Hospital Universitario de Salamanca

Background: The Quality of Life Index-Primary Education (QoLI-PE) is a quality of life (QoL) assessment instrument under development that seeks to enhance the inclusion of students with intellectual and developmental disabilities (IDD) enrolled in primary, general education in Spain. The goal of this work was to report evidence on its functioning through a pilot study and characterize the QoL of the participating students with IDD. Methods: 130 primary education students with IDD were assessed with the QoLI-PE. The pilot study involved analyzing the quality of the items, the internal structure of the tool using Confirmatory Factor Analysis (CFA), and its internal consistency (Cronbach's α, ordinal α, and ω). Descriptive statistics were calculated for each QoL domain to characterize the QoL of students with IDD. Repeated-measures ANOVA were run to compare the domains at the within-subjects level, while independent samples t test and one-way ANOVAs were performed to test for between-groups comparisons. Results: After refining the items, the CFA supported the internal structure of the instrument based on the theoretical model of QoL composed by eight first-order intercorrelated domains (χ²/df = 1.266; RMSEA =.045; CFI =.985; TLI =.984). Internal consistency was excellent for all the domains (all indices above.75). Emotional wellbeing and self-determination were identified as areas of concern. Significant differences were found between the levels of disability according to limitations in social skills (for material wellbeing) and in practical skills (physical wellbeing and self-determination). Conclusions: The QoLI-PE stands as a robust tool for its purpose. Strategies for QoL improvement are outlined, and future lines of research are provided.

Background and Objectives Lymphedema secondary to multimodal breast cancer treatment is a relatively common complication that significantly impacts patients' quality of life. Despite identifying several associated risk factors, accurately assessing individual risk remains challenging. This study aims to develop predictive tools integrating patient characteristics, tumor attributes, and treatment modalities to optimize clinical surveillance, enhance prevention, and enable earlier diagnosis. Methods Data were analyzed from 309 patients referred to the Lymphedema Unit of Rehabilitation Service who underwent lymphadenectomy for breast cancer between January 2016 and December 2021. Collected variables included patient demographics, tumor clinicopathological features, and treatment details. A lymphedema incidence study was conducted, complemented by univariate and multivariate regression analyses to identify risk factors. A nomogram was developed to predict high‐risk patients, facilitating personalized prevention and management strategies. Results The cumulative incidence of lymphedema was 18.4%. Independent risk factors included high body mass index, sedentary lifestyle, number of positive nodes (N stage), and radiotherapy, particularly targeting the breast, axilla, and supra‐infraclavicular regions. The logistic regression model demonstrated an area under the ROC curve (AUC) of 0.75, with acceptable calibration, validating the predictive model. Conclusions The predictive tools developed provide healthcare professionals with a means to identify patients at elevated risk of lymphedema, supporting individualized prevention and management.

The CORDELIA Study (Collaborative Cohorts Reassembled Data to Study Mechanisms and Long-term Incidence of Chronic Diseases) combines 35 Spanish population cohorts to investigate the clinical, environmental, genetic, and omics determinants of cardiovascular disease in the Southern European population. It aims to conduct the largest genome-wide association study to date on cardiovascular disease in this population, improve predictions of cardiovascular incidence using genomic and clinical data, and identify subgroups that would benefit most from targeted pharmacological and lifestyle interventions. CORDELIA includes 196,632 individuals (ages 18–84, 54% female, 96% born in Spain, 20% with higher education, recruited from 1989 to 2020, with follow-up periods ranging from 5 to 30 years), with DNA samples available for 117,342 participants (60%). Of the participants, 24% were current smokers, 43% hypertensive, 11% diabetic, 15% medicated with lipid-lowering drugs, 44% overweight, and 27% obese. If not already available, genotyping is being performed using the Axiom™ Spain Biobank array (~ 750,000 variants, including 115,000 specific and 50,000 rare functional variants from the Spanish population). The cohort also includes incident events (coronary heart disease, stroke, heart failure, peripheral artery disease, hypertension, diabetes); date and cause of death; and harmonized data on risk factors (body mass index, waist circumference, lipid profile, blood pressure, glucose, creatinine), lifestyle (smoking, physical activity, diet, alcohol), and socioeconomic status. 99,019 participants (50%) also provide plasma samples. CORDELIA will significantly contribute to understanding the complex interplay of risk factors contributing to cardiovascular disease and advance the fields of precision medicine and public health in Southern European individuals.

