Impact of pretransplant minimal residual disease in patients with multiple myeloma and a very good partial response or better receiving autologous hematopoietic stem cell transplantation.

BACKGROUND: The prognostic significance of minimal residual disease (MRD) status before autologous hematopoietic stem cell transplantation (autoHCT) in patients with multiple myeloma (MM) has not been clearly elucidated. METHODS: Retrospective single-center study of adult MM patients who achieved ≥very good partial response (VGPR) after induction therapy from 2015 to 2021 received upfront autoHCT and had available pretransplant MRD status by next-generation flow cytometry. The cohort was divided into pretransplant MRD-negative (MRDneg) and MRD-positive (MRDpos) groups. RESULTS: A total of 733 patients were included in our analysis; 425 were MRDneg and 308 MRDpos at autoHCT. In the MRDpos group, more patients had high-risk cytogenetic abnormalities (48% vs. 38%, respectively; p = .025), whereas fewer patients achieved ≥CR before autoHCT (14% vs. 40%; p < .001). At day 100 after autoHCT, 37% of the MRDpos versus 71% of the MRDneg achieved ≥CR, and at best posttransplant response 65% versus 88% achieved ≥CR, respectively. After a median follow-up of 27.6 months (range, 0.7-82.3), the median PFS was significantly shorter for patients in the MRDpos group compared to the MRDneg group: 48.2 months (95% confidence interval [CI], 0.3-80.5) versus 80.1 months (95% CI, 0.5-80.1), respectively (p < .001). There was no significant difference in overall survival between the two groups (p = .41). Pretransplant MRDpos status was predictive of shorter PFS in multivariate analysis (hazard ratio, 1.80; 95% CI, 1.31-2.46; p < .001). The impact of pretransplant MRD status was retained in most of the examined subgroups. CONCLUSIONS: In patients achieving ≥VGPR to induction, pretransplant MRDpos status was associated with a lower CR rate after autoHCT and a shorter PFS.

Real-World Immune-Related Adverse Events in Patients With Early Triple-Negative Breast Cancer Who Received Pembrolizumab.

PURPOSE: The addition of pembrolizumab to chemotherapy in high-risk early triple-negative breast cancer (TNBC) improves cancer outcomes. However, pembrolizumab induces varied immune-related adverse events (irAEs) where some can be severe or lifelong. This retrospective study describes real-world patterns of irAEs in patients with TNBC who received pembrolizumab. METHODS: We evaluated irAEs in patients with TNBC from a comprehensive cancer center and a community hospital who received pembrolizumab with chemotherapy between 2021 and 2023, excluding those enrolled in clinical trials. We used national guidelines to grade toxicities. Logistic regression assessed the effect of clinicopathologic variables on irAEs adjusting for covariates. RESULTS: We identified 233 patients with a median age of 51 years, 62% had stage II TNBC, 35% had stage III TNBC, 25% were Hispanic, 21% were Black, and 42% were White. Eighty patients (34%) developed 100 separate irAEs. The most common irAEs were endocrinopathies (52%) and GI (23%); there were 26 grade ≥3 irAEs, which all resulted in hospitalization, the most common being GI (13 instances); 45 required systemic steroids, 16 required additional immunosuppressive therapy, and 32 patients discontinued pembrolizumab because of irAEs. Two patients who developed colitis eventually died due to complications. Most (67 instances) irAEs were unresolved at the time of last follow-up, but 55% (37/67) had improved to grade 1. No clinicopathologic factors were associated with the development or severity of irAEs. CONCLUSION: In this real-world diverse population, we observed rates of irAEs comparable with KEYNOTE-522, where endocrinopathies were the most prevalent, but GI irAEs were also prevalent and severe. This emphasizes a critical issue as pembrolizumab is increasingly being used in early TNBC and could have long-term survivorship implications.

Investigating the diagnostic capacity of uric acid in the occurrence of preeclampsia.

OBJECTIVES: To compare the distribution of uric acid (UA) concentration in women with normal and preeclamptic pregnancy, to investigate the significance of UA concentration in diagnosis of preeclampsia, and to estimate the UA rate of change over time before delivery. STUDY DESIGN: A case-control study of singleton pregnancies was completed at a tertiary care center in Kingston, Ontario. Patients with preeclampsia were recruited through two prospective cohort studies (n = 218); the Preeclampsia New Emerging Team (September 2003-October 2009) and the Maternal Health Clinic (May 2011-June 2016). Individuals who had an uncomplicated pregnancy and delivered (July 2016-August 2017), were included in the control arm (n = 73). MAIN OUTCOME MEASURES: Longitudinal analysis using a linear mixed-effects model examined the UA rate of change over time. The distribution of the UA level was compared using a t-test. The significance of the UA level in the diagnosis of preeclampsia was examined using multiple logistic regression. RESULTS: The rate of change in UA before delivery had an increasing non-constant logarithmic trend with time. Mean UA level in preeclamptic pregnancies (369.53 ± 75.78 µmol/l) was significantly elevated compared with the normal pregnancies (292.55 ± 54.73 µmol/l). UA had an adjusted odds ratio of 1.39 (95%CI: 1.14-1.69; P = 0.001) associated with the incidence of preeclampsia and UA level >349 µmol/l close to delivery is an accurate measurement for diagnosing preeclampsia. CONCLUSION: The UA concentration in preeclamptic pregnancies is significantly increased compared to normal pregnancies and the level of UA may have diagnostic ability in the occurrence of preeclampsia.