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Clinical trials conducted by the Intergroup Rhabdomyosarcoma (RMS) Study Group and the Children's Oncology Group have been pivotal to establishing current standards for diagnosis and therapy for RMS. Recent advancements in understanding the biology and clinical behavior of RMS have led to more nuanced approaches to diagnosis, risk stratification, and treatment. The complexities introduced by these advancements, coupled with the rarity of RMS, pose challenges to conducting large‐scale phase 3 clinical trials to evaluate new treatment strategies for RMS. Given these challenges, systematic planning of future clinical trials in RMS is paramount to address pertinent questions regarding the therapeutic efficacy of drugs, biomarkers of response, treatment‐related toxicity, and patient quality of life. Herein, the authors outline the proposed strategic approach of the Children's Oncology Group Soft Tissue Sarcoma Committee to the next generation of RMS clinical trials, focusing on five themes: improved novel agent identification and preclinical to clinical translation, more efficient trial development and implementation, expanded opportunities for knowledge generation during trials, therapeutic toxicity reduction and quality of life, and patient engagement. The rarity and complexity of rhabdomyosarcoma makes early and systematic planning for the next generation of phase 3 trials essential. This commentary reviews the Children's Oncology Group Soft Tissue Sarcoma Committee's strategy for the design and conduct of their next generation of rhabdomyosarcoma trials. [ABSTRACT FROM AUTHOR]

Summary: Real‐world evidence comparing clinical outcomes between venetoclax and Bruton tyrosine kinase inhibitors (BTKis) in patients with frontline (1 L) chronic lymphocytic leukaemia (CLL) is lacking. We compared treatment effectiveness of 1 L venetoclax plus obinutuzumab (VenO) versus BTKi‐based regimens. This retrospective observational study using Optum Clinformatics Data Mart® included adult patients with CLL (≥2 outpatient or ≥1 inpatient claim) who received VenO or BTKi‐based regimens in 1 L (1/2019–9/2022). Baseline characteristics were balanced using stabilised inverse probability weighting. Outcomes included duration of therapy (DoT), persistence, time to next treatment or death (TTNT‐D), and time off‐treatment. Among 1506 eligible patients (VenO: 203; BTKi: 1303), the median follow‐up duration was 12.6 (VenO) and 16.2 months (BTKi). Median DoT for VenO was 12.3 months; persistence remained higher in VenO versus BTKi through expected 1 L fixed treatment duration. Median TTNT‐D was not reached for VenO; however, more VenO‐ versus BTKi‐treated patients had not switched therapies/experienced death through Month 12 (87.1% vs. 75.3%). Among patients that discontinued, median time to discontinuation was 11.7 vs. 5.9 months for VenO versus BTKi and median time off‐treatment was 11.3 vs. 4.3 months. In this real‐world study, VenO was associated with better effectiveness outcomes than BTKi‐based regimens in 1 L CLL. [ABSTRACT FROM AUTHOR]

Purposeof Review: Plasma Cell Leukemia (PCL) is a very rare and highly aggressive form of plasma cell dyscrasia. This review seeks to evaluate the outcomes of PCL in the context of combination novel agent therapy and stem cell transplant (SCT) protocols. Recent Findings: The diagnostic criteria for PCL have now evolved to include patients with 5% circulating PC. While management remains challenging, the incorporation of novel agent-based induction regimen has significantly improved early mortality and reduced attrition of patients proceeding to SCT. In recent prospective clinical trials, patients with PCL demonstrated an overall response rates of 69% to 86%, with progression-free and overall survival ranging from 13.8 to 15.5 months and 24.8 to 36.3 months, respectively. B-cell lymphoma 2 (BCL2) inhibitors, such as venetoclax present a targeted intervention opportunity for patients with PCL with t(11;14). Summary: Dedicated clinical trials tailored to PCL are crucial, integrating newer therapies in the frontline setting to further optimize responses and enhance overall outcomes. [ABSTRACT FROM AUTHOR]

Summary: The treatment landscape of acute myeloid leukaemia (AML) is evolving rapidly. Venetoclax in combination with intensive chemotherapy or doublets or triplets with targeted or immune therapies is the focus of numerous ongoing trials. The development of mutation‐targeted therapies has greatly enhanced the treatment armamentarium, with FLT3 inhibitors and isocitrate dehydrogenase inhibitors improving outcomes in frontline and relapsed/refractory (RR) AML, and menin inhibitors showing efficacy in RR NPM1mut and KMT2A‐rearranged AML. With so many new drugs approved, the number of potential combinatorial approaches to leverage the maximal benefit of these agents has increased dramatically, while at the same time introducing clinical challenges, such as key preclinical and clinical data supporting the development of combinatorial therapy, how to optimally combine or sequence these novel agents, how to optimise dose and duration to maintain safety while enhancing efficacy, the optimal duration of therapy and the role of measurable residual disease in decision‐making in both intensive and low‐intensity therapy settings. In this review, we will outline the evidence leading to the approval of key agents in AML, their on‐label current approvals and how they may be optimally combined in a safe and deliverable fashion to further improve outcomes in AML. [ABSTRACT FROM AUTHOR]

Breast cancer characterized as "cold tumors" exhibit low levels of immune cell infiltration, which limits the efficacy of conventional immunotherapy. Recent studies have focused on strategies using nanotechnology combined with tumor microenvironment modulation to transform "cold tumors" into "hot tumors". This approach involves the use of functionalized nanoparticles that target and modify the tumor microenvironment to promote the infiltration and activation of antitumor immune cells. By delivering immune activators or blocking immunosuppressive signals, these nanoparticles activate otherwise dormant immune responses, enhancing tumor immunogenicity and the therapeutic response. These strategies not only promise to increase the response rate of breast cancer patients to existing immunotherapies but also may pave new therapeutic avenues, providing a new direction for the immunotherapy of breast cancer. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and kidney disease are the main causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Globally, the incidence of T2DM continues to rise. A substantial increase in the burden of CVD and renal disease, alongside the socioeconomic implications, would be anticipated. Adopting a purely glucose-centric approach focusing only on glycemic targets is no longer adequate to mitigate the cardiovascular risks in T2DM. In the past decade, significant advancement has been achieved in expanding the pharmaceutical options for T2DM, with novel agents such as the sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide receptor agonists (GLP-1 RAs) demonstrating robust evidence in cardiorenal protection. Combinatorial approaches comprising multiple pharmacotherapies combined in a single agent are an emerging and promising way to not only enhance patient adherence and improve glycemic control but also to achieve the potential synergistic effects for greater cardiorenal protection. In this review, we provide an update on the novel antidiabetic agents in the past decade, with an appraisal of the mechanisms contributing to cardiorenal protection. Additionally, we offer a glimpse into the landscape of T2DM management in the near future by providing a comprehensive summary of upcoming agents in early-phase trials. [ABSTRACT FROM AUTHOR]

