Multi-center retrospective study evaluating the efficacy and safety of apixaban versus warfarin for treatment of venous thromboembolism in patients with severe obesity.

STUDY OBJECTIVE: Direct oral anticoagulants are the standard of care for venous thromboembolism (VTE) treatment. These agents are recommended regardless of patient weight and body mass index (BMI). However, there remains limited evidence supporting the use of apixaban in patients with severe obesity with a BMI ≥40 kg/m2 or weight ≥120 kg. The purpose of this study was to evaluate the efficacy and safety of apixaban for VTE in patients with a BMI ≥40 kg/m2 or weight ≥120 kg. DESIGN: This multi-center, retrospective study compared the use of apixaban versus warfarin in patients with severe obesity for the treatment of VTE between January 1, 2012, and December 31, 2019. Patients were identified by diagnosis codes for acute VTE and a weight ≥120 kg or BMI ≥40 kg/m2 . The primary efficacy outcome was time to recurrence of VTE within 12 months, and the primary safety outcome was time to major bleeding within 12 months. Secondary outcomes included incidence of recurrent VTE, major bleeding, clinically relevant non-major bleeding (CRNMB), all-cause mortality, number of total hospital encounters, and switch in anticoagulant. MAIN RESULTS: A total of 1099 patients were included in the study. Of these, 314 patients received apixaban and 785 received warfarin. The mean weight and BMI were 137 kg and 46 kg/m2 , respectively. Time to recurrent VTE was significantly longer in those treated with apixaban compared to warfarin (p = 0.018). After controlling for confounding factors, apixaban use was associated with a reduced risk of recurrent VTE compared to warfarin (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.29-0.97, p = 0.04). There were no significant differences in major bleeding, CRNMB, or all-cause mortality between groups. CONCLUSION: In patients with a BMI ≥40 kg/m2 or weight ≥120 kg, apixaban appears to be effective and safe for the treatment of VTE.

Evaluation of low dose famciclovir as herpes simplex virus and varicella zoster virus prophylaxis in cytomegalovirus low-risk solid organ transplant recipients.

OBJECTIVE: Famciclovir is a recommended option for herpes simplex virus (HSV) and varicella-zoster virus (VZV) prophylaxis in cytomegalovirus (CMV) low-risk solid organ transplant (SOT) recipients in current guidelines; however there is currently no data evaluating its use in SOT recipients. We conducted a multicenter provider survey on antiviral prophylaxis in CMV low-risk SOT recipients and evaluated the efficacy and safety of once daily famciclovir antiviral prophylaxis. METHODS: Two-part analysis consisting of a national provider survey and a retrospective chart review of 78 kidney transplant recipients at a single institution. RESULTS: Providers from 45 transplant centers within the United States responded to the survey. Across all organs, acyclovir 400 mg twice daily was utilized by the majority of respondents (70.4%), with most using prophylaxis for a duration of 3 months (68.8%). No respondents reported use of famciclovir at their institution. In the retrospective review there were no documented cases of HSV/VZV/CMV infection during the 3 months of famciclovir prophylaxis, and only one patient (1.3%) later developed VZV infection at 12 months post-transplant. One patient (1.3%) required premature discontinuation of famciclovir due to concern for acute interstitial nephritis. CONCLUSION: Nationwide, the most common antiviral prophylaxis used in CMV low-risk SOT recipients is acyclovir 400 mg twice daily. Among patients receiving once daily famciclovir for CMV low-risk antiviral prophylaxis, there was no HSV/VZV/CMV infection while on prophylaxis. Once daily famciclovir may provide an effective and convenient once daily dosing regimen for antiviral prophylaxis in CMV low-risk SOT recipients.

Lenalidomide Plus Hypomethylating Agent as a Treatment Option in Acute Myeloid Leukemia With Recurrent Genetic Abnormalities-AML With inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM.

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal hematopoietic neoplasm. The cytogenetic changes associated with AML affect the response rate and survival and are one of the most important independent prognostic factors. AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM accounts for 1% to 2% of all forms of AML and has been associated with a younger age at diagnosis, a poor response to standard induction chemotherapy, and very poor long-term prognosis. PATIENTS AND METHODS: We performed a single-center, retrospective cohort study comparing the outcomes with hypomethylating agent (HMA) plus lenalidomide to those with standard intensive induction therapies for newly diagnosed and relapsed/refractory AML with inv(3). RESULTS: Of the 15 patients, 4 (26.7%) had received lenalidomide and HMA as primary therapy. The overall response rate (ORR) was 100% for the 4 patients who had received lenalidomide with HMA as first-line induction therapy. The ORR was 27.3% (3 of 11) for the patients who had received other induction regimens (P = .0256). The duration of response for first induction therapy was an average of 7.4 months after lenalidomide plus an HMA and a mean of 1.5 months after induction with other chemotherapy regimen (P = .057). The ORR for induction and reinduction therapy was also assessed, with an ORR of 21.4% (6 of 28) for alternative chemotherapy regimens and an ORR of 75% (6 of 8) for induction and reinduction with lenalidomide plus HMA (P = .0046). CONCLUSIONS: The high ORR and reasonable duration of response could allow for potentially curative allogeneic hematopoietic cell transplantation for these patients with high-risk AML. Our initial data suggest that lenalidomide plus HMA is a promising approach for patients with AML with inv(3).

The FOSSIL Study: FLAG or standard 7+3 induction therapy in secondary acute myeloid leukemia.

Patients with secondary acute myeloid leukemia (sAML) have poor outcomes, with CR/CRi rates of 25-35% with standard 7 + 3 induction chemotherapy, while single center non-comparative analyses suggest promising outcomes with FLAG. We conducted a single-center, retrospective cohort study assessing outcomes in treatment-naïve patients with sAML treated with fludarabine, high-dose cytarabine, and granulocyte colony-stimulating factor (FLAG, n = 40) compared with 7 + 3 (n = 66). Median patient age was 63 years (range: 27-82) in the FLAG group and 60 years (range: 21-76) in the 7 + 3 group (P = 0.968). Patients treated with FLAG achieved higher overall response rates (CR + CRi + MLFS) compared to 7 + 3 (70% vs. 48%, P = 0.043). FLAG was well tolerated, with only one induction death (30-day mortality rate, 3% vs. 8%, P = 0.405) and no cases of cerebellar toxicity. Duration of neutropenia was significantly shorter with FLAG (median 16 vs. 23 days, P < 0.001). Half of the FLAG-treated patients proceeded to consolidative therapy compared with only 27% of those who received 7 + 3 (P = 0.022). Overall survival was comparable between groups (8.5 mos, FLAG vs. 9.1 mos, 7 + 3; P = 0.798). Thus, FLAG may represent a low-cost treatment strategy in sAML that produces higher response rates and promising survival outcomes with minimal treatment-related toxicity. Further studies are required to prospectively compare FLAG to the newly FDA-approved CPX-351 in sAML.

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG.

The 5-year overall survival (OS) in patients ≥ 60 years old with acute myeloid leukemia (AML) remains < 10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥ 60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P = 0.045) and OS (7.9 vs. 2.8 months, P = 0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P = 0.002). Finally, we performed a cost analysis that estimated savings to be $30,000-45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.