Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study.

Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.

Usability Evaluation of a Noninvasive Neutropenia Screening Device (PointCheck) for Patients Undergoing Cancer Chemotherapy: Mixed Methods Observational Study.

BACKGROUND: Patients with cancer undergoing cytotoxic chemotherapy face an elevated risk of developing serious infection as a consequence of their treatment, which lowers their white blood cell count and, more specifically, their absolute neutrophil count. This condition is known as neutropenia. Neutropenia accompanied by a fever is referred to as febrile neutropenia, a common side effect of chemotherapy with a high mortality rate. The timely detection of severe neutropenia (<500 absolute neutrophil count/µL) is critical in detecting and managing febrile neutropenia. Current methods rely on blood draws, which limit them to clinical settings and do not allow frequent or portable monitoring. In this study, we demonstrated the usability of PointCheck, a noninvasive device for neutropenia screening, in a simulated home environment without clinical supervision. PointCheck automatically performs microscopy through the skin of the finger to image the blood flowing through superficial microcapillaries and enables the remote monitoring of neutropenia status, without requiring venipuncture. OBJECTIVE: This study aimed to evaluate the usability of PointCheck, a noninvasive optical technology for screening severe neutropenia, with the goal of identifying potential user interface, functionality, and design issues from the perspective of untrained users. METHODS: We conducted a multicenter study using quantitative and qualitative approaches to evaluate the usability of PointCheck across 154 untrained participants. We used a mixed method approach to gather usability data through user testing observations, a short-answer qualitative questionnaire, and a standardized quantitative System Usability Scale (SUS) survey to assess perceived usability and satisfaction. RESULTS: Of the 154 participants, we found that 108 (70.1%) scored above 80.8 on the SUS across all sites, with a mean SUS score of 86.1 across all sites. Furthermore, the SUS results indicated that, out of the 151 users who completed the SUS survey, 145 (96%) found that they learned how to use PointCheck very quickly, and 141 (93.4%) felt very confident when using the device. CONCLUSIONS: We have shown that PointCheck, a novel technology for noninvasive, home-based neutropenia detection, can be safely and effectively operated by first-time users. In a simulated home environment, these users found it easy to use, with a mean SUS score of 86.1, indicating an excellent perception of usability and placing this device within the top tenth percentile of systems evaluated for usability by the SUS. TRIAL REGISTRATION: ClinicalTrials.gov NCT04448314; https://clinicaltrials.gov/ct2/show/NCT04448314 (Hospital Universitario 12 de Octubre registration) and NCT04448301; https://clinicaltrials.gov/ct2/show/NCT04448301 (Boston Medical Center registration).

Patient outcomes in light chain (AL) amyloidosis: The clock is ticking from symptoms to diagnosis.

INTRODUCTION: Symptomology of AL amyloidosis can be vague, with a broad range of manifestations and potential etiologies. We sought to determine whether time from initial patient-reported symptom onset to diagnosis was associated with survival. METHODS: The Boston University Amyloidosis Patient Database was queried for patients with AL amyloidosis who presented to the Center for initial evaluation from 2010 to 2015. RESULTS: A total of 324 patients with AL amyloidosis were evaluated for initial evaluation. The median time to diagnosis from initial symptom onset was 7.1 months (range, 0-61). At data cutoff, 60.2% (n = 195) of patients were alive; of those, the majority were diagnosed <6 months from initial symptoms (52.3%, n = 102). In contrast, time to diagnosis from symptom onset was >6 months in 63.6% (n = 82) of patients who did not survive at the time of data cutoff (P = .0005). Survival analysis of time from diagnosis to death or data cutoff stratified by time from patient-reported symptom onset to diagnosis (<6, 6-12, and >12 months) showed significant differences among groups (P = .001). Additionally, multivariable regression demonstrated that an increase in time from self-reported symptom onset to diagnosis was significantly associated with an increased risk of death (HR = 1.02, 95% CI = 1.01-1.04, P = .002). CONCLUSION: These results support the importance of early diagnosis for patients with AL amyloidosis.

