Synthetic antibiotics have captured the market in recent years, but the side effects of these products are life-threatening. In recent times, researchers have focused their research on natural-based products such as natural herbal oils, which are eco-friendly, biocompatible, biodegradable, and antibacterial. In this study, polyethylene oxide (PEO) and aqueous ginger extract (GE) were electrospun to produce novel antibacterial nanomembrane sheets as a function of PEO and GE concentrations. A GE average particle size of 91.16 nm was achieved with an extensive filtration process, inferring their incorporation in the PEO nanofibres. The presence of the GE was confirmed by Fourier transform infrared spectroscopy (FTIR) through peaks of phenol and aromatic groups. The viscoelastic properties of PEO/GE solutions were analysed in terms of PEO and GE concentrations. Increasing PEO and GE concentrations increased the solution’s viscosity. The dynamic viscosity of 3% was not changed with increasing shear rate, indicating Newtonian fluid behaviour. The dynamic viscosity of 4 and 5 wt% PEO/GE solutions containing 10% GE increased exponentially compared to 3 wt%. In addition, the shear thinning behaviour was observed over a frequency range of 0.05 to 100 rad/s. Scanning Electron Microscopy (SEM) analysis also specified an increase in the nanofibre’s diameter with increasing PEO concentration, while SEM images displayed smooth morphology with beadless nanofibres at different PEO/GE concentrations. In addition, PEO/GE nanomembranes inhibited the growth of Staphylococcus aureus, as presented by qualitative antibacterial results. The extent of PEO/GE nanomembrane’s antibacterial activity was further investigated by the agar dilution method, which inhibited the 98.79% Staphylococcus aureus population at 30% GE concentration.
Background: Multiple myeloma (MM) is a plasma cell disorder and demonstrates overexpression of B cell maturation antigen (BCMA). Our objective is to evaluate the safety and efficacy of chimeric antigen receptor T cells (CAR-T) against BCMA in patients with relapsed/refractory multiple myeloma (RRMM). Methods: We conducted a systematic literature search using PubMed, Cochrane, Clinicaltrials.gov, and Embase databases. We also searched for data from society meetings. A total of 935 articles were identified, and 610 were screened for relevance. Results: Data from thirty-one original studies with a total of 871 patients (pts) were included based on defined eligibility criteria, see Table 1. Hu et al. reported an overall response rate (ORR) of 100% in 33 pts treated with BCMA CAR-T cells including 21 complete response (CR), 7 very good partial response (VGPR), 4 partial response (PR). Moreover, 32 pts achieved minimal residual disease (MRD) negative status. Chen et al. reported ORR of 88%, 14% CR, 6% VGPR, and 82% MRD negative status with BCMA CAR-T therapy in 17 RRMM pts. In another clinical trial by Han et al. BCMA CAR-T therapy demonstrated an ORR of 100% among 7 evaluable pts with 43% pts having ≥ CR and 14% VGPR. An ORR of 100% with 64% stringent CR (sCR) and 36% VGPR was reported with novel anti-BCMA CART cells (CT103A). Similarly, Li et al. reported ORR of 87.5%, sCR of 50%, VGPR 12.5%, and PR 25% in 16 pts. BCMA targeting agent, JNJ-4528, showed ORR of 91%, including 4sCR, 2CR, 10MRD, and 7VGPR. CAR-T- bb2121 demonstrated ORR of 85%, sCR 36%, CR 9%, VGPR 57%, and MRD negativity of 100% (among 16 responsive pts). GSK2857916, a BCMA targeting CAR-T cells yielded ORR of 60% in both clinical trials. Three studies utilizing bispecific CART cells targeting both BCMA & CD38 (LCARB38M) reported by Zhao et al., Wang et al., and Fan et al. showed ORR of 88%, 88%, & 100% respectively. Topp et al. reported ORR of 31% along with 5 ≥CR and 5 MRD negative status in 42 pts treated with Bi T-cells Engager BiTE® Ab BCMA targeting antigen (AMG420). One clinical trial presented AUTO2 CART cells therapy against BCMA with an ORR of 43%, VGPR of 14%, and PR of 28%. CT053CAR-BCMA showed 14sCR and 5CR with a collective ORR of 87.5% and MRD negative status of 85% in 24 and 20 evaluable pts, respectively. Likewise, Mikkilineni et al. reported an ORR of 83%, sCR of 16.7%, and VGPR & PR of 25% and 41% in 12 pts treated with FHVH-BCMA T cells. Similar results are also reported in other clinical trials of BCMA targeting CART therapy (Table 1). The most common adverse effects exhibited were grade 1-3 hematologic (cytopenia) and cytokine release syndrome (CRS) (mostly reversible with tocilizumab). Conclusion: Initial data from ongoing clinical trials using BCMA targeting CAR-T therapy have yielded promising results both in terms of improved outcome and tolerable toxicity profiles. Although two phase 3 trails are ongoing, additional data is warranted to further ensure the safety and efficacy of anti-BCMA CAR-T cells therapy in pts with RRMM for future use. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.
