Incidence Of Peripheral Neuropathy Research Articles

First-line pemetrexed/carboplatin or cisplatin/bevacizumab compared with paclitaxel/carboplatin/bevacizumab in patients with advanced non-squamous non-small cell lung cancer with wild-type driver genes: A real-world study in China.

The study was conducted to compare the effectiveness and safety of pemetrexed/carboplatin or cisplatin/bevacizumab (PemPBev) and paclitaxel/carboplatin/bevacizumab (PacCBev) as first-line therapy for advanced non-squamous non-small cell lung cancer (NS-NSCLC) patients with wild-type driver genes in a real-world setting. We retrospectively collected the medical records of advanced NS-NSCLC patients with wild-type driver genes administered first-line PemPBev or PacCBev therapy at Shanghai Chest Hospital between January 2014 and June 2016, and analyzed the differences in survival outcomes, efficacy, and safety between PemPBev and PacCBev treatment. A total of 390 patients were included in our analysis: 249 in the PemPBev group and 141 in the PacCBev group. Patients administered PemPBev experienced significantly improved progression-free survival (PFS) and overall survival (OS) compared to those administered PacCBev (PFS 7.5 vs. 6.2 months, hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.53-0.84, P < 0.001; OS:18.6 vs. 16.0 months, HR 0.68, 95% CI 0.52-0.90, P = 0.002). The objective response rate (ORR) and disease control rate (DCR) were similar between the groups (ORR 21.7% vs. 30.5%, P = 0.053; DCR 69.1% vs. 67.4%, P = 0.728). There was no significant difference in the incidence of adverse events between the groups (64.7% vs. 68.8%; P = 0.407), but the incidence of peripheral neuropathy in the PacCBev group was higher than in the PemPBev group (7.8% vs. 2.4%; P = 0.012). Our study shows that for advanced NS-NSCLC patients with wild-type driver genes, first-line PemPBev might be a better treatment option compared to PacCBev.

Abstract P1-15-23: Higher efficacy of 2-week nab-paclitaxel compared to solvent-based paclitaxel in neoadjuvant chemotherapy of triple negative breast cancers

Abstract Background: Weekly nab-paclitaxel (nP) has better efficacy and safety for breast cancer patients compared with solvent-based paclitaxel (sP), but the result seems to be compromised when to 3-week nP though more convenient. However, reports about the 2-week nP in early breast cancer (EBC) are few. The current study aims to investigate whether 2-week nP is more effective than 2-week sP when added to an epirubicin/cyclophosphamide containing Neoadjuvant Chemotherapy (NAC) in Chinese EBCs . Methods: Patients included in current retrospective study must meet at least one of the following criteria: tumor size≥3cm; positive axillary lymph node; human epidermal growth factor receptor-2 (HER2) overexpression; triple negative breast cancer (TNBC, estrogen receptors (ER), progesterone receptors (PR), and HER2 negative); patients with willingness to receive breastconserving therapy. Based on expressive levels of ER, PR, HER2 and Ki-67, patients were divided into different subgroups. After dose dense EC (E, epirubicin 90 mg/m2; C, cyclophosphamide 600 mg/m2), patients were received either nP (260 mg/m2) q2w or sP (175 mg/m2) q2w, with or without herceptin (first time 8mg/kg and followed by 6mg/kg). The primary endpoint was the pathological complete response (pCR) rates (ypT0N0 and ypT0/isN0) and the second endpoint was the toxicity. Results: Total 151 patients were recruited from August 2013 to October 2017. Of them, 77 patients received nP and 74 received sP. Baseline characteristics are similar that the mean age was 47.68/51.82 years (nP/sP) and tumor size was 41.23/39.77 mm (nP/sP). After treatment, the pCR rate of TNBC patients was significantly higher in the group receiving nP (6/11, 54.4%) compared to sP (2/16, 12.5%, p=0.0332). No difference of pCR rates was found between nP and sP groups regarding to the threshold (20%) of Ki-67. Only few or no patients in subgroups of Luminal A, Luminal B HER2+ and Ki-67 ≤ 20% experienced pCR. Although the pCR was observed in other subgroups, there was no significant difference between patients with nP and sP . The side effects included peripheral neuropathy, allergic reactions, bone marrow suppression, and the incidence of peripheral neuropathy in nP was significantly increased. Table 1.pCR rates. nP(n=77)sP(n=74)P valueLuminal AypT0N00/150/5/ ypT0/isN00/150/5/Luminal B HER2-ypT0N03/202/330.3685 ypT0/isN04/202/330.1836Luminal B HER2+ypT0N00/00/3/ ypT0/isN00/01/3/HER2+ypT0N02/30/20.4000 ypT0/isN02/30/20.4000TNBCypT0N06/112/160.0332 ypT0/isN06/112/160.0332Luminal B HER2+ aypT0N01/151/60.4805 ypT0/isN02/151/61.0000HER2+ aypT0N03/135/90.1870 ypT0/isN05/136/90.3870Ki-67≤20%ypT0N00/160/12/ ypT0/isN01/160/12/Ki-67&amp;gt;20%ypT0N015/6110/620.2437 ypT0/isN019/6112/620.1320a, patients received EC-TH, other patients received EC-T. Conclusions: The results suggested that nP (260 mg/m2, q2w) was associated with a better efficiency profile compared to sP (175 mg/m2, q2w) in NAC for TNBC. Meanwhile, nP also brings more peripheral neuropathy. As a result, nP (260 mg/m2, q2w) is also an NAC option for TNBC in China. Citation Format: Wang J, Xie F, Zhang L, Chen R, Zhu Q, Yin Z, You S, Jiang C, Zha X. Higher efficacy of 2-week nab-paclitaxel compared to solvent-based paclitaxel in neoadjuvant chemotherapy of triple negative breast cancers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-23.