Induction Therapy with Bortezomib and Dexamethasone and Conditioning with High-Dose Melphalan and Bortezomib Followed by Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis: Long-Term Follow-Up Analysis.

In immunoglobulin light-chain (AL) amyloidosis, the depth of hematologic response to treatment is associated with improved survival and organ responses. We conducted a clinical trial using bortezomib in induction and in conditioning with melphalan before stem cell transplantation (SCT) for AL amyloidosis. The results of this clinical trial with a median follow-up of 36 months have been reported previously. Here we report the long-term results of this clinical trial with a median follow-up of 77 months. We describe survival, durability of hematologic and organ responses, and relapse rates. Thirty-five patients were enrolled between 2010 and 2013. Hematologic complete response and very good partial response (VGPR) were noted in 100% (27 of 27) of the evaluable patients at 6 months post-SCT. Four patients (15%) had hematologic relapse at a median of 42 months, and 1 patient (3.7%) had organ progression despite maintaining a VGPR at 37 months. The median overall survival and progression-free survival have not yet been reached at the time of this report. Renal and cardiac responses occurred in 65% and 88%, respectively, at 5 years post-SCT. The median time to renal and cardiac response was 12 months and 6 months, respectively. In conclusion, incorporating bortezomib into induction and conditioning yielded durable hematologic responses of AL amyloidosis, with corresponding organ responses and prolonged survival.

Assessment of Yersinia entomophaga as a control agent of the diamondback moth Plutella xylostella.

The application of the biocontrol bacterium Yersinia entomophaga as a foliar spray was assessed for its efficacy against larvae of the diamondback moth, Plutella xylostella. The bacterium was applied as either a broth suspension, or as a biopolymer-based gel foliar spray and compared with commercial insecticides Dipel (Bacillus thuringiensis) and Spinosad. The performance of Y. entomophaga was comparable with that of Dipel. The gel-based formulation extended leaf persistence over that of the basic broth culture spray, while also providing higher initial foliar deposition rates. The bacterium was found to multiply within the P. xylostella larvae to 5.8 × 105 cells per larva, while the median lethal dose (LD50) was determined to be 2.69 × 103 cells per larva. Importantly, B. thuringiensis Cry1A-resistant, Cry1C-resistant, indoxacarb/pyrethroid-resistant, and Spinosad-resistant P. xylostella larvae were susceptible to Y. entomophaga.

Modified High-Dose Melphalan and Autologous Stem Cell Transplantation for Immunoglobulin Light Chain Amyloidosis.

High-dose melphalan and autologous stem cell transplantation (HDM/SCT) have been used in patients with immunoglobulin light chain (AL) amyloidosis for over 2 decades now with durable responses, prolonged survival, and decreasing treatment-related mortality. Historically, patients with poorer baseline functional status, advanced age, renal compromise, and cardiac involvement have been treated with a risk-adapted modified conditioning dose of melphalan (mHDM) of 100 to 140 mg/m2 before SCT. In part because of these baseline characteristics, patients receiving mHDM/SCT have had poorer outcomes compared with patients receiving full-dose melphalan at 200 mg/m2. With the advent of novel therapeutic agents such as proteasome inhibitors, immunomodulatory agents, and monoclonal antibodies for the treatment of AL amyloidosis, it is imperative to understand the long-term effects of mHDM/SCT. Here we report the long-term outcomes of 334 patients with AL amyloidosis treated with mHDM/SCT. Median overall survival was 6.1 years and median event-free survival 4.3 years, with median overall survival reaching 13.4 years for patients who had achieved a hematologic complete response (CR). Overall hematologic response rate was 69%, and treatment-related mortality was 3% after 2010. Thus, mHDM/SCT leads to prolonged survival and favorable outcomes, especially if a hematologic CR is achieved.

Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial.

