Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 17 de 17
Filter
1.
HemaSphere ; 6:1548-1549, 2022.
Article in English | EMBASE | ID: covidwho-2032124

ABSTRACT

Background: Systemic AL amyloidosis is an incurable relapsing plasma cell disorder. Despite therapeutic advances, there are no approved treatments for relapse disease. Treatment is often challenging due to underlying organ dysfunction. Belantamab mafodotin is an antibody-drug conjugate targeting B-cell maturation antigen with approval for relapsed refractory myeloma. In multiply pre-treated myeloma, the DREAMM-2 phase II trial showed an overall response rate of 32% for those with 2.5 mg/kg dose administered every three weeks with 2/3rd patients reporting keratopathy. A small case series of 6 patients with relapsed AL amyloidosis (Zhang et al , ASH 2021) was recently reported and a phase 2 trial is recruiting for patients with refractory amyloidosis (NCT04617925). Aims: We report our initial results using Belantamab monotherapy for the treatment of patients with AL amyloidosis with relapsed disease. Methods: Data for consecutive patients who were administered Belantamab at a specialist referral centre, National Amyloidosis Centre, University College London, was analysed. Results: Eleven patients were included 8 male, 3 female. Median age at Belantamab initiation was 65 (range 42-74) years. Eight patients had λ AL-type and three κ AL-type. At diagnosis, median involved free light-chain concentration was 534 (range 73-7181) mg/l. A median of two organs involved at baseline (range 1-3): 4 had cardiac involvement (half Mayo stage 2;half Mayo stage 3a) and 8 had renal involvement. The median prior lines of therapy was 3 (range 2-5) with all exposed to prior immunomodulatory drugs, proteasome inhibitors and 73% to anti-CD38 antibody treatments. Thirty-six percent had relapsed after melphalan-conditioned autologous stem cell transplantation. A median of 3 cycles of belantamab were delivered (range 1-8). The most frequent adverse event was ocular toxicity which was experienced in 8 patients (grade 1-3), necessitating dose modification of the three-weekly schedule. One patient developed transient grade 1 dyspnoea and liver dysfunction. No patients developed cytopenias, unlike previous reports (Zhang et al , 2021), nor infections beyond COVID (2 patients mild with no hospital admissions). The majority of the cohort required dose reduction either at initiation (patient 4, due to end stage renal failure;patient 11, post-renal transplant) or during therapy (n=5;three to 1.9mg/kg, two to 1.25mg/kg) due to ocular toxicity. Only one patient remained on the standard dose of 2.5mg/kg for >3 cycles. Ocular toxicity improved after treatment interruption (drug intervals 4-6 weeks) and no patients required complete treatment cessation. One patient is too early to assess response. Haematological responses (PR or better) were seen in 7 patients with 3 complete responses and two very good partial responses (VGPR) which are ongoing. Both renal patients (patients 4 and 11) commenced a dose of 1.25mg/kg and sustained a VGPR with no additional toxicity. Patient 3 had a 42% reduction in sFLC after two doses but then a prolonged gap due to keratopathy and has lost the response. There were no cardiac or renal toxicities observed. Summary/Conclusion: Belantamab mafodotin demonstrates significant activity in patients with heavily pre-treated AL amyloidosis with 70% achieving a ≥PR. Apart from keratopathy requiring dose modification, no other substantial toxicity was observed. Two patients with renal impairment (stage V CKD and ESRD) and one patient post-renal transplant tolerated treatment with no additional toxicity. Belantamab mafodotin shows promise in treatment of relapsed AL and needs further prospective trials.

2.
Asia Pacific Journal of Educators and Education ; 37(1):19-45, 2022.
Article in English | Scopus | ID: covidwho-2026170

ABSTRACT

Students and lecturers are mostly accustomed to the physical learning environment in the classroom. The transition to online learning requires quick adaptation, and students often face challenges which cause hindrance in their learning. This paper aims at highlighting students’ adaptability in online learning which can help university students and management to respond effectively to the variable factors, namely, self-regulation and self-efficacy. Based on the social cognitive theory of motivation, this study examines the relationships between students’ selfregulation, self-efficacy and adaptability in online learning. Self-efficacy is examined as a mediator and moderator variable in the relationship between self-regulation and students’ adaptability. The samples comprised of 238 students from private universities in Malaysia through a survey questionnaire. Partial least squares-structural equation modelling (PLS-SEM) was used to test the hypotheses. The results showed a direct and positive relationship for all direct relationships between variables. In addition, self-regulation and students’ adaptability is significantly mediated by self-efficacy. However, in this study, the moderator analysis found no support. This study provides theoretical and practical implications to gain a better understanding of students’ adaptability in online learning and proposed intervention for higher education institution to address and promote self-regulation and self-efficacy among students. By implementing such interventions, it is hoped that students are better able to adapt, stay motivated and in getting the most out of online learning. © Penerbit Universiti Sains Malaysia, 2022.

