Impact of Body Mass Index on the Incidence of Bortezomib-induced Peripheral Neuropathy in Patients With Newly Diagnosed Multiple Myeloma.

BACKGROUND: Peripheral neuropathy is one of the most common dose-limiting toxicities associated with bortezomib; it can lead to dose reductions or therapy discontinuation. Obesity has been identified as being a risk factor for the development of peripheral neuropathy with other neurotoxic anticancer agents. We aimed to evaluate the impact of obesity on the incidence and severity of bortezomib-induced peripheral neuropathy. PATIENTS AND METHODS: This is a retrospective, single-center study of patients treated with subcutaneous bortezomib between January 1, 2012 and June 1, 2017. Eligible patients received at least 1 full cycle of subcutaneous bortezomib and had previously untreated, newly diagnosed multiple myeloma. Patients who received intravenous bortezomib or concomitant thalidomide were excluded. Patients were divided into 3 groups based on their body mass index (BMI): normal/underweight (BMI < 25), overweight (BMI = 25-29.9), and obese (BMI ≥ 30). RESULTS: A total of 143 patients fitting the inclusion criteria were identified. Patients across the 3 groups received bortezomib at similar doses and schedules (weekly vs. biweekly). Obese patients had an increased incidence in developing bortezomib-induced peripheral neuropathy (56.4%) compared with normal/underweight (17.3%) and overweight patients (26.9%). Further analysis showed that, compared with normal/underweight and overweight patients, obesity was not found to be associated with an increased risk of grade 3 to 4 bortezomib-induced peripheral neuropathy (P = .451). CONCLUSION: Obese patients were found to be at higher risk for the development of bortezomib-induced peripheral neuropathy compared with non-obese patients.

Fostamatinib for the treatment of immune thrombocytopenia in adults.

PURPOSE: The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of fostamatinib, a novel spleen tyrosine kinase inhibitor for the treatment of adult immune thrombocytopenia that has had an insufficient response to a previous treatment are summarized. SUMMARY: Fostamatinib is an oral inhibitor of spleen tyrosine kinase that is expressed on hematopoietic cells and plays a key role in the accelerated destruction of platelets through Fc-receptor activation. Fostamatinib is indicated for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment. In 2 parallel, identically designed, placebo-controlled Phase III trials, patients with persistent and chronic immune thrombocytopenia treated with fostamatinib demonstrated clinically meaningful responses in platelet counts with lower rates of moderate and severe bleeding-related adverse events. Overall, fostamatinib therapy is generally well tolerated; the most common adverse events reported in clinical trials were diarrhea, nausea, hypertension, liver function test elevations, and infection. Being primarily metabolized through the CYP3A4 pathway, fostamatinib is subject to drug-drug interactions and concomitant administration with strong CYP3A4 inhibitors or inducers can affect fostamatinib exposure. CONCLUSION: Fostamatinib is a first-in-class spleen tyrosine kinase inhibitor approved for the treatment of adults with immune thrombocytopenia that has had an insufficient response to a previous treatment.

Metastatic Soft Tissue Sarcomas: A Review Of Treatment and New Pharmacotherapies.

Soft tissue sarcomas represent a group of heterogeneous mesenchymal tumors that occur rarely in adults. While a variety of histological subtypes exist, some of the most common are leiomyosarcoma and liposarcoma. For eligible patients, standard first-line treatment of metastatic disease has typically comprised anthracycline-containing regimens. While traditional cytotoxic chemotherapy has been the mainstay of treatment in metastatic soft tissue sarcoma, emerging targeted and novel therapies are creating new frontiers of treatment for a variety of histological subtypes. Olaratumab (Lartruvo, Eli Lilly) in combination with doxorubicin represents a new potential first-line treatment option. Second-line therapy is often histology-driven, and novel treatment options include trabectedin (Yondelis, Janssen) and eribulin (Halaven, Eisai). This review discusses the diagnosis, role of chemotherapy in unresectable and metastatic disease, and role of emerging therapies in the treatment of metastatic soft tissue sarcoma.

Pulmonary infiltrates in acute myeloid leukemia during induction treatment: how much do we know?

