Cure Research Articles

Outcomes of patients registered with the Queensland Trophoblast Centre diagnosed with gestational trophoblastic neoplasia who develop resistance to chemotherapy.

To audit outcomes of patients registered in the Queensland Trophoblast Centre (QTC) database who develop resistance to primary chemotherapy. To determine any risk factors that may predict first-line chemotherapy resistance in patients diagnosed with gestational trophoblastic neoplasia (GTN). Patients within the QTC who were diagnosed with GTN between January 2012 and December 2020 were reviewed. Of 138 patients with GTN registered in the QTC, 22 (15.9%) patients developed resistance to first-line chemotherapy. Three had high-risk GTN and 19 had low-risk GTN. Of the three high-risk patients, one patient died. This patient had an epithelioid trophoblastic tumour (ETT). The remaining two high-risk patients had complete hydatidiform moles (CHM) with GTN. Both achieved complete remission with salvage therapy. Of the 19 low-risk patients, one patient had a partial hydatidiform mole (PHM). This patient achieved remission following third-line treatment. The other 18 low-risk patients had CHM with GTN. All but two of these 18 patients were successfully treated with second-line chemotherapy, with the remaining two patients achieving remission with third-line chemotherapy. Five of the 18 patients received either actinomycin-D or methotrexate as salvage therapy. Thirteen patients were given multi-agent chemotherapy for second-line treatment. One patient in this group died but this was not due to her disease. Initial β human chorionic gonadotropin levels were not predictive of number of chemotherapy cycles or number of lines of chemotherapy required to achieve remission. GTN is a curable condition. If resistance to first-line chemotherapy occurred, most patients achieved remission with salvage therapy.

Efficacy analysis of rituximab in treating patients with primary membranous nephropathy dependent on calcineurin inhibitors

BackgroundThis study evaluated the efficacy of rituximab (RTX) in primary membranous nephropathy (PMN) patients with incomplete remission and drug dependence after long-term use of calmodulin inhibitors (CNIs). It aims for complete clinical and immunological remission, and cessation of CNI dependence.MethodsThirty-six patients were enrolled in the study with two groups: drug-dependent and partial remission or immune non-remission group. Both groups underwent RTX therapy with gradual CNI tapering to end CNI dependency and induce complete remission. The primary outcome was overcoming CNI dependency and achieving complete remission after 12 months of RTX therapy. Secondary outcomes included immunological remission and recurrence rates.ResultsThe drug-dependent group (20 patients) achieved significant proteinuria reduction compared to the partial remission or immune non-remission group (16 patients) (P=0.016). After 12 months of RTX treatment, all drug-dependent patients overcame CNI dependency (average withdrawal period: 5.3 ± 3.7 months), with complete remission rates increased from 10% to 70.0% and complete immunological remission rates rose from 35.0% to 90.0%. In the partial remission or immune non-remission group, 14 patients discontinued CNI (average period: 4.6 ± 4.5 months), with complete remission rates increasing from 5.0% to 68.8% and complete immunological remission rates from 6.3% to 68.8%. During follow-up, serum albumin increased, and anti-PLA2R antibodies, 24-hour proteinuria, and CD19+ cell numbers reduced, while creatinine remained stable. Three patients relapsed, four encountered adverse events, and no malignancies or other fatal adverse events were reported.ConclusionsRTX effectively achieves complete clinical and immunological remission in PMN patients dependent on or partially responsive to long-term CNI therapy, reducing recurrence and minimizing prolonged immunosuppressive therapy risks.

Renal survival and treatment of adult patients with Primary Focal Segmental glomerulosclerosis: A historical cohort study of the National Greek Registry.