3.
Neurology ; 98(18 SUPPL), 2022.
Article in English | EMBASE | ID: covidwho-1925326

ABSTRACT

Objective: To describe the spectrum of acute neurological disorders among hospitalized patients who recently received COVID-19 mRNA vaccination. Background: The unprecedented pace of COVID-19 vaccine development, use of novel mRNA technology and large-scale vaccination programs have engendered concerns of adverse events following immunization. Design/Methods: We performed a multi-centre prospective observational study in 7 public acute hospitals. Hospitalized patients who were referred for neurological complaints and had COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, in the last 6 weeks were classified into central nervous system(CNS) syndromes, cerebrovascular disorders, peripheral nervous system(PNS) disorders, autonomic nervous system(ANS) disorders and immunization stressrelated responses(ISRR). To contextualize our findings, data from National Immunization Registry was probed for the total number and demographic of individuals vaccinated in the corresponding period. Results: From 30 December 2020 to 20 April 2021, 1,398,074 persons (median age 59 years, 54.5% males) received COVID-19 mRNA vaccine (86.7% BNT162b2, 13.3% mRNA-1273);915,344 (65.5%) completed 2 doses. Four hundred and fifty-seven (0.03%) patients were referred for neurological complaints [median age 67 years, 61.5% males;95.8% received BNT162b2 and 4.2% mRNA-1273];classified into 73 (16.0%) CNS syndromes, 286 (62.6%) cerebrovascular disorders, 59 (12.9%) PNS disorders, 0 ANS disorders and 39 (8.5%) ISRRs. Twenty-seven had cranial mononeuropathy, 11 of whom had Bell's palsy. Of 33 patients with seizures, only 4 were unprovoked and occurred within 2 weeks of vaccination. All strokes occurred among individuals with pre-existing cardiovascular risk factors. We recorded 2 cases of cerebral venous thrombosis;none associated with thrombocytopenia. Five had mild flares of immune-mediated diseases. Conclusions: Our observational study does not establish causality of the described disorders to vaccines and is limited by lack of baseline incidence data of several conditions. Nevertheless, we did not observe any obvious signal of serious neurological morbidity associated with mRNA vaccination. The benefits of COVID-19 vaccination outweigh concerns over neurological adverse events.

4.
British Journal of Haematology ; 197(SUPPL 1):147-148, 2022.
Article in English | EMBASE | ID: covidwho-1861242

ABSTRACT

Apixaban 2.5 mg twice-daily replaced low-molecular-weight-heparin as thromboprophylaxis (TP) for multiple myeloma (MM) patients receiving outpatientbased chemotherapy considered to be high-risk of venous thromboembolism (VTE) on 1st November 2019 in our regional centre. This prospective cohort study aimed to assess the safety and efficacy of apixaban as thromboprophylaxis in highthrombotic risk patients with MM. Data were systematically collected from the electronic noting system for service evaluation, retrospectively for the historic cohort (1st Nov 2018-1st Nov 2019) prior to the introduction of the novel thromboprophylactic strategy, and prospectively (1st Nov 2019-1st Nov 2020) following the change of local guidelines to include apixaban as TP in high-thrombotic risk patients with MM. Exclusion criteria included antithrombotic treatment other than thromboprophylaxis or contraindication to thromboprophylaxis such as thrombocytopenia or doxorubicin use (due to possible drug-drug interaction with apixaban leading to reduced levels). Data collected included previous VTE history, thromboprophylactic agent, thrombosis and bleeding events while on chemotherapy. Primary outcomes included thrombotic and bleeding events. Table 1 demonstrates patient characteristics and results. There were 102 MM patients in the historic and 147 in the prospective cohort. VTE prophylaxis was prescribed in 82 out of 102 (80%) of the historic cohort and 114 out of 147 (78%) of the prospective cohort. In patients not prescribed thromboprophylaxis, the chemotherapy regimen contained Daratumumab in 65% in the historic and 76% in the prospective cohort. After the introduction of the amended thromboprophylactic strategy, prescriptions of apixaban increased from 22out of 82 (27%) to 60 out of 114 (53%), while aspirin prescriptions fell from 51out of 82 (62%) to 47 out of 114 (41%). After the introduction of apixaban as recommended thromboprophylaxis for high thrombotic risk patients, thrombotic events reduced from 3% (3/102) to 1.4% (2/147). All thrombotic events (two deep vein thrombosis [DVT], one pulmonary embolism) in the historic cohort occurred despite aspirin as thromboprophylaxis and on a pomalidomidecontaining regimen. In the prospective cohort, the thrombotic events were a proximal DVT while on aspirin TP and a peripherally inserted central catheter (PICC)-associated thrombosis occurring on no TP. There were no thrombotic events in patients receiving prophylactic apixaban in either cohort. There were five bleeding events in the historic cohort. This included one major bleeding event of a traumatic subdural haematoma (on apixaban TP). There were two clinically relevant non-major bleeding (CRNMB): an episode of frank haematuria and a per rectum bleed secondary to haemorrhoids (aspirin as TP), and two minor bleeds. In the prospective cohort, there was one major bleeding event which was a gastrointestinal bleed requiring a two-unit blood transfusion (aspirin as TP). One CRNMB event included haemoptysis secondary to COVID-19 (apixaban as TP) and eight minor bleeding events, two of which occurred on no TP. Overall, major bleeding occurred in 1.2% (1/82) and CRNMB in 1.2% (1/82) patients on prophylactic apixaban across both cohorts. These data add further support to the use of apixaban rather than LMWH as thromboprophylaxis for myeloma patients is considered to be at high thrombotic risk, with very low rates of thrombosis and acceptably low rates of major and CRNMB..

