Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC).

PURPOSE: A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse. METHODS: Patients with either MRD (≥1 log10 rise) or oligoblastic relapse (blasts 5%-15%) received venetoclax 600 mg once daily D1-28 plus LDAC once daily D1-10 in 28-day cycles. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort. RESULTS: Forty-eight adults with either MRD (n = 26) or oligoblastic (n = 22) relapse were enrolled. Median age was 67 years (range, 18-80) and 94% had received previous intensive chemotherapy. Patients received a median of four cycles of therapy; 17% completed ≥12 cycles. Patients with oligoblastic relapse had more grade ≥3 anemia (32% v 4%; P = .02) and infections (36% v 8%; P = .03), whereas grade 4 neutropenia (32 v 23%) or thrombocytopenia (27 v 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant NPM1 (77%), CBFB::MYH11 (4%), RUNX1::RUNX1T1 (4%), or KMT2A::MLLT3 (4%). Three patients with a log10 rise in IDH1/2 (12%) were included. By cycle 2 in the MRD relapse cohort, a log10 reduction in MRD was observed in 69%; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% achieved CR/CRh/CRi. Overall, 21 (44%) underwent hematopoietic cell transplantation. Median overall survival (OS) was not reached in either cohort. Estimated 2-year OS rate was 67% (95% CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts. CONCLUSION: For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.

Does Dexamethasone Reduce Hospital Readiness for Discharge, Pain, Nausea, and Early Patient Satisfaction in Hip and Knee Arthroplasty? A Randomized, Controlled Trial.

BACKGROUND: Reduction in postoperative pain, nausea, and vomiting in patients undergoing total joint arthroplasty may facilitate earlier discharge from hospital and reduce healthcare costs. This study was performed to primarily assess whether perioperative dexamethasone reduced hospital length of stay and to assess the effect on pain, nausea and vomiting, and patient satisfaction. METHODS: One hundred sixty-four patients undergoing total hip arthroplasty or total knee arthroplasty were randomized to receive either 8 mg intravenous dexamethasone (n = 86) or placebo (n = 78) at induction and at 24 hours postsurgery. The primary outcome was length of stay and secondary outcomes were pain and nausea visual analog scale scores, analgesic and antiemetic usage, blood glucose level, and patient satisfaction. RESULTS: Participants in the study group achieved earlier readiness for discharge. There was a 20% reduction in pain scores and morphine usage was 27% lower in the study group. Nausea scores were similar in the 2 groups but there was lower antiemetic usage in the study group. Satisfaction scores at 6 weeks postsurgery in the dexamethasone group were significantly higher than the placebo group. There was no difference in complication rates between the 2 groups. CONCLUSION: The administration of intravenous dexamethasone could lead to earlier readiness for discharge especially in patients undergoing elective total hip arthroplasty, primarily by a reduction in postoperative pain scores and/or morphine requirements.