ABSTRACT
Information and Communication Technology (ICT) is used to improve the quality of many people's lives. However, heavy reliance on ICT can lead to technostress, causing health and productivity problems. Technostress has been analysed in organisations, but not in a university context, especially under remote learning during COVID-19. The purpose of this paper is to provide an explanatory contribution to knowledge regarding university students' experiences of technostress and how it impacts their academic productivity and performance. The data for this paper was collected using an online questionnaire among the students of one leading research university in Africa and used to test hypotheses related to a technostress theoretical model. The data was gathered from a convenience sample of 100 student responses. A technostress model (based on transaction theory of stress) was formed for hypothesis testing. Some hypotheses were not supported, but those that were indicated that universities should ensure that techno-complexity is reduced, and remote learning environments are improved. It was also found that technostress has a negative impact on academic productivity and performance, and that coping mechanisms can moderate the relationship between technostress and academic productivity and performance. The findings related to student remote learning environments and the moderating effect of student coping mechanisms are unique to this study. © 2022 International Association for Computer Information Systems
ABSTRACT
Collection of peripheral blood stem cells (PBSCs) for autologous stem cell transplant (ASCT) requires mobilization from the bone marrow. There is variation in mobilization choice;during the COVID-19 pandemic BSBMT&CT guidelines recommended using granulocyte-colony stimulating factor (G-CSF) alone to minimize the use of chemotherapy. We report on the impact of mobilization regimen on stem cell collection, and whether IMiD-containing induction therapy impacts on mobilization and consequently transplant engraftment times for 83 patients undergoing ASCT at Leeds Teaching Hospitals. Cyclophosphamide plus G-CSF (cyclo-G) mobilization yielded more CD34+ cells (8.94 vs. 4.88 x106/kg, p = < 0.0001) over fewer days (1.6 vs. 2.4 days, p = 0.007), and required fewer doses of salvage Plerixafor than G-CSF only (13.6% vs. 35%, p = 0.0407). IMiD-containing induction impaired all of these factors. CD34+ doses > 8x106/kg were more frequent with Cyclo-G (62% vs. 11%, p = 0.0001), including for those receiving IMiD 1st line induction (50% vs. 13.3%, p = 0.0381). Note that 92.6% of those receiving IMiD-free inductions were mobilized with Cyclo-G. The novel agents used in modern induction regimens (e.g Daratumumab) have been shown to impair yields, increasing the importance of optimizing mobilization regimens in the first instance. Furthermore, as cellular therapies become established in the management of multiple myeloma emerging data highlights the potential benefits of stem cell top up in the management of the haematological toxicities of these therapies. Our findings support re-adoption of Cyclo-G as the gold standard for mobilization to optimize PBSC harvesting and ensure sufficient cells for subsequent ASCTs.Copyright © 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.
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Purpose: This paper aims to explore the perceptions and experiences of a group of extra care tenants, who, as novice internet users, began to maintain their social relationships online. Housing transitions in later life may jeopardise existing social relationships, leading to loneliness and social isolation. More recently, Covid-19 restrictions have limited familial face-to-face contact and wider social interactions. Thus, extra care tenants, who are not already online, may benefit from acquiring internet skills. This paper aims to enhance understanding of the participants' transition from novices to experienced internet users and the impact on their social relationships and sense of self. Design/methodology/approach: A longitudinal, hermeneutic phenomenological study was conducted over eight months in two extra care housing schemes in north east England. Ten participants (56–98 years) with age-related physical, sensory and cognitive losses were recruited to the study. A series of semi-structured interviews and participant diaries captured the participants' experience as they developed internet skills and communicated online. Findings: All participants, including a blind individual, learnt to communicate online. Personalised adaptive strategies, peer support, training and management involvement facilitated internet uptake. Participants felt their social relationships were supported, and they regained biographical continuity, through being and feeling they belonged in the modern digital world. Originality/value: The online experiences of extra care tenants are rarely voiced. Their perceptions may assist others to engage online, maintaining social connections, which could otherwise be lost. © 2023, Emerald Publishing Limited.
