Long-acting muscarinic antagonist and long-acting ß2-agonist combination for the treatment of maintenance therapy-naïve patients with chronic obstructive pulmonary disease: a narrative review.

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Faster lung function impairment occurs earlier in the disease, particularly in mild-to-moderate COPD, highlighting the need for early and effective targeted interventions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024 report recommends initial pharmacologic treatment with a long-acting muscarinic antagonist (LAMA) and long-acting ß2-agonist (LABA) combination in group B (0 or 1 moderate exacerbation not leading to hospitalization, modified Medical Research Council score of ⩾2, and COPD Assessment Test™ score of ⩾10) and E (⩾2 moderate exacerbations or ⩾1 exacerbation leading to hospitalization and blood eosinophil count <300 cells/µL) patients. In randomized controlled trials (RCTs), LAMA/LABA combination therapy improved lung function, St. George's Respiratory Questionnaire (SGRQ) total score, and Transitional Dyspnea Index (TDI) focal score and reduced the use of rescue medications, exacerbation risk, and risk of first clinically important deterioration (CID), compared with LAMA or LABA monotherapy. However, there is limited evidence regarding the efficacy and safety of LAMA/LABA combination therapy versus LAMA or LABA monotherapy in maintenance therapy-naïve patients. This review discusses the rationale for the early initiation of LAMA/LABA combination therapy in maintenance therapy-naïve patients with COPD. In post hoc analyses of pooled data from RCTs, compared with LAMA or LABA monotherapy, LAMA/LABA combination therapy improved lung function and quality of life and reduced COPD symptoms, risk of first moderate/severe exacerbation, risk of first CID, and use of rescue medication, with no new safety signals. In a real-world study, patients initiating LAMA/LABA had significantly reduced risk of COPD-related inpatient admissions and rate of on-treatment COPD-related inpatient admissions over 12 months than those initiating LAMA. Consequently, LAMA/LABA combination therapy could be considered the treatment of choice in maintenance therapy-naïve patients with COPD, as recommended by the GOLD 2024 report.

Long-acting bronchodilator combination therapy for the treatment of maintenance therapy­naïve patients with chronic obstructive pulmonary diseaseChronic obstructive pulmonary disease (COPD) is a common lung disease that makes it hard to breathe and is a leading cause of death and disability worldwide. This disease tends to worsen lung function from an early stage, especially in people who only have mild or moderate symptoms. To help stop the loss of lung function and maintain the quality of life for patients with COPD, two main types of long-lasting inhaler medications are used: one type focuses on relaxing the muscles around the airways, and the other type helps open the airways making it easier to breathe. Some medications combine these two types of action and are approved for long-term management of COPD. However, there is not much information on the effectiveness and safety of these combination medications in patients who have never taken long-lasting COPD medication before. Current health guidelines suggest starting these combination medications in patients who are likely to see their symptoms get worse quickly, and who do not have a high level of a specific type of white blood cell. In this review, we discuss the evidence for starting these combination treatments early in patients who have never used long-lasting COPD medications before. There is no strong evidence yet that shows starting treatment early benefits patients with newly diagnosed COPD. However, about 30% of patients in clinical trials designed to study the effectiveness of these combination medications, had never received any long-lasting treatment before. After-the-fact analyses of these patients showed that these combination medications could reduce symptoms such as breathlessness, improve lung function, enhance quality of life, lessen the need for emergency medications, and decrease the risk of severe symptom flare-ups. Overall, the evidence supports using these combination inhaler medications as the first choice of treatment for patients with moderate COPD symptoms who have not previously been treated with long-lasting inhalers.

N-803, an IL-15 superagonist complex as maintenance therapy after allogeneic donor stem cell transplant for acute myeloid leukemia or myelodysplastic syndrome; a Phase 2 trial.

