Multiple Treatment Research Articles

Tratamiento de la esclerosis múltiple: situación a octubre del 2020 en los hospitales públicos de Costa Rica

IntroductionIn recent years, multiple treatments for multiple sclerosis have emerged for both, injectable and oral routes of administration. Most of these medications are currently available in Costa Rica. However, interferons are still the only available treatment in the public health system. An overwhelming administrative procedure is required to justify the purchase of the rest of the options in case they are needed for any specific patient. ObjectiveTo describe the treatment of multiple sclerosis in Costa Rica. Patients and methodsA longitudinal, observational and retrospective study of cases with the diagnosis of multiple sclerosis in the Costa Rican public hospital system was carried out between 1990 and December 2017. Drug treatment as of October 2020 was analyzed for those patients who met the 2010 McDonald's criteria. ResultsA total of 448 cases were obtained, of which 437 were under drug treatment. The most frequent used drugs were Interferón β1-a intramuscular (53.6%), Interferón β1-b (21.2%) and Interferón β1-a subcutaneous (7.9%). By 2020, 163 patients (36.4%) had continued with the first medication, meanwhile 274 persons (62.3%) needed a change of drug. Treatment failure was the main cause of change and fingolimod was the main alternative choice. Interferón β1-a intramuscular has a longer time of use and less change rate, while fingolimod and Interferón β1-a subcutaneous are more likely to require change in a shorter period of time. ConclusionIn Costa Rica, interferons are the most widely used treatments for multiple sclerosis in the public health system. Therapeutic failure is the main reason for changing medication, while fingolimod is the treatment of choice in most cases.

Epidemiology, site-specific characteristics and survival of carcinosarcoma: a retrospective study based on SEER database

ObjectivesCarcinosarcoma (CS) is a rare and biphasic malignancy characterised by a highly invasive biological nature and poor prognosis. This study explored the epidemiology, site-specific characteristics and survival outcome of CS.DesignWe...

Stem cells signaling pathways and surface receptors: Implications for multiple sclerosis treatment

Stem cells signaling pathways and surface receptors: Implications for multiple sclerosis treatment

Potential benefits of humour usage in the multiple sclerosis treatment: Scoping review

Potential benefits of humour usage in the multiple sclerosis treatment: Scoping review

Current Diagnosis and Treatment for Hepatocellular Carcinoma with Macrovascular Tumor Thrombosis

Abstract: Macrovascular tumor thrombosis (MVTT) is common among patients with advanced hepatocellular carcinoma (HCC), and it contains two main types, portal vein tumor thrombus (PVTT) and hepatic vein tumor thrombus (HVTT). MVTT is a significant prognostic factor, and the prognosis of HCC with MVTT remains unsatisfactory. The classification of MVTT varies in different studies, and the management of HCC and MVTT differs among Eastern and Western countries. Over the past years, a multidisciplinary approach, including surgical resection, radiotherapy, and transcatheter arterial chemoembolization, especially the advent of new targeted drugs and immune checkpoint inhibitors, has brought considerable survival benefits for HCC patients with MVTT. Recently, multiple novel treatment strategies, such as neoadjuvant therapy or tumor downstaging based on radiotherapy, immunotherapy, and molecular-targeted therapy, have broadened the treatment landscape of MVTT. In this review, we conclude the consensus and progress regarding diagnosis and treatment for patients with HCC and MVTT.

Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol

ObjectiveOvarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start phenotype-guided targeted therapy to improve survival without compromising quality of life. Study designPatients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. ConclusionThe results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.

Biomimetic platelet nanoparticles encapsulated with proteasome inhibitor bortezomib for multiple myeloma treatment

The discovery of bortezomib (BTZ) has been a major clinical breakthrough for multiple myeloma (MM) treatment. However, its clinical application is restricted to a low tumor-targeting ability, fast clearance, and treatment-related toxicity. Here, we report a targeting strategy of MM by poly(lactic-co-glycolic acid)(PLGA) nanoparticles cloaking with platelet membranes (PMs) encapsulating BTZ (PM/BTZNPs). The drug delivery system could encapsulate sufficient BTZ with suitable nanoparticle characteristics for cellular uptake via an easy fabrication process. Of note, PM coating markedly enhances the selectivity, cellular uptake, and anticancer effects of BTZ in LP-1 cells. PM/BTZNPs further display a targeted drug delivery system to MM, causing a low toxicity effect and exhibiting an obvious survival advantage compared to nontargeted BTZ. Therefore, PM/BTZNPs, as a biomimetic nanotherapeutic formulation, demonstrate a high potential for MM patients.