Matching adjusted indirect comparisons (MAICs) were performed to compare the efficacy of cilta-cel versus elotuzumab + pomalidomide + dexamethasone (EloPd), isatuximab + carfilzomib + dexamethasone (IsaKd), isatuximab + pomalidomide + dexamethasone (IsaPd), and selinexor + bortezomib + dexamethasone (SVd) in patients with relapsed or refractory multiple myeloma (RRMM) who have received at least one prior therapy and are lenalidomide-refractory. Unanchored MAICs were performed using individual patient-level data (IPD) for all apheresed patients randomized to the cilta-cel arm of CARTITUDE-4 (n = 208) and published arm-level data for EloPd from ELOQUENT-3 (n = 60), IsaKd from IKEMA (lenalidomide-refractory subgroup, n = 57), IsaPd from ICARIA-MM (n = 154), and SVd from BOSTON (lenalidomide-refractory subgroup, n = 53). Eligibility criteria from each comparator trial were applied to the cilta-cel arm IPD, and further imbalances in patient characteristics were adjusted by weighting the cilta-cel patient data to match the reported baseline characteristics of the comparator trials. Comparative efficacy was estimated for overall response rate, very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR) rate, progression-free survival (PFS), and overall survival (OS). After adjustment, cilta-cel patients were significantly more likely to achieve an overall response versus EloPd, IsaPd, and SVd, and were significantly more likely to achieve ≥ VGPR and ≥ CR versus all comparators. Cilta-cel patients also had significant reductions in the risk of disease progression or death (PFS) versus all comparators: 64% versus EloPd, 49% versus IsaKd, 69% versus IsaPd, and 62% versus SVd. Similarly, cilta-cel patients had significant improvements in OS for all feasible comparisons: 52% versus EloPd, 58% versus IsaPd, and 60% versus SVd. Cilta-cel patients demonstrated clinically meaningful benefits over EloPd, IsaKd, IsaPd, and SVd for response and survival outcomes, highlighting its superiority over alternative treatment options for patients with RRMM who have received at least one prior therapy and are refractory to lenalidomide.

Psoriatic arthritis (PsA) is a multifaceted chronic immune-mediated disease characterized by joint, skin, nail and entheseal involvement, affecting approximately 0.3–1% of the global population. In recent years, the treatment options for PsA have expanded from traditional nonsteroidal anti-inflammatory drugs and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) to include biologic DMARDs and targeted synthetic DMARDs. Owing to the heterogeneity of the disease and prevalence of comorbidities, the selection and sequence of treatment are often unclear. In this narrative review, we outline the patient journey from diagnosis through various treatment lines, from conventional therapies to bDMARDS and tsDMARDs, and the considerations for treatment sequencing in patients who do not achieve an adequate response. We examine the factors influencing treatment response, such as disease severity, predominant disease domain, comorbidities, genetic variations, pharmacokinetic and immunogenicity issues. We highlight the importance of identifying robust biomarkers to predict response and the need to determine patient-specific factors, including the contribution of inflammatory mechanisms to disease activity, to inform treatment strategies and improve long-term outcomes. Promising results with more recently marketed biologic and targeted synthetic DMARDs, and the use of combination treatment approaches, offer new options for managing treatment-experienced patients.

Higher-risk MDS (HR-MDS) with RARA gene overexpression is a subset of HR-MDS patients (pts) with an actionable target for tamibarotene, an oral and selective RARα agonist. Tamibarotene in combination with azacitidine (AZA) showed high complete remission (CR) rates in AML. SELECT-MDS-1 (NCT04797780) was a Phase 3 study comparing the activity of tamibarotene/ azacitidine (AZA) to placebo/AZA in newly diagnosed (ND) HR-MDS pts with RARA overexpression. Eligible patients had confirmed RARA overexpression by blood-based assay, untreated MDS with higher-risk features by IPSS-R and a bone marrow blast count >5%. Patients were randomized 2:1 to receive either tamibarotene/AZA or placebo/AZA, respectively. A total of 246 participants with HR-MDS and RARA overexpression were randomized with 164 and 82 in the tamibarotene/azacitidine and placebo/azacitidine groups, respectively. Baseline characteristics included: 69.9% male; median age 75 (38-93); primary MDS 89.8%; WHO 2016 classification MDS-EB-1 48%, MDS-EB-2 52%; median bone marrow blasts 9.0%; IPSS-R risk category intermediate (25.5%), high (35.7%), very high (38.9%). The study did not meet the primary endpoint of CR, with a p-value of 0.2084 for the treatment effect in the tamibarotene/AZA group compared to the placebo/AZA group. The CR rates were 23.81% and 18.75% in the tamibarotene/AZA and placebo/AZA groups, respectively. The use of tamibarotene-based therapy to target RARα as a novel approach in HR-MDS pts with RARA gene overexpression is not a paradigm which can augment response rates beyond HMA monotherapy. Further explorations of alternative approaches, including those with a biomarker, to alter the natural history of this disease are warranted.