Background: Allogeneic Stem cell transplant (Allo-SCT) is a widely used treatment for multiple hematological malignancies, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Relapse after Allo-SCT depends on the disease status prior to SCT, intensity of conditioning regimen and donor type. Disease relapse after SCT tends to have a poor prognosis with low probability of long term remission. This systematic review aims to assess the efficacy and safety of salvage therapies for disease relapse after first Allo-SCT. Methods: A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following mesh terms and Entree terms, "salvage therapy" AND "stem cell transplant" AND "acute myeloid leukemia" OR "myelodysplastic syndrome" from the inception of data till 06/20/2020. We screened 1,666 articles and included 4 clinical trials (N=134) and 18 observational studies (N=756) in this systematic review. We excluded case reports, case series, preclinical trials, review articles, meta-analysis and original studies not providing efficacy and safety of salvage therapy in AML/MDS patients relapsed after Allo-SCT. Results: Among 22 studies (N=888), the age range was 14-75 years (Table 1). In two observational studies (N=92) where second Allo-SCT was used as salvage therapy, complete response (CR) was seen in 74-84% of the patients. Stable CR was achieved in 15% of the participants, and 44% experienced disease relapse. Overall survival (OS) at 68 months was 14%. In the trial (N=8) evaluating, azacitidine in combination with sorafenib, CR rate was 50%, and 1-year OS was 31%. Hepatotoxicity was seen in these patients, none of the patients died or discontinued treatment due to treatment-related adverse events (TRAEs). Azacitidine monotherapy was associated with a CR rate of 13-32% (N=256). Overall response (ORR) of 15% and 56% was seen patients with hematological and molecular relapse, respectively. ≥Grade 3 TRAEs were infections, pneumonia, sepsis and hematological adverse events. Donor lymphocyte infusion (DLI) monotherapy (N=14) showed CR in 14% of the patients with a 2 yr OS of 42%. Decitabine in combination with DLI (N=36) led to CR in 17% of the patients with a median duration of response of 10 months. The incidence of acute and chronic graft vs. host disease (GvHD) was 19% and 5%, respectively. Similarly, azacitidine in combination with DLI (N=351) led to CR in 9.7-36% of the patients, with a 2-yr OS of 29-35%. In a retrospective study by Claiborne et al., 71% of patients experienced disease relapse at a median follow up of 6 months. Infections, neutropenia, and non-severe GI symptoms were attributed to azacytidine with DLI therapy. In a study on hypomethylating agents with lenalidomide (N=40), CR was seen in 21-36.4% of the patients, and 2-yr OS was 58%. Infections and neutropenia were reported in these patients. In 3 observational studies (N=48), venetoclax based regimens were associated with CR in 42-53% of the patients and 43% maintained the response for ≥3 months. More than 60% of patients died of infections in one of these studies. Conclusion: Azacytidine, decitabine, sorafenib, venetoclax, lenalidomide and DLI were well tolerated by patients with disease relapse after Allo-SCT. Hypomethylating agents (azacytidine and decitabine) were more effective in combination with DLI, lenalidomide and venetoclax rather than monotherapy. Among drug therapies, best efficacy outcomes were reported in studies on venetoclax based regimens. Additional multicenter randomized, double clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.