Maintenance therapy may improve natural killer (NK) cell surveillance after allogeneic donor hematopoietic cell transplant (HCT) for myeloid malignancies and represents a potential approach to improve cure rates. Interleukin-15 (IL-15) enhances lymphocyte proliferation and anti-tumor activity. In a prior Phase 1 study of an IL-15 superagonist (N-803) in patients with AML who relapsed after HCT, we observed in vivo expansion of NK cells and anti-tumor responses. The primary objective of this Phase 2 trial was to determine if post-transplant N-803 could reduce relapse. We administered N-803 (n=20) (dosed 6 mcg/kg subcutaneously (SQ) at day 60 after HCT to patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were in complete remission (CR). N-803 treatment was planned weekly, bi-weekly or every 4 weeks in 2 sequential cohorts. The most common adverse events after administration were self-limited injection sites skin rashes (n=20). One week after an N-803 dose, we observed enhanced NK cell proliferation and improved anti-tumor cytotoxicity without inducing immune exhaustion. Five patients who developed acute graft versus host disease (aGVHD) after N-803 responded promptly to steroids and 4 patients developed chronic GVHD. Patients receiving >4 doses of N-803 had a 3-fold decrease in relapse at two years (p=0.06). These findings support the safety, immune activation, and potential efficacy of N-803 to prevent relapse of AML/MDS after HSCT.

Efficacy of Probiotics Compared With Pharmacological Treatments for Maintenance Therapy for Functional Constipation in Children: A Systematic Review and Network Meta-analysis.

CONTEXT: There has been an increase in randomized controlled trials (RCTs) comparing probiotics with various maintenance therapies, such as polyethylene glycol, lactulose, and mineral oil, to treat functional constipation in children. OBJECTIVE: The aim was to compare probiotics with all other oral maintenance therapies for functional constipation in children and rank all treatments in terms of effectiveness in a network meta-analysis. METHODS: RCTs were identified through systematically searching the MEDLINE, Scopus, EMBASE, and Cochrane Library databases, trial registries, and forward and backward citation searching. Within-study risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and confidence in the estimates was assessed using the CINeMA (Confidence in Network Meta-Analysis) framework. Random-effects network meta-analyses were conducted. RESULTS: Data were pooled from 41 and 29 RCTs for network meta-analysis of defecation frequency and treatment success, respectively. Probiotics did not significantly increase the number of bowel movements per week when compared with any conventional treatment or placebo. A combination of mineral oil and probiotics was the most effective treatment for increasing defecation frequency (mean difference: 3.13; 95% confidence interval [CI]: 0.64, 5.63). The most effective treatments for increasing the risk of treatment success as compared with placebo were mineral oil (relative risk [RR]: 2.41; 95% CI: 1.53, 3.81) and a combined treatment of polyethylene glycol and lactulose (RR: 2.45; 95% CI: 1.21, 4.97). Confidence in the estimates ranged from very low to moderate. CONCLUSION: Currently, there is no evidence to suggest that probiotics should be used as a standalone treatment for functional constipation in children. More high-quality studies are needed to evaluate different strains of probiotics and their potential benefit as an additional treatment component to conventional treatments. Mineral oil and polyethylene glycol were the most effective treatments to increase defecation frequency and treatment success rates and should remain the first line of treatment for children with functional constipation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no.CRD42022360977 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=360977).

Patterns of Rescue and Maintenance Medication Claims Surrounding an Asthma Exacerbation in Patients Treated as Intermittent or Mild Persistent Asthma.