5.
ACS Applied Electronic Materials ; 4(4):1732-1740, 2022.
Article in English | Scopus | ID: covidwho-1839488

ABSTRACT

Since its beginning, various countries have gone through multiple waves of surging COVID-19 infections. With the emergence of variants like Delta and Omicron, the disease is highly contagious and has the ability to spread at an alarming rate. In such scenarios, a quick and effective detection system is highly desirable. In this study, we present the concept of a surface plasmon resonance (SPR) based sensing system that can be utilized efficiently and reliably for the detection of SARS-CoV-2 antigens. The SPR system offers multiple advantages like real-time and label-free sensing of analytes and commercial systems have been in the market for more than two decades. Antireflective coatings (ARCs) have a number of application areas because of their unique properties. But they have seldom been used in the area of SPR sensing Hence, with the help of simulation, we make use of these coatings as intermediate layers and propose an enhanced sensing scheme by making use of ARCs of TiO2and SiO2and perovskite materials-BaTiO3, PbTiO3, and SrTiO3. We found that, using TiO2, SiO2, and PbTiO3, a maximum sensitivity of 392 degRIU-1can be obtained which is 5.29-fold enhancement as compared to the standard SPR arrangement using gold. © 2022 ACS Applied Electronic Materials. All right reserved.

7.
Blood ; 138(SUPPL 1):1628, 2021.
Article in English | EMBASE | ID: covidwho-1770286

ABSTRACT

Background Plasma cell disorders (PCD) are at risk of inadequate immune responses to COVID-19 vaccines due to recognised humoral and cellular immune dysfunction which is multi-factorial and related to host and disease factors. With an estimated risk of 33% mortality from contracting COVID-19 in this population, protection with an anti-SARS-CoV-2 vaccination is critical. Initial extension to vaccination intervals in the United Kingdom to 12 weeks in December 2020 led to concerns that PCD patients would be left vulnerable for an extended period. Methods A clinical audit was performed on measured serological responses in PCD patients after first and second doses of the BNT162b2 and ChAdOx-1 nCoV-19 vaccines. Antibody levels were measured using Elecsys Anti-SARS-CoV-2S assay (Roche) for quantitative detection of IgG Abs, specific for the SARS-CoV-2 spike-protein. Positive cut-off of 0.80 U/mL defined serological response. Testing was performed at (or closest to) 4 and 8-weeks post-dose. Baseline nucleocapsid Ab results were available from previous screening in a subset of patients. All patients on CIT underwent 4-weekly swabs. Clinical information was retrieved from medical records. Results 188 PCD patients (155 multiple myeloma, 18 amyloid, 10 SMM/MGUS, other 5 PCD), median age 64 (range 32-84), had serological assessment after both vaccine doses. Fourteen with previous COVID-19 infection were excluded. Of 174 patients, 112 were tested after first dose. 88% (153) were on chemo-immunotherapy treatment (CIT). Seropositive rate after first dose was 63% (71/112);of those with available negative baseline antibody test, 62% (31/50) seroconverted. After second dose, 89% (154/174) were seropositive;of those with negative baseline antibody, 90% (61/68) seroconverted. Expectedly, paired median titres after second dose were significantly higher than post first dose (n=112, 3.245 U/mL (IQR 0.4-25.55) vs 518 U/mL (IQR 29.40-2187) p<0.0001) (Figure 1A). Of 41 patients seronegative after first dose, 25 (61%) seroconverted after second, though with lower titres than those only requiring one dose (Figure 1B). Active CIT, disease response less than PR, >=4 lines therapy, light-chain disease, male gender and not responding to first dose were significant factors for not responding to two vaccine doses. We explored <400 U/mL as sub-optimal response (in keeping with upcoming booster study eligibility, OCTAVE-DUO(1), also encompassing the lower quartile of reported healthy controls(2)), which included 43% (75/174) patients. Age 70 years, male gender, >=4 lines of treatment were independent predictors of less-than-optimal response (anti-CD38 CIT of borderline significance). Importantly, vaccine dosing intervals classified as =<42 vs >42 days (Figure 1C) or 28 +/- 14 days vs 84 +/- 14 days (excluding n=66 in neither) (Figure 1D) did not show difference in both definitions of response, neither did vaccine type. Fourteen with previous COVID-19 infection responded to one vaccine dose, median titres 2121 U/mL (IQR 23.48- 2500)) rising to median 2500 U/mL (IQR 2500-2500) after second dose (Figure 1E), significantly higher than those without previous infection. Conclusion Serological response to COVID-19 vaccine is lower in PCD patients than reported healthy controls at 63% after first dose, rising to 89% after second dose, despite extended dosing intervals. PCD patients should be prioritised for shorter intervals, as we show that patients seronegative after first dose, respond after second dose. Further work in PCD is needed to understand how Ab levels correlate to neutralisation capability, cellular responses, protection from infection and how long seroconversion lasts to better define correlates of protection. A booster vaccination or prophylactic passive antibody strategy may be required for those identified at risk, shown not to have responded to two vaccine doses or to have less-than-optimal response. Results from these trials will be eagerly awaited. (Figure Presented).

