Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer.

BACKGROUND: Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan is an antibody-drug conjugate composed of an antibody targeting the human trophoblast cell-surface antigen 2 (Trop-2), which is expressed in the majority of breast cancers, coupled to SN-38 (topoisomerase I inhibitor) through a proprietary hydrolyzable linker. METHODS: In this randomized, phase 3 trial, we evaluated sacituzumab govitecan as compared with single-agent chemotherapy of the physician's choice (eribulin, vinorelbine, capecitabine, or gemcitabine) in patients with relapsed or refractory metastatic triple-negative breast cancer. The primary end point was progression-free survival (as determined by blinded independent central review) among patients without brain metastases. RESULTS: A total of 468 patients without brain metastases were randomly assigned to receive sacituzumab govitecan (235 patients) or chemotherapy (233 patients). The median age was 54 years; all the patients had previous use of taxanes. The median progression-free survival was 5.6 months (95% confidence interval [CI], 4.3 to 6.3; 166 events) with sacituzumab govitecan and 1.7 months (95% CI, 1.5 to 2.6; 150 events) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32 to 0.52; P<0.001). The median overall survival was 12.1 months (95% CI, 10.7 to 14.0) with sacituzumab govitecan and 6.7 months (95% CI, 5.8 to 7.7) with chemotherapy (hazard ratio for death, 0.48; 95% CI, 0.38 to 0.59; P<0.001). The percentage of patients with an objective response was 35% with sacituzumab govitecan and 5% with chemotherapy. The incidences of key treatment-related adverse events of grade 3 or higher were neutropenia (51% with sacituzumab govitecan and 33% with chemotherapy), leukopenia (10% and 5%), diarrhea (10% and <1%), anemia (8% and 5%), and febrile neutropenia (6% and 2%). There were three deaths owing to adverse events in each group; no deaths were considered to be related to sacituzumab govitecan treatment. CONCLUSIONS: Progression-free and overall survival were significantly longer with sacituzumab govitecan than with single-agent chemotherapy among patients with metastatic triple-negative breast cancer. Myelosuppression and diarrhea were more frequent with sacituzumab govitecan. (Funded by Immunomedics; ASCENT ClinicalTrials.gov number, NCT02574455; EudraCT number, 2017-003019-21.).

Actigraphy measures show sleep improvement after parathyroidectomy for primary hyperparathyroidism.

IMPORTANCE: The symptoms of primary hyperparathyroidism are often subtle, such as fatigue, mood changes, and sleep disturbances. After parathyroidectomy, patients often report improvement in sleep and mood; however, objective data supporting these improvements is lacking. OBJECTIVE: This prospective study uses standard measures to objectively and subjectively assess sleep in patients with primary hyperparathyroidism before and after parathyroidectomy. DESIGN: A longitudinal prospective study was conducted over three one-week-long periods: pre-parathyroidectomy, 1-week post-parathyroidectomy, and three months post-parathyroidectomy. During each time point, patients wore an actigraphy device, recorded a sleep diary, and completed the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Depression Anxiety Stress Scale (DASS). Statistical analysis was performed using repeated measures models to compare the average measures among the three time points and test for trends over time. SETTING: Single institution, tertiary care center. PARTICIPANTS: Patients with primary hyperparathyroidism from ages 18 to 89 years old. EXPOSURE: Parathyroidectomy between September 2020 and January 2024. MAIN OUTCOMES AND MEASURES: Actigraphy data, consensus sleep diary, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Depression Anxiety Stress Scales - 21 Items (DASS). RESULTS: Thirty-six patients were enrolled, and 34 patients completed the study. Actigraphy data showed a significant negative trend in average sleep latency (p = 0.045) and average time in bed (p = 0.046). Sleep diary data showed additional differences in the number of awakenings (p = 0.002), wake after sleep onset (p < 0.001), sleep quality (p < 0.001), and sleep efficiency (p = 0.02) among the three time points and/or as a significant negative trend. PSQI and ISI scores were significantly different among the three time points (p = 0.002 and p < 0.001, respectively) and also declined significantly over time (p = 0.008 and p = 0.007, respectively). DASS depression, anxiety, and stress scores were significantly different among the three time points (p < 0.001, p = 0.01, and p < 0.001, respectively), and stress also declined significantly over time (p = 0.005). CONCLUSION AND RELEVANCE: This study represents the most extensive prospective study demonstrating objective and subjective sleep and mood improvement in patients with primary hyperparathyroidism after parathyroidectomy.