Primary Focal and Segmental glomerulosclerosis (FSGS) is one of the most common causes of idiopathic nephrotic syndrome. Our aim was to describe a large cohort of patients with primary FSGS, identify risk factors associated with worse renal survival and assess the impact of different immunosuppressive regiments on renal survival. This was a historical cohort study of adults who were diagnosed with primary FSGS from March 26, 1982, to September 16, 2020. The primary outcome was progression to ESRD. We included 579 patients. The mean age was 46 (±15) years of age, with 378 (65%) males and median 24-hour proteinuria was 3.8 (2-6) g. In multivariable analysis only eGFR (HR: 0.97 per ml/min increase, 95% CIs 0.95-0.98) and remission status (complete remission (HR: 0.03, 95% CIs 0.003-0.22) and partial remission (HR: 0.28, 95% CIs 0.13-0.61) compared to no remission) were associated with renal survival. Among patients who received immunosuppression compared to those that did not, there was a higher percentage of complete remission (121 (41%) vs. 40 (24%), p<0.001), and higher percentage of relapses (135 (64%) vs. 27 (33%), p<0.001). Immunosuppression and its type (glucocorticoids vs. cyclosporine ± glucocorticoids) were not associated with renal survival. In primary FSGS, complete and partial remission were associated with improved renal survival. Further randomized studies are needed to assess the efficacy of different therapeutic agents and guide treatment.

Endoscopic submucosal dissection versus endoscopic mucosal resection for laterally spreading rectal tumours.

Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are the two main techniques used for endoscopic resection of superficial rectal tumours. The aim of this study was to compare the outcomes of ESD and EMR in treating superficial rectal tumours. A retrospective observational study was conducted at two French centres including all patients treated with ESD or EMR for superficial rectal tumours. The primary outcome was the rate of local recurrence at the first follow-up endoscopy after endoscopic resection. Secondary outcomes included the curative resection rate, procedure duration, length of hospital stay, complication rates and the need for additional surgery. A total of 254 patients were included, 159 treated with ESD and 95 treated with EMR. The local recurrence rate at the first follow-up endoscopy was 8.6% and was significantly lower in the ESD group than in the EMR group (4.3% vs. 16.9%; p = 0.005). The rates of en bloc and histologically complete resections were higher in the ESD group (88.1% vs. 42.7% and 85.5% vs. 38.9%, respectively; p < 0.001), while the curative resection rate was 90.6% in the EMR group and 92.5% in the ESD group (p = 0.59). Mostly due to poor histoprognostical criteria, 6.0% of patients underwent additional surgery (6.3% vs. 5.2% in the ESD vs. EMR group, respectively; p = 0.73). ESD demonstrated higher rates of en bloc, R0 resection than EMR, translating into significantly lower rates of local recurrence at the first follow-up endoscopy.

Clinical variables and management of disseminated granuloma annulare- monocentric retrospective analysis of 33cases between 2021 and 2023

Granuloma annulare (GA) is anoninfectious, granulomatous dermatosis that is generally localized and self-limiting. In 15% of cases, the disease disseminates with protracted trajectories. This study aims to characterise the patient population with disseminated GA at aGerman university hospital and to explore treatment modalities. Aretrospective monocentric evaluation was conducted at the University Hospital Regensburg between 2021 and 2023 with descriptive statistical analysis of the patient population and the treatment modalities used. During the specified period, 239 patients with GA were identified, 33of whom had histologically confirmed disseminated GA. Of the patients, 25(76%) were women. Average age was 57.4 ± 14.4 years. Furthermore 17patients (53%) denied symptoms. Common symptoms included dysesthesia, itching and pain. Frequent concomitant diseases were diabetes mellitus, thyroid disease, atopic dermatitis and coronary heart disease. Topical glucocorticoids, systemic glucocorticoids, phototherapy, topical calcineurin inhibitors and dimethyl fumarate were used therapeutically in descending frequency. Only 6patients (18%) showed partial or complete remission. Due to the lack of approved therapies, disseminated GA is treated with inadequately effective regimens. Prospective randomized placebo-controlled trials are needed to investigate the efficacy of novel targeted therapies.

Psychogenic fever and neurodevelopmental disorders among Japanese children

BackgroundPsychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity.MethodsThis study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients’ medical records.ResultsOf the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6–14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7).ConclusionVarious comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment.