BACKGROUND: During induction treatment, acute myeloid leukemia patients may develop pulmonary infiltrates due to infectious or noninfectious etiologies. The risk association and the clinical outcome of such pulmonary infiltrates are poorly characterized in the literature. METHODS: We retrospectively reviewed 363 cases of acute myeloid leukemia patients who received induction therapy as inpatients over a period of 11 years at William Beaumont Health System. Of these 363 patients, 120 developed pulmonary infiltrates during induction therapy, those patients were divided into 2 groups based on distribution of the infiltrate presenting as localized or diffuse in nature. Data on patients characteristics, leukemia subtype, cytogenetic risk, microorganism type, white blood cell count at diagnosis, neutrophil count at the time the infiltrate was reported, response to antibiotic and/or antifungal therapy, using respiratory support, and mortality rate were retrieved through chart review. RESULTS: Thirty-three percent of patients developed pulmonary infiltrates during their induction therapy. Sixty-three patients (52.5%) had a localized infiltrates and 57 patients (47.5%) had diffuse infiltrates. Of the 120 patients with pulmonary infiltrates, 48 (40%) had at least 1 pathogenic microorganism identified, and 58 (48.7%) required intubation and ventilatory support. Patients with localized pulmonary infiltrates were more likely to have positive pathogenic microorganisms (68.3% vs. 8.8%, P<0.001), to be neutropenic (96.8% vs. 21%, P<0.001), and tended to have potentially reversible infiltrates after treatment (87.3% vs. 21%, P<0.001). Whereas patients with diffuse infiltrates were more like to require intubation (78.9% vs. 21%, P<0.001), to have leukocytosis (white blood cell >100 billions/L) at diagnosis (54.4% vs. 0%, P<0.001), and had a higher mortality rate (70.2% vs. 9.5%, P<0.001). CONCLUSIONS: The radiologic patterns of pulmonary infiltrates showed specific etiological and prognostic associations. Diffuse infiltrates are an unfavorable characteristic with overall dismal outcome.

How we treat tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncology emergency that occurs as a result of rapid tumor cell breakdown and the consequent release of massive amounts of intracellular contents, including potassium, phosphate, and uric acid, into the systemic circulation. These metabolic disturbances lead to life-threatening conditions and may cause sudden death if not treated. TLS commonly occurs following initiation of cytotoxic treatment in patients with high-grade lymphomas or acute lymphoblastic leukemia. Spontaneous cases involving both solid and hematologic tumors have also been reported. Rarely, TLS occurs following treatment with irradiation, corticosteroids, hormonal therapy, or biologic therapy. It is necessary to identify patients at risk for TLS early in order to initiate preventive measures. In the event that preventive measures fail, the clinical parameters and signs of TLS must be understood and recognized so that treatment can begin as soon as possible, as this condition is a significant cause of morbidity and mortality.

Venous thromboembolism in lymphoma: how effectively are we treating patients?

INTRODUCTION: Patients with solid tumors and venous thromboembolic episodes (VTE) have a high risk of recurrence and bleeding during oral anticoagulant treatment. However, we are unaware of studies expressly evaluating such risks in patients with lymphoma. Therefore, we conducted a retrospective study to determine the frequency of such complications during treatment of lymphoma patients who develop VTE. METHODS: Charts of patients with histologically proven non-Hodgkin lymphoma and Hodgkin lymphoma were retrospectively reviewed and patients with their first acute symptomatic VTE episode were identified (49 non-Hodgkin lymphoma, 8 Hodgkin lymphoma). Recurrence of VTE episodes and major and minor bleeding during treatment with warfarin or low molecular weight heparin (LMWH) were recorded. RESULTS: All 57 patients were initially treated with high-dose-adjusted intravenous heparin or body-weight-adjusted LMWH. Forty-six patients were started on oral warfarin and 11 patients continued LMWH. Recurrent VTE episodes occurred in 14 of 46 patients on warfarin therapy, whereas major bleeding was documented in 6 of 46 patients, and minor bleeding in 9 of 46 patients. Recurrent VTE episodes occurred in 1 of 11 patients treated with LMWH, whereas major bleeding occurred in 0 of 11 and minor bleeding in 3 of 11 patients. CONCLUSIONS: Lymphoma patients treated with warfarin experienced a 30.4% rate of recurrent thrombosis and 13% major bleeding. During this treatment most (65%), but not all, bleeding and thrombotic complications occurred with an international normalized ratio within the therapeutic range. The percentage of serious complications (recurrent VTE and major bleeding) during warfarin use was 44.5%, and the death rate was 6.5%, compared with 9% and 0%, respectively, during use of LMWH.

