Background: Randomised trials examining continuous lenalidomide maintenance after autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) have demonstrated progression free survival (PFS) and overall survival benefit compared to placebo. In 2021 the UK National Institute of Clinical Excellence (NICE) approved lenalidomide maintenance for all newly diagnosed National Health Service (NHS) patients receiving ASCT after induction chemotherapy. Patient-reported outcomes from observational studies suggest lenalidomide causes tolerable adverse effects. However, clinical trial data demonstrate that neutropenia, fatigue, neuropathy, and gastrointestinal issues are common, particularly in the first six months of treatment, and that lenalidomide increases the risk of secondary malignancies. Before lenalidomide maintenance was used in this setting, individuals would typically enter a treatment-free phase after ASCT, where they might experience a reasonable quality of life (QoL) without treatment burden. Studies suggest that medication breaks allow patients to detach from the ‘illness’ experience, but with continuous lenalidomide that opportunity is lost. Whilst the PFS benefit of lenalidomide maintenance is proven, both short- and longer-term toxicities reported in clinical trials suggest the trade-off between efficacy and harm should be considered. In-depth information about how continuous lenalidomide impacts individuals' QoL is scant. The overall objective of this qualitative service evaluation was to examine patients' experience of lenalidomide maintenance, including perceived impact on QoL and experience of side-effects. It was anticipated that findings would result in clinical service improvement through the delivery of communication better suited to patients' needs and priorities when facing treatment choices. Methods: We conducted 20 one-to-one semi-structured interviews with purposively selected patients (10 female and 10 male) from a specialist MM center in London. All participants had undergone induction chemotherapy followed by ASCT and were receiving continuous lenalidomide. Ages ranged from 45 to 71 years (median 58). The sample comprised 12 White British, 2 Black Caribbean, 1 Black African, 1 Asian Indian, 2 from other ethnic groups and 2 with undisclosed ethnicity. Lenalidomide treatment duration varied; seven patients had received lenalidomide for 1-6 months, five for 7-12 months, five for 13-18 months, one for 19-24 months, and two for over 24 months. Reflexive thematic analysis was used for data analysis. Results: Four themes were developed from the data: 1) Lenalidomide: understanding its role and rationale, 2) Reframing the loss of a treatment-free period to a return to normal life, 3) The reality of being on continuous lenalidomide maintenance: balancing hopes with hurdles, 4) Gratitude and Grievances: Exploring patients' mixed perceptions of care and communication. Most patients believed lenalidomide maintenance would double remission time and were compelled by the relative certainty it offered, which contrasted with the unpredictability of MM. Many participants reported that lenalidomide helped to diminish fears about relapse, and thus most did not feel they were missing out on a treatment break. The impact of lenalidomide maintenance on patients' QoL varied; younger patients reported no/negligible side-effects, while several older patients with comorbidities described significant symptom burden, such as skin rashes, debilitating fatigue, unpredictable gastric disturbances and bone pain, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. The transition from frontline to maintenance treatment required a return to greater patient autonomy as medical support was reduced. Some patients described anxiety and depression in this period, suggesting the need for greater support. The study also highlighted specific challenges that younger patients experience, such as concerns about sexual transmission and fertility, which merits further research. Conclusions: Understanding the real-world symptom burden in MM is key as continuous treatment becomes routine. Qualitative research on the impact of treatment could lead to a more comprehensive understanding, helping patients cope with the increasingly chronic nature of this disease.