Purpose: To examine patterns of short-acting ß2-agonist (SABA) and maintenance therapy claims surrounding the subset of severe asthma exacerbations associated with outpatient, urgent care, or emergency department visits or hospitalization (termed serious exacerbations) in patients treated as intermittent or mild persistent asthma. Methods: This was a retrospective study of 2010-2017 administrative claims from MerativeTM MarketScan® US databases for patients ≥12 years filling a SABA prescription for asthma (index). Patients had ≥12 months continuous insurance eligibility pre- and post-index and ≥1 additional SABA and/or maintenance medication fill appropriate for mild persistent asthma post-index. Prescription fills were assessed over 30 days before and after a serious exacerbation event. Results: Of 323,443 patients (mean [standard deviation] age: 34.9 [18.2] years; 62.0% female) treated as intermittent or mild persistent asthma, 51,690 (16.0%) experienced ≥1 serious exacerbation post-index. During the 30 days pre-event, a greater proportion of patients filled a SABA versus maintenance therapy (24.6% vs 19.0%; odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.35-1.43; p < 0.001); during the 30 days post-event, patients were more likely to fill maintenance medication versus SABA (88.6% vs 67.0%; OR [95% CI]: 3.88 [3.75-4.01]; p < 0.001). The closer in time prior to the event, the greater the likelihood of filling a SABA versus maintenance prescription (OR [95% CI]; 1-7 days pre-event: 1.42 [1.36-1.48]; 8-14 days pre-event: 1.34 [1.27-1.41]; 15-30 days pre-event: 1.18 [1.12-1.24]; all p < 0.001). Over 4.5 times more patients filled a maintenance therapy within 7 days post-event (45,014) versus all 30 days pre-event (9835) (OR [95% CI]: 28.7 [27.7-29.7]; p < 0.001). Conclusion: These patterns of SABA rescue and maintenance fills suggest that a "window of opportunity" may exist to interrupt a serious exacerbation occurrence for patients treated as intermittent or mild persistent asthma if symptoms and inflammation are addressed concomitantly.

[Analysis of the prognostic factors in primary plasma cell leukemia in the era of novel agents].

Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor (HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy (HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better (HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Healthcare Utilization and Costs Among Patients with Acute Myeloid Leukemia Receiving Oral Azacitidine Maintenance Therapy Versus No Maintenance: A US Claims Database Study.

INTRODUCTION: The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA. METHODS: Data from IQVIA PharMetrics® Plus (January 1, 2016-June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance ("watch and wait" [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs. RESULTS: After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months-NR] vs 3.3 months [0.8 months-NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001). CONCLUSIONS: Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice.

Efficacy and safety of anlotinib as maintenance therapy in patients with advanced non-small cell lung cancer achieving SD post first-line chemotherapy combined with immunotherapy.

Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.

Alectinib maintenance therapy following cord blood transplantation for relapsed pediatric anaplastic large cell lymphoma with central nervous system involvement.

Pediatric ALK-positive anaplastic large cell lymphoma is a rare subtype of non-Hodgkin lymphoma, and approximately 30% of patients relapse following treatment with conventional chemotherapy. Alectinib monotherapy has demonstrated excellent activity in relapsed and refractory ALCL, but its role as a maintenance therapy after hematopoietic cell transplantation is unclear. We experienced a relapse case of pediatric ALK-positive ALCL with central nervous system involvement treated with alectinib maintenance therapy following cord blood transplantation. The patient has maintained complete remission for more than 3 years after transplantation. There were no remarkable adverse effects that led to discontinuation of alectinib.

Analysis toolkit for evaluation of drug titration practice in acute lymphoblastic leukemia maintenance.

Objective: During the 2-year maintenance treatment phase (MT) of acute lymphoblastic leukemia (ALL), personalized patient-specified titration of oral antimetabolite drug doses is required to ensure maximum tolerated systemic drug exposure. Drug titration is difficult to implement in practice and insufficient systemic drug exposure resulting from inadequate dose titration increases risk of ALL relapse. Materials and Methods: We developed an open-source R-based analytical toolkit, including the allMT R package and an interactive web-based R Shiny VIATAMIN application, to evaluate antimetabolite drug titration during MT. Results: Evaluation is initiated with basic visualization analysis of drug titration, in both individual patients and patient cohorts. Observations are supplemented with descriptive analyses of hematological toxicity frequency and prescriber compliance rates with protocol drug titration rules. In individual patients, visual and quantitative analyses indicate recurring potentially correctable suboptimal drug titration patterns. In patient cohorts, the toolkit enables evaluation of the impact of interventions to optimize MT drug titration. Discussion: Incorporation of the toolkit in a forthcoming clinical decision support system for MT would enable real-time examination and course correction of drug titration practice. Conclusion: Future versions will be enhanced to include other variables that influence drug titration practice, including clinical toxicity data and later, pharmacological markers of antimetabolite, adherence, and drug activity.

