Prognostic significance of acquired 1q22 gain in multiple myeloma.

Gain of 1q22 at diagnosis portends poorer outcomes in multiple myeloma (MM), but the prognostic significance of acquired 1q22 gain is unknown. We identified 63 MM patients seen at Mayo Clinic from 1/2004 to 12/2019 without 1q22 gain at diagnosis who acquired it during follow up and compared them to 63 control patients who did not acquire 1q22 gain with similar follow up. We also compared outcomes in the acquired 1q22 gain group with outcomes in 126 patients with 1q22 gain present at diagnosis. The incidence of acquired 1q22 gain was 6.1% (median follow-up 6.8 years); median time to acquisition was 5.0 years (range: 0.7-11.5 years). Abnormalities on baseline fluorescence in situ hybridization (FISH) included trisomies (54%) and monosomy 13 (39%); 16 (25%) had high-risk (HR) translocations or del(17p). Median progression-free survival with front line therapy was 29.5 months in patients with acquired 1q22 gain, versus 31.4 months in control patients (p = .34) and 31.2 months in patients with de novo 1q22 gain (p = .04). Median overall survival (OS) from diagnosis was 10.9 years in patients with acquired 1q22 gain, versus 13.0 years in control patients (p = .03) and 6.3 years in patients with de novo 1q22 gain (p = .01). Presence of HR FISH at baseline increased risk of 1q22 gain acquisition. We demonstrate that acquisition of 1q22 gain is a significant molecular event in MM, associated with reduced OS. Among HR patients for whom this clonal evolution is determined, a risk-adapted approach and/or clinical trial should be considered.

Richter Transformation of Chronic Lymphocytic Leukemia-Are We Making Progress?

PURPOSE OF REVIEW: The treatment paradigm of chronic lymphocytic leukemia (CLL) has dramatically changed with the advent of novel targeted agents over the past decade. Richter transformation (RT), or the development of an aggressive lymphoma from a background of CLL, is a well-recognized complication of CLL and carries significantly poor clinical outcomes. Here, we provide an update on current diagnostics, prognostication, and contemporary treatment of RT. RECENT FINDINGS: Several genetic, biologic, and laboratory markers have been proposed as candidate risk factors for the development of RT. Although a diagnosis of RT is typically suspected based on clinical and laboratory findings, tissue biopsy is essential for histopathologic confirmation of diagnosis. The standard of care for RT treatment at this time remains chemoimmunotherapy with the goal of proceeding to allogeneic stem cell transplantation in eligible patients. Several newer treatment modalities are being studied for use in the management of RT, including small molecules, immunotherapy, bispecific antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy. The management of patients with RT remains a challenge. Ongoing trials show enormous promise for newer classes of therapy in RT, with the hope being that these agents can synergize, and perhaps supersede, the current standard of care in the near future.

Efficacy, Safety, and Usability of Remifentanil as Premedication for INSURE in Preterm Neonates.

Background: We previously reported a 67% extubation failure with INSURE (Intubation, Surfactant, Extubation) using morphine as analgosedative premedication. Remifentanil, a rapid- and short-acting narcotic, might be ideal for INSURE, but efficacy and safety data for this indication are limited. Objectives: To assess whether remifentanil premedication increases extubation success rates compared with morphine, and to evaluate remifentanil's safety and usability in a teaching hospital context. Methods: Retrospective review of remifentanil orders for premedication, at a large teaching hospital neonatal intensive care unit (NICU). We compared INSURE failure rates (needing invasive ventilation after INSURE) with prior morphine-associated rates. Additionally, we surveyed NICU staff to identify usability and logistic issues with remifentanil. Results: 73 remifentanil doses were administered to 62 neonates (mean 31.6 ± 3.8 weeks' gestation). Extubation was successful in 88%, vs. 33% with morphine premedication (p < 0.001). Significant adverse events included chest wall rigidity (4%), one case of cardiopulmonary resuscitation (CPR) post-surfactant, naloxone reversal (5%), and notable transient desaturation (34%). Among 137 completed surveys, 57% indicated concerns, including delayed drug availability (median 1.1 h after order), rapid desaturations narrowing intubation timeframes and hindering trainee involvement, and difficulty with bag-mask ventilation after unsuccessful intubation attempts. Accordingly, 33% of ultimate intubators were attending neonatologists, versus 16% trainees. Conclusions: Remifentanil premedication was superior to morphine in allowing successful extubation, despite occasional chest wall rigidity and unfavorable conditions for trainees. We recommend direct supervision and INSURE protocols aimed at ensuring rapid intubation.