Changes in DNA methylation are associated with systemic lupus erythematosus flare remission and clinical subtypes

BackgroundSystemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients.MethodsFifty-nine multi-ethnic SLE patients had clinical visits and DNA methylation profiles at a flare and approximately 3 months later. Methylation was measured using the Illumina EPIC array. We identified sites where methylation change between visits was associated with remission at the follow-up visit using limma package and a time x remission interaction term. Models adjusted for batch, age at diagnosis, time between visits, age at flare, sex, medications, and cell-type proportions. Separately, a paired T-test identified Bonferroni significant methylation sites with ≥ 3% change between visits (n = 546). Methylation changes at these sites were used for unsupervised consensus hierarchical clustering. Associations between clusters and patient features were assessed.ResultsNineteen patients fully remitted at the follow-up visit. For 1,953 CpG sites, methylation changed differently for remitters vs. non-remitters (Bonferroni p < 0.05). Nearly half were within genes regulated by interferon. The largest effect was at cg22873177; on average, remitters had 23% decreased methylation between visits while non-remitters had no change. Three SLE patient clusters were identified using methylation differences agnostic of clinical outcomes. All Cluster 1 subjects (n = 12) experienced complete flare remission, despite similar baseline disease activity scores, medications, and demographics as other clusters. Methylation changes at six CpG sites, including within immune-related CD45 and IFI genes, were particularly distinct for each cluster, suggesting these may be good candidates for stratifying patients in the future.ConclusionsChanges in DNA methylation during active SLE were associated with remission status and identified subgroups of SLE patients with several distinct clinical and biological characteristics. DNA methylation patterns might help inform SLE subtypes, leading to targeted therapies based on relevant underlying biological pathways.

Durable and deep response to CVD chemotherapy in SDHB-mutated metastatic paraganglioma: case report

IntroductionSuccinate dehydrogenase subunit B (SDHB)-mutated paragangliomas (PGLs) are rare neuroendocrine tumors characterized by increased malignancy, readily metastasizing, and poorer prognosis. Here we report a case of SDHB-mutated metastatic PGL, wherein the patient showed significant tumor shrinkage and complete symptom remission following chemotherapy. We aim to contribute additional evidence to the existing knowledge associated with SDHB-mutated PGLs.Case reportA 40-year-old male patient presented with recurrent hypoglycemia and hypertension crisis. Imaging revealed a huge left retroperitoneal tumor and multiple diffuse metastases in lungs. Catecholamine was also elevated, aligning with a diagnosis of metastatic PGL. Pathology also confirmed this diagnosis. Additionally, the immunohistochemistry indicated negative expression of SDHB and gene test showed somatic SDHB mutation. Given the SDHB mutation, cyclophosphamide-vincristine-dacarbazine (CVD) chemotherapy was initiated in critical conditions. Subsequently, a significant tumor shrinkage and complete biochemical response were observed after two treatment cycles. In September 2024, CT scan revealed new pulmonary lesions. The progression-free survival (PFS) with CVD chemotherapy was 24 months.ConclusionThis report reviews the distinct clinical and biochemical characteristics and treatment approaches of SDHB-mutated paragangliomas, emphasizing that the significance of incorporating both genetic testing and immunohistochemical analysis in clinical practice.

Anaemia of inflammation preceding dyspnoea, dry cough and weight loss in primary pulmonary lymphoma

Introduction: There is little information in the literature on the early, sub-clinical stage and laboratory test results in patients with primary mucosa-associated lymphoid tissue (MALT) lymphoma of the lung, a rare disease. Case description: In a 75-year-old man, an open lung biopsy-confirmed diagnosis of primary pulmonary lymphoma was preceded by almost six months of anaemia of inflammatory disease and monocytosis without any pulmonary symptoms. When he developed a dry cough, increasing dyspnoea and marked weight loss, these changes deepened and became associated with reactive thrombocytosis; markedly increased ferritin and C-reactive protein (positive acute-phase reactants), as well as reduced albumin and transferrin (negative acute-phase reactants). Globulins increased, due to an increase in the alpha1, alpha2 and gamma fractions, and mild hyponatraemia developed due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to the intrathoracic disease. All these changes were completely reversible following successful treatment and complete remission. Conclusion: The previously unreported detailed laboratory features of early, sub-clinical and advanced primary pulmonary lymphoma are presented. When a potentially susceptible patient develops an unexplained anaemia of inflammatory disease, primary pulmonary lymphoma should be added to the differential diagnosis.