Abstract P1-13-10: Comparison of overall and recurrence-free survival between four and six cycles of adjuvant docetaxel and cyclophosphamide in early stage breast cancer

Abstract Background: The ABC trials and the WSG Plan B trial demonstrated that certain early stage breast cancer patients can be appropriately treated with docetaxel and cyclophosphamide (TC) rather than doxorubicin and cyclophosphamide (AC); however both of these trials utilized six cycles of TC as the comparator. TC is given for 4 cycles based on the US Oncology 9735 trial. To our knowledge, there is no available data that has compared adverse events or outcomes of four versus six cycles of TC. Methods: This was a single-center, retrospective study evaluating recurrence-free survival, overall survival, and occurrence of toxicities between four and six cycles of docetaxel and cyclophosphamide adjuvant chemotherapy for early stage breast cancer at West Virginia University Cancer Institute. Results: 112 patients were included; 81 received four cycles and 31 received six. Recurrence free survival rates of patients that received four and six cycles of chemotherapy were 94% and 90%, respectively, at three years (P=0.68). Overall survival at three years was 99% versus 97% (P=0.49), respectively. The incidence of peripheral neuropathy requiring treatment was 42% in patients that received six cycles and 19% in patients that received four (P=0.015). Conclusion: The addition of two cycles of docetaxel and cyclophosphamide adjuvant chemotherapy for early stage breast cancer provides no additional recurrence-free or overall survival benefit but does increase the incidence of peripheral neuropathy requiring treatment. Table 1.Baseline Characteristics 4 Cycles (n=81)6 Cycles (n=31)P-valueAge, median years (range)57 (37-75)48 (32-71)0.001Receptor status, n (%) 0.63HR positive, HER2 negative61 (75)25 (81) Triple negative20 (25)6 (19) Cancer stage, n (%) 0.031I39 (48)9 (29) II39 (48)17 (55) III3 (4)5 (16) Lymph node involvement, n (%)24 (30)20 (65)0.001Ki67 (%), median (range)23 (2-99)23.5 (4-99)0.99Tumor grade, n (%) 0.07212 (2)4 (13) 242 (52)12 (39) 337 (46)15 (48) Surgery, n (%) Breast conservation35 (43)14 (45)0.99Unilateral mastectomy32 (40)9 (29)0.38Bilateral mastectomy14 (17)8 (26)0.43 Table 2.Adverse Events 4 Cycles (n=81)6 Cycles (n=31)P-valueDose reductions, n (%)17 (21)8 (26)0.62Dose delay, n (%)3 (4)1 (3)0.99Inpatient admissions, n (%)22 (27)8 (26)0.99Treatment for peripheral neuropathy, n (%)15 (19)13 (42)0.015 Citation Format: Mehmi I, Wight CE, Hill JL. Comparison of overall and recurrence-free survival between four and six cycles of adjuvant docetaxel and cyclophosphamide in early stage breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-10.

Associations of Serum S100B and S100P With the Presence and Classification of Diabetic Peripheral Neuropathy in Adults With Type 2 Diabetes: A Case-Cohort Study.

Novel biomarkers of diabetic peripheral neuropathy provide potentially useful information for early identification and treatment of diabetic neuropathy, ultimately serving to reduce the burden of disease. This study was designed to investigate the potential associations of serum S100B and S100P (calcium-modulated proteins) with the presence and classification of diabetic peripheral neuropathy in adults with type 2 diabetes. In a case-cohort setting, the data of 44 participants diagnosed with diabetic peripheral neuropathy, 44 control participants with type 2 diabetes but free of peripheral neuropathy and 87 healthy control individuals were collected and analyzed. Serum S100P concentrations were elevated in participants with diabetic peripheral neuropathy compared with their controls with type 2 diabetes (median [IQR]: 2,235 pg/mL [1,497.5 to 2,680] vs. 1,200 pg/mL [975 to 1,350)], respectively; p<0.001). Conversely, serum S100B values were comparable in these 2 groups (p=0.570). Those with the typical diabetic peripheral neuropathy had significantly higher serum S100P levels compared to their counterparts with the atypical group of diabetic peripheral neuropathies (p=0.048). The independent significant association between serum S100P and diabetic peripheral neuropathy persisted into the multivariable adjusted logistic regression model (OR for S100P: 1.004 [95% CI 1.002 to 1.006]; p<0.001). The present study's findings demonstrated that serum S100P is a more significant indicator of peripheral neuropathy in type 2 diabetes than is serum S100B. Prospective longitudinal studies are required to confirm the prognostic value of baseline serum S100P to predict incident peripheral neuropathy in people with diabetes.