The objectives of a phase 1/2 trial of pomalidomide with dexamethasone for the treatment of light chain (AL) amyloidosis were to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose, and hematologic and clinical response. A 3+3 dose-escalation phase (15 patients) was followed by an expansion cohort (12 patients) enrolled at the MTD. Pomalidomide was administered at 2 and 3 mg on days 1 to 28 (cohorts 1 and 2) and 4 mg on days 1 to 21 (cohort 3) every 28 days, with weekly dexamethasone at a dose of 20 mg. Twenty-seven patients with previously treated AL were enrolled, 15 during dose escalation (6 at 2 mg, 3 at 3 mg, and 6 at 4 mg) and 12 during dose expansion (all at 4 mg). One patient experienced dose-limiting toxicity at 4 mg; the MTD was determined as 4 mg. The most common grade ≥3 drug-related adverse events included myelosuppression and fatigue. Overall, hematologic response (HR) was 50% in 24 evaluable patients. The median time to best HR was 3 cycles, and median duration of HR was 15 months. Median overall survival has not yet been reached, with a median follow-up of 17.1 months and median event-free survival of 17.8 months. This trial was registered at www.clinicaltrials.gov as #NCT01570387.

Evaluation of a new continuous mononuclear cell collection procedure in a single transplant center cohort enriched for AL amyloidosis patients.

BACKGROUND: The Spectra Optia continuous mononuclear cell (CMNC) program is newly available, and herein validated in a single-center cohort enriched with AL amyloidosis patients to collect a target CD34+ yield of 2.5 × 106 cells/kg within 2 days. METHODS: Consecutive autologous transplant patients in 2016 are included. Patients undergo leukapheresis with Optia CMNC and Spectra v4.7 over a 2-day cycle. Data collection includes collection efficiency, adverse events and engraftment kinetics. RESULTS: 36 leukapheresis procedures on 18 patients are included. The diagnoses are AL amyloidosis (9), myeloma (7), lymphoma (2), and scleroderma (1). Median age is 60; 12 are men. Plerixafor was employed pre-emptively in 6 cycles. Median blood CD34+ on Day 1 of leukapheresis was 46 cells/uL. Median number of blood volumes processed on Day 1 was 3.1. All collection cycles were completed within 2 days; only one in a heavily pretreated lymphoma patient did not reach the target requiring a second mobilization attempt. Mean collection efficiencies were comparable between the two devices. There were 2 adverse events: tubing rupture on the Optia; and one case of hypotension. All 18 patients underwent high-dose chemotherapy: median cell dose infused was 7.7 × 106 CD34+ cells/kg. Median days to neutrophil and platelet engraftment were 10 and 13 respectively. CONCLUSION: The Optia CMNC collection protocol is safe and effective in a small single-center autologous stem cell transplant cohort enriched for high-risk patients with AL amyloidosis and cardiac involvement. Caution is needed for tubing setup because there is less cumulative experience with Optia.

A Single Swede Midge (Diptera: Cecidomyiidae) Larva Can Render Cauliflower Unmarketable.

Swede midge, Contarinia nasturtii Kieffer (Diptera: Cecidomyiidae), is an invasive pest causing significant damage on Brassica crops in the Northeastern United States and Eastern Canada. Heading brassicas, like cauliflower, appear to be particularly susceptible. Swede midge is difficult to control because larvae feed concealed inside meristematic tissues of the plant. In order to develop damage and marketability thresholds necessary for integrated pest management, it is important to determine how many larvae render plants unmarketable and whether the timing of infestation affects the severity of damage. We manipulated larval density (0, 1, 3, 5, 10, or 20) per plant and the timing of infestation (30, 55, and 80 d after seeding) on cauliflower in the lab and field to answer the following questions: 1) What is the swede midge damage threshold? 2) How many swede midge larvae can render cauliflower crowns unmarketable? and 3) Does the age of cauliflower at infestation influence the severity of damage and marketability? We found that even a single larva can cause mild twisting and scarring in the crown rendering cauliflower unmarketable 52% of the time, with more larvae causing more severe damage and additional losses, regardless of cauliflower age at infestation.