CPX-351 plus gemtuzumab ozogamicin for relapsed/refractory acute myelogenous leukemia: a University of California Hematologic Malignancies Consortium trial

In this multicenter phase Ib trial, we investigated the combination of CPX-351 and gemtuzumab ozogamicin (GO) in relapsed/refractory acute myeloid leukemia (AML). Cohort A received CPX-351 plus a single dose of GO, while cohort B received two doses of GO. Thirteen participants received investigational treatment. Dose-limiting toxicities (DLTs) occurred in one participant in each cohort, with manageable adverse events. No cases of hepatic sinusoidal obstructive syndrome occurred. Out of 12 evaluable participants, four achieved complete remission (CR), three of whom were negative for measurable residual disease. The median time to recovery of hematopoiesis for responders was 37 days. CPX-351 with GO was feasible with acceptable toxicity and marrow recovery kinetics. Further evaluation in a larger patient cohort is necessary to assess the efficacy of this regimen in relapsed/refractory AML.

Case report: Achieving significant tumor reduction in advanced pancreatic adenocarcinoma

Pancreatic cancer remains a highly malignant and challenging tumor with a dismal 5-year survival rate of only 13%. The majority of patients are diagnosed at advanced stages, where surgical options are limited, and prognosis is poor. Immunotherapy, particularly PD-1 inhibitors, has shown limited success in pancreatic cancer due to its unique tumor immune microenvironment. However, certain genetic profiles, such as BRCA1/2 mutations, high tumor mutational burden (TMB), or microsatellite instability-high (MSI-H), may enhance sensitivity to these therapies. This report presents two cases of advanced pancreatic cancer with BRCA1/2 mutations treated with a combination of chemotherapy and immune checkpoint inhibitors. The first patient, with TMB-H and stable microsatellites, achieved complete remission after conversion therapy and remains disease-free for over two years post-surgery. The second patient, with MSI-H and low TMB, experienced significant tumor regression and improved quality of life with a prolonged progression-free survival, although the patient ultimately declined surgery. These cases suggest that combined chemotherapy and immunotherapy may offer a promising treatment option for select pancreatic cancer patients, particularly those with specific genetic profiles, warranting further investigation into personalized approaches to immunotherapy in this malignancy.

Choice of therapy for HER2-positive metastatic breast cancer in real clinical practice: analysis of physician preferences in Russian Federation

Metastatic breast cancer still remains an incurable disease, requiring lifelong treatment. Introduction of targeted therapy into clinical practice has radically changed treatment approaches of HER2-positive breast cancer, making it possible to significantly increase the life expectancy. The treatment algorithm for HER2-positive metastatic breast cancer appears to be quite clear and is reflected in both international and Russian recommendations. To assess actual clinical practice in the Russian Federation, a survey study “Therapy of Her2-positive breast cancer” was conducted. This publication presents results dedicated to the treatment of metastatic HER2-positive breast cancer. 50 specialists from 43 cities took part in the survey. Only heads of departments or their deputies who were personally involved in determining the treatment for patients were allowed to participate. Expertise of this level allows us to reliably assess the actual clinical practice that has developed in the Russian Federation and determine directions for optimizing therapeutic approaches. Despite ongoing questions about the availability of drugs, doctors primarily focus on the effectiveness of treatment. The main first-line therapy in the Russian Federation is the combination of trastuzumab with pertuzumab. However, experts noted that in conditions of unlimited access to drugs, the number of prescriptions for this regimen in the first line would increase by 13%. Doctors also agree that the use of a subcutaneous form of this combination of drugs would optimize the treatment process. Trastuzumab emtansine remains the standard of second-line therapy and, according to the survey results, almost all patients for whom it is indicated receive this type of therapy. Experts predict more frequent use of trastuzumab emtansine in first-line therapy, given the widespread use of neoadjuvant regimens with pertuzumab. The most significant changes are expected in the third line of therapy with the introduction of the new conjugate – trastuzumab deruxtecan. The survey results demonstrate high awareness and commitment of physicians to modern principles of treatment of HER2-positive mBC.