Simple Summary: We evaluated the clinical features of primary and secondary plasma cell leukemia and the impact of current therapies. High-risk cytogenetics, low platelets, extramedullary disease and high LDH were independently associated with a poor outcome, with an overall survival of 11% at 5 years. Circulating plasma cells (CPCs) are detected in most multiple myeloma (MM) patients, both at diagnosis and on relapse. A small subset, plasma cell leukemia (PCL), represents a different biology and has a poor prognosis. In this retrospective analysis, we evaluated patients with primary (pPCL, n = 35) or secondary (sPCL, n = 49), with ≥5% CPCs and a smaller subset with lower CPCs of 1–4% (n = 20). The median age was 61 years; 45% were men and 54% were Black. High-risk cytogenetics were found in 87% and extramedullary disease in 47%. For the entire cohort, 75% received a proteasome inhibitor, 70% chemotherapy, 54% an immunomodulatory drug, 24% a daratumumab-based regimen and 26% an autologous stem cell transplant (ASCT). The treatments marginally improved the overall survival (OS) for pPCL vs. sPCL (13 vs. 3.5 months p = 0.002). However, the 5-year survival for the whole cohort was dismal at 11%. High-risk cytogenetics, low platelets, extramedullary disease and high LDH were independently associated with poor outcomes. Further research is urgently needed to expand the treatment options and improve the outcomes in PCL. [ABSTRACT FROM AUTHOR]

Background: Cancer is the second leading cause of death worldwide. Although great advancements have been made in the treatment and control of cancer progression, significant deficiencies and room for improvement remain. Several undesired side effects sometimes occur during chemotherapy. Natural therapies, such as the use of plant-derived products in cancer treatment, may reduce adverse side effects. Methods: Currently, a few plant products are being used to treat cancer. However, a myriad of plant products exist that have shown very promising anti-cancer properties in vitro but have yet to be evaluated in humans. Further study is required to determine the efficacy of these plant products in treating cancers in humans. Results: This review will focus on the various traditional medicinal plants and their chemical compounds that have, in recent years, shown promise as anticancer agents and will outline their potential mechanism of action. Conclusions: The current manuscript discusses natural products currently in clinical use, and under clinical trials, for cancer chemotherapy and chemoprevention. Future research focusing on natural anticancer agents can open a new horizon in cancer treatment, which will play a great role in enhancing the survival rate of cancer patients. [ABSTRACT FROM AUTHOR]

RCHOP is the standard of care for patients with diffuse large b-cell lymphoma (DLBCL) but failures occur in approximately 40% of them. We performed a meta-analysis of 21 randomized controlled trials (RCTs) comparing experimental regimens with RCHOP. We searched the database of PubMed with proper criteria, and data of efficacy (Progression Free Survival-PFS) in the ITT population were extracted and analyzed. Cross comparisons of RCTs were performed by using the CINEMA software. Odds ratio (OR) and 95% confidence intervals (95%, CI) are reported. The literature search yielded 21 RCTs including 5785 patients in the RCHOP arm and 5648 patients in the experimental arm. Odds ratio (OR) for PFS in the total cohort was OR (95%, CI): 0.87 (0.76–0.99), p=0.02. Among different strategies to improve RCHOP, addition of a novel agent on RCHOP improved PFS. In total 1740 patients in the RCHOP arm were compared with 1755 in the RCHOP plus a novel agent arm, and the OR (95% CI) for PFS was 0.84 (0.71–0.97), p=0.02. Indirect comparisons of nine studies adding a novel agent on RCHOP does not give prominence to any agent. Subgroup analysis according to cell of origin was performed for non-GC DLBCL patients. In this subgroup, 1546 patients treated with RCHOP were compared with 1538 patients treated with experimental regimens. The OR (95% CI) for PFS was 0.86 (0.73–1.02), p=0.34. Overall survival data extracted from 18 studies showed no superiority of experimental regimens over RCHOP. Efficacy of RCHOP backbone is marginally improved when adding a novel anti-lymphoma agent. [ABSTRACT FROM AUTHOR]

We studied whether 48 weeks of PEG‐IFN alfa‐2a add‐on increases HBsAg‐decline and clearance in HBeAg‐negative patients on long‐term nucleo(s)tide analogue (NA) therapy. In this investigator‐initiated, randomized, controlled trial conducted in Europe and Canada, HBeAg‐negative patients treated with NA > 12 months, with HBVDNA < 200 IU/mL, were enrolled. Patients were randomized 2:1 to 48 weeks of PEG‐IFN alfa‐2a add‐on (180 μg per week) or continued NA‐monotherapy with subsequent follow‐up to Week 72. Endpoints were HBsAg decline (≥1 log10 IU/mL) and HBsAg clearance at Week 48. Of the 86 patients in the modified‐intention‐to‐treat analysis, 58 patients received PEG‐IFN add‐on, and 28 continued NA monotherapy. At Week 48, 16(28%) patients achieved HBsAg decline ≥1 log10 in the add‐on arm versus none on NA‐monotherapy (p <.001), and HBsAg clearance was observed in 6 (10%) PEG‐IFN add‐on patients versus 0% NA‐monotherapy (p =.01). HBVRNA was only detected in 2% after PEG‐IFN treatment versus 19% in NA‐monotherapy (p =.002) at Week 48. PEG‐IFN add‐on therapy was well tolerated in majority of patients. Low baseline HBsAg levels (<10 IU/mL) identified patients most likely to achieve HBsAg loss with PEG‐IFN add‐on, whereas an HBsAg level > 200 IU/mL at on‐treatment Week 12 was highly predictive of non‐response (NPV = 100%). Addition of PEG‐IFN to long‐term NA enhanced HBsAg decline and increased the chance of HBsAg clearance in HBeAg‐negative patients on long‐term NA. On‐treatment HBsAg levels >200 IU/mL identify patients unlikely to benefit from PEG‐IFN add‐on and could be used as a potential stopping‐rule for PEG‐IFN therapy. Our findings support further exploration of immune modulation add‐on to antiviral therapy, preferably using response‐guided strategies, to increase functional cure rates in patients with CHB. [ABSTRACT FROM AUTHOR]