Real-world trends in the use of maintenance therapy in ovarian cancer across the United States from 2017 to 2021.

OBJECTIVE: We assessed real-world trends in the use of maintenance therapy [MT] (i.e., polyADP-ribose polymerase inhibitors (PARPi) and/or bevacizumab following platinum-based chemotherapy), among U.S. patients with ovarian cancer. METHODS: Using Medicare and commercial administrative health claims data from Optum's de-identified Clinformatics® Data Mart Database, we identified patients who had been diagnosed with ovarian cancer between January 1, 2010, and March 31, 2021, and received platinum-based chemotherapy and MT. Multivariable logistic regression and Cox proportional hazards regression were used to evaluate associations between demographic and clinical characteristics and MT use. RESULTS: Our study included 6339 patients, with a median age of 70 years. The majority were White (70.1 %), Medicare-insured (71.9 %), and were treated in the South (42.5 %). Of the 31.5 % who received MT, 18.1 % received bevacizumab alone, 10.2 % PARPi alone, and 3.3 % both. After adjusting for insurance type, PARPi and bevacizumab use increased significantly from 2017 to 2020. Patients with a high Elixhauser comorbidity index were more likely to receive MT than were patients with a low index [OR (95 % CI): 1.46 (1.28-1.67), p < 0.0001]. PARPi use was significantly associated with treatment in the South [1.42 (1.10-1.83), p = 0.01]. Compared to patients who received neither agents, those who received bevacizumab, alone or in combination with PARPi, had a higher risk of death [HR = 2.02 (95 % CI: 1.70-2.28, p < 0.0001) and 1.66 (1.24-2.23), p = 0.001, respectively]. CONCLUSIONS: The majority of patients with ovarian cancer are not utilizing maintenance therapy after platinum-based chemotherapy. Age, comorbidity status, and geographic region of treatment were associated with MT use. Understanding the factors and real-world outcomes associated with MT use is important to support patients in making value concordant and informed decisions.

Chidamide maintenance therapy after allo-HSCT in SET-NUP214 fusion positive T-ALL patients: A report of two cases.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly invasive hematological malignancy originated from T-lineage progenitor cells. The clonal proliferation and aggregation of primordial cells in bone marrow inhibit normal hematopoietic function, resulting in a series of hematocytopenia and infiltration symptoms. SET-NUP214 fusion is a recurrent event that is common in adult male T-ALL patients. It originates from chromosome del(9)(q34.11; q34.13) or t(9; 9)(q34; q34). Hematopoietic stem cell transplantation (HSCT) can significantly improve the survival rate of these patients. Due to the poor prognosis of patients and high relapse rate after remission, more effective strategies need to be proposed to improve prognosis and prevent relapse. Chidamide is a novel oral benzamide histone deacetylase inhibitor (HDACi) that can exert anti-tumor effects through multiple mechanisms. Here we report chidamide maintenance therapy after allo-HSCT in patients with SET-NUP214 fusion positive T-ALL. Both patients improved effectively during follow-up, confirming the efficacy of chidamide in improving the condition of these patients and may provide valuable clinical information for the treatment of this rare and understudied disease.

Factors associated with an inconclusive result from commercial homologous recombination deficiency testing in ovarian cancer.