PURPOSE Tumor Protein 53 (p53) expressed from gene TP53 is a seminal tumor suppressor. We aimed to characterize mutational and nonmutational mechanisms of p53 dysfunction in myelodysplastic syndromes (MDS) and to investigate their clinical effect. PATIENTS AND METHODS We analyzed a cohort of 6,204 patients with MDS and subsets of patients with available information on RNA sequencing of tumor cells (n = 109), high-dimensional phenotype of immune cells (n = 77), and multiomics analysis (RNA sequencing and proteomics) on single cells (n = 15). An independent validation was performed on 914 patients. RESULTS Biallelic TP53 inactivation was a powerful driver of disease progression and identified high-risk patients, regardless of variant allele frequency. Monoallelic and biallelic inactivation represent disease stages occurring as a multihit process in MDS with TP53 mutations, thus potentially refining the optimal timing of therapeutic interventions in these patients. We identified a subset of MDS (5%) characterized by TP53 wild-type and hyperexpression of abnormal p53 protein in bone marrow progenitors that exhibit dismal outcome. These patients presented upstream p53 signaling aberrations in Pi3K cascade; RAS, WNT, and NF-KB pathways; and MDM2 gene amplification, together with a downstream dysregulation of p53 targets. MDS with p53 dysfunction displayed a distinct immune dysregulation involving myeloid-derived inflammation and impaired antigen presentation, which may be a driver of their poor prognosis and provide the groundwork for innovative immunotherapies. CONCLUSION The identification of nonmutational p53 dysfunction in MDS may lay the foundation for a mechanistic classification of myeloid neoplasms, moving beyond a purely molecular stratification. The recognition of patients with p53 dysfunction is relevant to provide correct disease-risk assessment and interventions, as well as to refine the design of clinical trials

Background and Purpose Large‐bore aspiration catheters (LBACs) are used for thrombectomy in large vessel occlusion (LVO), either as a standalone direct aspiration first‐pass technique or combined with a stent retriever (ASR). LBAC design may influence ASR thrombectomy efficacy. We compared the safety and performance of the novel MIVI Q segmental catheter with the well‐established SOFIA aspiration device in ASR thrombectomy. Methods We analyzed data from the Registry cOmbined vS SinglE Thrombectomy TechnIques registry of consecutive patients with anterior circulation LVO and compared the outcomes of those treated with first‐line ASR thrombectomy using Q (Q5 or Q6) or SOFIA (5F or 6F Plus) catheters. Demographic, clinical, angiographic, and clinical outcome data (24‐h National Institute of Health Stroke Scale [NIHSS] and modified Rankin Scale score at 3 months) were compared. Results Of the 853 patients, 155 (18.2%) were treated with MIVI Q and 698 (81.8%) with SOFIA catheters. After adjusting for age, sex, NIHSS score at baseline, tPA use, site occlusion, anesthesia type, and diameter and length of SR, the MIVI Q group was comparable to the SOFIA group in terms of first‐pass effect or successful final recanalization and safety. However, the MIVI Q group had a shorter mechanical thrombectomy time (20 [10–45] min vs. 33 [20–51] min; odds ratio [OR] = 7.4, 95% confidence interval [CI]: 1.1–14; p = 0.021) and a lower rate of symptomatic intracerebral hemorrhage (3.3% vs. 8.8%; OR = 3.59, 95% CI: 1.45–10.9; p = 0.011). Conclusions In ASR neurothrombectomy, SOFIA aspiration catheters were not superior to MIVI Q in achieving successful and complete first‐passage recanalization; however, MIVI Q had shorter procedural times and a lower rate of symptomatic intracranial hemorrhage.