Simple Summary: This article summarises the international Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial for patients with rhabdomyosarcoma. The trial has multiple research questions relating to chemotherapy and radiotherapy and biological and imaging studies as well as to the introduction of novel drugs for patients with very high-risk disease. The rationale, background, and international collaboration of the trial are explained, and how the data will be used to inform future studies is outlined. The Frontline and Relapsed Rhabdomyosarcoma (FaR-RMS) clinical trial is an overarching, multinational study for children and adults with rhabdomyosarcoma (RMS). The trial, developed by the European Soft Tissue Sarcoma Study Group (EpSSG), incorporates multiple different research questions within a multistage design with a focus on (i) novel regimens for poor prognostic subgroups, (ii) optimal duration of maintenance chemotherapy, and (iii) optimal use of radiotherapy for local control and widespread metastatic disease. Additional sub-studies focusing on biological risk stratification, use of imaging modalities, including [18F]FDG PET-CT and diffusion-weighted MRI imaging (DWI) as prognostic markers, and impact of therapy on quality of life are described. This paper forms part of a Special Issue on rhabdomyosarcoma and outlines the study background, rationale for randomisations and sub-studies, design, and plans for utilisation and dissemination of results. [ABSTRACT FROM AUTHOR]

Summary: The achievement of treatment‐free remission (TFR) has become a significant clinical end‐point in the management of patients with chronic myeloid leukaemia (CML), providing an opportunity to discontinue therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep molecular response (DMR). Early studies, such as the French STIM trial, have demonstrated that a portion of patients can maintain DMR after treatment cessation, with rates ranging from 40% to 50%, and most relapses occurring within the first 6 months. Key prognostic factors for successful TFR, including treatment duration, duration of DMR, risk scores, and transcript type, have been identified. Optimal patient selection for TFR remains a challenge, but recent research provides insights into potential strategies to increase TFR eligibility. Evidence suggests that early intervention switching to achieve optimal response, treatment combinations, proactive switch in the case of absence of DMR, dose‐optimization and induction‐maintenance approach can improve molecular responses and, consequently, enhance TFR eligibility. In this review, we report and discuss all the potential therapeutic strategies that may enhance eligibility for a first attempt at TFR, with a particular emphasis on potential future approaches. [ABSTRACT FROM AUTHOR]

Background: Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to "accelerated CLL" (A-CLL) or to "Richter transformation" (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations. Summary: A-CLL is a rare and underdiagnosed entity that probably stands in the "gray zone" between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials. Key Messages: The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of "unmet need" and require further studies to identify the best diagnostic approach and a more effective treatment. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) and kidney disease are the main causes of morbidity and mortality in type 2 diabetes mellitus (T2DM). Globally, the incidence of T2DM continues to rise. A substantial increase in the burden of CVD and renal disease, alongside the socioeconomic implications, would be anticipated. Adopting a purely glucose-centric approach focusing only on glycemic targets is no longer adequate to mitigate the cardiovascular risks in T2DM. In the past decade, significant advancement has been achieved in expanding the pharmaceutical options for T2DM, with novel agents such as the sodium-glucose cotransporter type 2 (SGLT2) inhibitors and glucagon-like peptide receptor agonists (GLP-1 RAs) demonstrating robust evidence in cardiorenal protection. Combinatorial approaches comprising multiple pharmacotherapies combined in a single agent are an emerging and promising way to not only enhance patient adherence and improve glycemic control but also to achieve the potential synergistic effects for greater cardiorenal protection. In this review, we provide an update on the novel antidiabetic agents in the past decade, with an appraisal of the mechanisms contributing to cardiorenal protection. Additionally, we offer a glimpse into the landscape of T2DM management in the near future by providing a comprehensive summary of upcoming agents in early-phase trials.

Abstract The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future.

Purpose of Review: The treatment paradigm of chronic lymphocytic leukemia (CLL) has dramatically changed with the advent of novel targeted agents over the past decade. Richter transformation (RT), or the development of an aggressive lymphoma from a background of CLL, is a well-recognized complication of CLL and carries significantly poor clinical outcomes. Here, we provide an update on current diagnostics, prognostication, and contemporary treatment of RT. Recent Findings: Several genetic, biologic, and laboratory markers have been proposed as candidate risk factors for the development of RT. Although a diagnosis of RT is typically suspected based on clinical and laboratory findings, tissue biopsy is essential for histopathologic confirmation of diagnosis. The standard of care for RT treatment at this time remains chemoimmunotherapy with the goal of proceeding to allogeneic stem cell transplantation in eligible patients. Several newer treatment modalities are being studied for use in the management of RT, including small molecules, immunotherapy, bispecific antibodies, and chimeric antigen receptor T-cell (CAR-T) therapy. Summary: The management of patients with RT remains a challenge. Ongoing trials show enormous promise for newer classes of therapy in RT, with the hope being that these agents can synergize, and perhaps supersede, the current standard of care in the near future. [ABSTRACT FROM AUTHOR]

The long-term survival of Hodgkin lymphoma (HL) patients treated according to the current standard of care is excellent. Combined-modality schedules (ABVD plus radiotherapy) in early-stage disease, along with treatment intensity adaptation to early metabolic response assessed by PET/CT in advanced stage HL, have been the cornerstones of risk stratification and treatment decision-making, minimizing treatment-related complications while keeping efficacy. Nevertheless, a non-negligible number of patients are primary refractory or relapse after front-line treatment. Novel immunotherapeutic agents, namely Brentuximab Vedotin (BV) and immune checkpoint inhibitors (CPI), have already shown outstanding efficacy in a relapsed/refractory setting in recent landmark studies. Several phase 2 single-arm studies suggest that the addition of these agents in the frontline setting could further improve long-term disease control permitting one to reduce the exposure to cytotoxic drugs. However, a longer follow-up is needed. At the time of this writing, the only randomized phase 3 trial so far published is the ECHELON-1, which compares 1 to 1 BV-AVD (Bleomycin is replaced by BV) with standard ABVD in untreated advanced-stage III and IV HL. The ECHELON-1 trial has proven that BV-AVD is safe and more effective both in terms of long-term disease control and overall survival. Just recently, the results of the S1826 SWOG trial demonstrated that the combination nivolumab-AVD (N-AVD) is better than BV-AVD, while preliminary results of other randomized ongoing phase 3 trials incorporating anti-PD-1 in this setting will be soon available. The aim of this review is to present the recent data regarding these novel agents in first-line treatment of HL and to highlight current and future trends which will hopefully reshape the overall management of this disease. [ABSTRACT FROM AUTHOR]