INTRODUCTION: Homologous recombination deficiency (HRD) testing is used to determine the appropriateness of poly ADP-ribose polymerase inhibitors for patients with epithelial ovarian cancer and no germline/somatic BRCA1/2 alterations. Myriad MyChoice CDx reports a genomic instability score (GIS) to quantify the level of HRD, with a positive score defined as ≥42. The authors sought to define factors associated with obtaining an inconclusive HRD test result. METHODS: GIS was retrieved for patients at their institution with epithelial ovarian cancer without germline/somatic BRCA1/2 deleterious alterations who underwent HRD testing from April 2020-August 2023. Clinical data were abstracted from the medical record. RESULTS: Of 477 HRD test results identified, 57 (12%) were inconclusive. High-grade serous ovarian cancers had higher GIS than other histologic types (median 29 vs. 21, p < .001). Most HRD cases were of high-grade serous histology; no cases with clear cell or endometrioid histology were HRD-positive. On univariate analysis, interval versus primary cytoreductive surgery, other specimen sources versus surgical specimens, and chemotherapy exposure were risk factors for inconclusive HRD testing. On multivariable analysis, chemotherapy exposure, and tissue source were associated with an inconclusive test result, with surgical specimens more likely to yield a conclusive result than other sources (biopsy, cytology, other). Age, stage, self-reported race, and histology were not associated with an inconclusive result. CONCLUSIONS: Surgical tissue was more likely to yield a conclusive HRD test result versus other sources of epithelial ovarian cancer tissue acquisition. When feasible, laparoscopic biopsy before initiation of neoadjuvant chemotherapy may increase the likelihood of obtaining interpretable HRD test results.

Treatment patterns in patients with newly diagnosed COPD in the USA.

BACKGROUND: Prompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA. METHODS: This retrospective, noninterventional study used de-identified data from the Inovalon Insights' database (Commercial, Medicaid Managed Care, and Medicare Advantage-insured individuals) between January 1, 2015, and December 31, 2021. The "patient journey" from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns. RESULTS: The cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4). CONCLUSIONS: Most patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.

Patient Characteristics Associated with Time to Next Treatment in Patients with Ovarian Cancer Treated with Niraparib: The PRED1CT Real-World Study.

INTRODUCTION: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. METHODS: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. RESULTS: Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4-23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. CONCLUSION: This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes.

Effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with anti-PD-1/PD-L1 antibodies in extensive-stage small cell lung cancer: a real-world study.

Background: Currently, chemotherapy plus immunotherapy followed by maintenance therapy with immune monotherapy is the preferred first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), but with limited overall survival (OS) and progression-free survival (PFS) benefits. The combination of anti-angiogenic drugs with immunotherapy has shown encouraging anti-tumor activity and tolerability, with some degree of overcoming immune resistance. This study aimed to evaluate the effectiveness and safety of anlotinib plus anti-programmed cell death 1/ligand 1 (anti-PD-1/PD-L1) antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC. Methods: Between June 2020 and December 2021, 12 patients with newly diagnosed ES-SCLC in the First Affiliated Hospital of Army Medical University were retrospectively analyzed. All patients without disease progression after 4-6 cycles of first-line platinum-containing chemotherapy plus anti-PD-1/PD-L1 antibodies received anlotinib (12 mg oral/day, days 1-14, followed by 1 week off, every 3 weeks per cycle) plus anti-PD-1/PD-L1 antibodies as maintenance therapy. Several patients underwent chest radiotherapy (intensity-modulated radiotherapy using a 6 MV X-ray) without disease progression before maintenance therapy. The effectiveness and safety of anlotinib plus anti-PD-1/PD-L1 antibodies as maintenance therapy after first-line chemotherapy combined with immunotherapy in ES-SCLC were evaluated. Results: The median follow-up time was 31.1 months. During first-line treatment (including maintenance therapy), one patient achieved a complete response, eight patients achieved a partial response (PR), and three patients had stable disease, with an objective response rate of 75.0% and a disease control rate of 100.0%. During maintenance therapy with anlotinib plus anti-PD-1/PD-L1 antibodies, 50.0% of patients achieved further lesion remission on the basis of the prior initial treatment, of which one patient achieved a PR. The median PFS was 13.6 [95% confidence interval (CI): 11.2-15.6] months, and the median OS was 19.5 (95% CI: 14.5-24.5) months. Treatment-related any grade and grade 3-4 adverse events (AEs) were reported in 100.0% and 58.3% of patients, respectively. No life-threatening AEs were observed. Grade 3-4 AEs included leukocytopenia (58.3%, 7/12), thrombocytopenia (33.3%, 4/12), nausea (33.3%, 4/12), anemia (16.7%, 2/12), and fatigue (8.3%, 1/12). All AEs during maintenance therapy were tolerated and were regarded as grade 1-2, with the majority being fatigue, nausea, rash, and hemoptysis. Conclusions: The combination of anlotinib with anti-PD-1/PD-L1 antibodies demonstrated encouraging effectiveness and safety in treating patients with ES-SCLC, suggesting that it may be a preferred option for maintenance therapy after first-line chemotherapy combined with immunotherapy.

