LBA7506 Background: A growing number of patients (pts) entering second-line treatment (tx) are anti-CD38 monoclonal antibody (mAb)- and lenalidomide (LEN)-exposed, limiting tx options. Mezigdomide (Mezi), a potent oral CELMoD, induces maximal, rapid Ikaros/Aiolos degradation leading to enhanced MM cell death and immune stimulation vs IMiDs. We report initial results from SUCCESSOR-2 (NCT05552976), the first randomized phase 3 study of Mezi in RRMM, evaluating MeziKd vs Kd. Methods: In this phase 3, 2-stage, inferentially seamless trial, eligible adult pts had ≥1 prior line of therapy (LOT) including an anti-CD38 mAb and LEN. Pts were randomized 3:3:3:2 (Mezi 0.3, 0.6, 1.0 mg + Kd, or Kd) to identify the optimal Mezi dose in stage 1, and 3:2 to compare efficacy and safety of MeziKd vs Kd in stage 2. MeziKd was given in 28-day (D) cycles of Mezi (D1–21), 56 mg/m 2 carfilzomib (CFZ) weekly (QW), and 40 mg dexamethasone (DEX) QW. The Kd arm received CFZ 56 mg/m 2 twice weekly or 70 mg/m 2 QW + DEX. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival, selected Mezi dose (stage 1), overall response rate (ORR), and safety. Results: The Mezi dose selected for stage 2 was 1.0 mg. In total, 479 pts (288 MeziKd at 1.0 mg Mezi; 191 Kd) were included in the analysis. Median (range) age was 68 (30–85) y with 25.1% of pts ≥75 y; median (range) number of prior LOTs was 2 (1–9); 92.1% of pts were triple-class-exposed, with 85.8% refractory to an anti-CD38 mAb and 75.8% to LEN; 37.2% were exposed to pomalidomide and 7.3% to anti-BCMA tx. At data cutoff, median follow-up was 10.6 mo with 52.4% (MeziKd) and 31.4% (Kd) of pts still on tx. Median tx duration was 8.9 (up to 32.1) mo for MeziKd vs 6.2 (up to 25.0) for Kd. MeziKd significantly improved PFS vs Kd (median [95% CI], 18.0 [14.5–22.1] vs 8.3 [5.6–10.7] mo; HR, 0.48 [95% CI, 0.36–0.63]; P <0.0001), which was consistent across subgroups, including pts with >2 prior LOTs, prior tx exposure/refractoriness, high-risk cytogenetics, extramedullary disease, and age ≥75 y. Higher ORR (80.2% vs 53.4%) and complete response or better (26.7% vs 8.9%) were seen with MeziKd. Deaths were reported in 21.5% (MeziKd) vs 26.7% (Kd) of pts, mostly due to progressive disease. Grade (Gr) 3–4 treatment-emergent adverse events were seen in 83.7% vs 56.5% of pts, neutropenia in 61.1% vs 9.1%, and infections in 34.0% vs 15.6% with MeziKd and Kd, respectively; Gr 5 infections in this high-risk population were few (2.4 vs 1.1%). Conclusions: MeziKd showed a clinically meaningful PFS benefit as early as first relapse in predominantly triple-class-exposed, anti-CD38 mAb- and LEN-refractory pts, a population with significant unmet need. These data support Mezi, a potent oral tx with a predictable and manageable safety profile, as a readily accessible, potential new standard of care for RRMM across multiple settings. Clinical trial information: NCT05552976 .