Bendamustine-Induced Nephrogenic Diabetes Insipidus in a Patient With AL Amyloidosis.

Nephrogenic diabetes insipidus is a condition characterized by polyuria with dilute urine due to the inability of the principal cells of the renal collecting ducts to respond to antidiuretic hormone and concentrate urine. Nephrogenic diabetes insipidus can be drug induced, and several chemotherapeutic agents have been reported to cause it. Bendamustine is a traditional chemotherapeutic agent being studied for treatment for relapsed systemic AL amyloidosis. We report a case of a 59-year-old man with AL amyloidosis who developed partial nephrogenic diabetes insipidus after receiving bendamustine for treatment of AL amyloidosis. The nephrogenic diabetes insipidus responded well to sodium restriction, hydrochlorothiazide, and desmopressin treatment, allowing the patient to receive subsequent bendamustine cycles without polyuria. Nephrogenic diabetes insipidus resolved shortly after completion of bendamustine therapy.

The interaction of two-spotted spider mites, Tetranychus urticae Koch, with Cry protein production and predation by Amblyseius andersoni (Chant) in Cry1Ac/Cry2Ab cotton and Cry1F maize.

Crops producing insecticidal crystal (Cry) proteins from the bacterium, Bacillus thuringiensis (Bt), are an important tool for managing lepidopteran pests on cotton and maize. However, the effects of these Bt crops on non-target organisms, especially natural enemies that provide biological control services, are required to be addressed in an environmental risk assessment. Amblyseius andersoni (Acari: Phytoseiidae) is a cosmopolitan predator of the two-spotted spider mite, Tetranychus urticae (Acari: Tetranychidae), a significant pest of cotton and maize. Tri-trophic studies were conducted to assess the potential effects of Cry1Ac/Cry2Ab cotton and Cry1F maize on life history parameters (survival rate, development time, fecundity and egg hatching rate) of A. andersoni. We confirmed that these Bt crops have no effects on the biology of T. urticae and, in turn, that there were no differences in any of the life history parameters of A. andersoni when it fed on T. urticae feeding on Cry1Ac/Cry2Ab or non-Bt cotton and Cry1F or non-Bt maize. Use of a susceptible insect assay demonstrated that T. urticae contained biologically active Cry proteins. Cry proteins concentrations declined greatly as they moved from plants to herbivores to predators and protein concentration did not appear to be related to mite density. Free-choice experiments revealed that A. andersoni had no preference for Cry1Ac/Cry2Ab cotton or Cry1F maize-reared T. urticae compared with those reared on non-Bt cotton or maize. Collectively these results provide strong evidence that these crops can complement other integrated pest management tactics including biological control.

Pest control and resistance management through release of insects carrying a male-selecting transgene.

BACKGROUND: Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. RESULTS: Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli alone did not. CONCLUSIONS: These results support theoretical modeling, indicating that MS-engineered insects can provide a powerful pest population suppressing effect, and could effectively augment current Bt resistance management strategies. We conclude that, subject to field confirmation, MS insects offer an effective and versatile control option against P. xylostella and potentially other pests, and may reduce reliance on and protect insecticide-based approaches, including Bt crops.

Development and Evaluation of Degree-Day Models for Acrolepiopsis assectella (Lepidoptera: Acrolepiidae) Based on Hosts and Flight Patterns.