AbstractHigh‐dose melphalan followed by stem cell rescue is the standard consolidative therapy for transplant‐eligible patients with multiple myeloma (MM) in the United Kingdom. A melphalan dose of 200 mg/m2 (Mel200) is considered the “gold standard” for autologous stem cell transplant (ASCT) conditioning for fit patients ≤70 years old; however, with a peak diagnosis incidence at 80–89 years old in the UK dose adjustments will be inevitable to limit toxicities. In this single‐centre UK‐based retrospective analysis, data was collected from patients with plasma cell dyscrasias who underwent a first reduced‐intensity, Mel140, ASCT from 2006 to 2019, a total of 81 patients. We found that the procedure was overall safe with seven (9%) of patients requiring ITU admission and a single transplant‐related death within the initial autograft admission. The progression‐free survival (PFS) and overall survival were comparable with those previously reported in the literature with median PFS for our cohort of 31 months. Univariate analysis of our data showed an inferior PFS for patients aged ≥70 years. In conclusion, although this is a retrospective analysis, it demonstrates that dose‐reduced melphalan conditioning is safe and effective in patients deemed unfit for standard‐intensity conditioning.

High dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) remains the standard consolidation in transplant eligible multiple myeloma (MM) patients. The timing between HDM administration and hematopoietic stem cell return (HSCR) varies among institutions, with a 'rest period' of 48 hours (h) employed by some for patients with renal impairment (RI). We investigated the differences in hematopoietic recovery and HDM toxicity between MM patients with RI who had HSCR after 24 vs 48 h from HDM. Fifty MM patients with RI (48 h group; n = 31 and 24 h group; n = 19) were included. No statistically significant differences were noted in surrogates for hematopoietic recovery and HDM toxicity between both groups. Only one death occurred in the 24 h group. No patients required renal replacement therapy. Therefore, a 24 h period between HDM and AHSC infusion appears safe for MM patients with RI.

Achieving minimal residual disease (MRD) negativity following treatment for multiple myeloma (MM) is associated with improved progression free and overall survival. In the UK, MRD assessments in MM are not incorporated into routine clinical use outside trials. Widely used in other haematological malignancies, there is a role for widening the availability of myeloma MRD assays to laboratories outside larger treating centers.

Daratumumab, bortezomib and dexamethasone (DVd) is approved for patients with relapsed multiple myeloma following the CASTOR phase 3 clinical trial. This retrospective multicentre analysis assesses the overall response rate (ORR) and progression-free survival (PFS) in routine clinical practice for patients at first relapse treated with DVd incorporating weekly bortezomib. Data were collected from 296 sequential patients treated across 15 UK centres. After a median follow-up of 21 months, the ORR was 82% (26% partial response, 56% very good partial response or better) and the median PFS was 16 months [95% confidence interval (CI) 12-20 months]. Results were similar regardless of prior lenalidomide exposure. The median time to next treatment was 20 months (95% CI 15-25 months) and the estimated overall survival at two years was 74%. Patients with high-risk features (by cytogenetics, International Staging System or extramedullary disease) and those treated within 18 months of initiation of progression-free treatment, or within 12 months of autologous stem cell transplant, had significantly inferior outcomes. The grade 2 and 3 peripheral neuropathy rate was 7%. DVd with weekly bortezomib was effective in a heterogenous real-world population at first relapse with a low rate of peripheral neuropathy. However, high-risk patients had inferior outcomes and should be considered for alternative treatments.