Treatment of Pediatric Acute Lymphoblastic Leukemia in India as per modified BFM 95 protocol with Minimal Residual Disease monitoring

ABSTRACT Background: Survival outcomes of Pediatric Acute Lymphoblastic Leukemia (ALL) in the developing world have lagged. Here we report improved outcomes of pediatric ALL from India. Methods: We analyzed outcomes of children with ALL treated at our center between 2016 and 2021. They were treated as per the modified BFM 95 protocol with Minimal Residual Disease (MRD) monitoring by flow cytometry (FCM). Results: We diagnosed and managed 68 patients, 57 being Precursor B (Pre B) cell ALL and the rest of T cell ALL. With BFM 95 protocol-based risk stratification, 19/68, 44/68 and 3/68 patients were Standard risk (SR), Medium risk (MR) and High risk (HR), respectively and 2/68 were not stratified due to Induction mortality. With MRD-based risk stratification, 52/68, 11/68 and 2/68 patients fell in the SR, MR and HR category, respectively and 3/68 patients were not classifiable by MRD (2 Induction deaths and 1 refractory disease) and 65/68 patients achieved morphological complete remission (CR) at the end of Induction. Five out of 68 ALL patients underwent allogeneic hematopoietic stem cell transplant (HSCT) in CR1. Ten out of 68 patients had a relapse, 6 of whom are alive and in CR2 till the last follow-up. The mean duration of follow-up was 1150 days (median 1219 days). Treatment-related mortality was 4.4% in our cohort. The Event Free Survival (EFS) of our cohort was 79.4% and Overall Survival (OS) was 88.2% at a median follow-up of 1219 days. Conclusion: Survival outcomes have improved for children with ALL with modifications in BFM 95 protocol and incorporation of MRD assessment.

A Case Report on Prolonged Response with T-DM1 in Recurrent Advanced Breast Cancer Setting

Breast cancer holds the dubious distinction of being the most prevalent malignant tumour among women worldwide. The 5-year survival rate for patients with advanced or metastatic forms of the disease is estimated at a mere 23%, with approximately 20% of cases exhibiting an amplification of the human epidermal growth factor receptor 2 (HER2). HER2 overexpression was linked to a dismal prognosis prior to the advent of targeted HER2 therapies. The introduction of ado-trastuzumab emtansine (T-DM1) has emerged as one of the standard treatment options for HER2-positive breast cancer patients who experience a recurrence or progression of the disease. This case concerns a patient with recurrent metastatic breast cancer who achieved an unusually extended period of time without the disease progressing while on T-DM1 treatment. After experiencing disease progression on multiple treatment lines involving trastuzumab, the patient achieved a nearly complete clinical remission (cCR) with T-DM1 therapy. The availability of cost-effective biosimilars has expanded access to advanced biologic therapies, which were previously limited to a small segment of the population due to the cost barrier.