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Purpose of Study: Acute bacterial upper respiratory infections, such as acute otitis media, pharyngitis, and sinusitis, are common indications for antibiotics in pediatrics, and it is estimated one-third of these prescriptions may be inappropriate. Cefdinir is an oral cephalosporin commonly used in pediatrics due to taste and ease of once-a-day dosing. However, there are no evidencebased guidelines recommending it as a first-line agent. Outpatient clinician education has demonstrated some improvement in antibiotic prescribing habits but is often not sustainable long term. Clinical decision support systems in the form of pathways and order sets are more feasible in the outpatient setting and have demonstrated sustained improvements in provider prescribing habits. Best practice advisory alerts are commonly used in the inpatient setting and have shown promising results, but there are little data on their use in the outpatient setting. Methods Used: We developed an intervention in our electronic health record consisting of an order-set based on our local acute upper respiratory infection guidelines and a best practice advisory alert targeting Cefdinir use in non-penicillin allergic patients. The pre-intervention period was defined as April 2018 to December 2021. The post-intervention periodwas defined as January 2022 to December 2022. Data shown here are through September 2022. Oral antibiotic prescriptions from all general pediatric clinics within our institution with diagnosis codes pertaining to acute otitis media, pharyngitis, and sinusitis were included. Thesewere then grouped into first-line and non-first-line categories. Patient data were collected for each prescription, including diagnosis, date, sex, and race/ethnicity. The primary endpoint was the percentage of first-line prescribing. Summary of Results: A total of 45 038 prescriptions were included in our analyses with 36 578 in the pre-intervention period and 8460 in the post-intervention period. There was no difference noted between the pre- and postgroups in patient sex, however, there were notable differences in patient race/ethnicity and diagnosis. Firstline prescribing accounted for 73.5% of the pre-intervention group, and 81.9% of the post-intervention group (P = <0.001). Conclusion(s): Implementation of an outpatient order-set coupled with a best practice advisory alertwas associated with an 8.4% increase in first-line antibiotic prescribing for acute upper respiratory infections in outpatient pediatric clinics affiliated with our institution. Differences in diagnoses noted between pre- and post-intervention periods may be attributable to the COVID-19 pandemic. Copyright © 2023 Southern Society for Clinical Investigation.
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Background: The mechanism of bone loss in antiretroviral-treated HIV-positive patients is poorly understood. Plasma bone turnover markers(BTMs) suggest uncoupling of bone resorption and formation by a treatment effect on bone cells. Switching away from TDF to TAF-containing regimens has been associated with bone mineral density(BMD) gains measured by dual-energy X-ray absorptiometry (DXA). One explanation is reversal of ongoing subclinical bone loss in the TDF to TAF switchers. Quantitative imaging with 18F-PET/CT allows assessment of regional bone formation at specific skeletal sites and can help differentiate if BMD changes are associated with increased bone formation or reduced bone loss. Methods: PETRAM, an open-label, randomised study conducted at a single UK site, enrolled non-osteoporotic virologically suppressed HIV-positive males, on >24 weeks rilpivirine/emtricitabine/TDF (RPV/FTC/TDF). They were randomised 1:1 to remain on RPV/FTC/TDF or switch to RPV/FTC/TAF. The protocol specified scanning by DXA (to measure BMD) and 18F-PET/CT at several regions of interest-with primary focus on the lumbar spine (LS) and total hip (TH)-at baseline, 24 weeks, and 48 weeks. However, the timing of scans was disrupted, and in some cases considerably delayed, by COVID-19. The primary analysis was therefore based on change between the baseline and final scans, adjusting for the interval between them. Regions of interest were drawn on the PET/CT images and the standardised uptake value (SUV) measured. A sample of 30 (15 per arm) was estimated to provide 90% power to detect a difference in change of 25% in SUV between the randomised groups. Results: 32 males, median age 51 years, 76% White ethnicity, median duration RPV/FTC/TDF of 49 months, BMI 25.5 kg/m2 were enrolled;27(16 TAF:11 TDF) were included in the final analysis. The interval between baseline and final scans ranged between 23-103 weeks (median 55 weeks). There was no significant difference in change in SUV(18F-PET/CT) at the LS or TH between the TAF and TDF arms (Table);there was a trend towards improved LS BMD, but not TH BMD, in the TAF arm. Conclusion: As measured by 18F-PET/CT, regional bone formation at the hip or LS in patients replacing TDF with TAF in their ART combination did not differ, and contrary to our hypothesis, switching to TAF vs. remaining on TDF over 23-103 weeks did not change BMD or SUV at these key skeletal sites. The improved LS BMD in those switching to TAF is consistent with findings from other TAF-switch studies.