Delivery of Fecal Material to Terminal Ileum Is Associated with Long-Term Success of Fecal Microbiota Transplantation.

BACKGROUND: Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI). However, 10-20% of patients still fail to recover following FMT. There is a need to understand why these failures occur and if there are modifiable factors that can be addressed by clinicians performing FMT. AIMS: We sought to identify factors related to the FMT procedure itself which could impact FMT outcomes. We also aimed to identify patient demographics which might be associated with FMT outcomes and whether any factors were associated with early FMT failure compared to late CDI recurrence. METHODS: We performed a retrospective multicenter cohort analysis of FMT procedures between October 2005 and November 2020. We collected data on patient demographics, details of the FMT procedure, and procedure outcomes. Using univariate and multivariate regression, we evaluated whether these factors were associated with long-term FMT success, early FMT failure (less than 60 days following procedure), or late CDI recurrence (more than 60 days following procedure). RESULTS: Long-term success of FMT was strongly correlated with any delivery of stool to the terminal ileum (Odds Ratio [OR] 4.83, 95% confidence interval [CI] 1.359-17.167) and underlying neurologic disease (OR 8.012, 95% CI 1.041-61.684). Lower bowel prep quality was significantly associated with both early FMT failure (p = 0.034) and late CDI recurrence (p = 0.050). CONCLUSIONS: Delivery of stool to the terminal ileum is significantly associated with long-term success following FMT. This is a relatively safe practice which could easily be incorporated into the standard of care for colonoscopic FMT.

Opioid versus non-opioid postoperative pain management in otolaryngology.

BACKGROUND: The opioid epidemic in the United States has had devastating consequences, with many opioid-related deaths and a significant economic toll. Opioids have a significant role in postoperative pain management. Here we aim to analyze differences in postoperative opioid and non-opioid pain medications regimens following common otolaryngological surgeries between two large tertiary care medical centers: the Milton S. Hershey Medical Center, USA (HMC) and The Chaim Sheba Medical center, Israel (SMC). METHODS: A retrospective chart review of patients undergoing common otolaryngological procedures during the years 2017-2019 was conducted at two tertiary care centers, one in the U.S. and the other in Israel. Types and doses of postoperative pain medications ordered and administered during admission were analyzed. Average doses ordered and administered in 24 h were calculated. Opioid medications were converted to a standardized unit of morphine milliequivalents (MME). Chi-square test and Wilcoxon rank-sum test were used to compare the groups. RESULTS: The study included 204 patients (103 U.S., 101 Israel). Patient demographics were similar except for a longer length of stay in Israel (p < 0.01). In the U.S., 95% of patients were ordered opioids compared to 70% in Israel (P < 0.01). In the U.S., 68.9% of patients ordered opioids received the medications compared to 29.7% in Israel. The median opioid dose ordered in the U.S. was 45MME/24 h compared to 30MME/24 h in Israel (P < 0.01), while median dose received in the U.S. was 15MME/24 h compared to 3.8MME/24 h in Israel (P < 0.01). Opioid prescriptions at discharge were given to 92% of patients in the U.S. compared to 4% of patients in Israel (p < 0.01). A significantly higher number of patients in the U.S. were prescribed acetaminophen and ibuprofen (p < 0.0001). Dipyrone was prescribed to 78% of patients in Israel. CONCLUSIONS: HMC demonstrated a significantly more permissive approach to both prescribing and consuming opioid medications for postoperative pain management than SMC for similar, common otolaryngological surgeries. Non-opioid alternatives and examining the cultural and medical practice-based differences contributing to the opioid epidemic should be discussed and reevaluated.

Hypocalcemia after parathyroidectomy in patients taking proton pump inhibitors.