BACKGROUND:A growing number of patients with multiple myeloma are anti-CD38 antibody-exposed and lenalidomide-exposed at first relapse, subsequently limiting their treatment options. Mezigdomide, a potent cereblon E3 ligase modulator, induces maximal, rapid Ikaros and Aiolos degradation, resulting in enhanced myeloma cell cytotoxicity and immune stimulation versus immunomodulatory drugs. The SUCCESSOR-2 trial evaluates the efficacy and safety of mezigdomide in combination with carfilzomib and dexamethasone versus carfilzomib plus dexamethasone. METHODS:This phase 3, open-label, randomised controlled trial was conducted at 160 hospital-based sites in 26 countries using a two-stage, inferentially seamless design. Eligible adult patients had measurable multiple myeloma, had received at least one previous regimen (including anti-CD38 antibodies and lenalidomide) on which they had achieved minimal response or better, and documented disease progression during or after their most recent treatment. Interactive response technology was used to randomly assign patients, stratified by age (≤70 years or >70 years), number of previous lines of therapy (≤2 or >2), and International Staging System stage (I, II, or III). Patients received oral mezigdomide (days 1-21 of each 28-day cycle) plus intravenous carfilzomib (56 mg/m2 weekly) and oral or intravenous dexamethasone (40 mg weekly) or carfilzomib (56 mg/m2 twice weekly or 70 mg/m2 weekly) and dexamethasone (20 mg twice weekly or 40 mg weekly). In stage 1, mezigdomide dosing across three levels was optimised. In stage 2, patients were randomly assigned to the selected mezigdomide dose (1·0 mg) plus carfilzomib and dexamethasone or carfilzomib-dexamethasone alone. The primary endpoint was progression-free survival (PFS) evaluated in patients who received 1·0 mg mezigdomide plus carfilzomib and dexamethasone or carfilzomib-dexamethasone alone across both study stages. No imputation was planned for missing efficacy endpoint values or missing safety evaluations. The trial is registered with ClinicalTrials.gov (NCT05552976) and EUClinicalTrials.eu (EUCT number 2022-500861-29-00). The trial is active but not recruiting. FINDINGS:Between Feb 3, 2023, and Nov 28, 2025, 762 patients were assessed for eligibility, of which 606 patients were enrolled and 479 were included in the analyses (288 patients in the mezigdomide-carfilzomib-dexamethasone group and 191 patients in the carfilzomib-dexamethasone group). 252 (53%) patients were male, 411 (86%) were anti-CD38 antibody-refractory, and 363 (76%) were lenalidomide-refractory, with a median of two previous lines of therapy (IQR 2-4). At 10·6 months median follow-up, mezigdomide-carfilzomib-dexamethasone significantly improved PFS compared with carfilzomib-dexamethasone (median 18·0 months vs 8·3 months; hazard ratio 0·48 [95% CI 0·36-0·63]; p<0·0001). Grade 3 or 4 adverse events were observed in 241 (84%) patients receiving mezigdomide-carfilzomib-dexamethasone versus 105 (56%) patients receiving carfilzomib-dexamethasone, including neutropenia (176 [61%] vs 17 [9%]) and infections (98 [34%] vs 29 [16%]). Eight (3%; 95% CI 1-5) and one (1%; 95% CI 0-3) treatment-related grade 5 adverse events were reported with mezigdomide-carfilzomib-dexamethasone and with carfilzomib-dexamethasone, respectively (rate difference 2%; 95% CI -1 to 5). Deaths occurred in 62 (22%) patients in the mezigdomide-carfilzomib-dexamethasone group and 51 (27%) patients in the carfilzomib-dexamethasone group, mainly due to disease progression. INTERPRETATION:Mezigdomide-carfilzomib-dexamethasone provided a significant PFS benefit compared with carfilzomib-dexamethasone alone, with higher rates of grade 3 or 4 adverse events, including infections, which were mostly manageable with standard clinical practice and supportive care. These findings support mezigdomide-carfilzomib-dexamethasone as a clinically meaningful treatment option as early as first relapse in predominantly triple-class-exposed, anti-CD38 antibody-refractory and lenalidomide-refractory patients, a growing population with substantial unmet need. FUNDING:Bristol Myers Squibb.