Background: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in the US. Lenalidomide (Len), an immunomodulator, is used in the treatment of multiple hematological malignancies. This systematic review and meta-analysis aimed to assess the efficacy and safety of Lenalidomide based regimens in Newly Diagnosed (ND) and Relapsed/Refractory (R/R) DLBCL. Methods : A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following mesh terms and Emtree terms, "Lenalidomide" OR "Revlimid" AND "diffuse large B cell lymphoma" from the inception of literature till 06/20/2020. We screened 1640 articles and included 2 randomized clinical trials (N=72) and 21 single-arm clinical trials (N=860) in this meta-analysis. We excluded case reports, case series, preclinical trials, review articles, meta-analysis, observational studies, and clinical trials not providing any information about the lenalidomide efficacy or safety in DLBCL. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results : In 23 studies (N=932), Len based regimens were used in patients with age 19-92 years (range) Table 1. In 5 trials on R/R patients (N=252), Len was used as a maintenance therapy. Cumulative overall response rate (ORR) and cumulative complete response (CR) were 0.27 (95% CI 0.21; 0.33, I2=0%) (Fig1) and 0.10 (95% CI 0.07; 0.16, 8%) (Fig2), respectively. In one phase III trial, the ORR and CR were significantly improved in the Len arm vs investigator's choice drug. In 4 trials on R/R patients (N=207), Len with monoclonal antibodies (MoAb) was used. Cumulative ORR and CR were 0.40 (95% CI 0.28; 0.54, I2=71%) and 0.28 (95% CI 0.17; 0.42, I2=72%), respectively. In a trial on R/R patients (N=33), Len with Gemcitabine, Rituximab, and Oxaliplatin was used. Cumulative ORR and CR were 0.61 (95% CI 0.43; 0.76, I2=0%) and 0.39 (95% CI 0.24; 0.57, I2=0%), respectively. In a trial on R/R patients (N=15), Len with RICE was used with ORR and CR of 0.73 (95% CI 0.47; 0.90, I2=0%) and 0.60 (95% CI 0.35; 0.81, I2=0%), respectively. In a trial on R/R patients(N=55), Len with Everolimus was used. ORR and CR were 0.27 (95% CI 0.17; 0.40, I2=0%) and 0.07 (95% CI 0.03; 0.18, I2=0%), respectively. In a trial on R/R patients (N=19), Len with R-ESHAP was used. ORR and CR were 0.79 (95% CI 0.55; 0.92, I2=0%) and 0.47 (95% CI 0.27; 0.69, I2=0%), respectively. In a phase III trial on R/R patients (N=21), Len with Gemcitabine and Rituximab was used vs. placebo The ORR and CR were significantly improved in the Len arm vs placebo. In 4 trials on ND patients (N=158), Len with R-CHOP was used and the cumulative ORR and CR were 0.94 (95% CI 0.88; 0.97, I2=12%) and 0.81 (0.75; 0.87, I2=0%), respectively. In a trial on ND patients (N=15), Len with R-EPOCH was used with ORR and CR of 0.93 (95% CI 0.65; 0.99, I2=0%) and 0.87 (95% CI 0.59; 0.97, I2=0%), respectively. In 2 trials (N=103), Len with Ibrutinib and Rituximab was used. In R/R patients (N=45), cumulative ORR and CR were 0.38 (95% CI 0.25; 0.53, I2=0%) and 0.24 (95% CI 0.14; 0.39, I2=0%), respectively. In ND patients (N=58) has ORR and CR 0.86 (95% CI 0.75; 0.93, I2=0%), respectively. In 2 trials with a combination of ND and R/R patients (N=54), Len with Rituximab and Bendamustine was used. Cumulative ORR and CR were 0.63 (95% CI 0.49; 0.75, I2=0%) and 0.39 (95% CI 0.27; 0.52, I2=0%), respectively. The most common serious treatment-related adverse events (TRAE) were infection, thromboembolism, fatigue, sepsis, respiratory, neurological, cardiac (arrhythmias), gastrointestinal, rash, seizures, and hematological side effects (Table 1). Conclusion : Based on early phase trials, Len based regimens are well tolerated and effective in the treatment of both ND and R/R DLBCL patients. Combinations of lenalidomide with Tafasitamab and R-ESHAP have shown the highest response in R/R patients and combination with R-CHOP has shown the best response in ND patients. In randomized trials, lenalidomide has shown significant improvement in the survival of DLBCL patients as compared to placebo or physician's choice drug. Additional double-blind multicenter randomized clinical trials are needed to compare the efficacy and safety of lenalidomide based regimens in DLBCL patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.
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