-del(5q) patients was lower in monotherapy and CT responders than in NR (not statistically significant). Thrombocytopenia was significantly correlated with lenalidomide area under the plasma concentration-time curve (P = .0015), but severity of myelosuppression did not. The benefits of lenalidomide plus rhu-EPO are currently under investigation in a phase 3 Eastern Cooperative Oncology Group (ECOG)–sponsored intergroup study. This study is registered at www.clinicaltrials.gov as NCT00910858.