This study examined whether adults with Multiple Myeloma (MM) show measurable cognitive differences compared with neurologically healthy controls. The primary research question focused on identifying domain-specific cognitive deficits and determining whether standard screening tools adequately capture cognitive abilities. A cross-sectional design compared 45 adults with MM to 40 controls. Participants completed 40–50 min of cognitive and psychological assessments, including the Montreal Cognitive Assessment (MoCA), validated measures of mood and daily functioning, and a digitised cognitive battery assessing key cognitive domains. Group differences in reaction time (RTs) and accuracy were analysed using ANCOVAs adjusting for age and education. Bayesian analyses and EZ drift diffusion modelling (EZ-DDM) were used to characterise evidence strength, prevalence of domain-level inefficiencies, and latent decision-making processes. MoCA scores were lower in the MM group, although the group difference did not reach statistical significance. However, a higher proportion of MM participants met the criteria for possible cognitive impairment compared with controls. At the computerised task level, no significant group differences were observed in accuracy or mean RT. RT analyses showed significant effects of cognitive domain, age, and education, but no overall group effect or interaction. Despite this, threshold-based Bayesian analyses indicated that approximately 22

BACKGROUND:Approximately 3000 adult patients are diagnosed with AML in the UK each year. Current intensive treatments are not well-tolerated by elderly patients, and the 5-year survival rate is only 5-15%, highlighting the need for novel and effective therapies. Oncolytic viruses (OVs) preferentially replicate in cancer cells, resulting in direct oncolysis and induction of innate and adaptive anti-tumour immunity. Unfortunately, the efficacy of OVs remains relatively unexplored in AML. METHODS:Using human AML cell lines, healthy-donor peripheral blood mononuclear cells (PBMC) and AML patient samples, we investigated whether combination with clinically applicable apoptotic modulators (SMAC/BH3 mimetics) can potentiate OV-induced cytokine-mediated killing. RESULTS:We confirmed that OVs stimulate PBMCs to produce inflammatory cytokines, which can induce AML cell death. Bystander cytokine-mediated killing was also significantly enhanced in combination with SMAC/BH3 mimetics, with the optimal combination partner varying with AML subtype. We identified interferon (IFN)-α and tumour necrosis factor (TNF)-α as potential mediators of AML cytotoxicity, and SMAC/BH3 mimetics enhanced AML cell death following direct OV infection, indicating autocrine-paracrine signalling events. Pivotally, we confirmed that apoptotic modulators were effective in combination with both Live- and UV-inactivated virus. CONCLUSION:This work has identified a novel reovirus-based combination-immunotherapy for the treatment of AML.

Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell disorder with well described risks of progression to myeloma and lymphoplasmacytic lymphoma. Using data from an established UK population-based cohort of hematological malignancies and premalignancies, we investigated patient and disease characteristics, subsequent hematological malignancy, and survival in 4,651 people diagnosed with MGUS between 2005 and 2019. The 5-year net (relative) survival (disease-specific estimate of the probability of survival) for MGUS patients was 87.8% (95% confidence interval [CI]: 85.9-89.7), with males (83.8%; 95% CI: 81.0-86.6) more affected than females (92.2%; 95% CI: 89.7-94.7). The proportion of subsequent hematological malignancies was also higher in males than females (8.8% vs. 5.3%; P<0.00001); the average annual rates of transition being 1.81% (95% CI: 1.44-2.18) and 0.99% (95% CI: 0.72-1.27), respectively. Furthermore, whilst annual rates of transformation to myeloma (1.04%) and lymphoplasmacytic lymphoma (0.11%) were as expected, both were higher in males (1.23% and 0.18%) than females (0.87% and 0.06%). With a median time to diagnosis of 40 months, the incidence of myeloid malignancy was also raised in males (relative risk=3.6; 95% CI: 2.5-4.9), but not females (relative risk=1.0; 95% CI: 0.3-1.9). No associations between MGUS and subsequent development of chronic lymphocytic leukemia were observed. Providing new data on the nature of MGUS progression, our analyses revealed previously undescribed sex disparities; including worse survival and increased rates of myeloid malignancy in males with non-IgM MGUS. These findings have implications for future research, as well as risk stratification and monitoring of patients with this highly prevalent plasma cell dyscrasia.

AL amyloidosis is caused by a plasma cell clone that produces abnormal light chains that misfold and deposit as amyloid fibrils in tissues and thus affect organ function. The survival of patients with systemic amyloid light-chain (AL) amyloidosis largely depends on the extent of end-organ damage. Patients with early-stage disease can expect approximately 80% survival at 5 years with contemporary treatment, compared to less than 30% for those with advanced disease. The aim of this guideline is to facilitate recognition and raise suspicion of amyloidosis. It is important to recognise that amyloidosis can present in any clinic, including general medicine/care of the elderly and general practice.