PURPOSE: Long-term use of proton pump inhibitors is associated with metabolic derangements, including hypocalcemia. Hypocalcemia is also a known complication of parathyroidectomy. We sought to determine the rate of hypocalcemia following parathyroidectomy in patients on proton pump inhibitors. MATERIALS AND METHODS: The TriNetX Research Network was queried to identify patients with a history of primary hyperparathyroidism treated with parathyroidectomy between 2012 and 2022. The incidence of short-term (0-6 months following parathyroidectomy) and permanent (6-12 months following parathyroidectomy) postoperative hypocalcemia was compared between patients using proton pump inhibitors and those who were not. RESULTS: Of 34,595 total patients, 19.5 % (n = 6753) were taking proton pump inhibitors prior to surgery. Patients taking proton pump inhibitors were significantly more likely to experience both short-term (RR, 95 % CI, P) (1.5, 1.4-1.6, P < 0.001) and permanent (1.8, 1.6-2.1, P < 0.001) hypocalcemia, and were also more likely to be evaluated in the emergency department after surgery (1.5, 1.4-1.7, P < 0.001). CONCLUSIONS: Our study is the first to indicate an increased risk of hypocalcemia after parathyroidectomy in patients on proton pump inhibitors.

Management of compression symptoms of thyroid goiters: Hemithyroidectomy is equally as successful as total thyroidectomy.

PURPOSE: Patients with thyroid goiters and compressive symptoms are treated with surgery. The adequate extent of this surgery for these cases remains unclear. In the current study, we analyze the effect of surgery, total thyroidectomy versus hemithyroidectomy, on the resolution of various compressive symptoms. MATERIALS AND METHODS: This retrospective analysis utilized the TriNetX Research Network to recognize adults with thyroid goiters treated surgically. International Classification of Diseases 10 (ICD10) was used to identify patients. Two groups were created based on surgical treatment, for either a hemithyroidectomy or total thyroidectomy. The primary outcomes were compression symptoms, including dysphagia, choking/globus sensation, dyspnea, cough, and hoarseness/dysphonia. RESULTS: This retrospective review included 45,539 subjects. Of these, 9293 had a partial thyroidectomy, and 36,246 had a total thyroidectomy. After propensity score matching was done for compression symptoms before surgery, there were 8280 patients in each group. There were no differences in symptoms between the matched groups, except for increased hoarseness and dysphonia after total thyroidectomy (RR, 95 % CI) (0.781, 0.67-0.91). Compression symptoms significantly decreased after surgical treatment in both the hemithyroidectomy and total thyroidectomy groups. CONCLUSIONS: Hemithyroidectomy is associated with efficacy similar to total thyroidectomy in reducing compression symptoms postoperatively. Hemithyroidectomy may be able to alleviate compressive symptoms with less surgical risk.

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer.

BACKGROUND: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors. METHODS: We conducted a phase 1/2 single-group, multicenter trial involving patients with advanced epithelial cancers who received sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects. A total of 108 patients received sacituzumab govitecan-hziy at a dose of 10 mg per kilogram of body weight after receiving at least two previous anticancer therapies for metastatic triple-negative breast cancer. The end points included safety; the objective response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), which was assessed locally; the duration of response; the clinical benefit rate (defined as a complete or partial response or stable disease for at least 6 months); progression-free survival; and overall survival. Post hoc analyses determined the response rate and duration, which were assessed by blinded independent central review. RESULTS: The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies (range, 2 to 10). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in ≥10% of the patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months (95% CI, 4.9 to 10.8); as assessed by independent central review, these values were 34.3% and 9.1 months, respectively. The clinical benefit rate was 45.4%. Median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3), and overall survival was 13.0 months (95% CI, 11.2 to 13.7). CONCLUSIONS: Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer. Myelotoxic effects were the main adverse reactions. (Funded by Immunomedics; IMMU-132-01 ClinicalTrials.gov number, NCT01631552.).

Assessing nonsexual transmission of the human papillomavirus (HPV): Do our current cleaning methods work?

