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During the 2024 European Hematology Association (EHA) Congress, experts in the field of multiple myeloma sat down to discuss the effect of earlier lines of therapy on the disease. The [...]

Following on the heels of the 2022 American Society of Clinical Oncology Annual Meeting, several experts in multiple myeloma sat down to discuss real-world evidence as it applies to the [...]

•The study shows the safety and long-term efficacy of auto-HCT, even in patients with high-risk cHL who are traditionally considered chemotherapy refractory.•The study shows the long-term efficacy of auto-HCT, even in patients with high-risk cHL who are traditionally considered chemo refractory.

Low skeletal muscle mass (LSMM) and/or, function associated with an increased risk of treatment‐related toxicities and inferior overall survival (OS) among adults with solid malignancies. However, the association between LSMM and treatment‐related toxicities among adults with haematologic malignancies remains unclear. Using a pre‐published protocol (CRD42020197814), we searched seven bibliographic databases from inception to 08/2021 for studies reporting the impact of LSMM among adults ≥18 years with a known haematologic malignancy. The primary outcome of interest was OS, and secondary outcomes included progression free survival (PFS) and non‐relapse mortality (NRM). These effect sizes were quantified in terms of hazards ratio (HR) along with 95% confidence interval (CI) and pooled across studies using a DerSimonian–Laird random‐effects model. Heterogeneity was assessed using the Cochran's Qand the I2statistic. All hypothesis testing was two‐sided with an alpha of 0.05. Of 3791 studies screened, we identified 20 studies involving 3468 patients with a mean age of 60 years; 44% were female and the most common malignancy was diffuse large B‐cell lymphoma (42%). Most studies measured muscle mass using single slice computed tomography imaging at the L3 level. The presence of LSMM was associated with worse OS (pooled HR = 1.81, 95% CI = 1.48–2.22, P< 0.001) with moderate heterogeneity (Cochran's Q, I2= 60.4%), PFS (pooled HR = 1.61, 95% CI = 1.28–2.02, P< 0.001) with moderate heterogeneity (Cochran's Q, I2= 66.0%). Similarly, LSMM was associated with worse NRM (HR = 1.72, 95% CI = 1.34–2.22, P< 0.001) with little evidence of heterogeneity (Cochran's Q, I2= 0.0%). LSMM is associated with worse survival outcomes among adults with haematologic malignancies. Further research into understanding the underlying mechanism of this association and mitigating the negative effects of LSMM among adults with haematologic malignancies is needed.

For patients with newly diagnosed multiple myeloma, reaching minimal residual disease (MRD) negativity after treatment is associated with improved outcomes; however, the use of MRD to modulate therapy remains elusive. We present the final analysis of the MASTER trial of daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) therapy in patients with newly diagnosed multiple myeloma, in which MRD status is used to modulate treatment duration and cessation.

Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone (D-RVd) in the GRIFFIN study improved the stringent complete response rate by the end of consolidation in transplantation-eligible patients with newly diagnosed multiple myeloma. Here, we report the findings of the predefined final analysis.

Byline: Luciano Costa Supporters of WikiLeaks founder Julian Assange protest outside Westminster Magistrates Court on May 30 during a hearing in Assange's extradition case to the U.S. He did not [...]

Byline: Luciano Costa An Indian boy gets some temporary respite from the heat as he tries to cool off amid rising temperatures in New Delhi on May 29. The heat [...]

Byline: Luciano Costa U.S. President Donald Trump and First Lady Melania Trump accompany Japan's Prime Minister Abe Shinzo and his wife Abe Akie to a sumo demonstration in Tokyo on [...]

Byline: Luciano Costa Eighteen tornadoes with winds up to 170 miles per hour touched down in the Dayton area the evening of Monday, May 27th into Tuesday morning, leaving one [...]

•Four cycles of daratumumab quadruplet induction had no major effect on stem cell yield.•Plerixafor use resulted in higher stem cell yield than use of granulocyte colony-stimulating factor alone.•In the MASTER and GRIFFIN studies, stem cell yield was adequate for autologous stem cell transplantation in nearly all patients.