Peripheral neuropathy in patients with hepatitis C virus infection: a clinical and neurophysiological study

Background Hepatitis C virus (HCV)-positive patients may exhibit a wide range of extrahepatic manifestations, including peripheral neuropathy (PN). Aim The aim of this work was to study the incidence and patterns of PN among patients with HCV infection, with a special emphasis on the Egyptian HCV treatment protocol of direct-acting antiviral agents (DAAs). Patients and methods This was a case–control study carried out at the outpatient clinic of Neuropsychiatry and Tropical Medicine Departments in Tanta University Hospitals from August 2017 to April 2018. This study was applied on 60 patients with HCV infection targeting assessment of PN, clinically and neurophysiologically, before starting the Egyptian HCV treatment protocol of DAAs (visit 0) and 3 months later at the end of treatment with compliant drug therapy (visit 1), with follow-up of affected patients for 3 months after stoppage of treatment (visit 2). Results Clinical assessment of patients before treatment showed clinical diagnosis of neuropathy in 10% (6/60) of our patients, with sensory predominance, and by electrophysiology assessment, we found 15% (9/60) of our patients had PN, with sensory axonal type. After treatment, 30% (18/60) of our patients had a clinical evidence of PN with sensory predominance. By electrophysiology, 33.33% (20/60) of our patients were found with sensory axonal type. Follow-up showed partial regression of neuropathy at clinical and electrophysiological level. Conclusion DAAs induced PN in patients after receiving it at the end of treatment, with partial regression on follow-up.

Peripheral polyneuropathy in patients receiving long-term statin therapy.

Peripheral neuropathy is an important potential side effect of statin use. This study was an investigation of the incidence of peripheral neuropathy in patients taking atorvastatin or rosuvastatin for hypercholesterolemia and the relationship to the dose and duration of the treatment. In all, 50 patients using a statin treatment and 50 healthy controls matched for age and gender who had never taken a statin were included in the study. Polyneuropathy was assessed with a neurological examination and electroneuromyography (ENMG). While no polyneuropathy was detected in the control group, polyneuropathy was seen in 33 (66%) of the patients in the statin group (p<0.01). There was no significant difference between the 2 statin groups in the results of the neurological examination or the ENMG findings regarding the incidence of polyneuropathy (p=0.288 and p=0.720, respectively). Neuropathy was observed in a neurological examination performed within the first year in 50% of the rosuvastatin users and 18% of those taking atorvastatin. The severity of the polyneuropathy increased with the duration of the treatment in the atorvastatin group (p=0.030). This study revealed an increased risk of peripheral neuropathy with long-term statin use (>1 year). Electrodiagnostic changes have been detected in motor and sensory nerves in nerve conduction studies of patients on long-term statin treatment. The assessment of neurological symptoms, like tingling, numbness, pain and tremor in the hands and feet, and unsteadiness during walking associated with peripheral neuropathy may be useful in the follow-up of the patients on long-term statin treatment. Early detection of peripheral neuropathy and changing hypercholesterolemia treatment may prevent permanent nerve damage.

Benefit of Two Additional Cycles of Bortezomib/Thalidomide/Dexamethasone (VTD) Induction Therapy Compared to Four Cycles of VTD for Newly Diagnosed Multiple Myeloma

IntroductionFour cycles of bortezomib/thalidomide/dexamethasone (VTD) induction therapy followed by autologous stem cell transplantation (ASCT) is one of the standard therapy for patients aged less than 65 years with newly diagnosed multiple myeloma (NDMM). Complete remission (CR) status before ASCT is an important prognostic factor for progression-free survival (PFS). We analyzed whether two additional cycles of VTD improved the pre- and post-transplant responses as well as PFS compared to the four cycles of VTD induction therapy.MethodsA total of 222 patients with NDMM between September 2014 and August 2016 from eleven hospitals in South Korea were included in the current study. The patients received at least four or more cycles of VTD induction therapy before administration of high-dose therapy (HDT, melphalan 200mg/m2) followed by ASCT. VTD regimen was consisted of bortezomib subcutaneous infusion (1.3 mg/m2 on days 1, 4, 8, and 11), thalidomide (100 mg daily), and dexamethasone (40 mg on days 1-4, 8-11), which was administered every 4 weeks.ResultsThe median age was 57 years (range 30−64 years), and 120 patients (61.9%) were male. Revised international scoring system (R-ISS) classified 59 (30.4%), 86 (44.3%), and 49 patients (25.3%) as stage I, II, and III, respectively. VTD induction was administered 4 cycles in 194 patients (VTD4, 67.5%) and more than 4 cycles in 63 (VTD6, 32.5%) before HDT. Patient characteristics at diagnosis did not differ between VTD4 and VTD6. CR rate before HDT was significantly higher in VTD6 than VTD4 (31.7% vs 13.0%, P = 0.003). However, CR rate after HDT/ASCT was similar between VTD4 and VTD6 (69.0% vs 65.5%, P = 0.726). There was no difference in the incidence of peripheral neuropathy (PN) (≥ grade 2 or that required dose reduction) between two groups. The median follow-up duration was 18.0 months (range 7.0-43.8 months). The 2-year PFS did not differ between the two groups (51.7 ±5.7% in VTD4 and 62.1±8.6% in VTD6, P = 0.240). Multivariate analysis revealed that the achievement of CR was a favorable prognostic factor for PFS (HR 0.27 [0.08−0.90], P = 0.034). Deletion 17p (HR 2.87 [1.01−7.92], P = 0.048) and t(4;14) (HR 3.38 [1.76−6.48], P < 0.001) in FISH were adverse prognostic factors for PFS. Patients with stage I/II by R-ISS receiving additional two cycles of VTD showed prolonged PFS (median PFS not reached vs. 27.6 months, P = 0.034). In the multivariate analysis, VTD6 was a favorable prognostic factor for PFS for patients with stage I/II by R-ISS, (HR 0.11 [0.02−0.52], P = 0.005).ConclusionCR rates increased with additional cycles of VTD induction therapy for NDMM. However, the PFS benefit was observed only in patients with R-ISS stage I/II. For patients with high-risk MM, intensive induction therapy that overcome poor prognostic factors should be administered to improve long-term outcomes. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Impact of Modified Dose Schedule of Bortezomib, Melphalan, and Prednisone (VMP) for Previously Untreated, Transplant-Ineligible Patients with Multiple Myeloma (MM): A Matching-Adjusted Indirect Comparison