ABSTRACT
Collection of peripheral blood haematopoietic stem cells (PBSC) for autologous stem cell transplant (ASCT) requires mobilisation with granulocyte colony-stimulating factor either alone (GCSF) or in combination with chemotherapy, typically cyclophosphamide (Cyclo-G). There is variation between UK centres in mobilisation choice;during the Covid-19 pandemic BSBMT&CT guidelines recommend GCSF alone. Front-line myeloma induction regimens also vary across the UK;some centres favour IMiD-containing induction (VTd) and others cyclophosphamide-containing (VCd). This retrospective study evaluates the mobilisation strategies within a regional comprehensive cancer centre after IMiD-based and IMiDfree induction. Eighty-three patients underwent 86 mobilisation procedures between Jan 2016 and Sept 2021. Sixty-six harvests used Cyclo-G (Cyclophosphamide 2 g/m2 then GCSF 5 mcg/kg for 10 days), and 20 used GCSF (10 mcg/kg for 5 days). CD34+ minimum target was >4 × 106 /kg with an optimal target of >8 × 106 /kg, corresponding to safe and optimal doses, respectively, for two ASCTs. Outcomes included CD34+ yield, days of harvesting, rescue plerixafor use and complications. Groups were compared using the Mann-Whitney or Chisquared tests. 86.04% of harvests collected the minimum target (failure rates: Cyclo-G 10.6% vs. 25% for GCSF p = 0.1). Cyclo-G yielded higher CD34+ doses (8.94 vs. 4.88 × 106 /kg, p = <0.0001) and required fewer apheresis days (1.6 vs. 2.4 days, p = 0.007). Optimal harvest yield was more frequent with Cyclo-G (62% vs. 11%, p = 0.0001), including for those receiving IMiD 1st line induction (50% vs. 13.3%, p = 0.0381). CD34+ yields were lower after IMiD-containing (thalidomide or lenalidomide) induction (5.18 vs. 8.98 × 106 /kg, p = 0.00003, n = 32) though there was a trend towards higher yields when Cyclo-G was used (5.8 vs. 4.8 × 106 /kg, p = 0.34). In patients mobilising after 1st line IMiD therapy ( n = 27), Cyclo-G did result in higher yields (8.51 vs. 5.18 × 106 / kg, p = 0.0321). The improved mobilisation of PBSCs with Cyclo-G is reflected in increased preapheresis day 1 CD34+ counts (95 vs. 46.94 × 106 /kg, p = 0.06). More patients mobilised with GCSF required plerixafor (35% vs. 13.6%, p = 0.0407). Five patients receiving Cyclo-G were hospitalised, including one with neutropenic sepsis. There were no infective complications from mobilisation with GCSF. In summary, Cyclo-G mobilisation yielded more cells over fewer days, and required fewer doses of salvage plerixafor than GCSF-only. IMiD-based induction impaired all of these factors. Of note, 92.6% of those receiving IMiD-free inductions were mobilised with Cyclo-G, meaning differences may be attributable not only to mobilisation regimen but also in part to induction therapy. In the UK, where VTd versus VCd use varies, our study suggests mobilisation with Cyclo-G should be considered preferable in patients having VTd induction. Cyclo-G additionally saves costs by reducing plerixafor use and apheresis unit days. Commissioning arrangements for plerixafor mean access to this medication is not unlimited, which underlines the importance of achieving optimal CD34+ mobilisation without its use. Future myeloma therapies will incorporate more novel agents into induction regimens (e.g. daratumumab), which further compromises PBSC harvesting. Thought should be given to re-adoption of Cyclo-G as the gold standard for mobilisation to optimise PBSC harvesting and ensure sufficient cells for subsequent ASCTs. (Table Presented).