Simultaneous combined transplantation: Intricacies in immunosuppression management.

Simultaneous combined transplantation (SCT), i.e. the transplantation of two solid organs within the same procedure, can be required when the patients develop more than one end-stage organ failure. The development of SCT over the last 20 years could only be possible thanks to progress in the surgical techniques and in the perioperative management of patients in an ageing population. Performing such major transplant surgeries from the same donor, in a short amount of time, and in critical pathophysiological conditions, is often considered to be counterbalanced by the immune benefits expected from these interventions. However, SCT includes a wide array of different transplant combinations, with each time a different immunological constellation. Recent research offers new insights into the immune mechanisms involved in these different settings. Progress in the understanding of these immunological intricacies help to address the optimal induction and maintenance immunosuppressive treatment strategies. In this review, we summarize the different immunological benefits according to the type of SCT performed. We also incorporate the main outcomes according to the immunological risk at transplantation, and the deleterious impact of preformed or de novo donor-specific antibodies (DSA) in the different types of SCT. Finally, we propose comprehensive and evidence-based induction and maintenance immunosuppression strategies guided by the type of SCT.

Maintenance Intravenous Immunoglobulin Therapy for Chronic Inflammatory Demyelinating Polyneuropathy: 18-Month Post-marketing Surveillance in 103 Patients.

Objective The efficacy of maintenance intravenous immunoglobulin (IVIg) therapy has been established to prevent relapse in chronic inflammatory demyelinating polyneuropathy (CIDP). This prospective post-marketing surveillance study evaluated the treatment duration, efficacy, and safety of maintenance IVIg therapy in Japanese patients with CIDP. Methods Patients were registered between June 2017 and December 2018. After induction of IVIg therapy (0.4 g/kg/day for 5 consecutive days), patients received maintenance IVIg (1.0 g/kg every 3 weeks). The observation period was 18 months. Efficacy in preventing relapse was assessed using the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Relapse was defined as a worsening of the INCAT score by ≥1 from baseline. Patients The efficacy population comprised 103 patients (80 with typical CIDP and 23 with CIDP variants). Results During the observation period, 86 (83%) patients were scheduled to continue maintenance IVIg therapy during the observation period, and the relapse rate was 24% (21/86). In the remaining 17 patients who showed continuous remission, maintenance IVIg therapy was stopped (mean, 136 days after the start), and the relapse rate was 24% (4/17). One serious adverse drug reaction of cardiac failure was reported. Conclusion In this post-marketing surveillance, most (83%) patients with CIDP were scheduled to continue maintenance IVIg for 18 months, with a relapse rate of 24%, indicating long-term efficacy. Maintenance IVIg therapy was rarely withdrawn, and the relapse rate after withdrawal was 24%. Further studies are required to determine the optimal maintenance IVIg dose and duration.

CYP2B6 and ABCB1 genotypes predict methadone plasma exposure among patients on maintenance therapy against opioid addictions in Tanzania.