Impact of Modified Dose Schedule of Bortezomib, Melphalan, and Prednisone (VMP) for Previously Untreated, Transplant-Ineligible Patients with Multiple Myeloma (MM): A Matching-Adjusted Indirect Comparison

Evidence Based Recommendations for Supportive Care in Multiple Myeloma

Introduction:Multiple myeloma (MM) is associated with end organ damage that negatively impacts the quality of life (QOL)and supportive care has a potential to improve symptoms.Methods:After detailed search on Pubmed, Cochrane, Embase and Clinical Trials.gov, we finalized total 36 articles on supportive care published after 2004.Results:Management of skeletal events: Mhaskar et al. (2017, n=3257) compared bisphosphonates (BPs) with placebo (PBO) in preventing pathological vertebral fractures, skeletal-related events (SRE), reported risk ratio (RR) of 0.74 in each; 95% CI 0.62-0.89 and 0.63-0.88 respectively. Both zoledronic acid (ZA) and clodronic acid prevent SRE, but mortality rate was better reduced with ZA (hazard ratio [HR]=0.84; p=0.0118), (Gareth et al. 2010, n=1960). In a study by Zuradelli et al. (2009, n= 240); hypocalcemia developed in 93 (38.8%) patients on ZA for a median of 2.3 months (range, 0-34.9). Vitamin D and calcium replacement is essential in patients developing hypocalcemia with BPs, (Kennel et al. 2009). Vertebral augmentation procedures improved pain after compression fracture (n=923) by 4.8, 4.6 and 4.4 points at 1 week, 1 year and beyond 1 year respectively, (Khan et al. 2014). Valerie et al. (2011, n=84) analyzed improvement in bone pain with radiotherapy (median 45 grays) in 92 % patients.Prophylaxis of infections: Leng et al. (2018, n=70,687) observed reduced risk of herpes zoster (HZ) reactivation in patients on bortezomib or carfilzomib + HZ prophylaxis (2.4%) vs 5.8% in non-prophylactic group, (attributable risk reduction: 0.42; 95% CI 0.31-0.56). Teh et al. (2016, n=199) reported reduced risk of varicella zoster virus reactivation with valacyclovir (500 mg) in patients on bortezomib based therapy and following autologous stem cell transplant (ASCT) vs no prophylaxis (HR=0.06 vs 16.9; p<0.01). Dimopoulos et al. (2016, n=569) found higher risk of pneumonia, 8.2% in daratumumab group (n=286) vs 7.8% in control group (n=283). Prophylactic trimethoprim-sulfamethoxazole reduced risk of PCP in 85% patients after ASCT (RR=0.15; 95% CI 0.04-0.62), Stern et al. (2014, n=1000). Incidence of Community-acquired pneumonia (CAP), noninvasive CAP and invasive pneumococcal disease in elderly population (≥65 years) was seen in 49, 33 and 7 patients on Pneumococcal polysaccharide conjugate vaccine group as compared to 90, 60 and 28 patients in placebo group respectively, (Bonten et al. 2015, n=84,496).Role of plasmapheresis in renal impairment (RI): Alkhatib et al. (2017) showed that plasmapheresis reduced dialysis dependency by removing serum free light chains (sFLC) in patients with RI (n=147), (RR 0.45; P = 0.02). Yu-X et al. (2015, n=147), showed lower 6-month dialysis dependency ratio with plasmapheresis and chemotherapy (PP + CTH) vs CTH alone, (15.6% vs 37.2%; RR=2.02; p = 0.04). High cut-off hemodialysis lowered sFLC level in 61% (n=42) and 63% patients at day 12 and 21 respectively. Out of these, 71% and 69% patients became dialysis independent, (Hutchison et al. 2012, n=67).Peripheral neuropathy (PN): Bortezomib caused PN in 124/331 (37%) patients (Richardson et al. 2009) whereas with thalidomide, the incidence of PN was 38% and 73% at 6 and 12 months, respectively, (Mileshkin et al. 2006, n=75). PN improved in 68% patients on bortezomib with dose modifications (n=72) vs 47% patients, without dose modification (n=19). (Table 1 and 2). Significant improvement in PN was seen with duloxetine vs placebo (1.06 vs. 0.34; p= 0.003), (Smith et al. 2013, n=231). Arbaiza et al. (2007, n=36) showed improvement in neuropathic pain with tramadol (p= < 0.001).Epoetin and derivates for anemia: Castelli et al. (2017, n= 31; median creatinine 1.2 mg/dL (0.8-3.0)) reported hemoglobin (Hb) increase of ≥1g/dL and ≥2g/dL in 71% and 31.7% patients respectively with epoetin α, transfusions requirement reduced from 2.39 ± 1.05 to 1.23 ± 1.36 (p < 0.001). Begiun et al. (2013, n= 72) compared the effect of darbepoetin (D) ± iron (Fe) vs placebo on erythroid recovery after ASCT. All patients receiving D + Fe achieved Hb ≥13 g/dL (p<0.0001). Tonia et al. (2012, n= 16,093) showed 35% decrease in transfusion need with erythropoietin stimulating agents (RR=0.65; 95% CI 0.62-0.68). (Table 3)Conclusion:Along with anti-myeloma chemotherapy therapy, management of complications (anemia, infections, renal insufficiency) and other associated symptoms is necessary to improve the quality of life. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy and Tolerability of Daratumumab in Heavily Pretreated AL Amyloidosis: A Systematic Review