ABSTRACT
Background. The COVID-19 pandemic response may unintendedly disrupt multiple public health services, including tuberculosis control programs. We aimed to assess the cascade of care of latent tuberculosis infection (LTBI) in an urban US city during the COVID-19 pandemic response. Methods. We conducted a retrospective cohort study of adult patients who presented for LTBI evaluation at the Hamilton County Public Health Tuberculosis Clinic in Ohio between 2019 and 2020. We defined 01/2019 to 02/2020 as the pre-COVID-19 response period, and 04/2020 to 12/2020 as the COVID-19 pandemic response period. We reviewed electronic medical records and extracted sociodemographic information, medical history, and follow-up and treatment data to define steps within the LTBI cascade of care. Logistic regressions were used to assess factors associated with LTBI treatment acceptance and completion, adjusted by potential confounders and COVID-19 period. Results. Data from 312 patients were included. There was a significant decrease in the number of monthly LTBI referrals (median, 18 vs. 8, p=0.02) and LTBI evaluations (median, 17.5 vs. 7, p< 0.01) during COVID-19. There was a decrease in the proportion of immigrants as indication for LTBI testing (30% vs. 9%;p< 0.01), and an increase in LTBI diagnoses based on interferon-gamma release assay (IGRA;30% vs. 49%;p< 0.01) during COVID-19. The proportion of people who were recommended LTBI treatment was similar before and during COVID-19 (76% vs. 81%, p=0.41), as well as the LTBI treatment acceptance rates (56% vs. 64%, p=0.28), and LTBI treatment completion rates (65% vs. 63%, p=0.85). In multivariate analysis, LTBI treatment acceptance was associated with Hispanic ethnicity, younger age, male sex, IGRA use, no comorbidities, and non-healthcare occupation, independent of COVID-19 period. LTBI treatment completion was associated with taking a rifamycin-containing regimen, independent of COVID-19 period. Conclusion. We observed a significant decline in the number of monthly LTBI referrals and evaluations during COVID-19. Our findings indicate an unintended negative impact of the COVID-19 response in LTBI screening efforts in our region. LTBI treatment acceptance and completion rates were not affected during COVID-19.
ABSTRACT
Background Although the median age of patients with newly diagnosed multiple myeloma (MM) is 70-74 years, recruitment of frail older patients to clinical trials is poor. The International Myeloma Working Group (IMWG) frailty score predicts survival, adverse events and treatment tolerability using age, the Katz Activity of Daily Living, the Lawton Instrumental Activity of Daily Living, and the Charlson Comorbidity Index, rather than age alone. Despite IMWG score prognostic biomarker capability, to date no evidence exists of its predictive biomarker potential. The UK-MRA Myeloma Risk Profile (MRP) has also been shown in both clinical trial and real-world populations to be a prognostic biomarker in transplant ineligible patients but prospective comparisons of the two scores have not been previously conducted. Study Design/Methods The FiTNEss trial (Myeloma XIV, NCT03720041, Figure 1A) is a UK-MRA phase III, multi-centre, randomised controlled trial for newly diagnosed MM patients not suitable for stem cell transplant. The primary objectives are 1) to compare early treatment cessation (<60 days from randomisation) between patients randomised to standard (reactive) and frailty-adjusted (adaptive, based on IMWG score) induction therapy delivery with the triplet ixazomib, lenalidomide and dexamethasone (IRd) 2) to compare progression free survival for maintenance lenalidomide plus placebo (R) and lenalidomide plus ixazomib (IR). The FiTNEss trial is designed as an all-comers study with few exclusion criteria other than necessary for safety including some haematological and biochemical parameters, but there is no exclusion based on renal function. Patients with grade 2 or greater baseline peripheral neuropathy, current systemic infection or recent surgery or other cancer are excluded. Here we report the demographics for the first patients recruited, including IMWG frailty assessments and MRP to demonstrate the feasibility of recruiting frail patients to randomised phase III clinical trials. Results The FiTNEss trial opened on 04/08/2020 during the second wave of the COVID-19 pandemic in the UK. At the time of data cut off (14/07/2021) recruitment is active at 84 sites, with 180 patients randomised. Baseline characteristics for the randomised patients are shown in Figure 1B. The median age of patients is 77 years (range 64, 93) with 36.1% aged 