Human papillomavirus (HPV) is thought to be sexually transmitted; however, there have been a few studies investigating a possible iatrogenic source of infection. Therefore, it is important to assess the cleaning methods of reusable medical devices. This study assessed whether cleaning methods of flexible endoscopes in an otolaryngology clinic are effective against HPV. There were 24 patients with a history of head and neck cancer in the study; however, two outliers were excluded. Nine patients were confirmed to have HPV-associated cancer. PCR was used to measure and quantify the viral genomes of samples collected before and after cleaning. After cleaning, few HPV+ samples had endoscopes with less DNA than before cleaning. Additionally, for several patients with non-HPV-associated head and neck cancer, PCR showed more DNA after cleaning than before cleaning, suggesting residual HPV DNA within the cleaning solution. There was no significant difference (p > 0.05) between pre- and post-cleaning in both cohorts. Current cleaning methods of reusable endoscopes may not be effective in completely removing viral DNA.

Breast and thyroid cancer: A multicenter study with Accrual to Clinical Trials Network.

OBJECTIVE: To investigate a possible link between breast and thyroid cancer. METHODS: A multicenter retrospective review of patients in the electronic medical records of six Accrual to Clinical Trial (ACT) institutions with both breast cancer and thyroid carcinoma. Each center queried its data using a predefined data dictionary. Information on thyroid and breast cancer included dates of diagnosis, histology, and patient demographics. RESULTS: A random-effects model was used. There were 4.24 million women's records screened, 44 605 with breast cancer and 11 846 with thyroid cancer. The relative risks observed at each institution ranged from 0.49 to 13.47. The combined risk ratio (RR) estimate was 1.77 (95% confidence interval: 0.50-5.18). CONCLUSION: There was no association between the risk of developing thyroid cancer and being a breast cancer survivor compared to no history of breast cancer, but the range of relative risks among the participating institutions was wide. Our findings warrant further study of more institutions with larger sample size. Additionally, further analysis of the significance of regional RR differences may be enlightening.

Lowering the transmission and spread of human coronavirus.

The emergence of the severe acute respiratory syndrome coronavirus 2 pandemic has created an unprecedented healthcare, social, and economic disaster. Wearing of masks and social distancing can significantly decrease transmission and spread, however, due to circumstances such as medical or dental intervention and personal choice these practices have not been universally adopted. Additional strategies are required to lessen transmission. Nasal rinses and mouthwashes, which directly impact the major sites of reception and transmission of human coronaviruses (HCoV), may provide an additional level of protection against the virus. Common over-the-counter nasal rinses and mouthwashes/gargles were tested for their ability to inactivate high concentrations of HCoV using contact times of 30 s, 1 min, and 2 min. Reductions in titers were measured by using the tissue culture infectious dose 50 (TCID50 ) assay. A 1% baby shampoo nasal rinse solution inactivated HCoV greater than 99.9% with a 2-min contact time. Several over-the-counter mouthwash/gargle products including Listerine and Listerine-like products were highly effective at inactivating infectious virus with greater than 99.9% even with a 30-s contact time. In the current manuscript we have demonstrated that several commonly available healthcare products have significant virucidal properties with respect to HCoV.

A Qualitative Investigation Into Faith and LGBTQ Identities in a Nonclinical Sample of Readers of the Dear Abby Column: The Dear Abby Project.

ABSTRACT: To better understand the relationship between faith and LGBTQ+ identity, we conducted a qualitative analysis of 86 respondents to a general question posed through the Dear Abby column. Responses were anonymized and analyzed using a grounded theory approach. Analysis revealed six themes, reflecting a diversity of lived experience from community rejection to acceptance, and self-rejection to feelings of acceptance by God. Despite frequent media portrayals of conflict between faith and LGBTQ+ identity, the reality is more complex, and faith and LGBTQ+ identity development can be complementary.

Pleiotropic role for MYCN in medulloblastoma.

Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Sonic Hedgehog (SHH) signaling drives a minority of MB, correlating with desmoplastic pathology and favorable outcome. The majority, however, arises independently of SHH and displays classic or large cell anaplastic (LCA) pathology and poor prognosis. To identify common signaling abnormalities, we profiled mRNA, demonstrating misexpression of MYCN in the majority of human MB and negligible expression in normal cerebella. We clarified a role in pathogenesis by targeting MYCN (and luciferase) to cerebella of transgenic mice. MYCN-driven MB showed either classic or LCA pathologies, with Shh signaling activated in approximately 5% of tumors, demonstrating that MYCN can drive MB independently of Shh. MB arose at high penetrance, consistent with a role for MYCN in initiation. Tumor burden correlated with bioluminescence, with rare metastatic spread to the leptomeninges, suggesting roles for MYCN in both progression and metastasis. Transient pharmacological down-regulation of MYCN led to both clearance and senescence of tumor cells, and improved survival. Targeted expression of MYCN thus contributes to initiation, progression, and maintenance of MB, suggesting a central role for MYCN in pathogenesis.

Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study.

BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) 131 I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2 per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and 18 F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. RESULTS: After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24). CONCLUSIONS: Repeated RIT with 131 I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of 131 I-labetuzumab is a single administration of 50 millicuries/m2 . Cancer 2017;123:638-649. © 2016 American Cancer Society.

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics.

BACKGROUND: Sacituzumab govitecan (IMMU-132), an antitrophoblastic cell-surface antigen (anti-Trop-2) humanized antibody-SN-38 conjugate, had encouraging efficacy in the phase 1 clinical trial. This report further examines the pharmacokinetics and safety of multiple cycles of IMMU-132 at doses of 8 or 10 mg/kg in patients with diverse advanced epithelial cancers. METHODS: Patients who had multiple prior therapies received IMMU-132 on days 1 and 8 of 21-day treatment cycles. Trop-2 staining of archived tumor specimens, clearance of IMMU-132 and its constituents (ie, immunoglobulin G [IgG], SN-38 [a camptothecin, the active component of irinotecan], and glucuronidated SN-38 [SN-38G]), antibody responses, and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) levels were determined. Safety was assessed according to Common Terminology Criteria for Adverse Events version 4.0, and responses were assessed using Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS: Patients with diverse metastatic cancers who received IMMU-132 at 8 mg/kg (n = 81) and 10 mg/kg (n = 97) were examined. Trop-2 was positive in 93% of the available specimens. IMMU-132 cleared with a half-life of approximately 11 to 14 hours, reflecting the release of SN-38 from the conjugate; IgG cleared more slowly (half-life, approximately 103-114 hours). Most SN-38 in the serum (>95%) was bound to IgG. SN-38G concentrations were lower than SN-38 concentrations. Dose-limiting neutropenia after the first cycle was not correlated with SN-38 in serum or with UGT1A1 genotype. No antibody responses were detected. Objective responses were observed in several indications, including metastatic triple-negative breast cancer, confirming that 10 mg/kg produced an encouraging overall response. CONCLUSIONS: Sacituzumab govitecan has a predictable pharmacokinetic profile and manageable toxicity at doses of 8 and 10 mg/kg. With objective responses and a good therapeutic index at 10 mg/kg, this dose was chosen for future development. Cancer 2017;123:3843-3854. © 2017 American Cancer Society.

The effect of aging on the anatomic position of the thyroid gland.

Thyroid disease is common among elderly patients, frequently necessitating thyroid gland examination, imaging, and surgery. However, no prior studies have determined the effect of age on the anatomic position of the thyroid gland in the anterior neck. We hypothesized that the thyroid gland resides at a more caudal position in the neck in elderly patients as compared to younger patients. Head and neck CT scans were collected from 122 atraumatic patients without thyroid disease aged 18-39 years, 40-59 years, 60-79 years, and 80+ years. Measurements of thyroid gland position and other aspects of head and neck anatomy were conducted in the mid-sagittal plane. The distance between the thyroid gland and the sternal notch decreased from 45 ± 10.4 mm in the 18-39 age group to 30.8 ± 9 mm in the 80+ age group (P < 0.001). The position of the gland did not change significantly relative to anatomic landmarks in the head or neck, although the trachea was angled more closely to the horizontal plane in elderly patients (P < 0.001). Cervical spine height was also lower among patients ≥60 years of age compared to those <60 years of age (P < 0.001). Multivariate linear modeling suggested that thyroid gland position was dependent on changes in cervical spine height, hyoid bone to hard palate distance, and tracheal angle (P = 1.7 × 10-11 ; r2 = 0.37). Clinicians should be aware of the more caudad positioning of the gland when planning surgery or screening for thyroid disease in the elderly. Clin. Anat. 30:205-212, 2017. © 2016 Wiley Periodicals, Inc.

Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia.

We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066.