IntroductionLight chain (AL) amyloidosis is a low burden plasma cell disorder, characterized by deposition of misfolded lambda or kappa light chains. Kidney dysfunction is present in almost two-thirds of patients at the time of initial presentation, followed by diastolic heart failure in about 50% of cases, which is responsible for 75% of deaths in these patients. Autologous stem cell transplant (auto-SCT) remains the gold standard for the management of AL amyloidosis but is often impractical to perform by virtue of patients' age, medical comorbidities including cardiac involvement.MethodsWe conducted a literature search using three databases (PubMed, Embase,Web of Science). Our search strategy included MeSH terms and key words such as AL amyloidosis, daratumumab and darzalex from date of inception to March 2018. After excluding duplicates, reviews and non-relevant articles, we selected eight studies, including two case reports, two phase II prospective trials and four retrospective trials.ResultsData on 129 patients was included, there ages ranged from 43-83 years. Median number of prior therapies were 3 (range: 2-6), 106 (82%) received proteasome inhibitor (bortezomib) based therapy, and 69 (53.5%) received immunomodulatory (lenalidomide) based therapy. Another 41 (32%) received high dose melphalan (HDM) followed by auto-SCT. The time from the diagnosis of AL to the start of daratumumab therapy varied from 0.7-150 months. Eighty-nine (69%) patients had cardiac and 64 (49.6%) patients had renal involvement. A total of 114 (88%) patients received a daratumumab dose of 16 mg/kg weekly for 8 weeks followed by every 2 weeks for the next 8 weeks.A total of 104 patients were evaluable for hematological response, assessed by improvement in free light chain (FLC) levels. Daratumamab achieved an impressive overall response rate (ORR) of 72% (n=75). Complete remission (CR) in 15 (14%) of patients, very good partial response (VGPR) in 44 (42%) and a partial response (PR) in 16 (15%) of patients was noted. Thirty-four patients with cardiac involvement and 26 patients with renal amyloidosis were assessed for organ response across four studies. Thirteen (38%) patients with cardiac amyloidosis demonstrated an improvement in N-terminal pro brain natriuretic peptide (NT-proBNP) levels. Ten (38%) patients with renal involvement responded according to consensus criteria [Palladini et al 2014] for organ response. Another two had improvement in serum creatinine levels.Among the 129 patients treated with daratumumab for AL amyloidosis, 36 (32%) reported infusion related reactions (IRR). Most were mild (grade 1-2). Daratumumab infusion was well tolerated in patients with cardiac (n=54) and renal involvement (n=48). Only one patient needed adjustment in his diuretic dose, another one developed decompensated heart failure and one died due to progression of cardiac disease. Seven patients had worsening of their NT-proBNP levels. Similarly, no dose adjustments were required for patients with renal amyloidosis and one patient tolerated daratumumab infusion at a GFR<20 mL/min without any complications.ConclusionDaratumumab monotherapy is associated with deep and prompt hematological responses in patients with heavily pretreated AL amyloidosis, at the standard dosing regimens used for multiple myeloma, with a favorable safety profile. Furthermore, daratumumab performed well in patients with cardiac amyloidosis even though there is an increased risk of volume overload and infusion related morbidity. Given the high incidence of peripheral neuropathy with bortezomib, cardiotoxicity with carfilzomib based regimens in amyloidosis patients, daratumumab appears to be a suitable alternative. It has already been approved for relapsed amyloidosis (AL) patients in the European Union. Currently, it is being investigated as monotherapy for AL amyloidosis in phase 2 trials (NCT02841033 and NCT02816476) and in combination with bortezomib, cytoxin and dexamethasone (VCd) in a phase III trial (NCT03201965). [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Efficacy of Once-Weekly Bortezomib with Daratumumab for Patients with Relapsed or Refractory Multiple Myeloma