8.
Blood ; 138:4120, 2021.
Article in English | EMBASE | ID: covidwho-1582391

ABSTRACT

Introduction: Daratumumab in combination with bortezomib and dexamethasone (DVd) demonstrated a superior overall response rates (ORR) and progression free survival (PFS) compared to Vd in the CASTOR phase 3 trial for patients with RRMM. On this basis, DVd was recommended in March 2019 for UK patients with RRMM that had 1 prior line (PL). Discrepancies in outcomes between patients treated in clinical trials compared to routine practice is well recognised due to a combination of patient, disease and treatment-related factors. In addition, bortezomib is often administered once-weekly in routine practice to minimise neuropathy, while CASTOR used bi-weekly bortezomib dosing. As a result, the real-world outcomes of patients treated with DVd are yet to be determined. The primary aims of this analysis was to assess the ORR and PFS for patients with RRMM with 1PL treated with DVd in routine practice. Secondary aims were to assess OS, time to next treatment (TTNT), and efficacy in different sub-groups (high risk cytogenetics, previous proteasome inhibitor (PI) exposure, refractoriness of prior therapies, bi-weekly vs weekly bortezomib schedule, and previous treatment free interval (TFI)). Methods: This was a retrospective analysis from 14 centres (academic and community hospitals;7 within the West Midlands Research Consortium (WMRC)) treated with DVd between March 2019 and June 2021. Patients received daratumumab (IV and then SC from June 2020) weekly in cycles 1-3, on day 1 of a 3-week cycle during cycles 4-8, and then monthly from cycle 9 to progression. SC Bortezomib was predominantly given weekly for cycles 1-8 although 5 centres used bi-weekly dosing for selected patients with aggressive disease. Adverse events were graded as per CTCAE criteria. Results: 288 patients were included, with a median age of 69 years (range 20-88) (Table 1). Patients received a median of 1 PL (range 1-2) with 93% (269) 1PL, 7% (18) 2 PL (due to COVID-19 measures). The majority had an ECOG performance status of 0-2 (98%) and most received weekly bortezomib (n=201). This population differed from those with 1PL treated on CASTOR in being older, more were ISS 3 (31% vs 19%, p=0.0145), and more had prior bortezomib exposure (71% vs 51%, p=0.0003), 4% were PI refractory, 9% had a GFR of <30ml/min (<20ml/min was an exclusion from CASTOR), and 2% had an ECOG performance status of ≥3. The ORR was 76%, with >VGPR in 54% (Table 2), with no significant difference in response between patients receiving biweekly vs weekly bortezomib (85% vs 83%;p=0.71). The median time to response was 1.6m. With a median follow up of 15m, the median PFS was 14m (95% CI 11.6-16). High cytogenetic risk patients had inferior outcomes: median PFS 10m (95% CI 6-14) for high risk vs not reached for standard risk (p=0.043);as did those with advanced ISS: median PFS was not reached, 15 and 12m for stage I, II and III respectively (p=0.05). For 15 patients with extramedullary disease (EMD), the median PFS was 3m (95% CI 1-5). Median PFS for patients who were PI refractory was shorter (10m vs 15m for PI sensitive patients (p=0.006)). There was no difference in median PFS for patients with prior PI exposure vs no prior PI (15 vs 13m;p=0.75), or according to weekly or bi-weekly bortezomib schedule (11 vs 15m;p=0.14). The median TTNT was 21m (95% CI 17-25). Overall, the median duration of treatment was 8m and 25 patients (9%) stopped treatment to receive a second autologous stem cell transplant. Those that had a prior TFI of >12m had a longer median PFS of 21m vs 10m (p=0.0004). The median OS has not been reached, with an estimated 2-year OS of 74%. For patients with high risk cytogenetics the median OS was 16m (95% CI 9-23;vs not reached for standard risk;p=0.0006), with estimated 2-year OS in the high risk group of 36%. There was no difference in OS for patients treated with biweekly vs weekly bortezomib (not reached for either;p=0.38). DVd was generally well tolerated with 6% stopping due to adverse events (CASTOR 9.5%). Grade 3 or 4 toxicity occurred in 62 (22%) most comm nly neutropenia and thrombocytopenia, with any grade infusion reactions reported in 27 (9%). Conclusions: These real-world data of DVd at 1 st relapse demonstrated good tolerability and high response rates with a weekly bortezomib schedule despite a more heterogenous population. However, high risk patients by cytogenetics, ISS or EMD had inferior outcomes as did those treated within 12 months from first line treatment. [Formula presented] Disclosures: Cook: Karyopharm: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Sanofi: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria, Research Funding;Oncopeptides: Consultancy, Honoraria;Roche: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding. Pratt: Binding Site: Consultancy;BMS/Celgene: Consultancy;Gilead: Consultancy;Janssen: Consultancy;Takeda: Consultancy;Amgen: Consultancy. Kishore: Celgene: Other: Attending fees;Jannsen: Other: Attending fees;Sanofi: Other: Attending fees;Takeda: Other: Attending fees. Yong: Amgen: Honoraria;Autolus: Research Funding;BMS: Research Funding;Janssen: Honoraria, Research Funding;Sanofi: Honoraria, Research Funding;GSK: Honoraria;Takeda: Honoraria. Popat: Abbvie, Takeda, Janssen, and Celgene: Consultancy;Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES;GlaxoSmithKline: Consultancy, Honoraria, Research Funding;AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria;Janssen and BMS: Other: travel expenses.