The spectrum and prognosis of Sjögren's syndrome with membranous nephropathy

Abstract Background This study aims to investigate the spectrum and prognosis of membranous nephropathy (MN) in patients with Sjögren's syndrome (SS). Methods SS patients with biopsy-proven kidney involvement who were diagnosed at our center between April 2007 and February 2024 were retrospectively reviewed and analyzed. Results A total of 290 SS patients with kidney involvement were enrolled. The frequency of MN increased from 16.28% during the 2007–2010 period to 44.05% during the 2021–2024 period. After 2016, MN became the most common renal pathologic type, surpassing tubulointerstitial nephritis. PLA2R antibody or antigen was detected in 74 SS-MN patients, in whom 37 (50%) showed a negative result. Within the PLA2R-negative group, 5 out of 15 showed positivity for EXT1/EXT2 antigen and 1 out of 8 for THSD7A antigen. Sixty-one SS patients with MN were followed up for more than 6 months, and 44 (72.13%) of them achieved renal complete remission (CR). Compared with PLA2R-negative patients, PLA2R-positive patients spent a longer time to achieve CR [1.46 ± 1.16 vs. 0.74 ± 0.47 years, P = 0.015] and had a higher rate of progression to the renal endpoint (8/32 vs. 1/29, P = 0.028). After adjusting for age, proteinuria and eGFR, Cox regression analysis showed that PLA2R positivity remained a risk factor for CR (HR = 0.511, 95% CI [0.262 to 0.998], P = 0.049). Conclusions MN has become the predominant renal pathologic type in SS. PLA2R-positivity testing followed by EXT1/EXT2 and THSD7A testing is recommended for SS-MN patients. Although most patients can achieve renal CR, the prognosis is usually poor in PLA2R-positive SS-MN patients.

Спорадическая медуллярная карцинома щитовидной железы в детском возрасте: клиническое наблюдение

Medullary thyroid carcinoma (MTC) is one of the rarest tumors of the neuroendocrine system occurring in childhood. MTC represents approximately 4% to 8% of all thyroid malignancies in children with an incidence of 0.03 per 100,000 pediatric population per annum. As a rule, MCT in childhood is presented as part of hereditary syndromes (MEN2A, MEN2B) whereas the prevalence of the sporadic form has not been sufficiently studied as well as its molecular and genetic features. Authors represent the Russia’s first clinical case of sporadic MTC in a 16 years old child. The girl at the age of 14 y/o was examined by an endocrinologist at the place of residence due to the absence of menarche. According to the results of a comprehensive examination, a mass measuring of up to 27 mm was detected in the left lobe of the thyroid gland. Cytological examination revealed a picture suspicious for C-cell carcinoma. The basal calcitonin level was 2160 pg/ml (with 0 to 4.8 pg/ml as a norm). The patient had then underwent thyroidectomy with central lymphadenectomy as a result of histological and immunohistochemical studies of medullary thyroid carcinoma pT2N0 MxLV0Pn0. According to the results of molecular genetic study of peripheral blood, neither germinal pathogenic nor opportunistic mutations in RET gene were detected. Full-exome sequencing of DNA isolated from tumour tissue revealed as pathogenic/conditional pathogenic mutations RET p.M918T, CHEK2 p. R29X, VRK1 p.H119R and ARSE p. G422R. After 3.5 years of follow-up, the patient had a complete structural and biochemical remission of the disease.

Neurologic Outcomes in People With Multiple Sclerosis Treated With Immune Checkpoint Inhibitors for Oncologic Indications.

Immune checkpoint inhibitors (ICIs) are increasingly used against various cancers but are associated with immune-related adverse events (irAEs). Risk of irAEs may be higher in patients with certain preexisting autoimmune diseases, and these patients may also experience exacerbation of the underlying autoimmune disease following ICI initiation. People with multiple sclerosis (MS) have mostly been excluded from clinical trials of ICIs, so data on the safety of ICIs in MS are limited. This study aims to assess the rate of MS activity, as well as neurologic and nonneurologic irAEs in persons with MS treated with ICIs for cancer. Participating sites were invited to this retrospective observational study through the Medical Partnership 4 MS+ listserv. Seven large academic centers participated in the study, each conducting a systematic search of their electronic medical record system for patients with MS and history of ICI treatment. The participating neurologist reviewed each chart individually to ensure the inclusion criteria were met. Demographics and data on MS and cancer history, treatments, and outcomes were abstracted from patient charts using a structured instrument. We identified 66 people with MS (median age 66 years, 73% female, 68% not on disease-modifying therapy for MS) who were treated with ICIs for lung cancer (35%), melanoma (21%), or another oncologic indication. During post-ICI follow-up (median: 11.7 months, range 0.2-106.3 months), 2 patients (3%) had relapse or MRI activity, 3 (5%) had neurologic irAEs, and 21 (32%) had nonneurologic irAEs. At the last follow-up, 25 (38%) participants had partial or complete remission of their cancer, while 35 (53%) were deceased. In this multi-institutional systematic retrospective study of predominantly older patients with MS, most of whom were not on disease-modifying therapy, MS activity and neurologic irAEs following ICI treatment were rare. These data suggest that preexisting MS should not preclude the use of ICIs for cancer in older patients, but the results may not be generalizable to younger patients with active MS. Prospective studies of ICI safety that enroll younger patients with MS are needed.