BackgroundMultiple Myeloma (MM) is an essentially incurable hematologic malignancy with the goals of therapy being disease control, improved quality of life, and prolonged survival.1,2 Despite improved survival with proteasome inhibitors and immunomodulatory agents, outcomes for patients with refractory disease, resistant to these classes of therapy, are poor. Daratumumab, an anti-CD38 antibody, is a commonly utilized therapy for relapsed/refractory multiple myeloma (RRMM) as a single agent based on the SIRIUS study which resulted in adequate response and acceptable safety profiles.3,4 Currently, it is approved in various combinations including with bortezomib. The approval of daratumumab in combination with bortezomib days 1, 4, 8, and 11 of a 21-day cycle was based on the CASTOR study which resulted in high response rates and acceptable safety profiles.5With the addition of bortezomib, additional toxicities in this RRMM setting may be a concern.6 Previous studies of bortezomib in RRMM patients have demonstrated that once-weekly bortezomib is equally as efficacious and better tolerated than the standard twice-weekly schedule, with a lower incidence of peripheral neuropathy and myelosuppression.8,9 However, there are currently no published reports of combining once-weekly bortezomib with daratumumab for patients with RRMM.MethodsThe present study sought to evaluate the progression-free survival (PFS) of daratumumab administered with once-weekly bortezomib for patients with RRMM. Secondary objectives included evaluation of overall survival (OS), overall response rate (ORR), time to response (TTR), and toxicity of once-weekly bortezomib with daratumumab. Eighteen patients were identified in an Institutional Review Board (IRB)-approved retrospective review of our institutional experience with daratumumab and once-weekly bortezomib. The median age of patients was 65 years (range 47 - 76, Table 1). Ten patients (55.6%) had three or more prior lines of therapy. Twelve patients (66.7%) had previous autologous stem cell transplantation. Sixteen patients (88.9%) had prior proteasome inhibitor (PI) therapy. Thirteen patients (72.2%) had disease refractory to their last line of therapy.ResultsThe median PFS was 3.5 months. Median OS was not reached and TTR were undetermined due to the small sample size. The ORR was 33.3%, with 6 out of 18 patients experiencing an objective partial response or better (Table 2). Of those that responded, 4 patients (66.7%) remained on therapy at the time of data collection.The side effect profile was more tolerable, with less thrombocytopenia (27.8% all grade) and peripheral neuropathy (33.3% all grade) than previously reported (Table 3).ConclusionsDaratumumab monotherapy was approved in heavily pretreated RRMM based on the SIRIUS trial showing promising efficacy and a favorable safety profile.4 The median PFS was 3.7 months compared to our PFS of 3.5 months. The combination of daratumumab with bortezomib administered twice weekly was approved based results from the CASTOR trial showing superiority of daratumumab in combination with bortezomib and dexamethasone over bortezomib and dexamethasone.5 As depicted in Table 2, our ORR of 33.3% is similar to the ORR of 29.2% in the SIRIUS trial, however differs greatly from 82.9% in the CASTOR trial.While the present work is retrospective and hypothesis-generating, our results suggest that further prospective inquiry is necessary to determine the additional efficacy of adding once-weekly bortezomib to daratumumab. [Display omitted] DisclosuresDempsey:Heron Therapeutics: Honoraria; TESARO: Honoraria.

Longitudinal pattern of pain medication utilization in peripheral neuropathy patients.

We aimed to investigate the pattern and utilization of neuropathic pain medications in peripheral neuropathy patients. Using a privately insured, health care claims database from 2001 to 2014, we identified a retrospective cohort of incident peripheral neuropathy patients (validated ICD-9 definition) after excluding other chronic pain conditions. Outcome measures included opioid prescriptions, chronic opioid therapy (greater than or equal to 90 days of continuous supply), guideline-recommended medications for painful peripheral neuropathy (serotonin reuptake inhibitors, tricyclic antidepressants, and gabapentinoids), and pain specialists (neurologists, physiatrists, and anesthesiologists). Multivariable logistic regression was used to evaluate associations of patient-level factors with these outcomes. The peripheral neuropathy population included 14,426 individuals with a mean (SD) age of 43.1 years (2.8) and 52.4% men followed for 3.1 (1.7) years before and 4.5 (1.4) years after the diagnosis. In this population, 65.9% received ≥1 opioid prescription, and 8.8% received chronic opioid therapy. Of those receiving chronic opioid therapy, only 26.4% received a guideline-recommended medication before chronic opioid status. For guideline-recommended medications, 35.7% received ≥1, 12.4% ≥2, and 3.8% ≥3 different medications. No patient-level factors were associated with both high opioid utilization (initiation and chronic use) and low guideline-recommended medication utilization. Pain specialists were associated with high opioid utilization and high guideline-recommended medication utilization. In conclusion, opioid initiation and transition to chronic opioid therapy are frequent in a peripheral neuropathy population despite few patients receiving more than one guideline-recommended medication. Efforts to decrease opioid utilization and increase guideline-recommended medication use are needed to improve current neuropathic pain treatment.

Comparison of the Effects of Omega 3 and Vitamin E on Palcitaxel-Induced Peripheral Neuropathy.

BACKGROUND:Paclitaxel-induced peripheral neuropathy is the most important side effect limiting the use of this medication.AIM:This study aimed to compare the effects of omega-3 and vitamin E on the incidence of peripheral neuropathy in patients receiving Taxol.METHODS:In this clinical trial, 63 patients who were a candidate for receiving taxol, were enrolled based on inclusion and exclusion criteria. In group O, patients received 640 mg omega-3 three times a day, and group E, received 300 mg vitamin E two times a day. Patients took the supplements up to three months after the onset of Taxol. Group P received placebo for a similar period. All patients referred to a neurologist for electrophysiological evaluation before the onset of chemotherapy and at months 1 and 3. The presence of neuropathy and its progression was recorded by the neurologist.RESULTS:Neurological examination in this study indicated that 6 patients (28.6%) in Group O, 7 patients (33.3%) in group E, and 15 patients (71.4%) in placebo group started peripheral neuropathy. There was a significant difference between intervention groups and the placebo group (p = 0.0001) and no significant difference between intervention groups (p = 0.751).CONCLUSION:Our data suggested that vitamin E and omega-3 may significantly reduce the incidence of Paclitaxel-induced peripheral neuropathy. Routine administration of such supplements that have no special side effect for patients under chemotherapy may greatly enhance their quality of life.