10.
Clinical Lymphoma, Myeloma and Leukemia ; 21:S2-S3, 2021.
Article in English | EMBASE | ID: covidwho-1517533

ABSTRACT

Background: The role of upfront ASCT for NDTE MM remains under evaluation with high MRD rates following novel induction and consolidation (cons) strategies. K maintenance represents an alternative strategy to lenalidomide maintenance. The CARDAMON trial investigated K maintenance following KCd induction plus either ASCT or KCd cons. Methods: NDTE pts received 4 x KCd induction (K 20/56 mg/m2 biweekly, C 500 mg D 1,8,15, d 40mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons followed by 18 cycles K maintenance (56mg/m2 D1,8,15). Flow cytometric MRD (10-5) was assessed post induction, pre-maintenance and at 6 months maintenance. Primary endpoints were ≥VGPR post induction and 2-year PFS from randomisation. Secondary endpoints included improvements in disease response and MRD conversion following ASCT/ cons and maintenance. Results: 281 patients were registered, with 218 randomised to either ASCT or cons. The median PFS for ASCT was not yet reached vs 3.4 years for cons, with cons failing to show non-inferiority (difference in 2-year PFS 6.5%, 70% CI 1.0% to 11.1%). 196 patients received K maintenance (99 ASCT, 97 cons), 17 remain on treatment. A median of 16 cycles (1-18) were given over a median of 15.9 months (0-21.5). COVID-19 led to maintenance treatment interruptions in 41 (8 ASCT, 6 Cons) and treatment discontinuation in 15 (9 ASCT, 6 Cons). The median K dose given was 50.6mg/m2 and was similar across both arms (51.2 vs 49.4mg/m2, p=0.03). K maintenance was discontinued for PD in 14.1% (ASCT) vs 22.7% (cons), and for adverse events (AEs) in 7.1% (ASCT) vs 4.1% (cons). Most common AEs were hypertension and infections and more ≥G3 AEs were noted in ASCT vs cons (p=0.01). Patient/ clinician withdrawals from maintenance were low but occurred more in the ASCT arm (9.1% vs 1%). MRD neg patients post ASCT/ Cons had a longer PFS than MRD pos (p=0.002);with a higher MRD neg rate in the ASCT arm (53.6% vs 35.1% in Cons, p=0.01). MRD neg patients at 6 months post maintenance also had longer PFS (p=0.004 cf MRD pos patients);again with higher MRD neg rates in the ASCT arm (58.1% ASCT vs 40.5% Cons, p=0.02). There was no difference in PFS for MRD neg patients according to treatment arm from PBSCH, post-ASCT/ Cons or 6 months maintenance timepoints. Overall, 27.8% of MRD pos patients converted to MRD neg post ASCT/ Cons with more converting with ASCT (39.1% ASCT vs 16.1%, p=0.004). 23.5% of MRD pos patients converted to neg during maintenance (30.6% ASCT, 17.8%: p=0.2). Maintenance of MRD negativity over the first 6 months was similar between ASCT and Cons arms (p=0.3). There was no evidence that the timing of achievement of MRD negativity impacted PFS. Conclusions: K maintenance at 56mg/m2 weekly was deliverable and tolerable, with continued higher MRD neg rates at 6 months post-ASCT compared to post-Cons. However more ≥G3 AEs and discontinuations for AEs/ patient choice were noted for K maintenance after ASCT.