Introduction Updated primary prevention strategies are needed for post-infarction sudden cardiac death (SCD) based on implantable cardioverter-defibrillator (ICD). Current recommendations, based on left ventricular systolic function and functional class, may be obsolete because they are derived from ancient studies that do not incorporate the potential benefit of either current comprehensive treatment of ischaemic heart disease or modern device programming. Among patients with post-infarction left ventricular dysfunction, modern implantable cardiac monitoring devices (ICM) allow a unique opportunity to determine in real-time the burden of non-sustained ventricular tachycardias and their relationship to the subsequent occurrence of sustained or symptomatic events. Methods and analysis Approximately 200 patients with left ventricular ejection fraction (LVEF) equal to or less than 40% after acute myocardial infarction will be included in the study. They will be implanted with a Confirm RX, an ICM with real-time remote connection via a smartphone. At 6 months, LVEF and functional status will be re-evaluated and cardiac morpho-functional characterisation will be performed by MRI. At this time, and following current European guidelines, patients with an indication will receive an ICD; the others will continue to be monitored using an ICM for a minimum of 2 years. Patients are expected to be followed up for 4 years after the index event. More than 20 000 remote transmissions are expected to be analysed. The study will focus on the relationship between the detection of non-sustained ventricular tachycardias by ICMs (defined as at least 8 R-R intervals at 160 beats per minute) and the subsequent occurrence of symptomatic arrhythmic events. An advanced statistical analysis will be performed using machine and deep learning techniques to determine the clinical variables, those that are derived from monitoring and imaging tests and related to mid-term prognosis. Ethics and dissemination The study was approved by the Ethical Committee of the University Hospital of Salamanca (protocol number PI 2019 03 246) on 30 April 2020. Each patient will be informed about the study in both oral and written form by a physician and will be included in the study after written consent is obtained. For the first time, a study will provide real-time information on the arrhythmic burden of patients with post-infarction ventricular dysfunction and its prognostic implications in the medium term. Several publications in scientific journals are planned. Trial registration number NCT04765943 .

Introduction Haploidentical allogeneic hematopoietic cell transplantation (haplo-HCT) using post-transplant cyclophosphamide (PTCY) has become a standard approach for patients lacking HLA-matched donors. While effective in reducing graft-versus-host disease (GVHD), concerns about PTCY-associated cardiovascular toxicity remain. This study investigates the incidence, predictors, and impact of early cardiac events (ECE) in haplo-HCT recipients. Methods We conducted a retrospective, multicenter analysis of 268 patients with acute myeloid leukemia (AML) treated with anthracycline-based induction regimens and undergoing their first haplo-HCT with PTCY (50 mg/kg/day on days +3 and +4) between 2011 and 2022. ECEs, defined as any new cardiac event within 100 days post-transplant, were analyzed using cumulative incidence functions considering death and relapse as competing risks. Risk factors and the impact on non-relapse mortality (NRM) and overall survival (OS) were assessed via univariate and multivariate regression models. Results The median patient age was 57 years (range: 18–79), and pre-transplant comorbidities included hypertension (22.4%), dyslipidemia (13.1%), diabetes mellitus (6.7%), and prior cardiac history (14.2%). ECEs occurred in 23 patients (8.6%) at a median of 19 days post-transplant (IQR: 5–66), with a day +100 cumulative incidence of 8.6% (95% CI: 6.1–12.3). The most frequent complications were pericardial effusion/pericarditis (43.5%), arrhythmias (30.4%), and heart failure (17.4%). Severe ECEs (CTCAE grade 3–4) were observed in 30.4% of cases, and four deaths (17.4%) were directly attributed to ECEs. Univariate analysis identified dyslipidemia (HR: 3.87, p=0.001), hypertension (HR: 2.76, p=0.015), and moderate-severe veno-occlusive disease (HR: 4.94, p=0.002) as significant predictors of ECE. ECEs were associated with lower OS (HR: 1.78, p=0.04) and higher NRM (HR: 2.87, p=0.005). Discussion While the incidence of ECEs following haplo-HCT with PTCY was relatively low, their occurrence significantly worsened transplant outcomes. These findings underscore the importance of cardiovascular risk assessment and structured cardiac monitoring to mitigate complications in haplo-HCT recipients.