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Disparities in patients enrolled into clinical trials compared to real world populations have been reported, particularly with underrepresentation of different racial groups. However, disparities in clinical trial access may also relate to socioeconomic factors. Social deprivation has been shown to impact overall survival (OS) of multiple myeloma (MM) patients, and hence adequate sociodemographic representation is required for clinical trials to be truly informative. Aims: To identify the distribution of patients enrolled into MM clinical trials according to social deprivation and understand interactions with race, prognostic markers, and OS. Methods: This was a single centre retrospective analysis of MM patients treated between 2014-2023 from electronic medical records. Social deprivation was assessed by postcode using the English Indices of Multiple Deprivation (IMD) ranking, derived from income, employment, health, education, housing barriers, services, crime, and living environment. Comparator data for MM incidence by social deprivation in London and England was obtained from the National Cancer Registration and Analysis Service (NCRAS, 2006-2015). OS was estimated using Kaplan Meier Curves and correlative analysis by Cox regression models with GraphPad prism V9. Results: 580 consecutive patients at a single UK centre (University College London Hospital) receiving referrals from a wide geographical area were analysed. Patients were grouped in 3 cohorts: standard of care (SOC, n=212), clinical trials (n=355): early phase trials (EPT, Phase I/II, n=103) late phase trials (LPT, Phase II & III, n=252). Median age was 66 years (35-90), M:F ratio was 1.3:1 and had a median of 3 prior lines (0-14). 406 (70%) were White, 80 (13.8%) Black, 40 (6.9%) Asian, 38 (6.6%) Mixed/Other and 16 (2.8%) unknown. There was a significant difference in social deprivation ranking between those enrolled into clinical trials compared to that expected for England, with fewer patients from more deprived areas being enrolled(p=<0.0001, Table 1), in both EPT and LPT groups. External referrals comprised almost half of the trials cohort (n=169, 47.6%) and were chiefly from less deprived areas compared to NCRAS data for England (p=0.02). LPT patients from more deprived areas had an inferior OS to those from less deprived areas (p=0.03), although this was not observed for EPT (p=0.82). The distribution of SOC patients was also from less deprived areas than expected for London (p<0.0001) indicating that patient referrals were skewed rather than the selection of referred patients for trials. Overall the non-white trial patients were from more deprived areas than white patients (p=0.018), predominantly in the LPT group (p=0.003). No difference in social deprivation (p=0.25) was noted between white and non-white EPT patients. Whilst white patients were from less deprived areas than non-whites, there was a significantly negative OS in the socially deprived white patient group (p=0.04). This was not observed in non-white patients. Patients aged ≥ 75 with worse social deprivation indices had an inferior OS (p=0.01). This was not observed in those aged <75. Summary/Conclusion: Patients enrolled into clinical trials at our centre were from less socially deprived areas than expected from the distribution of MM in London and England, reflecting skewed referral patterns by socioeconomic status. As these differences may impact upon overall survival, it is vital that enrolment into clinical trials is monitored by socioeconomic deprivation to ensure there is adequate representation of the geographical population.Keywords: Clinical trial, Phase I/II, Multiple myeloma, Survival

Sickle cell disorder (SCD) is the commonest inherited single gene disorder in England with more than 14 000 individuals affected. It is seen mostly in people of African ancestry and as the life expectancy of those with SCD increases so will their lifetime risk of malignancy.1,2 There is an increased prevalence of multiple myeloma (MM) in people of African ancestry, and there are disparities in both treatments and survival outcomes compared with those of European ancestry.3 SCD is a multisystem disease and there is a progression of organ damage with age. Given the age incidence of MM, by the time those with SCD develop the disorder, there will frequently be significant organ dysfunction. As such, the myeloma and that of the underlying SCD must be carefully managed with