A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Financial burden associated with discordance to intravenous iron therapies in US patients with iron deficiency anemia.

BACKGROUND: Iron deficiency anemia (IDA) affects approximately 5 million people in the United States and has a significant impact on human health. Intravenous (IV) iron is indicated for treatment of IDA when oral iron is not effective or not tolerated. Several IV iron products are available, including oldergeneration and newer-generation products. Newer agents have certain benefits, including the ability to administer high iron doses in fewer infusions; despite the benefits, some payors require failure on older iron products before use of newer iron products in prior authorization processes. IV iron replacement regimens requiring multiple infusions may lead to patients not receiving recommended IV iron treatment per label; potential costs of this discordance may outweigh the difference in price between the older and newer products. OBJECTIVE: To quantify the burden of discordance to IV iron therapy and associated economic consequences. METHODS: This is a retrospective study using administrative claims data between January 2016 and December 2019 from adult patients who are enrolled in a commercial insurance program with a regional health plan. A course of IV iron therapy is defined as all infusions that occur within 6 weeks of the initial infusion. Discordance to therapy is defined as having received less than 1,000 mg of iron over a course of therapy. RESULTS: There were 24,736 patients included in the study. Baseline demographics were similar between the patients who received older- vs newer-generation products and patients who were concordant vs discordant. Discordance to IV iron therapy overall was 33%. Patients who received newer-generation products were less discordant to therapy (16%) than patients who received older-generation products (55%). In general, patients who received newer-generation products had a lower total cost of care than patients who received older-generation products. CONCLUSIONS: Discordance to the older-generation products was significantly higher than that to the newer-generation products. Patients who were concordant to therapy and on a newer-generation product had the lowest total cost of care, suggesting that overall cost of care is not necessarily proportional to the purchase price of the chosen IV iron replacement therapy. Optimizing concordance to IV iron therapy may lead to lower total cost of care in the IDA population. DISCLOSURES: Magellan Rx Management received funding for this study from Pharmacosmos Therapeutics Inc. AESARA contributed to study design and data analysis. Magellan Rx Management contributed to the study design, data analysis, and interpretation of results. Pharmacosmos Therapeutics Inc. participated in the study design and interpretation of results.

Ferumoxytol for the treatment of iron deficiency and iron-deficiency anemia of pregnancy.

INTRODUCTION: A litany of recent evidence supports the morbidity of intra-natal iron-deficiency anemia and its prodrome, iron deficiency. Oral iron administered during second and third trimesters does not get to the developing fetus if the mother is iron deficient. This is especially concerning as the rapidly developing fetal brain is in particular need of iron sufficiency. Intra-natal iron deficiency is associated with autism, schizophrenia and abnormal brain structure. The obstetrical literature reports an unacceptably high incidence of gastrointestinal adverse events with oral iron. The time iron honored standard in the United States for intravenous iron replenishment in gravidas is iron sucrose. While safe and effective, four to seven visits are required to accomplish what newer formulations can achieve with one. METHODS: Ferumoxytol is a superparamagnetic iron oxide linked to polyglucose sorbitol carboxymethylether-binding elemental iron tightly allowing administration of complete replacement doses in 15-30 min. Herein, we report the results of 131 consecutive, non-selected, iron-deficient second- and third-trimester pregnant women who received either 510 mg of intravenous (IV) ferumoxytol twice or 1020 mg once. RESULTS: Hemoglobin and iron parameter increments were highly statistically significant. No adverse events were reported. We report how a single infusion is safe and effective as the same dose over two visits, saving an unnecessary visit and IV placement, while reducing cost. CONCLUSION: Ferumoxytol represents an efficacious and safe method of administration of IV iron which improves convenience for patients and practitioners, and is cost saving due to fewer visits. PLAIN LANGUAGE SUMMARY: One or two infusions of intravenous iron for iron deficiency or iron-deficiency anemia of pregnancy simplifies careThis study was conducted to highlight the inconvenience of multiple doses of IV iron and how administering the same dose in one or two infusions simplifies care. We report how a single infusion is as safe and effective as the same dose over two visits, saving an unnecessary visit and IV placement, while reducing cost. This study supports a growing body of evidence, to date, unreported, with ferumoxytol in pregnancy, reporting improved convenience and decreased costs with higher doses of IV iron in one or two visits.

