In PACE, a phase 2 trial of ponatinib that included patients with chronic phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit:risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel response-based dose-reduction strategy for a TKI in CP-CML. Adults with CP-CML resistant/intolerant to at least 2 prior BCR-ABL1 TKIs, or with a BCR-ABL1 T315I mutation, were randomized 1:1:1 to ponatinib 45mg (45mg cohort), 30mg (30mg cohort), or 15mg (15mg cohort) once daily. Patients who received 45 or 30mg daily reduced their dose to 15mg upon achievement of response (BCR-ABL1IS transcript levels ≤1%). The primary end point was response at 12 months. Between August 2015 and May 2019, 283 patients were randomized; 282 (94/group) received treatment (data cutoff, 5/31/20). The primary end point (98.3% confidence interval) was achieved in 44.1% (31.7-57.0) in the 45mg cohort, 29.0% (18.4-41.6) in the 30mg cohort, and 23.1% (13.4-35.3) in the 15mg cohort. Independently confirmed grade 3/4 treatment-emergent AOEs occurred in 5, 5, and 3 patients in the 45, 30, and 15mg cohorts, respectively. All cohorts showed benefit in this highly resistant CP-CML population. Optimal benefit:risk outcomes occurred with the 45mg starting dose reducing to 15mg upon achievement of response (ClinicalTrials.gov number, NCT02467270).

Highlights d High rate of NF1 loss in the R0 compared to neoadjuvant chemotherapy (NACT) group d Lower chromothripsis-like pattern and higher neoantigens in the R0 versus NACT group d Increased number of infiltrated T cells and decreased macrophages in the R0 group d Significant transcriptomic and proteomic variations between HGSC subgroups

The 2010 Centers for Disease Control and Prevention (CDC) report indicates that 63.4% of Delaware’s adult population is overweight and 28% is obese. Here, the authors reveal analyses acquired from detailed investigations about the importance of gender, and other lifestyle factors and behaviors on the Body Mass Index (BMI) trends amongst an indiscriminate sample of the Wesley College (Wesley) undergraduate population. A 25-question paper-format survey was distributed to 307 randomly chosen Wesley undergraduates. The accrued qualitative (or categorical) data were transferred to an Excel spreadsheet to construct and observe frequency distributions. A Chi-square test of independence (χ2) was performed between BMI status (normal, overweight, obese) and the following factors: gender, diet plan, adherence to the United States Department of Agriculture (USDA) MyPlate nutrition guide, use of the seasonal flu shot, weekly workout schedule, supplement usage, participation on athletic teams, questioning of label nutritional facts, and the use of added salt in food. A 2-sample proportion test was performed between students who were overweight or obese for the same factors. Also performed were t-tests for mean BMI for those who followed USDA MyPlate guidelines and for those who did not. An analysis of 278 completed surveys show that 29.5% of the Wesley respondents are overweight and 19.8% are obese. The mean BMI for males was statistically higher than the mean BMI for females. The mean BMI for students living on-campus was statistically higher than the mean BMI for students living off-campus. The results also demonstrate that adhering to the USDA dietary recommendations for fruit and dairy can be important factors in reducing the risk of obesity.

7502 Background: In PACE (NCT01207440) heavily pretreated patients (pts) with chronic-phase CML (CP-CML) had deep, lasting responses to PON; long-term follow-up showed increasing rates of arterial occlusive events (AOEs). We present IA results from OPTIC (NCT02467270), evaluating the association between PON exposure, efficacy, and safety, and response-based dose reduction in pts with CP-CML. Methods: This ongoing, multicenter, randomized phase 2 trial enrolled pts with CP-CML resistant or intolerant to ≥2 TKIs or with a T315I mutation to receive PON at a starting dose of 45 mg (cohort A), 30 mg (B), and 15 mg (C) qd. Doses were reduced to 15 mg qd on achievement of ≤1% BCR-ABL1IS in A/B. Primary endpoint: 12 mo ≤1% BCR-ABL1IS; secondary endpoints include cytogenetic and molecular response and AOE, VTE, and TEAE rates. Results are descriptive at this IA and will be inferential by adjusting multiplicity across 3 cohorts at final analysis. Results: 283 pts were randomized (A/B/C: n = 94/95/94); median age 48 y (18‒81 y). 26% had hypertension history; 2/43/55% received 1/2/≥3 TKIs; 40% had ≥1 baseline (BL) mutations, with 23% T315I. At IA data cutoff (20 Jul 2019), 162 pts (57%; n = 57/51/54) remained on study treatment. Among 282 pts in the safety population, median duration of exposure was ≈1 y (A/B/C, 12.9/11.2/11.0 mo). At 12 mo, 39% (95% CI, 27.6, 50.6), 27% (17.6, 39.1), and 26% (16.5, 38.6) in A, B, and C, respectively, achieved ≤1% BCR-ABL1IS. Additional efficacy in Table. Dose reductions due to efficacy (A/B): 35/21%. Most common TEAEs (any grade/≥3): thrombocytopenia 39/27%, neutropenia 25/17%. AOEs/serious AOEs were reported by (A, B, C) 5%/2%, 4%/3%, and 1%/0%. Dose reductions due to TEAEs: (A/B/C): 44/31/28%; discontinuations due to TEAEs: 18/15/14%. There were 4 (1.4%) on-study deaths; A, sudden death, n = 2; C, pneumonia, n = 2; no deaths were due to AOEs. Clinical trial information: NCT01207440 . Conclusions: OPTIC IA shows a trend toward dose-dependent efficacy and safety and may provide a refined understanding of the PON benefit:risk profile and its relation to dose. Data from longer follow-up may support an alternate dosing regimen for pts with CP-CML. [Table: see text]

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HighlightsLMD was used to investigate 3-D molecular heterogeneity in ovarian cancer tissue Diverse molecular profiles were identified from 3-D spatially separated samples Molecular heterogeneity impacts HGSOC prognostic sub-type assignment Proteomic heterogeneity analysis web portal deployed at www. lmdomics.org

Measurable residual disease (MRD) evaluation may help to guide treatment duration in multiple myeloma (MM). Paradoxically, limited longitudinal data exist on MRD during maintenance. We investigated the prognostic value of MRD dynamics in 1280 transplant-eligible and -ineligible patients from the TOURMALINE-MM3 and -MM4 randomized, placebo-controlled, phase 3 studies of 2-year ixazomib maintenance. MRD status at randomization showed independent prognostic value (median progression-free survival [PFS]: 38.6 vs 15.6 months in MRD- vs MRD+ patients, HR 0.47). However, MRD dynamics during maintenance provided more detailed risk stratification. A 14-month landmark analysis showed prolonged PFS in patients converting from MRD+ to MRD- status vs those with persistent MRD+ status (76.8% vs 27.6% 2-year PFS rates). Prolonged PFS was observed in patients with sustained MRD- status vs those converting from MRD- to MRD+ status (75.0% vs 34.2% 2-year PFS rates). Similar results were observed at a 28-month landmark analysis. Ixazomib maintenance vs placebo improved PFS in patients who were MRD+ at randomization (median 18.8 vs 11.6 months, HR 0.65) or at the 14-month landmark (median 16.8 vs 10.6 months, HR 0.65); no difference was observed in patients who were MRD-. This is the largest MM population undergoing yearly MRD evaluation during maintenance reported to date. We demonstrate the limited prognostic value of a single timepoint MRD evaluation, because MRD dynamics over time substantially impact PFS risk. These findings support MRD- status as a relevant endpoint during maintenance and confirm the increased progression risk in patients converting to MRD+ from MRD- status.

En diciembre de 2019 se detectó por primera vez en China la existencia del SARS-CoV2, causante de la enfermedad COVID-19. El virus rápidamente se propagó por Europa y Asia, tardándose un par de meses antes de llegar a América Latina. Se ha demostrado que los pacientes que desarrollan una enfermedad severa y que tienen mayor riesgo de mortalidad por COVID-19 son aquellos con edades avanzadas y que presentan por lo menos una enfermedad crónica, incluyendo el cáncer. Debido a lo anterior, surgen muchas dudas en el grupo de profesionales encargados de brindar tratamiento a pacientes con cáncer durante la pandemia, pues se debe equilibrar el riesgo-beneficio de proveer tratamiento a pacientes que se encuentran de base con un riesgo incrementado para tener manifestaciones severas por COVID-19. En este consenso planteamos recomendaciones para los profesionales en hematología que brindan tratamiento a pacientes que padecen de algún tipo de linfoma, con el fin de aclarar el panorama clínico durante la pandemia.