Advanced and recurrent gynecological cancers lack effective treatment and have poor prognosis. Besides, there is urgent need for conservative treatment for fertility protection of young patients. Therefore, continued efforts are needed to further define underlying therapeutic targets and explore novel targeted strategies. Considerable advancements have been made with new insights into molecular mechanisms on cancer progression and breakthroughs in novel treatment strategies. Herein, we review the research that holds unique novelty and potential translational power to alter the current landscape of gynecological cancers and improve effective treatments. We outline the advent of promising therapies with their targeted biomolecules, including hormone receptor-targeted agents, inhibitors targeting epigenetic regulators, antiangiogenic agents, inhibitors of abnormal signaling pathways, poly (ADP-ribose) polymerase (PARP) inhibitors, agents targeting immune-suppressive regulators, and repurposed existing drugs. We particularly highlight clinical evidence and trace the ongoing clinical trials to investigate the translational value. Taken together, we conduct a thorough review on emerging agents for gynecological cancer treatment and further discuss their potential challenges and future opportunities. [ABSTRACT FROM AUTHOR]

The rapidly increasing use of high-throughput screening had produced a plethora of expanding knowledge on the molecular basis of natural killer/T-cell lymphoma (NKTCL), which in turn has revolutionized the treatment. Specifically, the use of asparaginase-containing regimens has led to substantial improvement in survival outcomes in NKTCL patients. Novel treatment strategies that are currently under development include cell-surface-targeted antibodies, immune checkpoint inhibitors, Epstein-Barr virus targeted cytotoxic T lymphocyte, immunomodulatory agents, chimeric antigen receptor T cells, signaling pathway inhibitors and epigenetic targeted agents. In almost all cases, initial clinical studies of newly developed treatment are conducted in patients relapsed, and refractory NKTCL due to very limited treatment options. This review summarizes the results of these novel treatments for NKTCL and discusses their potential for likely use in NKTCL in a wider setting in the future. [ABSTRACT FROM AUTHOR]

Idiopathic Pulmonary Fibrosis (IPF) is a progressive and devastating lung disease, characterized by progressive lung scarring. Prior to antifibrotic therapy (pirfenidone and nintedanib), there was no validated pharmaceutical therapy for IPF. Both antifibrotics can slow disease progression; however, IPF remains a detrimental disease with poor prognosis and treatment survival rates of less than 7 years from diagnosis. Despite their effect the disease remains non-reversible and progressing whilst their side effect profile is often challenging. Treatment of comorbidities is also crucial. In this review, we discuss the current pharmacological management as well as management of comorbidities and symptoms. We also reviewed clinicaltrials.gov and summarized all the mid- to late-stage clinical trials (phase II and III) registered in IPF over the last 7 years and discuss the most promising drugs in clinical development. Future for IPF management will need to focus on current unresolved issues. First a primary pathogenetic pathway has not been clearly identified. Future management may involve a combination of the brushstroke approach with antifibrotics with targeted treatments for specific pathways in patient subsets following an 'oncological' approach. Another unmet need is the management of exacerbations, which are deadly in most cases, as well as either treating or preventing lung cancer. [ABSTRACT FROM AUTHOR]

Introduction: Infections are a leading cause of morbidity and mortality in patients with multiple myeloma (MM). Methods: To examine the effects of modern second-generation novel agent therapy on immune cell subsets, in particular CD4+-T-cells, and infectious complications in patients with relapsed/refractory MM (RRMM), we conducted a prospective cohort study in 112 RRMM patients. Results: Substantially decreased CD4+-T-cells <200/µl before initiation of relapse therapy were detected in 27.7% of patients and were associated with a higher number of previous lines of therapy. Relapse therapy with carfilzomib or pomalidomide showed a significant further decrease of CD4+-T-cells. All novel agents led to a significant decrease of B-cell counts. Overall, infections were frequent with 21.3% of patients requiring antibacterial therapy within the first 3 months of relapse therapy, 5.6% requiring hospitalization. However, in the setting of standard antimicrobial prophylaxis in RRMM patients with very low CD4+-Tcells, no significant association of CD4+T-cell count and an increased risk of infection could be detected Discussion: Our findings imply that reduced CD4+-T-cell numbers and infections are common in patients with RRMM. We also demonstrate an association with the number of previous therapies and certain substances suggesting an increased need for personalized prophylaxis strategies for opportunistic infections in this patient cohort. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes or myelodysplastic neoplasms (both abbreviated MDSs) (Leukemia 2022;36:1703–1719) have historically been challenging diseases to treat owing to their complex biology, molecular diversity, and a patient population that is elderly with comorbidities. As the patients are living longer, incidence of MDSs is rising, and challenges in selecting MDS treatments or lack thereof have been becoming more apparent. Fortunately, with better understanding of molecular underpinnings of this heterogeneous syndrome, numerous clinical trials reflecting the biology of disease and catering to the advanced age of MDS patients are in development to maximize the likelihood of identifying active drugs. Addressing this diverse nature of genetic abnormalities, novel agents, and combinations are in development to formulate personalized treatment approaches for MDS patients. Myelodysplastic syndrome is categorized into subtypes that are associated with lower or higher risk for leukemic evolution, and that knowledge helps with therapy selection. Currently, as it stands, for those with higher-risk MDSs, hypomethylating agents are the first-line therapy. Allogenic stem cell transplantation represents the only potential cure for our patients with MDSs and should be considered for all eligible patients with higher-risk MDSs at the time of diagnosis. This review discusses current MDS treatment landscape, as well as new approaches in development. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor (DSRCT) is an extremely rare and highly aggressive soft tissue sarcoma, presenting mainly in male adolescents and young adults with multiple nodules disseminated within the abdominopelvic cavity. Despite a multimodal approach including aggressive cytoreductive surgery, intensive multi-agent chemotherapy, and postoperative whole abdominopelvic radiotherapy, the prognosis for DSRCT remains dismal. Median progression-free survival ranges between 4 and 21 months, and overall survival between 17 and 60 months, with the 5-year overall survival rate in the range of 10–20%. This review discusses the treatment strategies used for DSRCT over the years, the state of the art of current treatments, and future clinical prospects. The unsatisfactory outcomes for patients with DSRCT warrant investigations into innovative treatment combinations. An international multidisciplinary and multi-stakeholder collaboration, involving both pediatric and adult sarcoma communities, is needed to propel preclinical model generation and drug development, and innovative clinical trial designs to enable the timely testing of treatments involving novel agents guided by biology to boost the chances of survival for patients with this devastating disease. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma can be distinguished from asymptomatic myeloma and monoclonal gammopathy of uncertain significance thanks to CRAB factors. Objective: To assess role of CRAB factors in prognosis of cases who had multiple myeloma and being treated with novel therapeutic agents in comparison with non-novel agents. Patients and Methods: A comparative cross-sectional study was conducted in the Hematology Unit, Internal Medicine Department, in Zagazig University Hospitals on 100 patients with multiple myeloma. We looked at how the existence of CRAB factors affected the survival rates of individuals with symptomatic myeloma who were receiving novel therapies. Results: Hb, PLT, albumin were higher in Novel Containing Regimen (NCR) group than Non-Novel Containing Regimen (NNCR) group, while creatinine, Bence Jones protein in urine, serum beta-2-microglobulin and calcium were lower in (NCR) group than (NNCR) group. Bone marrow plasma cells after treatment, lytic lesion, anemia, hypercalcemia and renal insufficiency were lower in (NCR) group than (NNCR) group. About 91% of patients had M protein type IGG and 9% had IGA, the mean bone marrow plasma cells was 24.6 ± 4.3, 21% had abnormal cytogenetics, 25% had high risk FISH, 70% had lytic lesions, 17% had EMD at diagnosis, 29% had anemia (decrease of Hb more than 2 g/dl or to equal or less than 10 g/dl), 17% had hypercalcemia =11.5 mg/dl, 16% had renal insufficiency (increase of serum creatinine more than 2 g/dl). Conclusion: Overall survival and progression-free survival for myeloma patients treated with new medicines; both significantly improved. [ABSTRACT FROM AUTHOR]