Aromatase inhibitor-related musculoskeletal symptoms: is preventing osteoporosis the key to eliminating these symptoms?

BACKGROUND: Aromatase inhibitors (AIs) are an effective treatment for postmenopausal women with hormone receptor-positive breast cancer. However, patients receiving AIs report a higher incidence of musculoskeletal symptoms and bone fractures; the mechanism and risk factors for this correlation are not well studied. The aim of this study was to correlate these musculoskeletal symptoms and bone fractures in patients receiving AIs with bone mineral density (BMD), previous tamoxifen use, and administration of calcium/bisphosphonate (Ca/Bis). PATIENTS AND METHODS: We reviewed charts of 856 patients with hormone receptor-positive nonmetastatic breast cancer seen at our institution between January 1999 and October 2007. A total of 316 patients met the inclusion criteria of treatment with one of the AIs for > or = 3 months and availability of a dualenergy X-ray absorptiometry (DEXA) during this treatment. Arthralgia, generalized bone pain and/or myalgia, bone fracture after beginning AIs, any tamoxifen treatment, and Ca/Bis therapy were recorded. RESULTS: Our study demonstrates a significant association between symptoms and DEXA-BMD results (P < .001). Similarly, the group receiving tamoxifen before AIs had fewer patients with arthralgia or generalized bone pain/myalgia or bone fracture (P < .001). Furthermore, the group receiving AIs plus Ca/Bis had more patients without musculoskeletal symptoms and had fewer fractures. Finally, the group receiving steroidal AIs compared with nonsteroidal AIs had more patients with arthralgia or generalized bone pain and/or myalgia, and bone fractures (P < .001). CONCLUSION: Patients on AIs who develop osteoporosis are at increased risk of musculoskeletal symptoms and bone fracture. Comedication with Ca/Bis reduces the likelihood for osteoporosis and musculoskeletal symptoms. Patients who received tamoxifen before AIs were less likely to develop AI-related musculoskeletal symptoms. We recommend that patients on AIs should be offered Ca/Bis to reduce the incidence of musculoskeletal symptoms and fracture, especially if patients are receiving steroidal AI and/or did not receive tamoxifen before AIs.

Venous thromboembolism in patients with monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is defined by the presence of a serum M-protein at a concentration of 3 g/dL or less, with less than 10% plasma cells in the bone marrow, and the absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the plasma cell proliferative process. The annual risk of MGUS progressing to a symptomatic plasma cell proliferation or other related malignancy is approximately 1%. The association between malignancy and venous thromboembolism (VTE) is well recognized. In this retrospective study of MGUS patients, VTE was seen in 8% (9/112) of patients, a rate that is 22.8-fold higher than that in the general population (P is less than .001). Although many studies have identified VTE as a marker for subsequent malignancy, we did not find a significant difference in the incidence of VTE as a function of the risk factor group.

Primary pleuropulmonary synovial sarcoma.

Pleuropulmonary synovial sarcoma (PPSS) is increasingly recognized as a subtype of sarcoma because of the recent identification of a distinctive chromosomal translocation specific to synovial sarcoma. Soft-tissue synovial sarcoma is far more common than PPSS and typically develops in para-articular locations of the extremities, affects young and middle-aged adults, with no difference in distribution between the sexes, and has well-documented radiologic manifestations. Pleuropulmonary synovial sarcoma can arise in the chest wall, heart, mediastinum, pleura, or lung, and it shares patient demographics and several imaging features with its soft-tissue counterpart. Patients present with a cough, chest pain, or dyspnea. On chest radiographs, PPSS typically appears as a sharply marginated mass with uniform opacity, based in the pleura or in the lung, and often accompanied by an ipsilateral pleural effusion. Computed tomographic images show a well-circumscribed, heterogeneously enhanced lesion without associated involvement of bone and without calcifications (except in the case of a chest wall primary tumor). Magnetic resonance imaging provides superior demonstration of nodular soft tissue and multilocular fluid-filled internal components of PPSS, in addition to peripheral rim enhancement after the intravenous administration of a gadoliniumbased contrast material such as gadopentetate dimeglumine. Current treatment consists of surgical resection followed by chemotherapy, radiation therapy, or both.