Background Psoriasis is a chronic inflammatory disease with multiple comorbidities, including an increased risk of major adverse cardiovascular events (MACE). There is limited and contradictory evidence comparing the impact of systemic treatments for psoriasis on MACE. Objectives To evaluate the incidence of MACE associated with each systemic treatment used for patients with psoriasis and compare these rates to those observed with methotrexate (MTX). Methods We conducted a prospective cohort study using data from the BIOBADADERM registry. Propensity score matching was used to adjust for baseline differences between treatment groups. We calculated the incidence rate (IR) of MACE for each systemic treatment class, including biologics (anti‐TNF, IL‐12/23, IL‐17 and IL‐23 inhibitors), conventional systemic therapies (MTX, cyclosporine, dimethyl fumarate and acitretin) and apremilast (APR). The IR for each group was compared to those observed in patients treated with MTX using Poisson regression models adjusted for potential confounders, with 95% confidence intervals (95% CI). The primary outcome was the adjusted incidence rate ratios (IRR) for MACE between patients receiving MTX and those receiving another systemic treatment. Results We analysed data from 5622 patients, 11,368 treatment cycles and 21,762 person‐years (PYs). APR (IRR = 0.17; 95% CI, 0.04–0.70) and IL‐17 (IRR = 0.43; 95% CI, 0.20–0.91) were associated with a significant reduction in the risk of MACE compared to MTX. Cyclosporine was associated with an increased risk of MACE (IRR = 3.59; 95% CI, 1.17–10.99) compared to MTX. The remaining systemic psoriasis treatments were not significantly associated with an increased or decreased risk of MACE. Conclusions This real‐world evidence study indicates a potential association between APR and IL‐17 with a lower incidence of MACE, while CYC showed a higher incidence compared to MTX. These findings underscore the importance of considering cardiovascular outcomes when selecting systemic therapies for patients with psoriasis.

Background: The analysis of posture in the early stages of motor development has always been a subject of research and study. With the evolution of new technologies, the need arises to implement evaluation tools that allow an objective and effective assessment of postural control, which is intrinsically linked to motor development. Objectives: The objective was to analyze posture in babies from 0 to 6 months in ventral and dorsal decubitus using artificial intelligence to determine objective parameters of postural assessment. Methods: The study is an observational and cross-sectional study. The babies will be studied following a systematic kinesiological assessment, and the images of the babies will be taken, both in ventral and dorsal decubitus, on a glass platform, to analyze their posture by means of deep learning techniques. Results: Many authors have investigated posture in newborns. However, there is no method for assessing motor and postural development to determine the support area of typically developing babies. Artificial intelligence is postulated as an effective tool to objectively analyze the posture of babies and detect possible delays. Using deep learning techniques as a predictive tool, the support areas of each baby will be defined according to their age. Conclusions: Early detection of motor or postural developmental delays in babies to optimize effective treatment is of great importance. Artificial intelligence can help manage the complexity and growing volume of data in healthcare by knowing the correct postural control at each stage of a baby’s early months, while reducing the workload of healthcare professionals by facilitating decision-making.

Background and Purpose The superiority of achieving modified Treatment in Cerebral Ischemia (mTICI) from multiple passes versus mTICI 2b from a single pass remains uncertain. We aimed to assess whether additional passes in M1 occlusion patients with a first‐pass mTICI 2b score improved clinical and functional outcomes. Methods We analyzed Registry Combined vs. Single Thrombectomy Techniques registry data of consecutive M1‐occlusion patients, comparing outcomes of those with mTICI 2b‐stopped after the first pass versus continued mechanical thrombectomy (MT) to improve angiographic results (mTICI 2b or mTICI 2c/3). We compared demographic, clinical, angiographic, and clinical outcome data (National Institute of Health Stroke Scale [NIHSS] at 24 h and modified Rankin Scale at 3 months). Results Patients with first‐pass mTICI 2b had lower NIHSS scores at admission, fewer left‐side occlusions, and longer last‐seen‐well times. Endovascular techniques and time from groin puncture to revascularization were similar across groups. Patients with final mTICI 2c/3 had the highest distal embolism rates in a new territory (0% for mTICI2b‐stopped vs. 3% for final mTICI2b‐continued; 7.7% for final mTICI2c/3; p = 0.02). The groups had similar rates of death, symptomatic intracranial hemorrhage, same‐area distal embolism, other MT‐related complications, NIHSS at 24 h, NIHSS change from admission to 24 h, and same‐territory distal embolism. Conclusion Achieving mTICI 2b after the first pass in M1‐occlusion patients proved relevant. These patients had comparable clinical and functional outcomes and a lower risk of new territory distal embolisms compared to those with final mTICI 2c/3 scores.