This commentary highlights the key, recent advances made in the field of melanoma. Although significant gains have been made, particularly for resectable disease, ongoing challenges remain in the PD1‐refractory setting. [ABSTRACT FROM AUTHOR]

Simple Summary: Survival of patients with multiple myeloma continues to improve over time in parallel with the development of new treatments. The combination of novel agents in the first-line setting appears to be the main factor driving improvement, resulting in overall survival (OS) of more than 12 and 8 years in patients aged ≤ 70 and >70 years, respectively. In addition, different baseline characteristics have been identified that favorably affected the probability of long-term survival (≥10 years) compared with early death (≤2 years). Therefore, we could conclude that multiple myeloma has become a chronic and even curable disease, in a subset of patients with the current therapeutic approaches. (1) Background: New therapeutic strategies have improved the prognosis of multiple myeloma (MM), changing the accepted view of this disease from being incurable to treatable. (2) Methods: We studied 1001 patients with MM between 1980 and 2020, grouping patients into ten-year periods by diagnosis 1980–1990, 1991–2000, 2001–2010 and 2011–2020. (3) Results: After 65.1 months of follow-up, the median OS of the cohort was 60.3 months, and OS increased significantly over time: 22.4 months in 1980–1990, 37.4 months in 1991–2000, 61.8 months in 2001–2010 and 103.6 months in 2011–2020 (p < 0.001). Using novel agents in the front-line setting for myeloma patients yielded a significantly better OS than in those treated with conventional therapies, especially when combinations of at least two novel agents were used. The median OS of patients treated with the combination of at least two novel agents in induction was significantly prolonged compared to those treated with a single novel agent or conventional therapy in induction: 143.3 vs. 61.0 vs. 42.2 months (p < 0.001). The improvement was apparent in all patients regardless of age at diagnosis. In addition, 132 (13.2%) patients were long-term survivors (median OS ≥ 10 years). Some independent clinical predictors of long-term survival were identified: ECOG < 1, age at diagnosis ≤ 65 years, non-IgA subtype, ISS-1 and standard-risk cytogenetic. Achieving CR and undergoing ASCT were positively associated with >10 years of survival. (4) Conclusions: The combination of novel agents appears to be the main factor for the improvement in survival in MM, which is becoming a chronic and even curable disease in a subtype of patients without high-risk features. [ABSTRACT FROM AUTHOR]

Purpose of reviewHematologic malignancies are common and difficult to treat in older adults. In this review, we focus on recent updates in diseases with several novel agents relevant to older adults-acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM).Recent findingsIn AML, CPX-351 offers a new induction chemotherapy for secondary AML that prolongs survival, and venetoclax and IDH inhibitors are efficacious and well tolerated. In CLL, chemoimmunotherapy is being replaced by monoclonal antibodies and small molecule inhibitors that are more effective and better tolerated. In MM, new immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies have expanded treatment options for older patients. The introduction of novel agents has dramatically shifted the landscape of therapeutic options for older adults with hematologic malignancies. Clinical trials in older adults are needed to expand treatment options for these patients.

IntroductionInfections are a leading cause of morbidity and mortality in patients with multiple myeloma (MM). MethodsTo examine the effects of modern second-generation novel agent therapy on immune cell subsets, in particular CD4+-T-cells, and infectious complications in patients with relapsed/refractory MM (RRMM), we conducted a prospective cohort study in 112 RRMM patients. ResultsSubstantially decreased CD4+-T-cells