•Centers with previous experience with haploidentical bone marrow (haplo-BM) hematopoietic cell transplantation (HCT) had superior outcomes with this donor type.•Centers that were not experienced with haplo-BMT had similar outcomes with haplo-BMT and double umbilical cord blood (dUCB) HCT.•Haplo-BM HCT with post-transplantation cyclophosphamide may be the preferred platform in other centers with limited or no experience with dUCB HCT.

Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT).

Complex networks have certain properties that distinguish them from their respective uniform or regular counterparts. One of these properties is the variation of topological properties along different hierarchical levels. In this work, we study how networks that are constructed by repeatedly incorporating a given motif exhibit this property. A motif is henceforth understood as a small subgraph with a reference node where the incorporation respectively occurs. We generate fractal networks using different motifs and observe how their structures change along the growth stages. Two regimes are respectively identified: transient and equilibrium. The former is characterized by significant topological changes that depend on the motif topology, while the equilibrium regime shows more stable, parallel trajectories. A more systematic analysis revealed that the betweenness centrality and the average shortest path lengths were the main topological properties accounting for the changes along the network growth. • A method for generating fractal networks from motifs with references is described. • Two dynamic regimes along the growth stages are identified: transient and equilibrium. • Markedly distinct networks are obtained from the considered motifs. [ABSTRACT FROM AUTHOR]

Proteins in the antiapoptotic B-cell lymphoma 2 (BCL-2) family play a role in the pathophysiology of multiple myeloma (MM). Venetoclax is a highly selective, potent, oral BCL-2 inhibitor that induces apoptosis of MM cells, and its efficacy may be potentiated through combination with agents that increase BCL-2 dependency or have complementary mechanisms of action. The safety, tolerability, pharmacokinetics, and antitumor activity of venetoclax in combination with carfilzomib and dexamethasone (VenKd) in adults with relapsed/refractory MM (RRMM) were investigated in this phase 2 dose-escalation study. Oral venetoclax (400 or 800 mg) was administered daily in combination with intravenous carfilzomib (27, 56, or 70 mg/m2) and oral dexamethasone (20 or 40 mg) in 4 dose-finding cohorts. The expansion cohort received venetoclax 800 mg, carfilzomib 70 mg/m2, and dexamethasone 40 mg. Forty-nine patients received treatment. Median prior lines of therapy was 1 (range, 1-3), and median time in the study was 27 months. The most common treatment-emergent adverse events were diarrhea (65%), fatigue (47%), nausea (47%), and lymphopenia (35%). Serious adverse events occurred in 26 (53%) patients. Of 3 treatment-emergent deaths, 1 was considered treatment related. The overall response rate was 80% in all patients, 92% in patients with t(11;14) (n = 13), and 75% in patients without (n = 36). The rate of complete response or better was 41%. Median progression-free survival was 22.8 months. Treatment with VenKd was well tolerated and showed promising response rates in this RRMM patient population, with greater responses observed in patients with t(11;14). This trial is registered at www.clinicaltrials.gov as #NCT02899052.

Therapeutic practices for multiple myeloma (MM) have evolved, such that novel-agent–based therapy and autologous peripheral blood stem cell transplantation (aPBSCT) is the current standard. Whether cause-specific mortality has changed with time remains unclear. We examined late cause-specific mortality among patients with MM receiving aPBSCT from 1989 to 2014. We conducted a prospective cohort study using participants enrolled in the enrolled in the Blood or Marrow Transplant Survivor Study. We created 3 eras to reflect changing MM therapy: <2000 (pre-thalidomide); 2000-2005 (thalidomide); 2006-2014 (lenalidomide). We used Kaplan-Meier techniques and Cox regression for examining all-cause mortality, and subdistribution hazards models for cause-specific mortality. In total, 1906 patients were followed up for a median of 9.2 years. Conditional on surviving 2 years, the 10-year overall survival was 45%. The 10-year cumulative incidence of myeloma- and non-myeloma-related mortality was 33% and 13%, respectively. Multivariable analysis showed declining MM-specific mortality (subdistribution hazard ratio [SHR]2000-2005 = 0.80, 95% confidence interval [CI], 0.60-1.07; SHR2006-2014 = 0.46, 95% CI, 0.34-0.62; referent group: <2000), infection-related mortality (SHR2000-2005 = 0.50, 95% CI, 0.29-0.85; SHR2006-2014 = 0.35, 95%CI 0.21-0.60; referent group: <2000) and cardiovascular disease-related mortality (SHR2000-2005 = 0.45, 95% CI 0.20-0.99; SHR2006-2014 = 0.41, 95% CI 0.18-0.93; referent group: <2000). Although primary disease remains the major cause of late mortality, we observed a significant temporal decline in myeloma-, infection-, and cardiac-related late mortality over the past 25 years.

AbstractHerein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from “up” to “down” conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below –8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro.MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak. Communicated by Ramaswamy H. Sarma

Abstract: Tuberculosis (TB) has been described in association with malignancies including Hodgkin disease (HD). We report three cases of simultaneous occurrence of TB and HD. In two of these cases [...]

The benefits of pre-transplant induction chemotherapy in light chain (AL) amyloidosis, a low burden plasma cell (PC) neoplasm associated with multiorgan dysfunction, is debatable, although with the availability of bortezomib, this approach is being increasingly pursued. We analyzed the outcomes of AL amyloidosis patients undergoing autologous hematopoietic cell transplant between 2014 and 2018 that were reported to the Center for International Blood and Marrow Transplant Research database. Of 440 patients, 294 received bortezomib-based induction, and 146 received no induction. Patients receiving induction had greater PC burden compared to no induction (PC 10% or more, 39% versus 11%; P< .01). At 2 years, the induction group compared to no induction had lower relapse/progression: 13% (9% to 18%) versus 23% (16% to 32%) (P = .02); better progression-free survival (PFS): 82% (77% to 87%) versus 69% (61% to 77%) (P< .01); and similar overall survival (OS): 92% (88% to 95%) versus 89% (84% to 94%) (P = .22), findings that were confirmed on multivariate analysis. A subset analysis limited to patients with <10% PC also showed superior relapse/progression (hazard ratio [HR], .43; 95% confidence interval [CI], .24 to .78; P< .01) and PFS (HR, .43; 95% CI, .26 to .72; P< .01) for induction compared to no induction. Thus, we conclude that pre-transplant bortezomib-based induction was associated with improved relapse/progression and PFS in AL amyloidosis. Longer survival follow-up is warranted, as OS was excellent in both cohorts at 2 years.

The phase 2 GRIFFIN study of daratumumab plus lenalidomide/bortezomib/dexamethasone (D-RVd) for transplant-eligible, newly diagnosed multiple myeloma included a safety run-in phase followed by a randomized phase. The ongoing randomized phase has met its prespecified primary end point of an improved stringent complete response (sCR) rate after consolidation for D-RVd (reported elsewhere). Final analysis of the safety run-in cohort is reported herein and provides longer follow-up (median, 40.8 months) encompassing daratumumab plus lenalidomide (D-R) maintenance therapy. Patients in the safety run-in cohort (N = 16) received 4 induction cycles (D-RVd), high-dose melphalan supported by autologous stem cell transplant, 2 consolidation cycles (D-RVd), and 24 months of maintenance (D-R). By the end of consolidation, all patients had responded, with a best response of sCR in 9 (56.3%) patients; 8 (50.0%) patients were minimal residual disease (MRD) negative (10‒5 threshold). After maintenance, 15 (93.8%) patients had achieved a best response of sCR, and 13 (81.3%) patients were MRD (10‒5) negative. Estimated 36-month progression-free and overall survival rates were 78.1% and 93.8%, respectively. One death from progressive disease occurred in the patient who did not achieve sCR. Observed safety profiles were consistent with daratumumab and RVd. With >3 years of median follow-up, D-RVd achieved durable responses that deepened with D-R maintenance. This study was registered at www.clinicaltrials.gov as #NCT02874742.

•Patients with primary refractory diffuse large B cell lymphoma (DLBCL) who subsequently respond to salvage therapy can experience durable disease control with autologous stem cell transplantation (autoHCT).•Benefit of autoHCT is seen in patients who experience stable disease and progressive disease after frontline chemoimmunotherapy.

Minimal residual disease (MRD) assessment is incorporated in an increasing number of multiple myeloma (MM) clinical trials as a correlative analysis, an endpoint or even as a determinant of subsequent therapy. There is substantial heterogeneity across clinical trials in how MRD is assessed and reported, creating challenges for data interpretation and for the design of subsequent studies. We convened an international panel of MM investigators to harmonize how MRD should be assessed and reported in MM clinical trials. The panel provides consensus on which MM trials should include MRD, the recommended time points for MRD assessment, and expected analytical validation for MRD assays. We subsequently outlined parameters for reporting MRD results implementing the intention-to-treat principle. The panel provides guidance regarding the incorporation of newer peripheral blood-based and imaging-based approaches to detection of residual disease. Recommendations are summarized in 13 consensus statements that should be followed by sponsors, investigators, editors, and reviewers engaged in designing, performing, and interpreting MM trials.

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.

IMPORTANCE: The addition of daratumumab to backbone multiple myeloma (MM) regimens is associated with improved response rates and progression-free survival (PFS). Whether improved outcomes are also associated with this regimen among patients with cytogenetically defined high-risk MM (HRMM) remains unclear. OBJECTIVE: To measure PFS associated with adding daratumumab to backbone MM regimens among patients with HRMM. DATA SOURCES: For this systematic review and meta-analysis, MEDLINE, Embase, PubMed, Scopus, Web of Science Core Collection, Cochrane Library, clinical trials registries, and meeting libraries were searched from inception to January 2, 2020, using terms reflecting multiple myeloma and daratumumab. STUDY SELECTION: Included studies were phase 3 randomized clinical trials that compared backbone MM regimens with the same regimen plus daratumumab in newly diagnosed or relapsed or refractory MM, such that the only difference between the intervention and control groups was use of daratumumab and reported outcomes by cytogenetic risk. High-risk MM was defined as the presence of t(4;14), t(14;16), or del(17p). DATA EXTRACTION AND SYNTHESIS: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 2 investigators independently extracted study data, with disagreements resolved by a third investigator. Quality was assessed by the Cochrane risk-of-bias method. MAIN OUTCOMES AND MEASURES: Data on effectiveness were extracted using hazard ratios (HRs) for PFS. Relative log-HRs were pooled using a DerSimonian-Laird random-effects model. Heterogeneity was assessed using the Cochran Q and the I2 statistic. RESULTS: Of 5194 studies screened, 6 phase 3 trials were eligible, including 3 trials for newly diagnosed MM (2528 patients; 358 with HRMM) and 3 trials for relapsed or refractory MM (1533 patients; 222 with HRMM). Among patients with newly diagnosed HRMM, the addition of daratumumab to backbone regimens was associated with improved PFS (pooled HR, 0.67; 95% CI, 0.47-0.95; P = .02), with little evidence of heterogeneity (Cochran Q, P = .77; I2 = 0%). Similar results were seen among patients with relapsed or refractory HRMM (pooled HR, 0.45; 95% CI, 0.30-0.67; P &lt; .001), again with little evidence of heterogeneity (Cochran Q, P = .63; I2 = 0%). CONCLUSIONS AND RELEVANCE: This study suggests that incorporating daratumumab to backbone regimens may be associated with improved PFS among patients with newly diagnosed HRMM or relapsed or refractory HRMM.

Lithium-metal batteries are promising candidates to fulfill the future performance requirements for energy storage applications. However, the tendency to form metallic dendrites and the undesirable side reactions between the electrolyte and the Li electrode lead to poor performance and safety issues in these batteries. Therefore, understanding the interfacial properties and the Li-metal surface/electrolyte interactions is crucial to resolve the remaining obstacles and make these devices feasible. Here, we report a computational study on the interface effects in ternary polymer electrolytes composed by poly(ethylene oxide) (PEO), lithium salts, and different ionic liquids (ILs) confined between two Li-metal slabs. Atomistic simulations are used to characterize the local environment of the Li+ions and the transport properties in the bulk and at the interface regions. Aggregation of ions at the metal surface is seen in all investigated systems; the structure and composition are directly correlated to the IL components. The strong interactions between the electrolyte species and the Li-metal atoms result in the structuring of the electrolyte at the interface region, in which comparatively small and flat ions result in a well-defined region with extensive Li+populations and high self-diffusion coefficients. In contrast, large ions such as [P222mom]+increase the PEO density in the bulk due to large steric effects at the interface. Therefore, the choice of specific ILs in ternary polymer electrolytes can tune the structure–dynamic properties at the Li-metal surface/electrolyte interface, controlling the SEI formation at the electrode surface, and thereby improve battery performance.

Contrary to tandem autologous transplant (auto-auto), autologous followed by reduced intensity conditioning allogenic transplantation (auto-allo) offers graft-versus-myeloma (GVM) effect but with higher toxicity. Trials comparing these two strategies relied on availability of HLA-matched sibling donors for arm allocation (biological randomization) and yielded conflicting results. A pooled analysis of multiple trials with extended follow up provides an opportunity to compare these strategies. We obtained individual patient data from participants of four trials comparing auto-auto vs. auto-allo after induction therapy. There were 899 patients in auto-auto and 439 in auto-allo. Median follow up of survivors was 118.5 months. Median overall survival (OS) was 78.0 months in auto-auto and 98.3 months in auto-allo (HR = 0.84, P= 0.02). OS was 36.4% vs. 44.1% at 10 years (P= 0.01) for auto-auto and auto-allo, respectively. Progression-free survival was also improved in auto-allo (HR = 0.84, P= 0.004). Risk of non-relapse mortality was higher in auto-allo (10 year 8.3% vs. 19.7%, P< 0.001), while risk of disease progression was higher in auto-auto (10 year 77.2% vs. 61.6%, P< 0.001). Median post relapse survival was 41.5 months in auto-auto and 62.3 months in auto-allo (HR = 0.71, P< 0.001). This supports the existence of durable GVM effect enhancing myeloma control with subsequent therapies.

While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2df/+mouse model of 16p11.2 deletion ASD syndrome. We discover that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2df/+mice, endothelial dysfunction results in impaired cerebral angiogenesis at postnatal day 14, and in altered neurovascular coupling and cerebrovascular reactivity at postnatal day 50. Moreover, we show that there is defective angiogenesis in primary 16p11.2df/+mouse brain endothelial cells and in induced-pluripotent-stem-cell-derived endothelial cells from human carriers of the 16p11.2 deletion. Finally, we find that mice with an endothelium-specific 16p11.2 deletion (16p11.2?EC) partially recapitulate some of the behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.

Lenalidomide, bortezomib, and dexamethasone (RVd) followed by autologous stem cell transplantation (ASCT) is standard frontline therapy for transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The addition of daratumumab (D) to RVd (D-RVd) in transplant-eligible NDMM patients was evaluated. Patients (N = 207) were randomized 1:1 to D-RVd or RVd induction (4 cycles), ASCT, D-RVd or RVd consolidation (2 cycles), and lenalidomide or lenalidomide plus D maintenance (26 cycles). The primary end point, stringent complete response (sCR) rate by the end of post-ASCT consolidation, favored D-RVd vs RVd (42.4% vs 32.0%; odds ratio, 1.57; 95% confidence interval, 0.87-2.82; 1-sided P= .068) and met the prespecified 1-sided α of 0.10. With longer follow-up (median, 22.1 months), responses deepened; sCR rates improved for D-RVd vs RVd (62.6% vs 45.4%; P= .0177), as did minimal residual disease (MRD) negativity (10−5threshold) rates in the intent-to-treat population (51.0% vs 20.4%; P< .0001). Four patients (3.8%) in the D-RVd group and 7 patients (6.8%) in the RVd group progressed; respective 24-month progression-free survival rates were 95.8% and 89.8%. Grade 3/4 hematologic adverse events were more common with D-RVd. More infections occurred with D-RVd, but grade 3/4 infection rates were similar. Median CD34+cell yield was 8.2 × 106/kg for D-RVd and 9.4 × 106/kg for RVd, although plerixafor use was more common with D-RVd. Median times to neutrophil and platelet engraftment were comparable. Daratumumab with RVd induction and consolidation improved depth of response in patients with transplant-eligible NDMM, with no new safety concerns. This trial was registered at www.clinicaltrials.govas #NCT02874742.

Increasing the ionic conductivity has for decades been an overriding goal in the development of solid polymer electrolytes. According to fundamental theories on ion transport mechanisms in polymers, the ionic conductivity is strongly correlated to free volume and segmental mobility of the polymer for the conventional transport processes. Therefore, incorporating plasticizing side chains onto the main chain of the polymer host often appears as a clear-cut strategy to improve the ionic conductivity of the system through lowering of the glass transition temperature (Tg). This intended correlation between Tgand ionic conductivity is, however, not consistently observed in practice. The aim of this study is therefore to elucidate this interplay between segmental mobility and polymer structure in polymer electrolyte systems comprising plasticizing side chains. To this end, we utilize the synthetic versatility of the ion-conductive poly(trimethylene carbonate) (PTMC) platform. Two types of host polymers with side chains added to a PTMC backbone are employed, and the resulting electrolytes are investigated together with the side chain-free analogue both by experiment and with molecular dynamics (MD) simulations. The results show that while added side chains do indeed lead to a lower Tg, the total ionic conductivity is highest in the host matrix without side chains. It was seen in the MD simulations that while side chains promote ionic mobility associated with the polymer chain, the more efficient interchain hopping transport mechanism occurs with a higher probability in the system without side chains. This is connected to a significantly higher solvation site diversity for the Li+ions in the side-chain-free system, providing better conduction paths. These results strongly indicate that the side chains in fact restrict the mobility of the Li+ions in the polymer hosts.

•With longer follow-up, significantly longer median PFS was maintained with ide-cel vs SRs; safety remained consistent.•OS analysis was confounded by patient crossover from SRs to ide-cel; crossover adjustment showed a trend of improved OS with ide-cel vs SRs.

Microelectrode voltammetry was employed to gain information on the behavior of potassium hexacyanoferrate(II/III) in acetonitrile/water binary mixtures in order to understand the bulk properties of the mixture and the electrode/binary solution interface properties. The first analysis of the obtained data demonstrated that the diffusion coefficient values of hexacyanoferrate(III) apparently do not respect the Stokes–Einstein equation, considering the hydrodynamic radius does not change with acetonitrile content. Another interesting observation is the adsorption of electrogenerated potassium hexacyanoferrate(II) onto the electrode surface in binary mixtures with 50 mol % acetonitrile or higher. Molecular dynamics simulations showed that acetonitrile molecules accumulate on the surface of an electrode model and also that ionic species tend to form clusters in acetonitrile-rich mixtures. Since potassium hexacyanoferrate(II) is not soluble in acetonitrile, the adsorption of the iron complex onto the electrode is related to the formation of the acetonitrile layer on the surface of the electrode. The diffusion coefficient of hexacyanoferrate(III) in the mixtures decreases because of the ion clustering and the formation of an acetonitrile layer on the surface of the electrode, which is an obstacle that the ions have to overcome to reach and leave the electrode.