The leek moth, Acrolepiopsis assectella (Zeller), was first discovered in Ottawa, Canada, during the 1993 growing season, representing the first known occurrence of this species in North America. Since then, it has become a significant concern in Allium vegetable production including garlic, leeks, and onions. Acrolepiopsis assectella was first detected in the contiguous United States during the 2009 growing season in northern New York. In this study, we evaluated the development of the US A. assectella population in the laboratory and commercial onion fields. Our results showed that this population required 443.9 degree-days to complete its life cycle on onions in the laboratory. The development of A. assectella on onion did not significantly differ from populations reared on garlic or leeks. Field studies revealed three distinct flight periods for overwintered, first- and second-generation adult males in northern New York. Life cycle duration in the field ranged from 4 to 8 wk. The degree-day prediction model evaluated in this study provided accurate estimates of the occurrence of the following generation. We conclude that this model can help growers to implement appropriate management strategies for different life stages in a timely manner and lessen damage by this new invasive pest.

Induction Therapy with Bortezomib Followed by Bortezomib-High Dose Melphalan and Stem Cell Transplantation for Light Chain Amyloidosis: Results of a Prospective Clinical Trial.

The depth of hematologic response has been shown to correlate with survival and organ responses for patients with light chain (AL) amyloidosis. We conducted a prospective trial of 2 cycles of induction with bortezomib and dexamethasone on a twice a week schedule followed by conditioning with bortezomib and high-dose melphalan (HDM) and autologous stem cell transplantation (SCT). The objectives were hematologic responses, tolerability, and survival. Thirty-five patients were enrolled from 2010 to 2013. Of these, 30 proceeded with SCT, whereas 5 did not because of clinical deterioration during induction (n = 3) or complications after stem cell collection (n = 2). Two patients developed features of an autologous graft-versus-host disease-like syndrome post-SCT, which responded to steroids; no other unusual complications were seen. Treatment-related mortality occurred in 8.5% (3/35). Hematologic responses were achieved by 100% of the 27 assessable patients (63% complete response, 37% very good partial response [VGPR]) who completed the planned treatment. By intention-to-treat, hematologic responses occurred in 77% of patients (49% complete response, 29% VGPR). With a median follow-up of 36 months, the median overall survival and progression-free survival were not reached. In conclusion, incorporating bortezomib into induction and conditioning yielded a high rate of hematologic responses after HDM/SCT in patients with AL amyloidosis.

Resistance of Trichoplusia ni populations selected by Bacillus thuringiensis sprays to cotton plants expressing pyramided Bacillus thuringiensis toxins Cry1Ac and Cry2Ab.

Two populations of Trichoplusia ni that had developed resistance to Bacillus thuringiensis sprays (Bt sprays) in commercial greenhouse vegetable production were tested for resistance to Bt cotton (BollGard II) plants expressing pyramided Cry1Ac and Cry2Ab. The T. ni colonies resistant to Bacillus thuringiensis serovar kurstaki formulations were not only resistant to the Bt toxin Cry1Ac, as previously reported, but also had a high frequency of Cry2Ab-resistant alleles, exhibiting ca. 20% survival on BollGard II foliage. BollGard II-resistant T. ni strains were established by selection with BollGard II foliage to further remove Cry2Ab-sensitive alleles in the T. ni populations. The BollGard II-resistant strains showed incomplete resistance to BollGard II, with adjusted survival values of 0.50 to 0.78 after 7 days. The resistance to the dual-toxin cotton plants was conferred by two genetically independent resistance mechanisms: one to Cry1Ac and one to Cry2Ab. The 50% lethal concentration of Cry2Ab for the resistant strain was at least 1,467-fold that for the susceptible T. ni strain. The resistance to Cry2Ab in resistant T. ni was an autosomally inherited, incompletely recessive monogenic trait. Results from this study indicate that insect populations under selection by Bt sprays in agriculture can be resistant to multiple Bt toxins and may potentially confer resistance to multitoxin Bt crops.

Eliminating host-mediated effects demonstrates Bt maize producing Cry1F has no adverse effects on the parasitoid Cotesia marginiventris.