Introduction Frail myeloma (MM) patients remain at risk of greater toxicity and shorter survival outcomes. Approaches to improve this by therapy adaptation include delivering different therapeutic combinations or dose adjusting components of therapy. Understanding which of these approaches to adopt is timely as 4-drug combinations are now approved for transplant ineligible (TNE) patients but were only trialled in non-frail patients. Methods The UK-MRA, Myeloma XIV FiTNEss trial (NCT03720041) is a phase III, multi-centre, randomised controlled trial for newly diagnosed TNE MM patients. The primary objectives are to compare standard and frailty-score adapted (FA) induction therapy with an oral PI/IMiD combination (ixazomib, lenalidomide, dexamethasone, IRD) for 12 cycles and, after a second randomisation (R2), to compare maintenance R to IR. Frailty status was assessed using the full IMWG frailty score. The primary endpoint, early treatment cessation (ETC) in UNFIT/FRAIL patients within 60 days of R1, was reported at ASH 2024 with no significant difference, but there was significant heterogeneity in this outcome with UNFIT patients having a benefit from FA treatment (OR 0.34 [0.16,0.72])​ not seen in FRAIL patients (OR 1.33 [0.79,2.25]). With longer follow-up we now present data exploring the pathway and outcomes of UNFIT and FRAIL patients, including updated analysis of EFS, PFS and OS. Results The FiTNEss trial randomised 733 patients from 04/AUG/20 - 01/MAR/24 at 84 UK sites. 239 (32.6%) were UNFIT and 296 (40.4%) FRAIL. In the UNFIT group the median (IQR) age was 77 years (75-78), 56.9% were male, ISS was I in 25.9%, II 43.9% and III 30.1%, 13% had ECOG >=2. In the FRAIL group the median age was 81 years (78-84), 55.4% were male, ISS was I in 14.2%, II 48.6% and III 36.8%, 43.2% had ECOG >=2. Across the primary endpoint population (UNFIT/FRAIL combined) after median follow up of 26 (IQR 16,38) months (m) median EFS was not significantly different between FA and standard dosing (FA 2m [95% CI 1,3] vs standard 1m [1,2]). PFS and OS also appeared similar (median PFS: FA 23m [19,34] vs standard 27m [21,36] HR 1.12 [0.87,1.43], p=0.372; 3yr OS: FA 69.5% [61.9,75.9] vs standard 66.4% [59.2,72.7], HR 0.87 [0.63,1.20], p=0.399). Due to the heterogeneity in the ETC primary endpoint we performed subset analysis in UNFIT and FRAIL patients for EFS, PFS and OS. In UNFIT patients FA therapy was associated with improved EFS and OS (median EFS FA 5m [95% CI 3,9] vs standard 2m [1,4]; median PFS FA 34m [20,46] vs standard 37m [26,NR]; 3yr OS: FA 84.9% [75.4,91.0] vs standard 75.2% [65.1,82.7]). FRAIL patients had inferior outcomes across all endpoints compared to UNFIT patients and did not appear to gain any benefit from FA dosing (median EFS FA 1m [0,1] vs standard 1m [0,1]; median PFS FA 19m [14,26] vs standard 21m [16,33]; 3yr OS: FA 55.2% [43.6,65.3] vs standard 58.7% [48.1, 67.8]). Most EFS events were >=G3 non-haematological toxicities (most frequently infections and skin/subcutaneous disorders). These comprised a lower proportion of events in the FA group (UNFIT 70/104, 67.3%; FRAIL 92/138, 66.7%) compared to standard (UNFIT 78/104, 75.0%; FRAIL 105/140, 75.0%). FRAIL patients were more likely to have >=G4 haem toxicity, withdrawn or died as their EFS event, and these comprised a slightly higher proportion of events in the FA group, leading to the similar EFS in this group. FRAIL patients had a shorter median duration of induction therapy even with FA dosing (UNFIT: FA 12 cycles [95% CI NR] vs standard 12 [10,NR]; FRAIL: FA 7 [4,10] vs standard 9 [6,11]). FRAIL patients in both arms were much less likely to reach R2 (UNFIT: FA 55%, standard 46%; FRAIL: FA 29%, standard 30%). Unacceptable toxicity was the most reported reason for withdrawal from treatment. Conclusions Results from FiTNEss suggest that ETC, EFS and OS were improved by FA dosing in UNFIT but not FRAIL patients. In FRAIL patients, shorter durations of treatment and shorter EFS/PFS/OS persist with PI/IMiD combinations even with prospective treatment modifications. Data from other trials suggest anti-CD38/IMiD combinations may be better tolerated in FRAIL patients, with improved outcomes. Our data suggest the recently approved anti-CD38/IMiD/PI combinations should be used cautiously in FRAIL patients even with FA dosing strategies. Future studies should explore other approaches such as treatment switching for FRAIL patients with a suboptimal response.