An efficient approach on alcohol dependence syndrome

Alcohol consumption results in multiple end-organ damages. Predominantly the nervous system is affected in the form of Wernicke encephalopathy, Korsakoff psychosis, cerebellar ataxia and peripheral neuropathy. Neuropathy due to alcohol consumption depends on the period and extent of total lifetime of alcohol consumption. Cultural and racial factors also play a role in the development of alcohol neuropathy. Alcohol consumption results in multiple end-organ damages. Alcoholic neuropathy is the most common harmful effects of excessive alcohol intake. The incidence of alcoholic neuropathy in the standard population is not accurate as the percentage varies extensively contingent on the description of chronic alcoholism and the criteria used to detect and classify neuropathy. According to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), studies involving clinical and electrodiagnostic tests prove that neuropathy is present in 25-66%. Alcoholic neuropathy depends on the extent and extent of total lifetime of alcohol consumption. Cultural and racial factors also play a role in resulting in alcohol neuropathy. Few studies suggest that the incidence of peripheral neuropathy is higher in alcoholic patients who have a family history of alcohol dependence syndrome. This is study finds the Common peroneal and sural nerves are the most common nerves to be involved in neuropathy. Predominantly axonal degeneration is the main pathology. Units of alcohol and CAGE criteria score has a 100% specificity in detecting patients prone to neuropathy.

Preventive Effects of Renin-angiotensin System Inhibitors on Oxaliplatin-induced Peripheral Neuropathy: A Retrospective Observational Study

PurposeOxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy. MethodsThis study retrospectively analyzed data from cancer patients who had received chemotherapy including oxaliplatin and were treated with or without RAS inhibitors. This retrospective observational study was conducted at Ehime University Hospital using electronic medical records from May 2009 to December 2016. The primary end point was the incidence of severe peripheral neuropathy during or after oxaliplatin treatment, according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate Cox proportional hazards model analysis was used to identify risk factors. FindingsA total of 150 patients were included in the study. The estimated incidence of peripheral neuropathy was 36.9% and 91.7% in the RAS inhibitor group and the non–RAS inhibitor group, respectively. The multivariate analysis using a Cox proportional hazards model showed that the RAS inhibitor group was slightly associated with a decreased risk of neurotoxicity (adjusted hazard ratio, 0.42 [95% CI, 0.18–0.99]; P = 0.048). ImplicationsThe present findings suggest that RAS inhibitors have the ability to prevent oxaliplatin-induced peripheral neuropathy.

Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation

BackgroundMantle cell lymphoma (MCL) is an aggressive and incurable lymphoma. Standard of care for younger patients with MCL is induction chemotherapy followed by autologous stem cell transplantation (auto-HCT). Rituximab maintenance after auto-HCT has been shown to improve progression-free survival (PFS) and overall survival (OS) in MCL. Bortezomib maintenance therapy has also been shown to be tolerable and feasible in this setting. However, the combination of bortezomib and rituximab as maintenance therapy post-auto-HCT has not been studied.MethodsWe conducted a multicenter, phase II trial of bortezomib given in combination with rituximab as maintenance in MCL patients after consolidative auto-HCT. Enrolled patients (n = 23) received bortezomib 1.3 mg/m2 subcutaneously weekly for 4 weeks every 3 months (up to 24 months) and rituximab 375 mg/m2 intravenously weekly for 4 weeks every 6 months (up to 24 months) for a total duration of 2 years. The primary study endpoint was disease-free survival (DFS).ResultsWith a median follow-up of 35.9 months, the 2-year DFS probability was 90.2% (95% CI 66–97), and 2-year OS was 94.7% (95% CI 68–99). The most frequent grade 3/4 toxic events were neutropenia (in 74% of patients) and lymphopenia (in 35%). The incidence of peripheral neuropathy was 48% for grade 1, 9% for grade 2, and 0% for grade 3/4. We also examined the role of quantitative cyclin D1 (CCND1) mRNA in monitoring minimal residual disease.ConclusionCombined bortezomib and rituximab as maintenance therapy in MCL patients following auto-HCT is an active and well-tolerated regimen.Trial registrationClinicalTrials.govNCT01267812, registered Dec 29, 2010.

Impact of adjuvant FOLFOX on quality of life and peripheral neuropathy incidence in patients with localized gastric cancer.

e16039Background: In localized gastric cancer there is evidence supporting a survival benefit for perioperative chemotherapy, adjuvant chemotherapy and adjuvant chemoradiotherapy. However, there is...