due consideration to both disorders to ensure the best outcomes for patients.4,5 Autologous stem cell transplant (ASCT) for transplanteligible MM patients has become the standard of care (SoC).6 However, limited guidance exists on mitigating complications and optimising outcomes for these patients receiving ASCT. We report on our experiences with haematopoietic progenitor cell (HPC) mobilisation in three patients with MM and SCD, two of whom proceeded to highdose therapy (HDT). HDT was deferred for Patient 2 due to the risk of infection during the peak of the COVID19 pandemic. HDT may be required at a later date. The use of granulocytecolony stimulating factor (GCSF) is an approved and wellpractised strategy for HPC mobilisation.6 However in patients with SCD, GCSF has been associated with an increased risk of severe and even fatal VOC.7 Plerixafor is effective in HPC mobilisation for SCD.8– 10 Plerixafor is a CXCR4 antagonist which directly inhibits the binding of stromacellderived factor1a to its CXC chemokine receptor on HPCs.10 Plerixafor is safe and welltolerated in patients with SCD who have received prior red cell exchange (RCE).9 However these reports are predominantly in the context of gene therapy. For ASCT, the minimum threshold for CD34+ cell collection is currently defined as 2.0 × 106 cells/kg6 or if the CFUGM is >20 × 104 cells/kg (as practised in our centre). Successful HPC mobilisation was achieved in three patients with SCD and MM using plerixafor alone (Table 1). However, HPC yields were modest, only allowing enough cells for a single ASCT. This may limit optimal treatment for patients with highrisk diseases requiring tandem transplants. Standard dosing of plerixafor was administered (0.24 mg/kg, capped at 20 mg if weight ≤83 kg). The timing of plerixafor administration is different to that used for GCSF HPC mobilisation. Given CD34+ cell counts decline after 6 h with plerixafor,10 we suggest administering plerixafor 2– 4 h prior to apheresis and ensuring peripheral blood CD34+ dose is ≥10/μL, prior to mobilisation. Two to three daily doses are likely required to ensure adequate CD34+ yields.11 In contrast, most patients collect HPCs in 1 day with GCSF alone.12 Limited data exist for sicklerelated complications during HDT with available reports predominantly for allogeneic transplants. All ASCT planning should follow a multidisciplinary approach and include the patient's primary red cell, myeloma and transplant teams to optimise patient safety during ASCT. Maintaining HbS ≤30% is the gold standard in primary and secondary prevention as well as treatment of complications in SCD.2 To limit sicklerelated complications during ASCT we suggest considering a RCE reducing haemoglobin S (HbS) to ≤30%.8,9,13 We recommend RCE at least 7 days before HDT and to maintain the HbS ≤30%. If the patient was already established on regular RCE this should be timed to have their last preASCT, such that the HbS is <30% at day 0. Patients should receive intermittent simple transfusions to maintain the low HbS% for the peritransplant period. It is not necessary to perform RCE prior to administering plerixafor. SCD patients receiving regular blood transfusions are at risk of developing RBC alloantibodies. Patient 3 had known multiple RBC alloantibodies and so received a partial RCE with antigennegative units, intravenous immunoglobulin (IVIg) and methylprednisolone cover. A new red cell alloantibody appeared alongside engraftment and led to a profound delayed haemolytic transfusion reaction on day+13 treated with erythropoietin, IVIg, methylprednisolone and eculizumab. With appropriate supportive care, she did not require further transfusion and made a full recovery. People with SCD should be counselled regarding the risk of alloimmunisation, cumulative iron overload and transfusion Received: 5 February 2023 | Accepted: 10 July 2023