11.
HemaSphere ; 5(SUPPL 2):462, 2021.
Article in English | EMBASE | ID: covidwho-1393377

ABSTRACT

Background: Plasma cell disorder (PCD) patients are extremely vulnerable to SARS-CoV-2 infection due to disease-related impaired humoral and cellular immunity as well as the receipt of immunosuppressive therapy. Reported mortality in a large cohort of patients with plasma cell disorders is 33%. The roll out of the COVID-19 vaccine is welcomed in this population, however there is concern of suboptimal antibody responses, from previous experience with the influenza vaccine. There is urgent need to understand the humoral response to SARSCoV- 2 infection in these patients, in the context of systemic anti-cancer therapy (SACT). Aims: We aimed to investigate the presence of SARS-CoV-2 antibodies in a cohort of PCD patients, the relationship with symptomatic infection, PCD characteristics and receipt of SACT. Methods: SARS-CoV-2 antibody screening with the Elecsys Anti-SARSCoV- 2 assay (Roche Diagnostics, Basel, Switzerland), a semi-quantitative assay of IgG and IgM against the nucleocapsid (N) antigen was introduced for PCD patients at our institution in July 2020. Clinical information was retrieved from the medical records. Patients with unexpected positive antibody tests were asked about possible past contacts and exposure to SARS-CoV-2. Results: We report on a six-month period of routine SARS-CoV-2 antibody screening. Two-hundred and forty-three PCD patients had one antibody test, 106 had serial samples. Total seroprevalence was 10.7% (26/243), of which 12 were patients with known PCR-swab positive COVID-19 disease. In a separate but overlapping cohort, 41 patients have had PCR confirmed COVID-19 disease;20 of these patients were tested, and 12 (60%) had seroconverted. Median time to testing from positive PCR test in the antibody positive patients was 86.5 days (range 22-256) and in antibody negative patients, 30.5 days (range 5-176 days). No PCD or COVID-19 disease factors were found to influence the likelihood of mounting an antibody response after PCR-confirmed COVID-19 disease in these 20 patients. In our screened cohort, 14 (6.3%) patients were unexpectedly antibody positive. Their clinical course is summarised in the included figure. The majority 85.7% (12/14) of patients described no COVID-19 symptoms. Seven (50%) patients were on SACT (including ixazomib, pomalidomide, lenalidomide and dexamethasone combinations) throughout the period from possible exposure to positive antibody test, with no interruption to their ongoing oral immunomodulatory treatment. Ten antibody positive patients had serial positive results at median 45 days (range 21-119) apart, demonstrating persistence, but some decline in titre over time. Summary/Conclusion: Our seroprevalence of 10.7% is lower but not dissimilar to that reported in the London population over a similar time period reflecting shielding behaviours in our patients but also the challenges of protecting them during high SARS-CoV-2 incidence in the community. Nevertheless, PCD patients retain the ability to seroconvert, even with asymptomatic COVID-19 disease and while on immunomodulatory therapy. Seroconversion rates following symptomatic infection appear lower however, with evidence of delay compared to the general population. These data support the advice for COVID-19 vaccination to be offered to all PCD patients although the suboptimal humoral response calls for close antibody monitoring of all vaccinated PCD patients and timely booster doses.