F34. Effects of impaired glucose regulation on large and small fibers in peripheral nerve

Introduction We use nerve conduct study (NCS) to evaluate the function of large fibers, skin sympathetic response (SSR) and contact heat evoked potential (CHEP) to evaluate the function of small fibers in patients with impaired glucose regulation (IGR), The occurrence of peripheral neuropathy and damage characteristics are analyzed. Methods According to the classification criteria of glucose metabolism proposed by WHO 2006,we selected 120 patients with IGR, and 60 normal subjects as the control group.All subjects received median, ulnar, tibial, peroneal, sural nerve conduction study (NCS), skin sympathetic response (SSR) and contact heat evoked potential (CHEP) were performed using the Keypoint.net (Medoc Ltd) electromyogram device. Results 1.The abnormal rate of NCS in IGR patients were 22.5%; the abnormal rate of SSR was 39.2%, All patients with NCS abnormalities were associated with abnormal SSR 2.Compared with the control group, the tibial, sural nerve sensory nerve action potential (SNAP) amplitude decreased in IGR group, (2.01 ± 1.5) vs (1.51 ± 1.3) uV, t = −3.01, P = 0.003; (10.5 ± 2.0) vs (6.5 ± 1.9) uV, t = −2.82, P = 0.005 respectively; SSR amplitude reduced in upper and lower limbs (2124 ± 1346) vs (1463 ± 1140) uV, t = −3.21, P = 0.002; (892 ± 387) vs (531 ± 501) uV, t = −6.18, P = 0.00 respectively; CHEP amplitude decreased in dorsum hand and peroneal area stimuli respectively (63.0 ± 10.0) vs (52.4 ± 12.6) uV, t = 3.09, P = 0.003; (44.7 ± 12.5) vs (29.3 ± 12.1) uV, t = 5.84, P = 0.00.3.Compared with the control group, CHEP amplitude decreased in peroneal area stimuli in SSRN group [(44.7 ± 12.5) vs (33.1 ± 18.9) uV, t = 2.94, P = 0.00]; In NCSN group, CHEP amplitude decreased in dorsum hand and peroneal area stimuli compared with the control group respectively (44.7 ± 12.5) vs (28.4 ± 17.4) uV, t = 1.88, P = 0.00; (63.0 ± 10.8) vs (52.4 ± 15.3) uV, t = 2.22, P = 0.00. Conclusion The incidence of peripheral neuropathy (PN) in patients with IGR was 39.2%, Neuropathy showed large and small fiber damage, mainly manifested as small fiber and lower limb sensory nerve fiber damage,CHEP can find small fiber damage earlier than SSR and NCS in patients with IGR.

Evaluation of Peripheral Neuropathy in Diabetic Adults with and without Foot Ulcers in an African Population

Background: Foot ulcers frequently precede lower extremity amputations (LEA) in diabetic subjects. Peripheral neuropathy (PN) is a strong risk factor for diabetic foot ulceration. Majority of diabetic patients with PN are asymptomatic; hence foot ulceration may be the first clinical presentation. Early detection of PN can forestall the development of foot ulcers through active preventive strategies. Few studies have been done to assess PN in diabetic individuals in Africa. The study aims to evaluate the incidence and risk factors for PN in diabetic adults with and without foot ulcers in an indigenous African population. Method: This cross-sectional study involved 90 diabetic adults, 45 with foot ulcers and 45 without foot ulcers. Assessment of PN was done with the Michigan Neuropathy Screening Instrument (MNSI), the 10 g Semmes-Weinstein monofilament (SWM) and the 128-Hz vibrating tuning fork (VTF). Demographic data were collected by questionnaire. Associations between PN and risk factors such as age, alcohol consumption, duration of diabetes, cigarette smoking, BMI, height and sex were also investigated. Results: There were 59 males (65.6%) and 31 females (34.4%) in the study. The mean age of the subjects with foot ulcers was 59.62 years (SD = 6.47), while those without ulcers was 57.47 years (SD = 6.94). Forty-two subjects (93.33%) with foot ulcers have PN using the MNSI, while 33 subjects without foot ulcers (73.33%) have PN. Both the SWM and the VTF showed a high positive correlation with themselves and with the MNSI. Advancing age, duration of diabetes, alcohol intake, hyperglycaemia and cigarette smoking showed a significant association with peripheral neuropathy, while BMI, height and sex did not. Conclusion: The incidence of PN is quite high in diabetic adults in Africa. This calls for early screening and aggressive control of risk factors to prevent the development of diabetic foot ulceration.

Neurologic injury and patient displacement in gynecologic laparoscopic surgery using a beanbag and shoulder supports

To quantify the incidence of peripheral neuropathy in gynecologic laparoscopic surgery using a combination of beanbag, eggcrate foam, and shoulder supports; and to assess patient displacement during surgery in a steep Trendelenburg position and determine variables correlated with displacement. A retrospective study included all gynecologic laparoscopic surgeries performed by one high-volume surgeon at a US center between September 15, 2007, and September 15, 2012. Data included neurologic deficits or extremity pain, any other complications, and-for the final study year-surgical time as well as patient and beanbag displacement. Among 967 patients, no long-term neuropathy was reported, 6 (0.6%) patients had transient shoulder pain beyond the first 24hours (resolved by initial postoperative visit), and 7 (0.7%) were lost to follow-up. No neurologic complications were reported. Median beanbag and total patient displacement were 0cm (interquartile range 0-0) and 0cm (interquartile range 0-2), respectively. Patient displacement relative to the table was correlated with the total surgical time (P=0.025) and patient weight (P=0.023). The median displacement was greater in hysterectomy than non-hysterectomy procedures (P=0.003). Use of beanbags with shoulder supports and convoluted foam armboard pads was associated with minimal patient displacement and risk of arm and leg neurologic injury.