Real World Effectiveness of Oral Cladribine in Multiple Sclerosis Treatment, Report from a Single Saudi Center

Real World Effectiveness of Oral Cladribine in Multiple Sclerosis Treatment, Report from a Single Saudi Center

Clinical decision-making based on 11C-methionine PET in recurrent Cushing's disease with equivocal MRI findings.

Diagnosis and accurate localization of recurrent tumors in Cushing's disease (CD) are challenging, especially after multiple transsphenoidal surgeries (TSSs) or radiosurgery. Even experts face difficulties in detecting these recurrent tumors, and a favorable surgical outcome is not guaranteed. In this report, the authors aimed to determine the usefulness of 11C-methionine positron emission tomography (MET-PET) for evaluating patients with recurrent CD with inconclusive magnetic resonance imaging (MRI) lesions and to develop a treatment protocol for these cases. In this retrospective study of patients with recurrent CD in the period between April 2018 and December 2022, the authors assessed the usefulness of MET-PET in determining whether equivocal MRI findings were recurrent tumors or postsurgical cavities and deciding further treatment options. All patients had undergone at least one TSS, and most had undergone multiple TSSs and had pathologically confirmed corticotroph tumors with hypercortisolemia. Overall, 15 patients with recurrent CD (10 females and 5 males) were included, all of whom had undergone MET-PET. All patients had been subjected to multiple treatments, including TSSs or radiosurgeries. Their MRI scans demonstrated less-enhanced lesions that were not confirmed as recurrences even with cutting-edge MRI because they could not be distinguished from postsurgical changes with confidence. MET uptake was positive in 8 patients (9 examinations) and negative in 7. Following MET-PET, repeat TSS was performed in 5 patients. Corticotroph tumors were identified in all 5 patients, even though one of them had negative MET uptake. The MET uptake precisely identified a tumor location on the opposite side of the MRI-suspected lesion in 2 patients. Meanwhile, patients with negative uptake and mild hypercortisolism were only observed. Nonsurgical options were also used in other patients: temozolomide (TMZ) was administered in 2 patients owing to a prior history of multiple TSSs and radiosurgery and the drug-resistant nature of the disease. TMZ was highly effective in these patients; their Cushing's symptoms ameliorated, and their adrenocorticotropic hormone and cortisol levels continued to decline. Interestingly, MET uptake disappeared following TMZ treatment. MET-PET is extremely useful for confirming equivocal lesions on MRI in patients with recurrent CD and for deciding further treatment options. The authors propose a novel protocol based on MET-PET results for treating patients with relapsing CD in whom the recurrent tumors cannot be confirmed with MRI.

Cross-sectional study assessing health outcome priorities of older adults with multimorbidity at a primary care setting in Singapore

ObjectivesManaging older adults with multimorbidity may be challenging due to the conflicting benefits and harms of multiple treatments. Thus, it is important to identify patients’ health outcome priorities to align...

MSR9 Adjusting for Switches to Multiple Treatments in Randomised Controlled Trials: A Comparison of Inverse Probability Weighting and Two-Stage Estimation Methods

MSR9 Adjusting for Switches to Multiple Treatments in Randomised Controlled Trials: A Comparison of Inverse Probability Weighting and Two-Stage Estimation Methods

OP51 Use Of Real-World Data In Cost-effectiveness Analysis Of Sequential Biologic Treatment For Rheumatoid Arthritis

IntroductionIn health technology assessment (HTA), economic evaluations assessing biologic drugs for rheumatoid arthritis (RA) involve modeling patients’ responses to multiple treatments given sequentially over a lifetime horizon. When data from randomized controlled trials (RCTs) are scarce, data from non-randomized studies (e.g., single-arm trials [SATs] and disease registries) can be used to supplement the evidence base. This research aimed to demonstrate meta-analytic methods for combining effectiveness data from randomized and non-randomized studies and their corresponding impact on cost-effectiveness estimates.MethodsData comparing patients receiving second-line rituximab with continued background non-biologic treatment were extracted from one RCT and six SATs identified in an HTA assessing second-line rituximab for RA, and from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis, by applying a target trial emulation approach. A binomial meta-analysis model was used to estimate the probabilities of achieving the European League against Rheumatism (EULAR) response criteria by pooling data from the RCT, SATs, and the registry. The probabilities were entered into a decision model from a previous HTA to derive incremental cost-effectiveness ratio (ICER) estimates for treatment strategies with and without biologic drugs.ResultsCompared with the original analysis, the estimated probability of at least a moderate EULAR response on rituximab from combined sources was substantially lower. For example, the probability obtained from an RCT was 0.68 (95% credible interval [CrI]: 0.345, 0.907), but only 0.29 (95% [CrI]: 0.242, 0.333) when using RCT plus registry data and 0.29 (95% CrI: 0.244, 0.336) for combined RCT, registry, and SAT data. In the cost-effectiveness analysis, the median ICERs were higher when including real-world data.ConclusionsSynthesis of all relevant data, including RWD, provides additional information regarding the variability in cost-effectiveness estimates and can be considered in sensitivity analyses for HTA decision-making.