Introduction Evidence for disease outcomes in Multiple Myeloma (MM) is largely derived from clinical trials which often exclude frail patients. UNCOVER is a blood cancer health data research programme that utilises the National Cancer Registration Dataset (NCRD). NCRD includes information on all patients diagnosed with all types of cancer in NHS institutions in England (Int J Epidemiol 2020; 49(1):16–16h). Here, we report the demographics, incidence and survival of patients with myeloma in the UNCOVER dataset with particular emphasis on frailty. Methods Data was selected for patients diagnosed with MM (ICD-O-3: 97323, 97343, 97313) between Jan 2014 and Dec 2021 with follow-up until July 2023. International Myeloma Working Group (IMWG) modified frailty scores (non-frail 0-1, frail 2-5. Facon et al, 2019) could be assigned to patients who received systemic anti-cancer treatment (SACT). Crude and adjusted incidence rate ratios (IRRs) were estimated and compared between groups using Poisson regression, and calendar time trends were assessed. All-cause overall survival (OS) was assessed using KM methods and an adjusted Cox regression model. Cause-specific (Fine-Gray model) and relative (Pohar Perme method) survival were estimated. All models were adjusted for age at diagnosis, gender, index of multiple deprivation (IMD) quintile and government region, while Cox and Fine-Gray models were also adjusted for ethnicity and Charlson co-morbidity index (CCI). OS and net survival (NS) were estimated for frail and non-frail groups and a multivariable Cox model fitted that included frailty status. Results 39,521 MM patients were identified in total. 25.3% were >80 years of age, with the majority being <75 (58.5%). Frailty score was available for 23,674 patients [frail n=9,487 (40.1%); non-frail 14,187 (59.9%)]. 4,416 (11.2%) patients had a score >3 and would be considered 'ultra-frail’. In all MM patients, adjusted IRRs increased with age and were higher in males [1.62 (1.59-1.66, 95% CI), p<0.001], in most deprived IMD quintiles compared to the least deprived [IMD1 vs 5, 1.05 (1.01-1.08), p<0.001], and lower in all 8 provincial regions compared to London [North West 0.63 (0.61-0.66), p<0.001]. Adjusted IRRs were higher for Black people [1.45 (1.38-1.53), p<0.001] and lower for Asian people [0.44 (0.42-0.47), p<0.001] and those of mixed/other ethnicity [0.47 (0.43-0.50), p<0.001] compared to White people. Median follow-up was 33.7 (IQR: 14.3–58.7) months. 21,987 (55.6%) patients died with median OS 49.5 (48.5–50.5) months and NS 58.7% and 45.3% at 3 and 5 years. Hazard ratio (HR) for all-cause mortality was higher for males [1.06 (1.03–1.08)] and increased with age [10.2 (8.1–12.1) for 81–99 vs <40], deprivation [1.29 (1.22–1.34) for IMD1 vs 5], comorbidity [1.46 (1.41–1.50) for CCI>1 vs ≤1], and provincial regions vs London [1.21 (1.15–1.28) for North West]. HR was lower in all other ethnic groups compared to White [Black,0.77 (0.72-0.83); Asian, 0.80 (0.65, 0.98); p<0.001]. OS and NS increased for cohorts diagnosed in successive years until 2019 [HR 0.81 (0.77, 0.85) for 2019 vs 2014]. Compared to non-frail patients, frail patients had a shorter OS (median 31 vs 78 months; p<0.001), higher all-cause mortality [HR 1.75 (1.66-1.84), p<0.001] and shorter NS (44.5% vs 73.1% at 3 years, 26.0% vs 58.1% at 5 years). Patients aged 76-80 who were classified as frail had a shorter NS at 5 years compared to non-frail patients aged 76-80 (28.2% vs 39.1%). Deprivation was associated with lower NS at 5 years in both non-frail (51.6% vs 61.4% for IMD1 vs IMD5) and frail (23.9% vs 26.1%) patients. The same was true of region (NS at 5 years for North East vs London: 55.9% vs 61.4% in non-frail group; 22.6% vs 30.0% in frail group). Conclusion