Introduction: BCMA targeted therapies have demonstrated single agent efficacy for patients with triple class exposed or refractory multiple myeloma (RRMM). Teclistamab and Belantamab Mafodotin (Belamaf) are currently approved for RRMM in Europe with several Bispecific T Cell Engagers (TCE) under investigation. However, whilst TCEs have higher response rates and progression free survival to Belamaf, adverse events, particularly infections may influence treatment choice particularly for frailer patients. Intravenous Immunoglobulin (IVIg) is recommended to prevent infections once IgG levels fall <4g/L or even as prophylaxis with anti-BCMA TCEs. Methods: This was a retrospective review of MM patients treated with anti-BCMA monotherapies at University College London Hospitals between 28/07/2015 and 15/06/2023. IVIg was given according to UK guidelines: IgG of <3g/L and recurrent infections/ one severe infection, despite 6 months of prophylactic antibiotics. IgG levels between 3-4g/L also required failure of a vaccine challenge. IVIg for asymptomatic patients was not permitted. Statistics was performed using GraphPad Prism. Results: 55 patients were treated with anti-BCMA monotherapies: 21 with TCE and 34 with Belamaf. The median age was 61 years (range 45-79), 43% female, 80% white and 5.6% Black. The median time from diagnosis to treatment was 5.8 years with a median of 5 prior lines (range 2-15). 51.9% of patients had high risk cytogenetics. Patients were a median of 59 years for TCE (range 47-73) vs 64 years (range 45-79) with Belamaf. Both groups had a median of 5 prior lines and a median Charlson co-morbidity index of 2, but 40% of TCE were classified frail by modified IMWG score vs 61.8% with Belamaf. CD38 exposure was 100% for TCE patients and 76% Belamaf. Severe hypogammaglobulinemia (<4g/L) at baseline prior to anti-BCMA treatment was present in 75% of TCE and 53% of Belamaf patients. Further significant reductions in median IgG levels occurred during treatment (TCE: 3.04g/L to 1.06g/L, p=0.01; Belamaf: 3.9g/L to 1.9g/L p=0.002). Nadir IgG levels were significantly lower with TCE than Belamaf (p=0.047). All patients received aciclovir prophylaxis, PJP prophylaxis (co-trimoxazole/ azithromycin) was given in 100% with TCE and 82% with Belamaf, with anti-fungal prophylaxis in 1 TCE patient. IVIg was used prior to anti-BCMA treatment in 3 patients (2 TCE, 1 Belamaf). Whilst on anti-BCMA treatment, IVIg was used in 38% for TCE and 5.9% for Belamaf. The risk for all grade infection per patient was 3.7 times higher for TCE vs Belamaf (increased risk TCE vs Belamaf: G1-2: 3.3, G3: 2.1, G4: 2.1). There was a total of 104 infection episodes, 57% with TCE, 43% with Belamaf (see Figure). The median time to first infection was 45 days for TCE and 34 days for Belamaf. Most infections were low grade with 20 patients having ≥1 infection (10/21 (48%) TCE, 10/34 (29%) Belamaf). At Grade 1-2, there were 1.8 infections per patient for TCE vs 0.7 for Belamaf. For G3-5, 1.0 infections per patient vs 0.6 for Belamaf. There was 1 grade 5 infection with TCE, 0 for Belamaf. Respiratory infections predominated (TCE: 80% vs Belamaf: 73%) followed by urinary (TCE: 5% vs Belamaf 16%), blood (TCE 10% vs Belamaf 5.4%) and GI (TCE 3% vs Belamaf 5%). 96/ 104 infections were identified, most were viral (TCE 71% vs Belamaf 62%) with few fungal infections (6% vs 4%). More bacterial infections occurred with Belamaf possibly due to lower antibacterial prophylaxis and IVIg use (TCE: 23% vs Belamaf: 35%). Since commencing IVIg, 5 of 8 (63%) TCE patients had at least 1 infection, mainly viral. A median of 1 further infection (range 0-14) occurred over a median of 3.2m (range 0.6-28.3m) of monthly IVIg infusions. Routine blood viral PCR monitoring for CMV, EBV & Adenovirus was performed in 30% of patients. 13 (65%) of TCE patients had 197 blood viral PCR tests performed of which 3 patients (23%) tested positive (2x adenovirus and 1 CMV). Of these 2 (both adenovirus) had symptoms requiring intervention. Of the 8.8% of Belamaf patients tested, 0 were positive. Conclusions: Patients treated with Belamaf were frailer than those receiving TCE. Hypogammaglobulinemia was more profound with TCE and the per patient risk of infections was higher. IVIg use was substantially higher for TCE than Belamaf. Blood viral PCR monitoring for TCE patients only detected symptomatic reactivations in 2 out of 13 patients suggesting this was an infrequent event.

Patients with plasma cells disorders (PCD) who contract COVID-19 have higher morbidity and mortality compared to those without [1 – 3]. Mortality from COVID-19 is also increased in those undergoing autologous stem cell transplantation (ASCT) [4,5]. Preventing infection with COVID-19 vaccination in this vulnerable group is key, but patients with PCD have been shown to mount subopti-mal responses to vaccination We previously reported 68% seropositivity after one vaccine, rising to 89% seroconversion after two vaccines [7], similar to reports elsewhere [8 – 10]. It is also evident that serology titers decline over time [7], but it is unclear how these levels change following ASCT.

