A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies.

Prognostic use of lactate to predict inpatient mortality in acute gastrointestinal hemorrhage.

BACKGROUND: Gastrointestinal hemorrhage (GIH) is a common complaint seen in the emergency department (ED) and carries a small but significant mortality rate. The principal purpose of this investigation was to determine whether an ED venous lactate as part of initial laboratory studies is predictive of mortality in patients admitted to the hospital for GIH. METHODS: Retrospective cohort study for 6 years at an urban tertiary referral hospital included all ED patients with the charted diagnosis of acute GIH. Serum lactate was drawn at the bedside as part of patient care after arrival to the ED at the discretion of the clinical team. Clinical parameters and inpatient mortality were collected from the medical record. Optimal cut points for lactate were derived using receiver operating characteristics curves and imputed into a multivariable logistic regression model. RESULTS: Of the 2834 medical records that had GIH diagnoses, 1644 had an ED lactate recorded. A lactate greater than 4 mmol/L conferred a 6.4-fold increased odds of in-hospital mortality (94% specificity, P < .001). Controlling for age, initial hematocrit, and heart rate, every 1-point increase in lactate conferred a 1.4-fold increase in the odds of mortality. CONCLUSIONS: Elevated initial lactate drawn in the ED can be associated with in-hospital mortality for ED patients with acute GIH. Prospective validation studies are warranted.

Glucarpidase (voraxaze), a carboxypeptidase enzyme for methotrexate toxicity.

Glucarpidase (Voraxaze) for methotrexate toxicity.

The Risks of Patient Pill Splitting: A Case Report and Review.

The cutting or splitting of pills can be used by patients to create an intermediate dose or to save money in situations where a higher dose is priced at relatively the same cost as a lower dose. A number of studies of selected medications have concluded that pill splitting in general can be done without adverse effects, with the exception of enteric-coated medications and extended-release medications. Individual patients should be assessed for evidence of patient understanding, as well as the physical abilities for pill splitting. Here, we present the case of a patient whose lack of understanding and inability to organize the pill-splitting process led to poor control of her hypertension, resulting in an emergency department (ED) evaluation.

Bridging advanced myeloma patients to subsequent treatments and clinical trials with classical chemotherapy and stem cell support.

Rapidly progressing relapsed/refractory multiple myeloma (RRMM) patients with compromised marrow have limited treatment options. Thus, non-myeloablative chemotherapy with a stem cell boost (SCB) may provide disease control and hematopoietic improvement as bridge to subsequent therapies. We identified 96 patients who received a SCB between January 2011 and December 2019 at the Mount Sinai Hospital. Patients had a median age of 64 years, received a median of 7 prior lines of therapy and 68 and 42% were triple-class and penta-drug refractory, respectively. Chemotherapy included melphalan (MEL) (n = 16), melphalan + carmustine (BCNU/MEL) (n = 52) or a variant of DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin) (n = 28). Median time to neutrophil recovery was 10 days and was significantly lower with DCEP (8 days) compared to MEL and BCNU/MEL (10-11 days) (p = 0.0047). Time to progression, progression-free survival and overall survival were 3.19, 2.7 and 8.38 months, respectively. The BCNU/MEL group had the highest response rate of 85% (p = 0.05), clinical benefit rate of 94% (p = 0.0014), progression-free survival of 3.3 months (p = 0.4) and overall survival of 8.7 months (p = 0.5). Sixty-six patients (69%) were bridged to new lines of therapy, including clinical trials. Non-myeloablative chemotherapy with SCB provides rapid disease control and marrow recovery with potential to receive further therapy.

A Walk in the Park: A Case of Babesiosis in the South Bronx.

Babesiosis, mainly endemic within the Northeastern and upper Midwestern regions of the United States, is a zoonotic disease that invades and lyses red blood cells, which can result in hemolytic anemia. Its decreased incidence in comparison to Lyme disease is often attributed to the greater asymptomatic infection proportion and insufficient physician awareness or suspicion of this disease. Here we describe a case of undifferentiated febrile illness with hemolytic anemia that yielded the diagnosis of babesiosis.