This review provides an overview of histopathology, clinical presentation, molecular pathways, and potential new systemic treatments of high-grade chondrosarcomas (CS), including grade 2–3 conventional, dedifferentiated, and mesenchymal CS. The diagnosis of CS combines radiological and histological data in conjunction with patient clinical presentations. Conventional CS is the most frequent subtype of CS (85%) and represents about 25% of primary bone tumors in adults; they can be categorized according to their bone location into central, peripheral, and periosteal chondrosarcomas. Central and peripheral CS differ at the molecular level with either IDH1/2 mutations or EXT1/2 mutations, respectively. CDKN2A/B deletions are also frequent in conventional CS, as well as COL2A1 mutations. Dedifferentiated CS develops when low-grade conventional CS transforms into a high-grade sarcoma and most frequently exhibits features of osteosarcoma, fibrosarcoma, or undifferentiated pleomorphic sarcoma. Their molecular characteristics are similar to conventional CS. Mesenchymal CS is a totally different pathological entity exhibiting recurrent translocations. Their clinical presentation and management are different too. The standard treatment of CSs is wide en-bloc resection. CS are relatively radiotherapy resistant; therefore, doses >60 Gy are needed in an attempt to achieve local control in unresectable tumors. Chemotherapy is possibly effective in mesenchymal chondrosarcoma and is of uncertain value in dedifferentiated chondrosarcoma. Due to resistance to standard anticancer agents, the prognosis is poor in patients with metastatic or unresectable chondrosarcomas. Recently, the refined characterization of the molecular profile, as well as the development of new treatments, allow new therapeutic options for these rare tumors. The efficiency of IDH1 inhibitors in other malignancies suggests that these inhibitors will be part of IDH1/2 mutated conventional CS management soon. Other treatment approaches, such as PIK3-AKT-mTOR inhibitors, cell cycle inhibitors, and epigenetic or immune modulators based on improving our understanding of CS molecular biology, are emerging. [ABSTRACT FROM AUTHOR]

From a historic lens, treatment for patients with relapsed/refractory multiple myeloma (R/R MM) has advanced significantly since the advent of immunomodulatory agents (IMiDs) in the 1990s, proteasome inhibitors in the 2000s, monoclonal antibodies in the 2010s, and CAR-T treatments in the 2020s. However, the availability of multiple new therapies has also created significant ambiguity regarding therapy selection and sequencing, as consensus guidelines are limited, and cross-trial comparisons of the novel agents are challenging. In this focused review, we discuss the novel Food & Drug Administration (FDA)-approved medications for R/R MM, including the recently approved first-in-class BCMA-directed bispecific antibody teclistamab. We highlight the seminal clinical trials data and discuss optimal sequencing considerations based on the goal of treatment, with an emphasis on the two novel CAR-T cell products. We consider the limited tolerability of certain agents, prospects for our aging population, and financial aspects of these therapies. Finally, we spotlight ongoing trials involving promising agents making their way through the pharmacologic pipeline including the BCMA-directed bispecific antibody elranatamab and the GPRC5D-directed bispecific antibody talquetamab. We summarize our recommendations based on the best available evidence as we enter 2023. [ABSTRACT FROM AUTHOR]

Despite recent therapeutic advancements in the general field of non-Hodgkin lymphoma, effective treatment of relapsed or refractory (R/R) mantle cell lymphoma (MCL) remains a challenge. The development of Bruton tyrosine kinase (BTK) inhibitors has revolutionized the field and these agents are now the mainstay of R/R MCL management. However, BTK inhibitors are not curative, and as they are increasingly being incorporated into frontline regimens, the shifting treatment landscape for R/R disease presents new challenges. Here we review data for commonly employed treatment strategies including BTK inhibitors, the BCL2-inhibitor venetoclax, lenalidomide-based regimens, and chimeric antigen receptor T-cell therapy. We additionally review data for promising novel agents including antibody-drug conjugates and bispecific antibodies before highlighting some emerging targeted agents that continue to bring promise for improved outcomes in R/R MCL. [ABSTRACT FROM AUTHOR]

Treatment of multiple myeloma (MM) has advanced dramatically in the past two decades. However, under the conditions of the COVID-19 pandemic, treatment strategies have been modified accordingly. Numerous novel agents, updated trials, and major advances in myeloma have been reported in the American Society of Hematology 2020 annual meeting, either for transplant-eligible or ineligible patients. Hot topics such as the significance of autologous stem cell transplantation (ASCT), development of novel agents, and chimeric antigen receptor-T (CAR-T) cells have been widely discussed. The triplet regimen bortezomib, lenalidomide, and dexamethasone (VRd) is recommended as the standard first-line treatment, and the addition of a fourth drug improves efficacy and survival. The value of ASCT remains undoubtful, even in the era of quadruplet induction. Dual-drug maintenance, including proteasome inhibitors and immunomodulatory drugs, overcomes unfavorable outcomes in high-risk patients. For relapsed/refractory myeloma (RRMM) patients, novel agents such as selinexor and venetoclax are superior. CAR-T cells and other cell-surface-targeted therapies also appear promising.

Major improvements in outcome of older patients with multiple myeloma (MM) have been achieved with the introduction of novel agents. Their impact in real‐life treatment of older patients is unclear. In this single center retrospective study, we analyzed the outcome of patients >65 years treated with first‐generation (FGNA) and second‐generation novel agents (SGNA) within two time periods 2012–2014 and 2015–2017. Patients were analyzed based on age, Charlson Comorbidity Index (CCI), International Staging System stage, year of diagnosis and withdrawal of agents due to toxicities. Overall 96 patients were included for analysis. Median age was 73 years (range 65–90), 55 (57%) patients were 65–75 years and 41 (43%) were >75 years old. 84 patients received a first‐line therapy, whereas 45 patients had ≥2 lines of systemic therapy. 20 patients were consolidated with autologous stem cell transplantation. 12 patients had no systemic therapy at all. In 17 of 21 cases a FGNA and in 4 of 21 a SGNA was withdrawn due to toxicity. Median overall survival (OS) for all patients with systemic therapy was 4.75 years (95% CI, 3.05‐NA). Borderline significant improvement of OS was observed in patients diagnosed 2015–2017 compared to 2012–2014 with HR 0.57 (95% CI, 0.31–1.02) p = 0.06. OS significantly differed for comorbid patients with low and intermediate risk CCI, HR 1.94 (95% CI, 1.07–3.54), p = 0.03 in the overall population. OS in patients treated with SGNA was not significantly different in patients with intermediate versus low risk CCI (HR 1.48 (95% CI 0.43–5.14, p = 0.54)). In conclusion, we found a trend toward improved survival for older MM patients after the introduction of novel agents during the observed time period. In patients treated with SGNA a smaller effect that comorbidity negatively affects survival was observed. [ABSTRACT FROM AUTHOR]