Background High-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML) remain therapeutic challenges with suboptimal outcomes. The only potentially curative treatment is allogeneic stem cell transplantation (allo-SCT). The most frequent pre-allo-SCT treatment is monotherapy with hypomethylating agents (HMA), but approximately 40% of patients cannot proceed to allo-SCT, mainly due to disease progression. Recent evidence suggests that combining HMA with venetoclax (HMA/VEN) could increase HMA efficacy in HR-MDS but it remains unclear if this combination could bridge more patients to allo-SCT. Methods We retrospectively evaluated HMA/VEN as a bridge to allo-SCT in 30 patients with HR-MDS or CMML eligible for transplant. Eighteen patients were treatment-naïve and 12 were refractory or relapsed (R/R). Results As defined by the IWG 2023 criteria, the overall response rate (ORR) was 90% and the composite complete response rate was 77%. For the R/R patients, ORR was 83%. The allo-SCT rate was 83%, and the allo-SCT rate of those patients treated exclusively with HMA/VEN without further bridge therapies was 76%. One- and two-year post-allo-SCT survival was 75% and two-year cumulative incidence of relapse was 30.5%. Follow-up of measurable residual disease identified some molecular relapses that were controlled with preemptive treatment. Conclusions Our findings indicate that HMA/VEN combination therapy shows promise as a bridging strategy to allo-SCT in HR-MDS and CMML.

Background Although mechanical thrombectomy (MT) is an effective treatment for large vessel occlusion (LVO) with a high successful recanalization rate, MT failure (MTF) occurs in 10–15% of cases and is associated with unfavorable outcomes. However, little is known about the clinical, technical, and radiological reasons for MTF. We investigated the technical factors associated with MTF. Methods We conducted a retrospective analysis of consecutive patients with anterior LVO prospectively included in the ongoing observational multicenter ROSSETTI registry. Patients were categorized according to the success (≥mTICI 2b) or failure (<mTICI 2b) of the MT procedure. Baseline clinical and demographic characteristics, endovascular MT techniques, and angiographic and clinical outcomes were compared. Multivariate analysis for prediction of MTF was performed. Results We analyzed 4135 patients, including 325 patients (7.9%) with MTF. Patients in the MTF group had a significantly lower Alberta Stroke Program Early CT Score (ASPECTS) at baseline (8 (7–10) vs 9 (8–10)), longer time since last time seen well (279 min vs 262 min), increased MT procedure time (76 min vs 31 min), higher rate of complications (23% vs 4%), higher symptomatic intracerebral hemorrhage (21% vs 7.9%), higher 24 hour National Institutes of Health Stroke Scale score (19 vs 6), worse functional outcome at 3 months (modified Rankin Scale score 0–2, 15.6% vs 53%), and higher mortality (45% vs 20%). Four or more passes were an independent predictor of MTF (OR 3.46, 95% CI 2.58 to 4.63; P<0.001). None of the endovascular techniques demonstrated a higher likelihood of MTF. Conclusion In this study, MTF in anterior circulation LVO was associated with a high complication rate and worse outcomes.

Background: Daratumumab-based regimens represent the gold-standard therapy for newly diagnosed AL amyloidosis patients. However, there are few studies about the efficacy of this treatment in real life. Methods: This study included 99 patients: 27 (27.3%) received daratumumab and proteasome inhibitor-based schemes, 46 (46.4%) were treated with proteasome inhibitors and/or immunomodulator-based regimens, and 26 (26.3%) were treated with chemotherapy. Results: Patients receiving daratumumab and proteasome inhibitor-based regimens achieved higher rates of partial haematological responses or better (100.0% vs. 78.3% vs. 58.3%; p = 0.009 and p < 0.001) and complete responses (74.1% vs. 37.0% vs. 12.5%; p = 0.003 and p < 0.001) than the proteasome inhibitors and/or immunomodulators and chemotherapy groups, respectively. Daratumumab and proteasome inhibitor-based schemes resulted in a shorter time to haematological response (1 month to partial response or better and 4 months to complete response). Moreover, in the group treated with daratumumab and proteasome inhibitor-based regimens, there was a trend of obtaining better and faster organ responses. The benefit of daratumumab and proteasome inhibitor-based regimens was that they resulted in an improvement in progression-free survival (not reached) compared to the proteasome inhibitor and chemotherapy groups (18 months; p = 0.022 and 6 months; p = 0.002). In addition, the clinical benefit was consistent in patients with Mayo Clinic stages III–IV. Conclusions: This study supports the efficacy and superiority of adding daratumumab to the frontline treatment over proteasome inhibitor-based regimens and chemotherapy in AL amyloidosis, including in advanced cardiac disease.