12.
HemaSphere ; 5(SUPPL 2):571-572, 2021.
Article in English | EMBASE | ID: covidwho-1393371

ABSTRACT

Background: ASCT is standard of care in biologically fit, newly diagnosed MM (NDMM) patients (pts), offering deeper responses with prolonged progression free/overall survival and improved quality of life (QOL). However, with the UK's 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT for MM due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to pts' treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QOL. Aims: To provide a snapshot of how COVID-19 affected the MM ASCT service in a single UK institution, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. To gain insight into MM pts' understanding of their disease, initial therapy and ASCT, and their response to therapy changes. Methods: We collected data on 115 NDMM pts who had a stem cell harvest (PBSCH) for upfront ASCT from December 2019-January 2021. During this time, 3 national lockdowns led to the ASCT service being suspended twice (March-June 2020 and January-February 2021). 25 pts within this cohort underwent a semi-structured interview via telephone. Inductive and deductive framework analysis was utilised to determine key themes and subthemes. Results: Pts were discussed in multidisciplinary meetings and decisions taken to delay or defer ASCT based on pt fitness, disease risk and depth of response. 73 (63%) proceeded to ASCT and 42 (37%) were deferred indefinitely (ASCTdef). The 2 groups were similar in terms of gender, age and ISS, but there were more pts with adverse risk cytogenetics in the ASCT group (26% vs 12%). Both groups were predominantly treated with bortezomib-based induction;in 11/73 (15%) ASCT and 7/42 (16.7%) ASCTdef pts treatment was changed to an oral, lenalidomide- based regimen to reduce hospital attendances for parenteral therapy. Overall response to induction in the 2 groups was similar;97.3% and 95.2% and 3VGPR 59% and 52.4% in ASCT and ASCTdef pts respectively. 28/73 ASCT pts had no delay to ASCT and none received bridging chemotherapy;45/73 had delayed ASCT (median 11 months [5-17] from start of induction) of whom 31 were put on bridging chemotherapy. In the 42 ASCTdef pts, 5 relapsed within ≤6 weeks of PBSCH and received 2nd line therapy, 30 were put on holding chemotherapy (previously not offered in the UK) as per NHS England COVID-19 interim guidance and 7 remained treatment-free post-induction. Thematic analysis identified 6 overarching themes: a) psychological response to diagnosis and initial therapy, b) beliefs and opinions about the benefits of ASCT, c) perceptions of information provided about MM and ASCT, d) high levels of fear and anxiety around COVID-19 and e) feelings about ASCT disruption or delay due to COVID-19 f) perceptions of care. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment and devastation at COVID-related treatment delays (in spite of high anxiety about infection) and exceptionally high levels of trust in the transplant team.

13.
British Journal of Haematology ; 193(SUPPL 1):157-158, 2021.
Article in English | EMBASE | ID: covidwho-1255353

ABSTRACT

Content: Introduction: Myeloma patients who have completed chemotherapy moved from an intensive period of interaction with healthcare professionals, to less frequent visits. At this time, they often struggle with disease burden, treatment side effects and age-related co-morbidities. Improved patient survival with novel therapies has resulted in increasing patient numbers in outpatient haematology clinics. Centralisation of services means that many patients travel long distances to maintain contact with their transplant centres because they value the access to new drugs and clinical trials, and expertise in management of transplant-related complications and relapse. Faced with growing numbers of patients in follow up with survivorship needs, a new patient-centred model of care is needed. Method: The Promoting Individualised Self-Management and Survivorship (PrISMS) clinic was designed for myeloma patients who are off treatment and in plateau phase. This remote clinic is staffed by a doctor, a nurse specialist and a physiotherapist, a multidisciplinary team (MDT) approach to holistic management centred on patient needs and providing consistent individualised physical activity and lifestyle advice. Two weeks before the consultation, patients complete a questionnaire about their concerns, symptoms and ways in which they would like to improve their health. This allows the MDT to prepare appropriate advice for each patient, ensuring efficient use of consultations. Patients are also required to have a blood test either locally or at University College London Hospital before the clinic. Results: From March 2019 to October 2020, 54 patients were enrolled into the pilot PrISMS clinic and 197 telephone or video consultations were held. The median call duration was 12 minutes. Most patients had their blood tests (89%) and questionnaires (84%) completed before the appointment. Patients needing closer monitoring or active treatment due to disease relapse (9/54) were referred immediately back to face-to-face clinics. 78% and 89% of patients received nurse specialist's and physiotherapist's advice respectively at any point in time, with 11 patients (20%) referred to local exercise programmes. Patients were signposted to survivorship tools such as online exercise videos and lifestyle mobile applications when appropriate. Patient feedback was positive, with 31 of the 36 surveyed patients (86%) agreed or strongly agreed that they felt more confident in self-managing myeloma after PrISMS consultations. 94% (34/36) agreed or strongly agreed that their concerns and symptoms were addressed, and 77% (28/36) gave an overall service rating of good or excellent. Thematic analysis of telephone feedback interviews with 22 participants revealed additional benefits of reduction in travel costs and time, substantially shorter clinic waiting times and reduction in associated psychological stress (Table 1). Conclusion: This new patient-centred model of care has been demonstrated to be safe and feasible, with good patient satisfaction. We hope that this MDT approach will empower patients, improve their clinical experience, and build trust in their clinical teams, as well as reducing patients' sense of isolation and vulnerability particularly in this time of COVID-19 crisis. Future work is needed to formally confirm its effects on patient reported outcome measures, safety and healthcare resource usage.