Results of the First American Prospective Study of Intravenous Iron in Oral Iron-Intolerant Iron-Deficient Gravidas.

BACKGROUND: Anemia affects up to 42% of gravidas. Neonatal iron deficiency is associated with low birth weight, delayed growth and development, and increased cognitive and behavioral abnormalities. While oral iron is convenient, up to 70% report significant gastrointestinal toxicity. Intravenous iron formulations allowing replacement in one visit with favorable side-effect profiles decrease rates of anemia with improved hemoglobin responses and maternal fetal outcomes. METHODS: Seventy-four oral iron-intolerant, second- and third-trimester iron-deficient gravidas were questioned for oral iron intolerance and treated with intravenous iron. All received 1000 mg of low-molecular-weight iron dextran in 250 mL normal saline. Fifteen minutes after a test dose, the remainder was infused over the balance of 1 hour. Subjects were called at 1, 2, and 7 days to assess delayed reactions. Four weeks postinfusion or postpartum, hemoglobin levels and iron parameters were measured. Paired t test was used for hemoglobin and iron; 58/73 women were questioned about interval growth and development of their babies. RESULTS: Seventy-three of 74 enrolled subjects completed treatment. Sixty had paired pre- and posttreatment data. The mean pre- and posthemoglobin concentrations were 9.7 and 10.8 g/dL (P < .00001), transferrin saturations 11.7% and 22.6% (P = .0003), and ferritins 14.5 and 126.3 ng/mL, respectively (P < .000001). Six experienced minor infusion reactions. All resolved. Data for 58 infants were available; one was low on its growth charts for 11 months. The remaining 57 were normal. None were diagnosed with iron deficiency anemia. CONCLUSION: Intravenous iron has less toxicity and is more effective, supporting moving it closer to frontline therapy.

Safety and efficacy of rapid (1,000 mg in 1 hr) intravenous iron dextran for treatment of maternal iron deficient anemia of pregnancy.

Maternal iron deficiency anemia (IDA) is associated with risk of adverse perinatal outcomes. Oral iron is recommended to reverse anemia, but has gastrointestinal toxicity and frequent non-adherence. Intravenous (IV) iron is reserved for intolerance of, or unresponsiveness to, oral therapy, malabsorption, and severe anemia (1% with hemoglobin [Hgb] levels <7 g/dL). With rare (<100 per one million) adverse events (AEs) ability to infuse a sufficient dose of low molecular weight iron dextran (LMWID) over 60 min, LMWID is an attractive option. This study demonstrated safety and efficacy of rapid IV infusion of 1,000 mg LMWID to gravidas with moderate to severe IDA. An observational treatment study of 1,000 mg LMWID administered over 1 hr for IDA in 189 consecutive, unselected second and third trimester gravidas after oral iron failure was conducted. All received a test dose of 25 mg LMWID and were monitored for AEs during the 60-min infusion. No premedication was administered unless more than one drug allergy or asthma was present in which case IV methylprednisolone was administered. All were followed through pregnancy and delivery. Monitored parameters included Hgb, mean corpuscular volume, serum ferritin, and percent transferrin saturation. About 189 subjects received 1,000 mg LMWID. No serious AEs occurred. About 2% experienced transient infusion reactions. Hgb improved by 1-1.9 g/dL in 82% and ≥2 g/dL in 24%. Second trimester treatment was not associated with greater Hgb improvement than third trimester treatment. Anemia resolved in 95%. Administration of a single large dose of IV LMWID was effective, safe, and convenient. Am. J. Hematol. 91:590-593, 2016. © 2016 Wiley Periodicals, Inc.

A case of CLL that was successfully treated resulted in the immediate development of AML from a coexistent myeloid line that had been suppressed.

An 83 year-old Caucasian male presented to the emergency room with confusion and lethargy. A complete blood count revealed lymphocytosis, anemia, and thrombocytopenia. A bone marrow examination revealed chronic lymphocytic leukemia (CLL), along with a small population of abnormal immature myeloid cells. Chemotherapy for CLL was started. After one cycle, repeat bone marrow examination revealed normalization of the lymphocyte count and a proliferation of the previously noted myeloid population, consistent with acute myeloid leukemia (AML). This report presents the microscopic, immunophenotypic, and cytogenetic evidence to document the development of AML after one cycle of chemotherapy for CLL.

Safety and efficacy of total dose infusion of 1,020 mg of ferumoxytol administered over 15 min.

For the majority of patients with iron deficiency anemia (IDA), a full course of intravenous (IV) iron is 1 g. Most IV irons require 5-10 administrations of 100-300 mg. We have successfully employed 1 g low molecular weight iron dextran over 1 hr. For further convenience for patients and physicians, we explored the administration of 1.02 g of ferumoxytol over 15 min instead of the approved 2 × 510 mg injections. Sixty patients with IDA, (hemoglobin <11 g/dL, transferrin saturation [TSAT] ≤20%, and ferritin <100 ng/mL) with an inadequate response or intolerance to oral iron, received 1020 mg ferumoxytol over 15 min. Vital signs were measured for 1 hr. Adverse events (AEs) were collected via telephone at 1, 2, and 7 days. Follow-up visits occurred at 4 and 8 weeks for efficacy assessments. The primary endpoint was safety and tolerability. Secondary efficacy endpoints included mean change in hemoglobin, TSAT, and red cell distribution width. No serious adverse events (SAEs) occurred. Fifty-eight patients received the planned dose. Twenty-six out of sixty (43.3%) patients reported AEs of which 13 were mild and transient during infusion. All resolved within minutes. Fourteen patients reported self-limited arthralgias, myalgias, and/or headache within 24-48 hr. At Baseline, the mean hemoglobin was 9.4 g/dL. The mean increments at Week 4 and 8 were 2.1 and 2.6 g/dL, respectively. Ferumoxytol, administered as 1.02 g infusion over 15 min was well tolerated with no SAEs and demonstrated excellent efficacy. If corroborated in future studies this represents an improved method of treating IDA.

The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia.

Restless Legs Syndrome (RLS) a common, under-recognized disorder disrupts sleep and diminishes quality of life. Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficient anemic (IDA) populations is unknown. In this study all new patients referred for anemia to a community-based hematology practice over a 1-year period (March 2011-2012) were included if they had IDA and no RLS treatment. Patients completed a validated questionnaire identifying RLS, blood tests, and a sleep-vitality questionnaire (SVQ). Patients with RLS were compared to patients with no RLS for differences on SVQ, blood tests, baseline characteristics, and sleep quality. Three hundred forty-three patients were evaluated and 251 (89.2% female, average age of 45.6 years) included in the study. The prevalence of clinically significant RLS (RLS sufferers) was 23.9%, nine times higher than the general population. IDA-RLS sufferers reported poorer quality of sleep, decreased sleep time, increased tiredness, and decreased energy during the day compared to patients with IDA without RLS. Blood tests did not relate to RLS diagnosis but RLS was less likely for African-American than Caucasian patients. Clinically significant RLS occurs commonly with IDA producing much greater disruption of sleep and shorter sleep times than does IDA alone. This indicates the need for identification of RLS with IDA and consideration of appropriate therapeutic interventions for this sizeable subgroup: either aggressive iron treatment to reduce the RLS symptoms or medications for RLS or both.

Rituximab maintenance therapy until progression after rituximab and chemotherapy induction in patients with follicular lymphoma.

INTRODUCTION: The PRIMA (Primary Rituximab and Maintenance) study established 2 years of maintenance rituximab (MR) as a standard of care for follicular lymphoma (FL) patients who achieve an objective response after induction chemotherapy. A 17% improvement in progression-free survival (PFS) compared with those who did not receive MR was observed. However, the decision to stop MR after 2 years was arbitrary, and the PRIMA study reports only short-term follow-up of 3 years. Longer series on FL outcomes describe ubiquitous relapse and death following recurrence. The optimal duration of MR is under investigation. Herein, we report our experience with prolonged MR in FL. PATIENTS AND METHODS: In this retrospective analysis, the outcome of 25 consecutive, unselected, previously untreated patients with low-grade high tumor burden FL in need for treatment is described. All patients achieved a partial or complete response to induction immunochemotherapy and received ongoing MR therapy. RESULTS: With a median follow-up of 5.0 years and 5.2 years mean duration of MR, there are no relapses. Five deaths have occurred, unrelated to lymphoma or therapy. Prolonged MR treatment has been well-tolerated. Hypogammaglobulinemia is the only observed adverse event, with only one patient requiring monthly intravenous gamma globulin infusions due to recurrent pneumonia. There has been no discontinuation of MR or refusal to remain on MR. CONCLUSION: These provocative long-term results suggest that continuous MR beyond 2 years is safe and may be associated with prolonged PFS in patients with FL who achieve an objective response after immunochemotherapy.

Experience with carboplatin and etoposide maintenance chemotherapy in patients with extensive stage small cell lung cancer.

PURPOSE: To determine whether maintenance therapy with carboplatin and etoposide improves progression-free and overall survival in patients with extensive stage small cell lung cancer, compared to the standard four to six cycles of cisplatin and etoposide. METHODS: Forty-two patient records (25 males and 17 females) were retrospectively reviewed in a single community practice. All patients were over the age of 18, with pathologically and radiographically proven extensive stage small cell lung carcinoma (SCLC). The starting doses of chemotherapy were carboplatin, AUC (area under the curve) of 6 IV day 1, and etoposide, 100 mg/m2 IV days 1-3. The regimen was administered every 3 weeks and increased to every 4 to 5 weeks as tolerated or until documented progression occurred. Varying second-line chemotherapies were used. RESULTS: Median overall survival was 17 months from diagnosis, with a progression-free survival of 15 months. Seventy-nine percent of the patients survived more than 10 months. The 1- and 2-year overall survival (OAS) rates were 0.74 (31 patients) and 0.31 (13 patients), respectively. The 1- and 2-year progression free survival (PFS) rates were 0.50 (21 patients) and 0.21 (9 patients), respectively. CONCLUSION: The improved overall and progression-free survival compared to the current standard in this small single center cohort suggests that maintenance therapy with carboplatin and etoposide to progression may be a prudent area for further investigation in a properly powered randomized, controlled trial.

Rituximab-induced severe acute thrombocytopenia: a case report and review of literature.

Rituximab, an anti-CD20 monoclonal antibody, is generally a safe and well-tolerated drug. Severe acute thrombocytopenia following administration of rituximab is a rare phenomenon, with few previously reported cases in the literature. We report a case of an 84-year old male with a diagnosis of mantle cell lymphoma who suffered severe acute thrombocytopenia following rituximab infusion. A literature review of the previously published cases is also presented.

Lyme disease mimicking central nervous system lymphoma.

A 33-year-old male presented with a complaint of intermittently blurred vision and right facial weakness. MRI of the brain and orbits revealed numerous cranial nerve abnormalities. There were no focal brain or spinal cord lesions. Cerebral spinal fluid flow cytometry revealed a monoclonal population of B-lymphoid cells. No other evidence of disease was found. Serum Lyme antibody was reported to be IgM positive. Therapy with ceftriaxone, was followed by improvement in his symptoms. Although flow cytometry is a useful tool in distinguishing malignancy from inflammatory disorders it does not always establish the diagnosis of malignancy by itself.

Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial.

PURPOSE: Recombinant human erythropoietin (rHuEPO) is the standard of care for patients with chemotherapy-related anemia. Intravenous (IV) iron improves hemoglobin (Hb) response and decreases dosage requirements in patients with anemia of kidney disease, but its effect has not been studied in randomized trials in cancer patients. METHODS: This prospective, multicenter, open-label, randomized trial enrolled 157 patients with chemotherapy-related anemia (Hb