The utility of 18-F-fluorodeoxyglucose positron emission tomography in evaluation of bone marrow involvement by non-Hodgkin lymphoma.

PURPOSE: In non-Hodgkin lymphomas (NHLs), the bone marrow (BM) involvement is a sign of extensive disease and the iliac crest BM biopsy (BMB) is the established method for the detection of BM infiltration. However, iliac crest BMB is associated with a high rate of false negative results. We assess the ability of 18-F-fluorodeoxyglucose positron emission tomography (F-FDG PET) scan to ascertain the presence of BM involvement in NHL. METHODS: After reviewing charts of histologically proven NHLs, 97 patients were eligible for our study. All patients were examined by whole-body F-FDG PET scan for initial staging, and all had unilateral posterior iliac crest BMB. BM involvement was established after the result of unilateral posterior iliac crest BMB and image-guided BMB after positive F-FDG PET scan in selected patients. RESULTS: Our data demonstrate an overall sensitivity of 79% for the F-FDG PET scan detecting BM involvement in all patients and specificity of 91%. Further analysis revealed no significant difference in the ability of the F-FDG PET scan to detect BM involvement between the indolent-NHL and the aggressive/highly aggressive-NHL groups (sensitivity P = 0.23, specificity P = 0.64). CONCLUSION: F-FDG PET scan shows potential to detect BM involvement in NHL. In particular, image-guided repeat BMB should be considered in patients with negative initial iliac crest BMB, whose F-FDG PET scan demonstrates BM involvement in a different site.

Complete remission of metastatic carcinoma of the prostate with bicalutamide withdrawal.

An 83-year-old man was diagnosed with stage 4 prostate cancer with a Gleason score of 7 (3+4). His initial prostate-specific antigen (PSA) level was 965 ng/dL, and he demonstrated extensive metastatic disease of the thoracic spine. After an initial response to monthly leuprolide injections, his PSA level began to increase and bicalutamide was added. An initial decrease in his PSA level was observed; however, the level gradually rose to 212 ng/dL and bicalutamide was discontinued. Three months later, his PSA level was <0.05 ng/dL and has remained <1 ng/dL for the past 27 months. Bicalutamide withdrawal usually leads to transient remission, with PSA level dropping to approximately 50% of the initial level. The duration of the remission is usually limited to approximately 6 months. However, the sustained response that was observed in our patient suggests that a trial of androgen withdrawal, even in the setting of rising PSA levels, might be reasonable before initiating more toxic therapies.

Recurrent bronchial epithelial-myoepithelial carcinoma after local therapy.

We present a rare case of recurrent multiple lesions of bronchial epithelial-myoepithelial carcinoma in a 74-year-old man treated with local resection. Two cellular types were found: epithelial cells and myoepithelial cells. The patient remains asymptomatic at 4-years of follow-up, supporting the fact that epithelial-myoepithelial carcinoma is a tumor of low-grade malignancy.

Secondary myelodysplastic syndrome after hydroxychloroquine therapy.

Primary myelodysplastic syndromes (MDS) occur in the absence of exposure to ionizing radiation, chemotherapeutic agents or myelotoxic drugs, whereas secondary MDS occurs in the presence of such exposure. We encountered 4 patients among 217 patients on hydroxychloroquine for rheumatological conditions in 2005 diagnosed with MDS. Two patients were male and two were female; the median age was 69.75 years, (range 65-76). The dose of hydroxychloroquine for all patients was 400 mg daily with median treatment duration of 10.5 years and a range of 6-16. All patients had bone marrow biopsy confirmation of the diagnosis of MDS. The incidence of MDS in a group older than 70 years ranges from 15 to 50/100,000 persons per year. The diagnosis of 4 cases of MDS among 217 patients in 1 year is approximately 123-137-fold higher than the risk of MDS in the general population aged more than 70 years (P < 0.001) and suggests that long-term treatment with hydroxychloroquine is associated with an increased risk of developing secondary MDS.