14.
HemaSphere ; 5(SUPPL 1):45-46, 2021.
Article in English | EMBASE | ID: covidwho-1240935

ABSTRACT

Myeloma patients who have completed chemotherapy move from an intensive period of interaction with healthcare professionals, to less frequent visits. At this time, they often struggle with disease burden, as well as treatment related toxicities and age-related co-morbidities. We previously reported from focus group interviews that patients need lifestyle support and advice to return to their pre-morbid social, psychological and economic functionality. Improved patient survival with novel therapies has resulted in increasing patient numbers in outpatient clinics. Centralisation of services means that many patients travel long distances to maintain contact with their transplant centre because they value the access to optimal treatment and clinical trials. Faced with growing numbers of patients in follow up with survivorship needs, we designed the Promoting Individualised Self- Management and Survivorship (PrISMS) clinic for myeloma patients who are off treatment and in plateau phase in early 2019. This remote clinic is staffed by a doctor, a nurse specialist and a physiotherapist, a multidisciplinary team approach to holistic management centred on patient needs and providing consistent individualised physical activity and lifestyle advice. Two weeks before the consultation, patients are required to have a blood test locally or at our hospital, and to complete a questionnaire about their concerns, symptoms and ways in which they would like to improve their health. We did not know at the time that such model of care would become especially pertinent as a result of the COVID-19 pandemic. From March 2019 to October 2020, we enrolled 54 patients into the pilot PrISMS clinic and held 197 telephone or video consultations. The median call duration was 12 minutes, with most patients having had their blood tests (89%) and questionnaires (84%) completed before the appointment. Patients needing closer monitoring or active treatment due to disease relapse (9/54) were referred immediately back to face-to-face clinics. 78% and 89% of patients received nurse specialist's and physiotherapist's advice at any point in time, with 11 patients (20%) referred to local exercise programmes. Regarding patients' feedback, 31 of the 36 surveyed patients (86%) agreed or strongly agreed that they felt more confident in self-managing myeloma after the consultations. 94% (34/36) of the survey patients agreed or strongly agreed that their concerns and symptoms were addressed, and 77% (28/36) gave an overall service rating of good or excellent. Thematic analysis of telephone interviews with 22 participants revealed additional benefits of reduction in travel costs and time, shorter waiting times and reduction in associated psychological stress (Table 1). PrISMS clinic aims to empower patients through patient-centred care by providing tailored advice, through enhancing patients' competences by signposting them to various survivorship tools (Table 2), and through active patient participation by setting achievable goals. We hope that this new care model will improve patients' clinical experience and build trust in their clinical teams particularly at this time of crisis, and to reduce their sense of isolation. We continue to evaluate this service based on patients' feedback to optimise individualised care and resource allocation. Future work is needed to formally confirm its effects on patient reported outcome measures, safety and healthcare resource usage. (Table Presented).

17.
Transplant Proc ; 52(9): 2642-2653, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-894249

ABSTRACT

BACKGROUND: As the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a viral pandemic, data on the clinical characteristics and outcomes of patients with SARS-CoV-2 infection undergoing solid organ transplant are emerging. The objective of this systematic review was to assess currently published literature relating to the management, clinical course, and outcome of SARS-CoV-2 infection in liver, kidney, and heart solid organ transplant recipients. METHODS: We conducted a systematic review to assess currently published literature relating to the management, clinical course, and outcome of SARS-CoV-2 infection in liver, kidney, and heart solid organ transplant recipients. Articles published through June 2020 were searched in the MEDLINE, ClinicalTrials.gov, and PubMed databases. We identified 49 eligible studies comprising a total of 403 solid organ transplant recipients. RESULTS: Older age, male sex, and preexisting comorbidities, including hypertension and/or diabetes, were the most common prevailing characteristics among the solid organ transplant recipients. Clinical presentation ranged from mild to severe disease, including multiorgan failure and death. We found an overall mortality rate of 21%. CONCLUSION: Our analysis suggests no increase in overall mortality or worse outcome in solid organ transplant recipients receiving immunosuppressive therapy compared with mortality in the general surgical population with SARS-CoV-2. Our findings suggest that transplant surgery and its immunosuppressive effects should not be a deterrent to proper surgical care for patients in the SARS-CoV-2 era.


Subject(s)
Coronavirus Infections/immunology , Immunocompromised Host , Pneumonia, Viral/immunology , Transplant Recipients , Aged , Betacoronavirus , COVID-19 , Comorbidity , Coronavirus Infections/mortality , Female , Humans , Male , Organ Transplantation , Pandemics , Pneumonia, Viral/mortality , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL