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AbstractDespite significant advancements in multiple myeloma (MM) treatment, including novel therapies and combination strategies, the translation of findings from randomized controlled trials (RCTs) into real-world clinical practice has been associated with several challenges. Specifically, the principles and criterion that shape the current design of MM RCTs have left out a sizable portion of patients that would particularly benefit from trial inclusion. In addition, RCTs may use primary outcomes which only partially cover patient-relevant endpoints important for evaluating treatment efficacy and quality of life. In this review, we explore the current MM RCT landscape and suggest possible solutions to improve generalizability of trial results, mitigate logistical pitfalls, and integrate real-world evidence into trials. Together, these strategies are designed to refine MM treatment guidelines and improve outcomes for all patient populations. [ABSTRACT FROM AUTHOR]

Quadruplet regimens (anti-CD38 monoclonal antibodies (mAbs) with proteosome inhibitor (PI) and immunomodulatory (IMID) drugs) are increasingly being investigated in newly diagnosed multiple myeloma (NDMM). The objective of our study was to conduct a systematic review and meta-analysis to measure the efficacy and toxicity of quadruplet regimens utilized in NDMM. Embase, Medline, Web of Science, Cochrane Library, clinical trial registries, and meeting libraries from inception to January 24, 2024, in addition to ASCO conference abstracts 2024 were searched using terms reflecting MM and component of the quadruplet regimen. Included studies were randomized controlled trials (RCTs) that compared backbone regimens consisting of a PI and IMID versus the same regimen plus an anti-CD38 mAb in NDMM. We identified seven RCTs including 3716 patients. Compared to triplets, quadruplets increase the overall response rate (ORR, relative risk [RR] 1.03, 95% confidence interval [CI] 1.01-1.05), and progression free survival (PFS, hazard ratio [HR]] 0.55, 95% CI 0.46-0.66). Quadruplets increase the rates of minimal residual disease (MRD) negativity at 10-5 (RR 1.39, 95% 1.23-1.58) and at 10-6 (RR 1.62, 95% CI 1.36-1.94). Quadruplets improve overall survival (OS, HR 0.65, 95% CI 0.53-0.79). There was a slight increase in the rates of grade 3-4 infections (RR 1.22 [95% CI 1.07-1.39]) noted with quadruplets compared to triplets. Overall, in this meta-analysis quadruplets were associated with improved efficacy including ORR, MRD negativity, PFS and OS with a slight increase in infection rates. Quadruplet regimens represent a new standard of care particularly in transplant eligible NDMM., (Copyright © 2024 American Society of Hematology.)

We retrospectively reviewed 292 patients who received a second line of therapy post ASCT for their light chain amyloidosis. Most patients (40%) were treated with an alkylator + PI ± dex or PI ± dex followed by an alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex (26%), an alkylator ± steroid or steroid monotherapy (19%), a 2nd-gen IMiD + PI ± dex (6%), an alkylator + thalidomide ± dex (5%), or daratumumab-based therapy (4%). The rate of CR or VGPR was 70% among the daratumumab-based group, 62% in the alkylator + PI ± dex or PI ± dex group, 55% in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 47% in the 2nd-gen IMiD + PI ± dex group, 24% in the alkylator ± steroid or steroid monotherapy group, and 18% in the alkylator + thalidomide ± dex group. The median OS was NR for the 2nd-gen IMiD + PI ± dex group and the daratumumab group, 130.4 months in the alkylator + 2nd-gen IMiD ± dex or 2nd-gen IMiD ± dex group, 100 months for the alkylator + PI ± dex or PI ± dex group, 36 months for the alkylator ± steroid or steroid monotherapy group, and 21 months for the alkylator + thalidomide ± dex group (P < 0.0001). The median OS was 100 months in patients who received melphalan 200 mg/m 2 compared to 41 months in the 140 mg/m 2 group (P < 0.0001). In conclusion, patients receiving novel therapy post ASCT and melphalan conditioning dosing at 200 mg/m 2 at diagnosis had better outcomes., (© 2022. The Author(s).)

Sickle cell trait (SCT) is typically an asymptomatic carrier state, but sickling complications can occur under extreme conditions. Priapism is known to be associated with sickle cell disease (SCD); The link with SCT is less well established. We report the case of a 19-year-old man with SCT presenting with prolonged priapism and a refractory, stuttering course requiring multiple invasive procedures over a 5-day period with no clear alternative triggers. In light of ongoing, stuttering priapism, he underwent red blood cell (RBC) exchange transfusion with decrease of hemoglobin S from 45.8% to 11.7%. This was followed by immediate and sustained cessation of stuttering priapism, with no further episodes at 5 months. Multiple cases of priapism associated with SCT have been reported in the literature. In most cases invasive interventions were required but RBC exchange was not attempted. RBC exchange has been reported in 2 people with exertional rhabdomyolysis in the context of SCT, with improvement in 1 case. In patients with SCT and priapism, conservative measures are used to treat brief episodes, but invasive management is required for persistent or prolonged episodes. RBC exchange transfusion may be considered for treatment of refractory, stuttering priapism in individuals with SCT., (© 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Autologous stem cell transplant (ASCT) is an established treatment for patients with newly diagnosed multiple myeloma (NDMM). Understanding the symptom burden associated with ASCT may be an important consideration for patients with NDMM when selecting treatment options., Patients and Methods: We conducted a population-based study of patients who underwent an ASCT for NDMM in Ontario, Canada, between 2007 and 2018. The patient-reported outcome, Edmonton Symptom Assessment System (ESAS) score, which captures nine common cancer-associated symptoms and is routinely collected at all outpatient visits, was linked to provincial administrative healthcare data. The monthly prevalence of moderate or severe symptoms (ESAS ≥ 4) each month in the first year following ASCT was analyzed. A multivariable logistic regression model was used to identify factors associated with moderate to severe symptoms., Results: In our final cohort of 1969 patients who had undergone an ASCT, a total of 12,820 unique assessments were captured. Symptom burden was highest at 1 month post-ASCT, with moderate to severe tiredness and impaired well-being being the two most common symptoms. Symptom burden substantially improved by 3 months post-ASCT, reaching a new baseline for the year following. On multivariable analysis, female sex, increased co-morbidities, earlier year of diagnosis, and myeloma-related end-organ damage (specifically, bone and kidney disease) were associated with a higher odds of reporting moderate to severe symptoms., Conclusion: In this large population-based study using patient-reported outcomes, there was a substantial burden of symptoms noted among NDMM patients 1 month post-ASCT, which improved over time. Tailored supportive care interventions should focus on strategies to optimize management of identified symptoms., (Copyright © 2021. Published by Elsevier Inc.)

Background and Aims: In sickle cell disease (SCD) patients admitted for intensive care, evaluation of platelet counts in different types of sickle cell complications and its prognostic relevance are not well-studied. Illuminating these aspects were the objectives of this study., Materials and Methods: A chart review of 136 adult SCD patients consecutively admitted to our Intensive Care Unit (ICU) was done. The prognosis on day 1 was assessed by Acute Physiology and Chronic Health Evaluation (APACHE II) and multiple organ dysfunction scores (MODS). Receiver operating characteristic (ROC) curves evaluated the ability of platelet counts, MODS, and APACHE II scores to predict survival., Results: The most common types of crises were severe pain ( n = 53), acute chest syndrome ( n = 40), and infection ( n = 18); 17 patients were nonsurvivors. Platelet counts varied widely (range, 19-838 × 10 9 /L) with thrombocytopenia ( n = 30) and thrombocytosis ( n = 11). Counts correlated directly with leukocytes and reticulocytes; inversely with lactate dehydrogenase, APACHE, and MODS scores. Areas under ROC curve for platelets, MODS, and APACHE scores to predict survival were 0.73, 0.85, and 0.93, respectively., Conclusions: In severe sickle cell crisis thrombocytopenia is more common than thrombocytosis. In the ICU, day 1 platelet counts correlate inversely with prognostic scores and are significantly reduced in multi-organ failure and nonsurvivors. A platelet count above 175 × 10 9 /L predicts patient survival with high specificity and positive predictive value but lacks sensitivity., Competing Interests: There are no conflicts of interest.