Despite the achievements that have increased viability after the transplantation of allogeneic hematopoietic stem cells (aHSCT), chronic graft-versus-host disease (cGVHD) remains the main cause of late complications and post-transplant deaths. At the moment, therapy alternatives demonstrate limited effectiveness in steroid-refractory illness; in addition, we have no reliable data on the mechanism of this condition. The lack of drugs of choice for the treatment of GVHD underscores the significance of the design of new therapies. Improved understanding of the mechanism of chronic GVHD has secured new therapy goals, and organized diagnostic recommendations and the development of medical tests have ensured a general language and routes for studies in this field. These factors, combined with the rapid development of pharmacology, have helped speed up the search of medicines and medical studies regarding chronic GVHD. At present, we can hope for success in curing this formidable complication. This review summarizes the latest clinical developments in new treatments for chronic GVHD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical characteristics and outcomes of patients with nephropathy associated with POEMS syndrome who received novel agents in combination with dexamethasone therapy, and renal pathological changes based on repeat biopsy in some patients after these novel-agent-based therapies. Methods: The records of patients with nephropathy associated with POEMS syndrome in a single hospital from May 2017 to February 2021 were retrieved and studied in detail. All the patients received four cycles of initial novel-agent-based regimens such as bortezomib and dexamethasone (BD) or thalidomide plus dexamethasone (TD) or lenalidomide plus dexamethasone (RD) treatment. We further evaluated the pathological efficacy of these novel agents by repeat renal biopsy. Results: Twelve patients with an average age of 48.6 ± 8.3 years diagnosed with nephropathy associated with POEMS syndrome were enrolled in this study. The duration from disease onset to renal biopsy was 28(8.3 ~ 54.5) months. All patients achieved good clinical responses in different degree after four cycles of initial novel agents in combination with dexamethasone therapy. After the treatment with novel-agent-based regimens, the levels of proteinuria decreased in most patients and were negative in five patients. The levels of serum creatinine (SCr) decreased in ten patients. Serum M protein was negative in four patients and still positive in the other eight patients. The levels of serum vascular endothelial growth factor (VEGF) were detected in seven patients, which were all decreased. The levels of interleukin-6 (IL-6) were detected in eight patients, which were also decreased. Repeat biopsies were performed after four cycles of novel-agent-based therapies in four patients who were all treated with BD treatment. Mesangiolysis, mesangial cells proliferation, endothelial cells proliferation, subendothelial space widening and acute renal tubulointerstitial lesions improved, the chronic renal tubulointerstitial lesions were stable. Conclusions: Novel agents improved clinical manifestations in patients with nephropathy associated with POEMS syndrome. In addition, novel-agent-based regimens such as BD treatment improved renal pathological manifestations, which suggested that novel agents could improve renal prognosis of the patients from the perspective of renal pathology. [ABSTRACT FROM AUTHOR]

Background: Invasive candidiasis (IC) is increasing due to the rising numbers of immunocompromised patients. Increasing azole resistance rates and daily dosing required for most echinocandins have complicated its treatment. The approval of rezafungin has provided an option for weekly echinocandin treatment. The susceptibility of less common Candida spp. to rezafungin is unclear. We looked at the minimum inhibitory concentrations (MICs) of rezafungin and comparator agents against Candida spp. collected as part of a global surveillance program., Method: The CLSI reference broth microdilution method was performed to test 590 clinical isolates of 28 different Candida species, including Candida auris. Species-specific interpretative criteria by breakpoints or epidemiological cutoff values were applied where available., Results: Rezafungin was within ±2-fold MIC 50 / 90 values of other echinocandins against all Candida spp. The lowest rezafungin MIC 50 / 90 values were noted against C. kefyr (0.03/0.06 mg/L) and C. pelliculosa (0.015/0.03 mg/L). Higher rezafungin MIC 50 / 90 values were noted for C. guilliermondii (1/1 mg/L) and for isolates in the C. parapsilosis complex (C. orthopsilosis, 0.5/1 mg/L, C. metapsilosis, 0.12/0.5 mg/L). Rezafungin was active against 97.7% of C. dubliniensis and 95.4% of C. auris by CLSI breakpoints. For fluconazole, 69.7% of C. guilliermondii, 85.7% of C. orthopsilosis, and 100% of C. metapsilosis were wildtype by ECV, and 10.8% of C. auris were susceptible by CDC breakpoint., Conclusions: Rezafungin was highly active by in vitro testing against less common Candida spp. Rezafungin MICs were comparable to other echinocandins. Rezafungin is a desirable therapeutic alternative due to its reduced dosing frequency., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Introduction: Accessing compassionate access schemes to obtain novel therapeutic agents for children with hard-to-treat cancers can be fraught with challenges such as regulatory barriers and limited resources. This study aimed to explore clinician perspectives on the barriers, impacts and ethical considerations of accessing novel therapeutic agents within the context of a paediatric oncology precision medicine trial., Methods: We gathered data from 37 semi-structured interviews with paediatric oncologists participating in the PRecISion Medicine for Children with Cancer (PRISM) study, a precision medicine clinical trial in Australia. The interviews, conducted over 2 years, focused on paediatric oncologist's experiences with the PRISM trial. Interviews were re-analysed to identify themes related to access pathways and any challenges in obtaining novel agents through thematic analysis. The resulting thematic framework was discussed and refined by a multidisciplinary team., Results: Three main themes were identified: (i) barriers to access, including poor drug availability, lack of evidence and the time burden of the application process; (ii) impacts of inaccessibility, encompassing medical consequences and financial burden on families; and (iii) ethical considerations, centred around balancing realistic expectations and providing compassionate care to patients and families. Paediatric oncologists expressed frustration with the complex regulatory landscape and the lack of systematic reporting on applications and outcomes of obtaining novel agents. Lengthy wait times for decision notifications were also highlighted, raising concerns about missed therapeutic opportunities for patients., Conclusion: This study provides insight to the challenges faced when seeking access to novel therapies for paediatric oncology patients. There is a clear need for improved communication, streamlining processes and increased resources to facilitate access to novel agents. Further resource development is necessary to address these complexities in accessing novel therapy agents to ultimately ensure equitable and timely access., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