This national cohort study highlights variation in incidence, survival, and mortality outcomes within the English MM population. Deprivation and regional disparities in survival were evident in both frail and non-frail cohorts, suggesting a synergistic effect between frailty and socioeconomic disadvantage. Disparities persisted among patients categorised as frail by modified IMWG due to factors other than age (<80 years), suggesting that frailty plays a prognostic role independently of age. These findings highlight the need for tailored clinical approaches and policy interventions to improve outcomes in multiple myeloma.

Natural killer (NK) cells play a key role in the innate immune response against tumour progression. While the immune microenvironment in multiple myeloma (MM) becomes increasingly dysfunctional during disease evolution, little is known about changes in the NK cell compartment. Using primary samples from clinical trial patients, we performed detailed phenotypic analyses of bone marrow mononuclear cells from MGUS, SMM, and newly diagnosed MM patients. We found that disease progression is associated with an increase in CD56bright NK cells with a dynamic positive association between this NK cell subset and local tumour burden. We generated a large single-cell RNA sequencing dataset of >100,000 NK cells from healthy donor individuals and plasma cell disorder patients and identify a bone marrow specific CD56bright-like NK cell population (BM-NK) that is enriched in the marrow of MM patients. These findings highlight the evolution of the NK-cell compartment in MM and suggest a role for BM-resident CD56bright NK cells with impaired cytotoxicity in promoting immune evasion. ### Competing Interest Statement The authors have declared no competing interest.

Belantamab Mafodotin (Belamaf) is a BCMA targeted antibody drug conjugate with a multi-modal mechanism of action including direct MMAF induced cellular cytotoxicity as well as immunogenic cell death. Belamaf in combination with bortezomib and dexamethasone (BVd) demonstrated superior progression-free and overall survival for patients with relapsed or refractory multiple myeloma (RRMM) compared to daratumumab, bortezomib and dexamethasone (DREAMM-7 trial) leading to regulatory approvals. However, the mean Belamaf compliance when dosed Q3W in DREAMM-7 was 51%, decreasing as treatment progressed (77% 0-6m, 68% 6-12m, 28% >12m) suggesting that further optimisation of the schedule is possible. Ocular adverse events with Belamaf mean eye examinations are recommended prior to dosing, adding to the treatment burden for patients and placing additional demands on healthcare resources. The Ocular Surface Disease Index (OSDI), a patient questionnaire, was retrospectively evaluated in the DREAMM-2 trial as a potential surrogate for ocular examinations. Notably, a negative questionnaire was able to rule out grade 3-4 keratopathy in 93.5% of examinations (Popat et al., ASH 2021). This questionnaire was adjusted to a 9-item Visual Related Anamnestic Tool (VRAT) to assess eye symptoms and vision related function. This can be used by healthcare professionals to evaluate ocular side-effects associated with Belamaf, potentially streamlining monitoring and improving patient experience. ProMMise is phase I/II muti-centre platform trial investigating Belamaf combinations for patients with RRMM after 1-3 prior lines of therapy. The ProMMise D arm will be conducted in two stages, with a primary objective of determining if BVd can be safely given using the VRAT without the need for mandated eye examinations. Secondary objectives include: to assess the agreement between the VRAT and eye care specialist-led dosing, and to assess treatment compliance and efficacy using a