Background: Advances in treatment options for Multiple Myeloma (MM), have significantly improved life expectancy. MM related organ dysfunction, treatment toxicity, age and overall health comorbidities have major impact on patients' Quality of Life (QoL). Several QoL Questionnaires (QLQs) are used in clinical and research practice, although these were developed and validated years prior to the plethora of the current novel therapies. The aim of this study was to evaluate the relevance of these QoLQs to the QoL of MM patients in the current era. Methods: MM Patients and MM Healthcare Professionals (HCPs) (physicians, nurses, physiotherapists, dieticians and pharmaceutical representatives) were asked to complete online surveys assessing the relevance of the total of 149 questions from the internationally commonly used QoLQs (EORTC QLQ-C30, EORTC QLQ-MY20, EORTC QLQ-CIPN20, EQ-5D-3L, FACT-G, FACT-MM, FACT-N, FACIT-F) to the MM patients' QoL. HCPs and patient demographics, disease and treatment characteristics were collected for each survey. The relevance of each question of the MM QoLQs was graded using the 5-point Likert scale: not relevant, slightly relevant, relevant, fairly relevant, and very relevant. Separate analysis was performed for HCPs and MM patients' responses. MM patients' results were further stratified based on age, treatment lines, active treatment and time from diagnosis. Analysis was performed initially for (I) the not relevant versus very relevant questions and further analysis was conducted to sense relevance for (II) non relevant + slightly relevant versus the fairly relevant +very relevant and (III) non relevant + slightly relevant and the relevant+ fairly relevant +very relevant. Relevance was defined as agreement ³ 50% between respondents. Results: 224 MM patients of different age, racial origin, time from diagnosis and on different treatment regimens and 39 HCPs completed the surveys. From the MM patients' perspective, only eight questions addressing their social, family and emotional well-being [{FACT-G} GS2, GS4, GS5, GS6 GE2, GF3-4; {FACT-N} N2 ] were graded as very relevant irrespective of their age, disease status and prior therapy lines. Further subgroup analysis identified a trend for significant relevance between the ≤70 years vs >70 years old age groups for the FACTG QoL subscales: Physical (PWB), Functional (FWB), Emotional (EWB) and Social/Family (SWB) Well-Being and the FACT-N N2. Sub-analysis of the responses, revealed 5 further relevant questions in stage II: {FACT-G} GS1, GS2, GS4, GF3, GF4 and 28 in stage III of the analysis: {EORTC QLQ-C30} Q1, 2, 29, 30; {EORTC QLQ-MY20} Q48; {EORTC 5D-3L} Q16; {FACT-G} GS1-5, GE6, GF1-7; {FACT-MM} P2, N3, Leu6; {FACT-N} An5, N2-3; {FACIT-F} An5, 7, 13. These questions explore further aspects of FWB, EWB and SWB of the patients. However, 27/149 of the total QoL questions were considered as non-relevant by the MM patients. Interestingly, the >70 years old age-group did not consider the MM-associated mobility issues as relevant to their QoL that could be partially explained by the co-existing comorbidities. In contrast, HCPs survey response graded the majority of the existing QoL questions at least somewhat relevant. HCPs valued 61 questions referring -in addition to the emotional issues that patients raised- to reduced vitality, limitations in physical ability, effects on the family role, working capacity, neuropathy and pain as very relevant QoL aspects when caring for MM patients. Conclusions: This survey on assessing how MM patients and HCPs graded the relevance of the >15 years old, validated MM QoL questionnaires showed significant differences between the 2 groups' responses. From the MM patients' perspective, the majority of the current QoLQ were not relevant in representing their disease or treatment -related QoL issues. There was a trend for significant difference in QOL issues for age groups that could be incorporated with frailty. This survey results stress the need to develop an updated patient centric QoLQ, which would assist HCPs in therapy decision-making.

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