76-80 and 26.1% over 80. In keeping with the older patient population 26.6% have an ECOG performance status of 2 or 3 and 31.7% ISS stage III. The IMWG frailty classification at baseline is FIT 43/180 (23.9%), UNFIT 53/180 (29.4%) and FRAIL 84/180 (46.7%). The effect of using age groups on the definition of patient frailty was explored. The IMWG frailty score defines all patients over 80 as FRAIL whilst an age of 76-80 contributes one point to the score. An analysis of patients' frailty was repeated with the contribution of age removed. For those aged over 80 years (n=47, 100% FRAIL) we found that 20 (42.6%) would have been re-classified as FIT and 18 (38.3%) as UNFIT, with only 9 (19.2%) retaining the FRAIL category. For those aged 76-80 (n=65, 53.8% UNFIT, 46.2% FRAIL) all 35 patients previously classified as UNFIT became FIT (53.8%) whilst 19 (29.2%) classed as FRAIL became UNFIT with 11 (16.9%) remaining FRAIL. The MRP classification, using age as a continuous variable, was Low-risk 45/180 (25.0%), Medium-risk 46/180 (25.6%), High-risk 75/180 (41.7%) and not available for 14/180 (7.8%) patients. Concordance between the IMWG frailty score and the MRP occurred in 48.9% of patients (88/180). 37.2% of FIT patients were classified as MRP Low-risk, 32.1% of UNFIT patients as MRP Medium-risk and 65.5% of FRAIL patients as MRP High-risk. Discussion The FiTNEss trial demonstrates the feasibility of recruiting older, less fit patients to clinical trials. Recruitment of patients classified as FRAIL was very high despite the COVID pandemic, likely due to the all-oral nature of the regimen under investigation enabling patients to avoid attendance at hospital day units for treatment and associa ed exposure risk. In the population recruited to date we found age to be a key contributor to the FRAIL category of the IMWG frailty score. Concordance between IMWG frailty score and MRP was highest in FRAIL/High-risk patients. The first interim analysis of the primary objectives is planned when 50% of required participants for R1 have reached 60 days post R1, which is anticipated in Q2 of 2022. [Formula presented] Disclosures: Cook: Amgen: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Roche: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria;Oncopeptides: Consultancy, Honoraria;Takeda: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding. Pawlyn: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene / BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria. Royle: BMS: Research Funding;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Coulson: BMS / Celgene: Honoraria;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Jenner: BMS/Celgene: Consultancy, Honoraria, Speakers Bureau;Janssen: Consultancy, Honoraria, Speakers Bureau;Pfizer: Consultancy;Takeda: Consultancy. Kishore: Sanofi: Other: Attending fees;Celgene: Other: Attending fees;Takeda: Other: Attending fees;Jannsen: Other: Attending fees. Rabin: BMS / Celgene: Consultancy, Honoraria, Other: Travel support for meetings;Takeda: Consultancy, Honoraria, Other: Travel support for meetings;Janssen: Consultancy, Honoraria, Other: Travel support for meetings. Best: BMS/Celgene: Research Funding;Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Gillson: BMS / Celgene: Research Funding;Meck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding. Henderson: Takeda: Research Funding;Amgen: Research Funding;Merck Sharpe and Dohme: Research Funding;BMS / Celgene: Research Funding. Olivier: Merck Sharpe and Dohme: Research Funding;Takeda: Research Funding;Amgen: Research Funding;Celgene / BMS: Research Funding. Kaiser: AbbVie: Consultancy;GSK: Consultancy;Karyopharm: Consultancy, Research Funding;Pfizer: Consultancy;Amgen: Honoraria;Seattle Genetics: Consultancy;Takeda: Consultancy, Other: Educational support;Janssen: Consultancy, Other: Educational support, Research Funding;BMS/Celgene: Consultancy, Other: Travel support, Research Funding. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Jones: Janssen: Honoraria;BMS/Celgene: Other: Conference fees. Cairns: Merck Sharpe and Dohme: Research Funding;Amgen: Research Funding;Takeda: Research Funding;Celgene / BMS: Other: travel support, Research Funding. Jackson: celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau;amgen: Consultancy, Honoraria, Speakers Bureau;takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau;GSK: Consultancy, Honoraria, Speakers Bureau;J and J: Consultancy, Honoraria, Speakers Bureau;oncopeptides: Consultancy;Sanofi: Honoraria, Speakers Bureau. OffLabel Disclosure: Frailty-score adapted dosing strategies
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.
