Hypomethylating agents are associated with high rates of hematologic toxicity in patients with secondary myeloid neoplasms developing after acquired aplastic anemia.

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Parent Penalty: Parental Leave Experiences of Trainees and Early-Career Faculty in Oncology Subspecialties.

PURPOSE: Prime childbearing years occur during medical training and early career, leaving physicians with tough choices between family planning and career growth. Restrictive workplace parental leave (PL) policies may negatively affect physician well-being. We evaluate existing PL and lactation policies, as well as return-to-work experiences, among oncology trainees and early-career faculty. METHODS: An anonymous 43-question cross-sectional survey was distributed via e-mail and social media channels between May and June 2021 to oncology trainees and physicians within 5 years of terminal training in the United States. The survey was administered through SurveyMonkey. Descriptive statistics were used to analyze data. Two hundred seventy-five participants were recruited via social media and outreach to program directors and coordinators in adult hematology/oncology and radiation oncology program directors. RESULTS: The average duration of PL was <6 weeks for most participants. Among those who used PL, 50% felt pressured to work while on PL, 60% felt guilty asking coworkers for help, and 79% were overwhelmed with demands of work and home, whereas only 27% had resources available at workplace to assist with transition back to work. Among those who breastfed at return to work, 31% did not have access to a lactation room, 56% did not have adequate pumping breaks, and 66% did not have pumping breaks mandated in contract. CONCLUSION: Our findings underline the immense magnitude of problems surrounding inadequate PL and support for lactating mothers among trainees and early-career physicians in oncology subspecialities. Policies and practices around PL and lactation should be restructured to meet the needs of the evolving oncology workforce.

Real-world effectiveness of intensive chemotherapy with 7&3 versus venetoclax and hypomethylating agent in acute myeloid leukemia.

Intensive chemotherapy with cytarabine and anthracycline (7&3) remains the standard therapy for patients medically fit for induction, but the assessment of fitness remains controversial. Venetoclax and hypomethylating agent (ven/HMA) combination therapy has improved outcomes in unfit patients but no prospective study has assessed ven/HMA versus 7&3 as initial therapy in older, fit patients. Given no studies and expectation of ven/HMA use in patients outside of trial criteria, we evaluated retrospective outcomes among newly diagnosed patients. A nationwide electronic health record (EHR)-derived database and the University of Pennsylvania EHR identified 312 patients receiving 7&3 and 488 receiving ven/HMA who were 60-75 years old without history of organ failure. Ven/HMA patients were older and more likely to have secondary AML, adverse cytogenetics, and adverse mutations. Median overall survival (OS) for patients receiving intensive chemotherapy was 22 versus 10 months for ven/HMA (HR 0.53, 95% CI 0.40-0.60). Controlling for measured baseline characteristic imbalances reduced survival advantage by half (HR 0.71, 95% CI 0.53-0.94). A sub-group of patients with equipoise, likelihood at least 30%-70% of receiving either treatment, had similar OS outcomes (HR 1.10, 95% CI 0.75-1.6). Regarding safety outcomes, 60-day mortality was higher for ven/HMA (15% vs. 6% at 60 days) despite higher documented infections and febrile neutropenia for 7&3. In this multicenter real-word dataset, patients selected for intensive chemotherapy had superior OS but a large group had similar outcomes with ven/HMA. Prospective randomized studies, controlling for both measured and unmeasured confounders, must confirm this outcome.

Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma: a multicenter cohort study.

Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.

Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia.

CPX-351 and venetoclax and azacitidine (ven/aza) are both indicated as initial therapy for acute myeloid leukemia (AML) in older adults. In the absence of prospective randomized comparisons of these regimens, we used retrospective observational data to evaluate various outcomes for patients with newly diagnosed AML receiving either CPX-351 (n = 217) or ven/aza (n = 439). This study used both a nationwide electronic health record (EHR)-derived de-identified database and the University of Pennsylvania EHR. Our study includes 217 patients who received CPX-351 and 439 who received ven/aza. Paitents receiving ven/aza were older, more likely to be treated in the community, and more likely to have a diagnosis of de novo acute myeloid leukemia. Other baseline covariates were not statistically significantly different between the groups. Median overall survival (OS) for all patients was 12 months and did not differ based on therapy (13 months for CPX-351 vs 11 months for ven/aza; hazard ratio, 0.88; 95% confidence interval, 0.71-1.08; P = .22). OS was similar across multiple sensitivity analyses. Regarding safety outcomes, early mortality was similar (10% vs 13% at 60 days). However, documented infections were higher with CPX-351 as were rates of febrile neutropenia. Hospital length of stay, including any admission before the next cycle of therapy, was more than twice as long for CPX-351. In this large multicenter real-world dataset, there was no statistically significant difference in OS. Prospective randomized studies with careful attention to side effects, quality of life, and impact on transplant outcomes are needed in these populations.

Acute Myeloid Leukemia with t(8;16)(p11.2;p13.3)/ KAT6A-CREBBP in a Patient with an NF1 Germline Mutation and Clinical Presentation Mimicking Acute Promyelocytic Leukemia.

OBJECTIVES: Acute myeloid leukemia (AML) with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP is an uncommon subtype of AML accounting for less than 0.5% of AML cases. AML with t(8;16)/KAT6A-CREBBP has characteristic clinical and pathologic features including disseminated intravascular coagulation (DIC), leukemia cutis, hemophagocytosis, monocytic or myelomonocytic differentiation, is frequently associated with therapy-related AML and has a poor prognosis. We present a classic case of AML with t(8;16)/KAT6A-CREBBP occurring in a patient with both a germline NF1 mutation and recent cytotoxic therapy for embryonal rhabdomyosarcoma.