The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is an important pest of maize in the United States and many tropical areas in the western hemisphere. In 2001, Herculex I(®) (Cry1F) maize was commercially planted in the United States to control Lepidoptera, including S. frugiperda. In 2006, a population of S. frugiperda was discovered in Puerto Rico that had evolved resistance to Cry1F maize in the field, making it the first well-documented case of an insect with field resistance to a plant producing protein from Bacillus thuringiensis (Bt). Using this resistant population, we conducted tri-trophic studies with a natural enemy of S. frugiperda. By using resistant S. frugiperda, we were able to overcome possible prey-mediated effects and avoid concerns about potential differences in laboratory- or field-derived Bt resistance. We used the Cry1F-resistant S. frugiperda to evaluate effects of Cry1F on Cotesia marginiventris (Cresson) (Hymenoptera: Braconidae), a larval endoparasitoid of S. frugiperda, over five generations. Our results clearly demonstrate that Cry1F maize does not affect development, parasitism, survivorship, sex ratio, longevity or fecundity of C. marginiventris when they parasitize Cry1F maize-fed S. frugiperda. Furthermore, the level of Cry1F protein in the leaves was strongly diluted when transferred from Bt maize to S. frugiperda and was not detected in larvae, cocoons or adults of C. marginiventris. Our results refute previous reports of C. marginiventris being harmed by Bt proteins and suggest that such results were caused by prey-mediated effects due to using Bt-susceptible lepidopteran hosts.

Single agent lenalidomide three times a week induces hematologic responses in AL amyloidosis patients on dialysis.

The combination of lenalidomide and dexamethasone can produce hematologic responses in previously treated patients with AL amyloidosis. Because lenalidomide is primarily excreted unchanged by the kidney, adjustments to the starting dose of lenalidomide are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis. Here, we report on a study of patients with AL amyloidosis on dialysis treated with lenalidomide at a dose of 10 mg orally three times a week. Seven patients were enrolled. All patients had received prior treatment, with 57% receiving prior high-dose melphalan and stem cell transplantation. Two patients died before evaluation of response. The most common adverse event was infection; no thromboembolic complications were seen. One patient required dose-modification. Hematologic responses were obtained by four of the five evaluable patients. Median overall survival was 18 months. In conclusion, adjusted dose lenalidomide was reasonably tolerated and induced sustained hematologic responses in previously treated patients with AL amyloidosis on dialysis.

Effects of Bt cotton on Thrips tabaci (Thysanoptera: Thripidae) and its predator, Orius insidiosus (Hemiptera: Anthocoridae).

Laboratory studies were conducted to investigate tritrophic transfer of insecticidal Cry proteins from transgenic cotton to an herbivore and its predator, and to examine effects of these proteins on the predator's development, survival, and reproduction. Cry1Ac and Cry2Ab proteins from the bacterium Bacillus thuringiensis (Bt) produced in Bollgard-II (BG-II, Event 15985) cotton plants were acquired by Thrips tabaci Lindeman (Thysanoptera: Thripidae), an important sucking pest of cotton, and its generalist predator, Orius insidiosus (Say) (Hemiptera: Anthocoridae). The average protein titers in BG-II cotton leaves were 1,256 and 43,637 ng Cry1Ac and Cry2Ab per gram fresh leaf tissue, respectively. At the second trophic level, larvae of T. tabaci reared on BG-II cotton for 48-96 h had 22.1 and 2.1% of the Cry1Ac and Cry2Ab levels expressed in leaves, respectively. At the third trophic level, O. insidiosus that fed on T. tabaci larvae had 4.4 and 0.3% of the Cry1Ac and Cry2Ab protein levels, respectively, expressed in BG-II plants. O. insidiosus survivorship, time of nymphal development, adult weight, preoviposition and postoviposition periods, fecundity, and adult longevity were not adversely affected owing to consumption of T. tabaci larvae that had fed on BG-II cotton compared with non-Bt cotton. Our results indicate that O. insidiosus, a common predator of T. tabaci, is not harmed by BG-II cotton when exposed to Bt proteins through its prey. Thus, O. insidiosus can continue to provide important biological control services in the cotton ecosystem when BG-II cotton is used to control primary lepidopteran pests.