In recent years, an explosion of novel agents has shifted the treatment paradigm for patients with acute myeloid leukemia. The optimal place in therapy for many of these novel agents remains unknown due to limited guidance from national guidelines and the way these agents were studied prior to entering the market. A critical evaluation of the literature and incorporation of oncology stewardship principles can be helpful in determining an optimal place for these agents while being mindful of the overall cost that is associated with therapies. The purpose of this review is to critically evaluate the efficacy and safety data for five controversial agents and provide examples of the use of stewardship practices in determining their place in the treatment of acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Classical Hodgkin lymphoma (cHL) is the most common type of HL that occurs mainly in people aged between 15-30 and over 55 years. Although its general prognosis is favorable, 10%-30% of patients with cHL will ultimately develop relapsed or refractory disease (r/r cHL). Improving the cure rate of r/r cHL has proven to be challenging. Some novel agents, such as brentuximab vedotin and immune checkpoint inhibitors, which have been used in conventional regimens for patients with r/r cHL in the past decade, have been shown to have good curative effects. This paper reviews the conventional regimens for patients with r/r cHL and focuses on the newest clinical trials and treatment measures to prolong prognosis and reduce adverse events. The evaluation of prognosis plays a vital role in analyzing the risk of relapse or disease progression; thus, finding new predictive strategies may help treat patients with r/r cHL more efficaciously. [ABSTRACT FROM AUTHOR]

Treatment for the older adult with acute myeloid leukemia (AML) is challenging, due to both more aggressive disease biology as well as patient-related risk factors that limit tolerance of intensive chemotherapy. The use of prognostic models and comprehensive geriatric assessments can help hematologists evaluate the suitability of intensive chemotherapy for individual patients. For older patients considered fit for intensive chemotherapy, standard induction therapy should be given, followed by consideration of reduced intensity allogeneic stem cell transplantation. Patients considered unfit for intensive therapy are standardly treated with hypomethylating agents. Several new therapeutic agents have shown promising results either by improving intensive chemotherapy (CPX-351), by improving upon lower intensity therapy (venetoclax, antibody drug conjugates), or by targeting somatic mutations (FLT3 inhibitors and others).

Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive extranodal type of non-Hodgkin lymphoma. After the introduction and widespread use of high-dose-methotrexate (HD-MTX)-based polychemotherapy, treatment responses of PCNSL have been improved. However, long-term prognosis for patients who have failed first-line therapy and relapsed remains poor. Less invasive diagnostic markers, including the circulating tumor DNAs (ctDNAs), microRNAs, metabolomic markers, and other novel biomarkers, such as a proliferation inducing ligand (APRIL) and B-cell activating factor of the TNF family (BAFF), have shown potential to distinguish PCNSL at an early stage, and some of them are related with prognosis to a certain extent. Recent insights into novel therapies, including Bruton tyrosine kinase (BTK) inhibitors, immunomodulatory drugs, immune checkpoint inhibitors, PI3K/mTOR inhibitors, and chimeric antigen receptor (CAR) T cells, have revealed encouraging efficacy in treatment response, whereas the duration of response and long-term survival of patients with relapsed or refractory PCNSL (r/r PCNSL) need further improvement. In addition, the diagnostic efficiency of novel markers and the antitumor efficacy of novel therapies are needed to be assessed further in larger clinical trials. This review provides an overview of recent research on novel diagnostic markers and therapeutic strategies for PCNSL. [ABSTRACT FROM AUTHOR]

Brain tumors are the most widespread malignancies in children around the world. Chemotherapy plays a critical role in the treatment of these tumors. Although the current chemotherapy process has a remarkable outcome for a certain subtype of brain tumor, improving patient survival is still a major challenge. Further intensive treatment with conventional non-specific chemotherapy could cause additional adverse reactions without significant advancement in survival. Recently, patient derived brain tumor, xenograft, and whole genome analysis using deep sequencing technology has made a significant contribution to our understanding of cancer treatment. This realization has changed the focus to new agents, targeting the molecular pathways that are critical to tumor survival or proliferation. Thus, many novel drugs targeting epigenetic regulators or tyrosine kinase have been developed. These selective drugs may have less toxicity in normal cells and are expected to be more effective than non-specific chemotherapeutics. This review will summarize the latest novel targets and corresponding candidate drugs, which are promising chemotherapy for brain tumors according to the biological insights. [ABSTRACT FROM AUTHOR]

Simple Summary: The outcomes of patients with multiple myeloma have significantly improved over the years, following autologous stem cell transplant and the introduction of novel agents. In this study, we performed a retrospective survival analysis on newly diagnosed MM patients receiving ASCT from 1992–2016 at the Ohio State University. We observed that newly diagnosed MM patients' survival and responses to standard of care treatment have improved dramatically since 1992, primarily due to the inclusion of novel and maintenance therapies. There was an improvement in patient remission status, PFS, and OS, suggesting that evolving standards of therapy for MM are enhancing patient outcomes. These findings highlight the importance for newer interventions to build on prior successes. Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992–2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992–2016), there was a statistically significant improvement in both PFS (p < 0.01) and OS (p < 0.01). Significant improvements in both PFS and OS were seen in patients ≤65 years (p < 0.001 and p = 0.002) and >65 years old (p < 0.001 and p = 0.001), respectively. Improved PFS and OS were seen in both standard-risk (p < 0.001 and p < 0.001) and high-risk patients (p < 0.001 and p = 0.019). The post-transplant response showed statistically significant improvement across the years (p < 0.01). Survival rates for NDMM patients have significantly improved primarily due to the inclusion of novel therapies and post-ASCT maintenance. [ABSTRACT FROM AUTHOR]

Utilization of novel agents such as brentuximab vedotin (BV) and check-point inhibitors (CI) has increased in patients with relapsed/refractory (r/r) classical Hodgkin Lymphoma (cHL). We conducted a retrospective study of 209 patients who had ASCT for r/r cHL at our institution and compared outcomes of those who had ASCT from 2010–2018 (cohort 2, n = 110) with those who had ASCT between 2000 and 2009 (cohort 1, n = 99). The median OS was 7.6 years for cohort 1 [HR 2.08; 95% CI 1.14–3.80; p = 0.017] and not reached for cohort 2; with 4-year improved OS difference of 15% (80% vs 65%) in cohort 2 vs cohort 1. The median PFS of cohort 1 was 30 months vs 39 months for cohort 2[HR 1.24; 95% CI 0.82–1.88; p = 0.3]. This study highlights improved OS of r/r cHL patients who have received ASCT in the novel agent era due to the exposure to agents such as BV and CIs. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD. [ABSTRACT FROM AUTHOR]