ABSTRACT
Background: Successful vaccination against SARS-CoV2 is highly effective in preventing serious COVID-19 illness and is particularly recommended for at risk populations including patients with multiple myeloma (MM). However, there is uncertainty to which extent modern intensified therapies targeting plasma cell features might attenuate vaccination responses;some early vaccination recommendations for MM have proposed extended treatment breaks of several weeks to maximise vaccination success. Such an approach can be challenging in UHiR MM and pPCL, where maintaining treatment intensity is hallmark for preventing rapid relapse of the aggressive tumor. To address this uncertainty, we measured post-vaccination serological responses in patients treated uniformly with intensified Dara-VR consolidation and Dara-R maintenance post-ASCT for UHiR NDMM or pPCL in the UK OPTIMUM/MUKnine trial (NCT03188172). Methods: Between Sep 2017 and Jul 2019, 107 patients with UHiR NDMM or pPCL were recruited to OPTIMUM and received intensified post-ASCT consolidation with Dara-VR(d) for 18 cycles followed by maintenance with Dara-R until progression. In an exploratory analysis, centrally stored serum samples available for patients with a completed and documented vaccination history of two doses of an anti-SARS-CoV2 vaccine were analyzed for serological vaccine responses Total IgG/IgA/IgM Anti-SARS-CoV-2 spike glycoprotein was measured by ELISA (MK654;The Binding Site). As per UK national guidance and local availability, patients received two vaccine doses 12 weeks apart of either tozinameran (Pfizer/Biontech) or vaxzevria (AstraZeneca);serum taken at least 3 weeks after patients received their second dose was analyzed. Results were correlated with baseline characteristics and annotated with treatment and response data. Patient with available matched serological and vaccination status data at time of data cut-off (09 JUL 2021) were included. Collection of vaccination status data is ongoing and updated results comprising additional patients enrolled in OPTIMUM, as well as antigen levels, will be presented. Data will also comprise longitudinal antibody level measurements for patient with available sequential material. Results: Serological vaccine response data was available for 40 OPTIMUM patients with documented completed double vaccination status. Median patient age was 58.5 years (range 39-70) and clinical and molecular tumor features were similar to the overall trial safety population. All patients had received their second dose before June 2021. Of the 40 patients, 42.5% had received tozinameran and 57.5% vaxzevria. Baseline characteristics of the two groups were comparable. At time of second vaccine dose, 55% of patients were receiving Dara-VR consolidation treatment and 45% Dara-R maintenance. There was no recommendation to pause trial treatment for purposes of vaccination and no extended times off treatment for this reason were reported. Overall, 72.5% of patients had a positive vaccine antibody level as per manufacturer cut-point for high specificity evidence of antigen exposure (infection or vaccine). The response rate was nominally higher for vaxzevria (91.3%) than for tozinameran (47.1%), a dysbalance that will be further investigated with ongoing extension of the cohort. Of note, 90% of patients analyzed had reached a complete response (CR) of their MM prior to being vaccinated, and the majority of patients not in CR had a positive vaccine response. Response rates were nominally slightly higher in patients in receipt of Dara-R maintenance at time of second dose with 77.8% compared to Dara-VR consolidation with 68.2%. Conclusions: These results show a high serological response rate to COVID-19 vaccination in UHiR MM patients receiving intensified post-ASCT consolidation and maintenance therapy in remission. Findings suggest that continuation of intensified post-ASCT therapy for patients with aggressive tumors and a high risk of relapse are compatible with serological responses to commonly used COVID-19 vaccines. Disclosures: Jen er: Janssen: Consultancy, Honoraria, Speakers Bureau;BMS/Celgene: Consultancy, Honoraria, Speakers Bureau;Takeda: Consultancy;Pfizer: Consultancy. Hall: BMS/Celgene: Research Funding;Janssen: Research Funding. Garg: University Hospital Leicester: Current Employment;Takeda Janssen Novartis Sanofi: Other: Travel Accommodations, Expenses;Amgen Janssen Novartis Sanofi Takeda: Honoraria. Jackson: J and J: Consultancy, Honoraria, Speakers Bureau;GSK: Consultancy, Honoraria, Speakers Bureau;takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau;amgen: Consultancy, Honoraria, Speakers Bureau;celgene BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau;oncopeptides: Consultancy;Sanofi: Honoraria, Speakers Bureau. Pratt: Binding Site: Consultancy;BMS/Celgene: Consultancy;Gilead: Consultancy;Janssen: Consultancy;Takeda: Consultancy;Amgen: Consultancy. Cook: Karyopharm: Consultancy;Sanofi: Consultancy;Takeda: Consultancy, Research Funding;Janssen: Consultancy, Research Funding;BMS/Celgene: Consultancy, Research Funding;Amgen: Consultancy. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company. Kaiser: BMS/Celgene: Consultancy, Other: Travel support, Research Funding;Janssen: Consultancy, Other: Educational support, Research Funding;GSK: Consultancy;Karyopharm: Consultancy, Research Funding;Pfizer: Consultancy;Amgen: Honoraria;Seattle Genetics: Consultancy;Takeda: Consultancy, Other: Educational support;AbbVie: Consultancy.