Hedy Smith

Efficacy and safety of OBI‐1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A

Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI‐1 is an investigational, B‐domain deleted, recombinant FVIII, porcine sequence, with low cross‐reactivity to anti‐hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI‐1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg−1, OBI‐1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI‐1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti‐porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI‐1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI‐1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients.

Managing a pregnant patient with paroxysmal nocturnal hemoglobinuria in the era of eculizumab

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal stem cell disorder, which affects women of child-bearing age. PNH is associated with thrombotic complications, which are the main causes of morbidity and mortality. Management of a pregnant woman with PNH remains a challenge due to high incidence of thrombotic complications and the difficulty of differentiating a PNH crisis from the complications of pregnancy. PNH is associated with an increased rate of premature labor and fetal loss. Eculizumab, a humanized monoclonal antibody directed against the terminal complement protein C5, has revolutionized treatment of PNH. However, the role of eculizumab in pregnancy is unclear. We review the current strategies for the management of pregnant women with PNH, underline the controversies and present our recommendations.

Cost-Effectiveness of Autologous Hematopoietic Stem Cell Transplantation for Elderly Patients with Multiple Myeloma using the Surveillance, Epidemiology, and End Results–Medicare Database

In the past decade, the number of autologous hematopoietic stem cell transplants (Auto HSCT) for older patients with multiple myeloma (MM) has increased dramatically, as has the cost of transplantation. The cost-effectiveness of this modality in patients over age 65 is unclear. Using the Surveillance, Epidemiology, and End Results-Medicare database to create a propensity-score matched sample of patients over age 65 between 2000 and 2007, we compared the survival and cost for those who received Auto HSCT to those who did not undergo transplantation but survived at least 6 months after diagnosis, and we calculated an incremental cost-effectiveness ratio (ICER). Two hundred seventy patients underwent transplantation. Median overall survival from diagnosis in those who underwent transplantation was significantly longer than in patients who did not (58 months versus 37 months, P < .001). For patients living longer than 2 years, the median monthly cost during the first year was significantly different, but the middle and last year of life costs were similar. The median cost of the first 100 days after transplantation was

Bortezomib Subcutaneous Injection in Combination Regimens for Myeloma or Systemic Light-Chain Amyloidosis: A Retrospective Chart Review of Response Rates and Toxicity in Newly Diagnosed Patients

60,000 (range,

Mitomycin-C-Induced TTP/HUS Treated Successfully with Rituximab: Case Report and Review of the Literature

37,000 to

Myelodysplastic Syndrome and Autoimmunity: A Case Report of an Unusual Presentation of Myelodysplastic Syndrome

85,000). The resultant ICER was

Sickle cell disease due to compound heterozygosity for Hb S and a novel 7.7-kb β-globin gene deletion

72,852 per life-year gained. Survival after transplantation was comparable to that in those who underwent transplantation patients under 65 years and significantly longer than older patients who did not undergo transplantation. With an ICER less than

CHOP Chemotherapy Followed by Tositumomab and Iodine-131 Tositumomab for Previously Untreated Diffuse Large B-cell Lymphoma

100,000/life-year gained, Auto HSCT is cost-effective when compared with nontransplantation care in the era of novel agents and should be considered, where clinically indicated, for patients over the age of 65.

Cost Implications of Comorbidity for Autologous Stem Cell Transplantation in Elderly Patients with Multiple Myeloma Using SEER-Medicare

BACKGROUND Bortezomib is a first-in-class proteasome inhibitor approved by the US Food and Drug Administration for the treatment of all phases of multiple myeloma (MM) and it is also used for the treatment of [corrected] light-chain amyloidosis (AL). The subcutaneous formulation of bortezomib was approved in 2012 based on data from Phase III studies in patients with relapsed MM. OBJECTIVE This article reports experience with subcutaneous bortezomib in patients with newly diagnosed MM or AL in a tertiary care center. METHODS This retrospective study analyzed data from all patients newly diagnosed with MM or AL and treated at our center between April 1, 2011, when the hospital pharmacy approved and implemented the option of subcutaneous bortezomib, and April 1, 2013. Patients who received subcutaneous bortezomib as a part of the first line of therapy were identified through the pharmacys database. Data were abstracted from electronic medical records, and data on demographic characteristics, disease profiles, toxicities, responses, and survival were collected. RESULTS Data from 29 patients (MM, 16; AL, 13; 62% male; median age, 66 years [range, 46-84]) were analyzed. Ninety percent of patients received cyclophosphamide, bortezomib, and dexamethasone (CyBorD) as the first line of treatment. None of the patients developed grade 3/4 peripheral neuropathy, whereas 1 patient experienced grade 3 diarrhea, and 2 patients developed grade 3 thrombocytopenia requiring dose reductions. The overall response rate was 93%, with 59% of patients achieving very good partial response or complete response. CONCLUSIONS With the use of subcutaneous bortezomib in combination regimens in patients with newly diagnosed MM or AL, there was a high overall response rate and minimal toxicity. These results are consistent with the findings from prior studies and provide a basis for further studies comparing new proteasome inhibitors to subcutaneous bortezomib in combination regimens for patients with newly diagnosed MM or AL.

Acquired von Willebrand Syndrome with a Type 2B Phenotype: Diagnostic and Therapeutic Dilemmas

Microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, renal failure, and neurologic symptoms comprise the cardinal features of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Etiologies can include medications, infections, cancers, or transplantation. We present a patient with a history of rectal cancer treated with mitomycin-C who developed MAHA, acute kidney injury, and thrombocytopenia 6 months after completing therapy and to did not respond the plasmapheresis or steroids. She was treated with four weekly doses of rituximab with full recovery.