less intensive dosing schedule without eye assessments. In stage 1, 40 patients will have eye assessments prior to the first 3 doses as well as completing the VRAT. Dosing will be interrupted for ≥ grade 3 events or a positive VRAT. A safety assessment for the use of the VRAT will be performed following this by an independent Safety Review Committee. Thereafter, Stage 2 will enrol 60 patients with no mandated on-treatment eye assessments and ocular adverse events assessed using the VRAT alone prior to each Belamaf dose. If the questionnaire is positive, treatment will be interrupted. A multiple outcome Bayesian monitoring strategy will be used to monitor ocular toxicity in the short-term for participant safety and in the longer-term to assess the suitability of this approach. Patients will receive BVd in a less intensive schedule to DREAMM-7 based on the trial post-hoc analysis of actual treatment received to improve Belamaf compliance. A weekly bortezomib schedule is used in line with real world practice to reduce peripheral neuropathy, with home administration permissible for patient convenience. The ProMMise D schedule being evaluated is: Belamaf 2.5mg/kg for cycle 1 then 1.9mg/kg Q8W with bortezomib 1.3mg/m2 s.c. and 40mg dexamethasone weekly for 6 months. Following that, Belamaf monotherapy maintenance will commence Q12W until disease progression or intolerance. ProMMise D gained regulatory approval in December 2024. Enrolment is ongoing with results from Stage 1 expected in the first half of 2026. The ProMMise D trial aims to investigate a patient-centred approach to delivering Belamaf with bortezomib and dexamethasone with less intensive dosing to improve compliance and replacing ocular examinations with a simple questionnaire (VRAT). GSK provided funding and Belamaf supply. This study was also supported by Myeloma UK through the UKMRA-MUK- concept and access research programme. Trial registration number: ISRCTN19869915

Autologous stem cell transplant (ASCT) requires the collection of hematopoietic progenitor cells, commonly by apheresis (HPC-A). These CD34+ cells can be mobilized using Granulocyte Colony Stimulating Factor (G-CSF) only or chemomobilization plus G-CSF. Both methods may additionally include Plerixafor. The emergence of COVID-19 led to recommendations for preferential G-CSF only mobilization. To assess the impact of this recommendation on HPC-A harvesting, we analyzed data from the NHS Blood and Transplant Stem Cell Collection Registry for 1342 patients undergoing 2431 HPC-A procedures between 01/01/2019 and 31/12/2021. We compared G-CSF only, cyclophosphamide plus G-CSF (Cyclo-G) and G-CSF plus alternative chemotherapy (Chemo+G) mobilization. The outcomes collected were pre-apheresis CD34+ count, CD34+ yield per procedure, total CD34+ yield, number of apheresis procedures required to achieve the CD34+ target, mobilization failure, and Plerixafor use (+P). In multiple myeloma (MM), Cyclo-G (+/-P) mobilization produced significantly higher CD34+ yields than G-CSF only (7.44 vs. 4.75 × 106/kg; p < 0.0001). In Hodgkin lymphoma (HL) there was no statistically significant difference between regimes (CD34+ yield 4.53 × 106/kg with G-CSF only (+/-P), 5.52 × 106/kg with Cyclo-G (+/-P), 4.32 × 106/kg with Chemo+G (+/-P)). In Non-Hodgkin lymphoma (NHL), Chemo+G (+/-P) was the most successful regime (5.98 × 106/kg vs. 3.7 × 106/kg with G-CSF only (+/-P) vs. 3.69 × 106/kg with Cyclo-G (+/-P); p < 0.00001). On demand Plerixafor use resulted in > 95% successful mobilization in MM and NHL. CD34+ yields are higher using Cyclo-G and Chemo+G in NHL. In MM, G-CSF only resulted in yields sufficient for at least one transplant. In HL, our data show no evidence to support the use of Cyclo-G over G-CSF only.