Preliminary study of cine-MRI compression in MR-guided radiotherapy.

Cine-magnetic resonance imaging (MRI) is currently used in real-time tumor tracking during magnetic resonance (MR)-guided radiotherapy. As a type of MRI specified for motion tracking, a few minutes' acquisition results in thousands of 2-dimensional (2D) images. For MR-guided radiotherapy consisting of multiple treatment fractions, the large number of cine-MRI images would be disproportionate to the tight clinical data storage available. To alleviate this issue, the feasibility of compression of cine-MRI via video encoders was investigated in this study. The cine-MRI images were first sorted into 3 sequences according to their plane orientations. Then, each sequence was reordered according to their acquisition times [time-based (TB)] or content similarities [similarity-based (SB)]. As a result, 3 sequences were obtained for 3 plan orientations. Next, the obtained sequences were processed by a video encoder and the corresponding 3 video files were achieved. We employed 3 popular video encoders: Motion JPEG (M-JPEG), Advanced Video Coding (AVC), and High Efficiency Video Coding (HEVC). The performances of the sequence reordering methods and video encoders were evaluated based on a total of 150 image sets. The mean correlation quantities for SB sequences were higher than those for TB sequences by 3% (sagittal), 2% (coronal), and 1% (transverse), respectively. The average compression ratio (CR) yielded by the SB sequences was higher than that achieved by the TB sequences. Comparing with M-JPEG, the CRs obtained by AVC and HEVC were increased by 58% and 62% (sagittal), 16% and 23% (coronal), and 48% and 56% (transverse), respectively. Among the 3 video encoders, the highest CRs and restoration accuracy were achieved by HEVC. HEVC with inter-frame coding is more effective in reducing the redundant information in consecutive images. It is feasible to implement the video encoder for high-performance cine-MRI compression.

Testing Lansoprazole on Human Gut Microbiota using a Gastroesophageal Reflux Model In Vitro

One in five Americans experience Gastroesophageal Reflux Disease, but the disease has multiple treatments, such as Proton Pump Inhibitors (PPI). However, the effects of PPIs may induce more harmful effects on the gut microbiome, and less treatable symptoms such as inflammatory bowel disease, diabetes, obesity, and even cancer may occur. PPIs reduce acid secretion within the stomach and reduce stomach acid in the esophagus. The side effects of PPIs on the gut microbiome have yet to be researched extensively. This study suggests that Lansoprazole, a PPI, may cause significant changes in gut bacteria growth. An adapted method of in vitro digestion modeled the digestive systems of a human. Solutions replicating the environment of the mouth, stomach, and intestines were combined with a human dosage of Lansoprazole, and the pH was adjusted at different segments to model the low pH environments of the stomach and the neutral pH of the intestines. The respective solutions were then exposed to gut bacteria, E. coli, and S. epidermidis. These gut bacterias represent specific bacteria species within the intestinal tract. Data indicated that E. coli grew approximately 50% as much as the control at 20-minutes and less than 25% as much as the control at 40-minutes. S. epidermidis grew significantly less than the control, with approximately 60% as much at 20-minutes and approximately 15% as much at 40-minutes. In conclusion, studies indicate Lansoprazole treats GERD, but side effects from consuming the drug may cause gut dysbiosis, which may lead to the side effects previously mentioned.

Cognitive Improvement through Breathing Exercises in Post-Stroke Respiratory Sarcopenia: A Review

PURPOSE: The first purpose of this study is to investigate the relationship between Post-Stroke Respiratory Sarcopenia (PSRS) and Cognitive Impairment (CI) through Breathing Exercise (BE) as a respiratory rehabilitation after stroke (ST). The second purpose is to introduce a pilot study design set to investigate and compare the acute effects of each BE to develop a BE protocol for further studies.METHODS: Pubmed, Scopus, Web of Science and Google Scholar search engines were used to identify the definition and mechanism of ST, CI and respiratory sarcopenia (RS), and to find cases of application of BE in such conditions.RESULTS: Review; BEs that improve ST, RS, and CI symptoms are Box Breathing (Tactical Breathing), Fast-Breathing, Slow-paced Breathing, Inspiratory Diaphragmatic Breathing+Expiratory Pursed-lip Breathing Exercise. However, the effect is still unclear as post-stroke patients undergo multiple medical treatments other than BE. Pilot Study Prospective results; Inspiratory Diaphragmatic Breathing+Expiratory Pursed-lip Breathing Exercise, Slow-paced Breathing, Box Breathing (Tactical Breathing) and Fast-Breathing will be performed by 40 healthy college students through a randomized controlled trial for 4 weeks. Respiratory functions, exercise intensity, active oxygen level, blood lactate level, cerebral oxygen saturation and cognitive function will be measured pre- and post-intervention along with acute and 2 week mid-intervention. BEs are expected to improve respiratory function, cognitive performance and energy levels while reducing HR, BP, and stress. However, individual response to BE may vary according to health, physical fitness and life styles. All BE will be conducted in an evenly controlled and supervised environment for accurate data collection.CONCLUSIONS: Further study will be done to develop an appropriate BE protocol for PSRS patients per this review. Follow-up studies may also use this review as a reference for the application of BEs in PSRS patients with CI.

Daratumumab in the Treatment of Multiple Myeloma

A monoclonal antibody called Daratumumab (trade name: Darzalex) was created by Janssen Biotech, a division of Johnson & Johnson. The U.S. Food and Drug Administration originally approved it in November 2015 as a treatment for multiple myeloma in patients who had already tried at least three other lines of treatment. Daratumbabab has transformed multiple myeloma treatment since it was approved, and it has now acquired further approvals for a number of applications, reaffirming its place as a prominent therapeutic choice in the management of this challenging condition. It has been very effective in combating multiple myeloma. Although certain symptoms are present, its efficacy is still quite good. Daratumumab's ability to provide positive results in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation has been further supported by the Maia trial, a crucial study in this area. Daratumumab works by targeting CD38, a cell surface glycoprotein that is abundantly expressed in malignant plasma cells. This causes antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and direct activation of death. Daratumumab is becoming more and more important as a good therapeutic choice for people with multiple myeloma as a result of a thorough understanding of its effectiveness, symptoms, and mechanism of action.

A Pilot Study to Determine the Safety and Efficacy of Repeated Hyperbaric Oxygen Therapy in Multiple Myeloma Patients Undergoing High-Dose Therapy and Autologous Stem/Progenitor Cell Transplantation

Background Serum erythropoietin (EPO) negatively impacts hematopoietic stem cell homing and engraftment. Hyperbaric oxygen (HBO) therapy can reduce serum EPO in healthy volunteers and when given prior to stem cell infusion may improve engraftment after hematopoietic stem cell transplant (HSCT). We previously performed a phase II trial randomizing patients with multiple myeloma undergoing high dose melphalan and autologous HSCT 1:1 between a single HBO treatment and no HBO. HBO was given as 100% oxygen, 2.5 ATA for a total of 90 min, in a single treatment on Day 0 prior to the transplant. A total of 99 patients were enrolled with 52 randomized to HBO. HBO significantly reduced EPO levels for the first 24 hours after auto transplant, but EPO levels quickly rebounded by 48 hours after transplant. We hypothesized multiple HBO treatments will keep EPO levels low during the duration of stem cell homing (i.e: the first 72 hours after HSCT) and may improve neutrophil and NK cell recovery. Methods We performed a pilot study to evaluate the safety and tolerability of multiple HBO treatments during autologous HSCT. Patients with multiple myeloma undergoing autologous HSCT were eligible. Patients received HBO therapy, consisting of hyperbaric oxygen at 2.5 ATA for a total of 90 minutes breathing 100% oxygen on days 0 (prior to HSCT), 1, and 2 of transplant. The primary objective of this pilot study was to determine the safety of repeated HBO therapy in the setting, as defined by treatment limiting toxicity (TLT) including occurrence of seizure disorder, pneumothorax, death, or any irreversible grade Ill or any grade IV toxicity within 24 hours of HBO therapy. Secondary objectives were to determine the effects of multiple HBO therapy on neutrophil count recovery and the effect of multiple HBO on serum EPO. Results 10 patients have been enrolled that are evaluable for the primary objective. All patients had multiple myeloma and 4 were female. 9/10 patients successfully completed all 3 HBO treatments and 1/10 completed HBO on days 1 and 2 only because of ear pain on day 0. No patients experienced treatment limiting toxicity. The median times to neutrophil and platelet engraftment was 12 days (range 11-14) and 16 days (range 14-28), respectively. The median length of hospitalization was 13 days (range 12-16). Febrile neutropenia occurred in 3/10 patients with just one incidence of documented infection. This was significantly less than the rate of febrile neutropenia in patients receiving a single treatment of HBO or no HBO (81% and 47%, respectively, p<0.05). 3 patients required red blood cell transfusion and 5 platelet transfusion. Conclusions Multiple HBO treatment were well tolerated without treatment limiting toxicity during autologous HSCT for multiple myeloma.

Efficacy Evaluation of a Tetracyclic Triterpene Compound Targeting Multiple Apoptosis Proteins for the Development of a Multiple Myeloma Treatment

Introduction:Multiple myeloma (MM) is an incurable hematologic cancer that originates in plasma cells and occurs primarily in older patients over 60. This study screened for hit compounds for MM treatments targeting mitochondria and apoptosis proteins. Further, non-clinical testing, including molecular docking analysis, was performed. Methods: Based on our previous studies, candidate compounds targeting mitochondria were screened (www.medchemexpress.com). The killing effect of the compounds on MM cell lines (RPMI8226, IM9, and U266) was examined using a sulforhodamine B assay. Apoptosis mechanisms were investigated in vitro. Complex immunocompromised mice were established by injecting RPMI8226-RFP-FLuc cells through the tail vein. Efficacy of the KBB-N2 activity was assessed following intraperitoneal (15 or 30 mg/kg/day) and tail vein (7 mg/kg/day) infusions for three days a week at daily intervals. Toxicity, pharmacokinetics, and molecular docking analyses were performed according to the established protocols. Results: The hit compound, KBB-N2, a tetracyclic triterpene, was identified as an MM-targeted compound with cytotoxic effects. The primary mechanism of action of KBB-N2 in MM cells was inhibiting the activity of the mitochondrial electron transport (ETC) complex, resulting in the generation of excess intracellular reactive oxygen species (ROS), which led to tumor cell death by ROS-mediated apoptosis. In addition, exposure to KBB-N2 inhibited the activity of catalase, a powerful antioxidant enzyme in MM cells. Severe suppression of normal hematopoietic stem cell function was observed with lenalidomide administration at a concentration of 25 μM. However, this toxicity was not observed when KBB-N2 was administered at doses up to 60 μM. KBB-N2 activity involves PARP cleavage and caspase activation in the apoptotic pathway. Furthermore, KBB-N2 inhibited cell growth and exerted cytotoxicity. KBB-N2 induced apoptosis by activating the P53 apoptosis pathway in MM cells. In vivo, all untreated tumor-bearing mice showed rapid tumor growth and severe plasmacytomas, which led to death within seven weeks. Mice treated with KBB-N2 had significantly inhibited tumor growth and longer survival times. The molecular docking assay revealed the optimal docking conformation binding energy of KBB-N2 with docking scores (kcal/M) of -7.3 and -9.8 for ETC complexes I and III, respectively. Conclusions: The triterpene compound, KBB-N2, was identified as a hit compound and may act as a targeted agent for MM treatment. The antimyeloma activity of KBB-N2 involves interference with the ETC complex and leads to MM cell death.

Integrative analysis of the molecular signature of target genes involved in the antitumor effects of cantharidin on hepatocellular carcinoma

BackgroundCantharidin (CTD) is the active ingredient of Chinese medicine, which has been traditionally used in multiple cancers treatment, especially in hepatocellular carcinoma (HCC). However, a comprehensive analysis of the CTD-related molecular mechanism is still necessary to understand its functions in HCC treatment. This study aimed to reveal the novel molecular targets and regulatory networks of CTD in HCC.MethodsA model of H22 tumour-bearing mice was constructed, and the function of CTD in tumour growth was evaluated. An integrated approach of CTD associated transcriptional profiling and biological systems analysis was used to identify key regulators involved in antitumour pathways. The identified differential expression patterns were supported by the results of Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyse, and by protein-protein interaction (PPI) network construction. The relationships between gene expression and tumour immunity were evaluated using Tumour Immune Estimation Resource (TIMER). Prognostic value was analyzed with Kaplan-Meier plotter.ResultsIn the present study, the therapeutic effect of CTD on HCC was evaluated in vivo. We obtained the CTD-related transcriptional profiles, systematically and intuitively illustrated its possible pharmacological mechanisms in HCC through multiple targets and signalling pathways. These results revealed that the CTD-related differentially expressed genes were involved in autophagy, transcription factors (TFs) related transcriptional regulation, fatty acid metabolism and immune response in HCC. We found that MAPT, TOP2A, CENPF and MEFV were hub genes of CTD targets involved in autophagy regulation. Totally, 14 TFs have been confirmed to be critical for transcriptional regulation, and 33 TF targets were identified as the hub genes in transcriptional mis-regulation pathway in cancer. These TFs were associated with the immune response and immune cell infiltration. In addition, the downregulated genes were significantly enriched in metabolic regulation pathways, especially fatty acid metabolism after CTD treatment. Furthermore, the network of CTD associated miRNAs with these fatty acid metabolism-related targets was constructed in HCC.ConclusionsTaken together, our results comprehensively elucidated that CTD could act on multiple targets in HCC therapy, affecting autophagy, transcriptional regulation, the immune response and fatty acid metabolism. Our results provide a foundation for the study of the molecular mechanistic of CTD and its clinical application in the treatment of HCC.

Unravelling Transplant-Ineligible Newly Diagnosed Multiple Myeloma Treatment in Real-World Practice in Spain. Carinae Study

Introduction: There is little data regarding real-world treatment patterns and outcomes of transplant-ineligible newly diagnosed multiple myeloma patients (TIE-NDMM) in Spain. In recent years, several treatment regimens have been authorized as effective options for TIE-NDMM, providing patients with better outcomes and quality of life, as evidenced in clinical trials (Mateos et al. Lancet 2020). However, the contribution of incorporating these new treatments into the daily therapeutic arsenal has not been widely explored. Methods: Observational, ambispective, multicenter ongoing study on TIE-NDMM patients who started antineoplastic treatment in the context of daily clinical practice in Spanish hospitals. Group A: started treatment with a combination of ≥2 drugs, between Sep/01/2018 and Aug/31/19. Group B: started treatment with daratumumab in combination with bortezomib, melphalan and prednisone (DVMP group), between Sep/01/19 and Nov/30/20. Here, we present the efficacy and safety outcomes obtained in the second interim analysis after ≈24-month study initiation. Results: 117 patients were recruited, and 108 were evaluable for efficacy in this interim analysis (group A n=51; group B n=57). No significant differences were observed in basal clinical and demographics characteristics between groups (table 1): mean age 76.9 years; male (53.7%); cardiopathy 28.7%; renal failure 25%; pulmonary obstructive disease 8.3%; peripheral neuropathy 2.8%; median ECOG PS 1; most common myeloma type was IgG (49.5%); 13.9% had a high-risk cytogenetic profile, defined by one of the following alterations: t(4;14), t(14;16) and del 17p13; plasmacytoma 24.3 %. More than 90% of the patients in group A started treatment with schemes based on bortezomib, lenalidomide, or both. Median follow-up was 36.3 versus 23.3 months for groups A and B, respectively, since the initiation of first-line treatment (p<0,0001). Probably in relation to the different follow-ups, the median PFS for Group A was 32.78 months and not reached for Group B (p=0,1129), figure 1. The progression rate at 18 months was 27.5% and 10.5% for Group A and B respectively (p=0,0238). Rates of ≥VGPR and ≥CR, were 60% and 30% in Group A whilst 75.4% and 33.3% in Group B, table 2. 36.9% of the patients showed adverse drug reactions (ADR) related to the first-line treatment during the prospective period. 10.6% of the reported ADRs were serious with no significant differences between groups. No unexpected ADRs were observed. Additional data will be presented at the Congress. Conclusions: In this interim analysis, a significant clinical benefit has been identified in patients treated with DVMP, with improved PFS indicators vs. other treatment alternatives. Along with the deeper hematological responses observed, we expect this benefit to be consolidated in the final PFS analysis of the Carinae study. These real-world practice data continue to support the choice of daratumumab regimens in frontline TIE-NDMM patients.