AIMS: Methadone maintenance therapy (MMT) exhibits significant variability in pharmacokinetics and clinical response, partly due to genetic variations. However, data from sub-Saharan African populations are lacking. We examined plasma methadone variability and pharmacogenetic influences among opioid-addicted Tanzanian patients. METHODS: Patients attending MMT clinics (n = 119) in Tanzania were genotyped for common functional variants of the CYP3A4, CYP3A5, CYP2A6, CYP2B6, CYP2C19, CYP2D6, ABCB1, UGT2B7 and SLCO1B1 genotypes. Trough plasma concentrations of total methadone, S-methadone (S-MTD) and R-methadone (R-MTD), with their respective metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The methadone-to-EDDP metabolic ratio (MMR) was used to categorize the phenotype. RESULTS: The proportions of MMR-predicted ultrarapid, extensive, intermediate and slow methadone metabolizer phenotypes were 2.5%, 58.2%, 23.7% and 15.6%, respectively. CYP2B6 genotype significantly correlated with S-methadone (P = .006), total methadone (P = .03), and dose-normalized methadone plasma concentrations (P = .001). Metabolic ratios of R-methadone (R-MTD/R-EDDP), S-methadone (S-MTD/S-EDDP), and total methadone (MMR) were significantly higher among patients homozygous for defective variants (*6 or *18) than heterozygous or CYP2B6*1/*1 genotypes (P < .001). The metabolic ratio for S-MTD and total methadone was significantly higher among ABCB1c.3435T/T than in the C/C genotype. No significant effect of CYP2D6, CYP2C19, CYP3A4, CYP3A5, CYP2A6, UGT2B7 and SLCO1B1 genotypes on S-methadone, R-methadone, or total methadone was observed. CONCLUSIONS: Approximately one in six opioid-addicted Tanzanian patients are methadone slow metabolizers, influenced by genetic factors. Both the CYP2B6 and ABCB1 genotypes are strong predictors of methadone metabolic capacity and plasma exposure. Further investigation is needed to determine their predictive value for methadone treatment outcomes and to develop genotype-based dosing algorithms for safe and effective therapy.

Prescribers and patients drive maintenance therapy patterns in a community oncology practice: National guidelines versus the real-world experience.

Objective: Previous studies have shown that first-line (1L) maintenance therapy (MT) with poly(ADP-ribose) polymerase inhibitors and/or bevacizumab improves outcomes among patients with advanced ovarian cancer (OC); however, these treatments are underutilized. This study aimed to provide a real-world understanding of MTs among patients with advanced OC who received 1L platinum-based chemotherapy (PBC). Methods: A retrospective chart review using iKnowMed electronic health records to identify patients aged ≥18 years with advanced OC who initiated 1L PBC between January 1, 2018-December 31, 2020. Following 1L PBC, patients could have received MT or active surveillance (AS). Kaplan-Meier methods were used to estimate time to treatment discontinuation (TTD), real-world progression-free survival (rwPFS), and overall survival (OS). Results: Of the 600 chart-reviewed patients included, 239 (39.8 %) received MT and 315 (52.5 %) received AS. Patients who were <65 years of age, or those with higher-stage disease or those who had received neoadjuvant treatment, were more likely to initiate MT than AS. Genetic testing rates were low across both cohorts. Median (95 % confidence interval [CI]) TTD for the MT cohort was 13.6 months (11.0, 21.2). Median (95 % CI) rwPFS was 26.9 months (21.3, not reached) and 11.3 months (9.5, 13.0) for the 1L MT and AS cohorts, respectively (p < 0.0001). OS at 36 months was 82.4 % in the 1L MT cohort and 58.0 % in the 1L AS cohort. Conclusions: This study reinforces clinical trial findings that 1L MT improves outcomes in patients with advanced OC; however, genetic testing rates and 1L MT remained low.

Maintenance therapy for CTCL: importance for prevention of disease progression.

There are no established maintenance protocols for cutaneous lymphomas. We aim to determine patient treatments and outcomes during the COVID-19 pandemic in order to uncover the most effective maintenance protocols for cutaneous lymphomas and impact of treatment interruption. Data was collected retrospectively from nine international institutions, including 149 patients. Younger patients had earlier stages of disease and were most frequently treated with skin-directed therapies including topical steroids, mechlorethamine gel, and phototherapy. Treatment interruption varied by treatment type and stage, with patients on topical therapies and earlier stages of disease being least likely to experience interruption. Treatment interruption was significantly associated with progression of disease and worse outcomes, with twice as many patients progressing who had interruption compared to those without interruption. This study may demonstrate the significance of continuous maintenance therapies, even in younger patients with early stages of disease.