Treatment of Pediatric, Adolescent, and Young Adult Patients With Fusion-Positive Alveolar Rhabdomyosarcoma Infiltrating Regional Lymph Nodes in the European CWS-2002P and RMS 2005 Studies and the Soft Tissue Sarcoma Registry.

Patients with alveolar rhabdomyosarcoma (ARMS) with regional lymph node involvement (N1) are defined as "very-high-risk rhabdomyosarcoma" in Europe. Different chemotherapy regimens were used in European study protocols. Patients with FOXO1 fusion-positive N1 ARMS registered in the CWS-2002P study, the EpSSG RMS 2005 study, and SoTiSaR were retrospectively investigated. Patients received systemic treatment with chemotherapy (CHT) and local treatment of primary tumor (PT) and involved lymph nodes (LN) with radiotherapy (RT) and/or surgery. Kaplan-Meier estimators and Cox regression were used to examine event-free survival (EFS) and overall survival (OS) according to prognostic factors and treatment. A total of 156 patients registered in RMS 2005 (n = 99), CWS-2002P (n = 20), and SoTiSaR (n = 37) between 2003 and 2020 were eligible for this analysis. Median age at diagnosis was 10.2years [0.1-21.9]. Treatment comprised CHT with IVADo (ifosfamide, vincristine, actinomycin-D, doxorubicin, n = 93; 60%), VAIA (vincristine, actinomycin-D, ifosfamide, adriamycin/doxorubicin, n = 53; 34%) or other regimens (n = 10; 6%); resection of the PT (n = 89; 57%), LN sampling or dissection (n = 92; 59%), and/or RT (n = 139; 89%). Maintenance treatment (MT) was added in n = 99/135 (73%) patients who achieved complete remission. Five-year EFS and OS of the cohort were 45% and 47%, respectively. Age and tumor size were independent prognostic factors for EFS. Local treatment applied to the LN with surgery, RT or both significantly improved EFS (p = 0.02) and OS (p = 0.04), with no difference between the modalities (p = 0.7). Patients with fusion-positive N1 ARMS carry a poor prognosis. Adequate local treatment of LN improved survival.

DL-ICE as a bridge to allogeneic transplantation in relapsed/refractory PTCL: survival outcomes and prognostic factors

IntroductionPeripheral T-cell lymphomas (PTCLs) have poor outcomes in the relapsed/refractory (R/R) setting. In this study, we evaluated the efficacy of dexamethasone, L-asparaginase, ifosfamide, carboplatin, and etoposide (DL-ICE) chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with R/R PTCLs.MethodsWe retrospectively analyzed 80 adult patients with R/R PTCLs treated with DL-ICE chemotherapy between September 2009 and March 2023. Patients achieving complete or partial remission were eligible for consolidative allo-HSCT. Overall survival (OS) and progression-free survival (PFS) were evaluated.ResultsThe overall response rate to DL-ICE was 37.5%, with 30% achieving complete remission (CR). With a median follow-up of 96.4 months, the median OS and PFS were 8.9 and 3.8 months, respectively. Seventeen patients (21%) underwent allo-HSCT, including 11 with non-CR status. The 5-year OS was significantly higher in the allo-HSCT group compared to that in the group with chemotherapy alone (64.7% vs 18.3%, p &amp;lt;0.001). Multivariate analysis identified advanced stage, EBV viremia, and non-CR status as poor prognostic factors.DiscussionDL-ICE chemotherapy demonstrated modest activity in R/R PTCLs. Consolidation with allo-HSCT, even in patients who do not achieve CR, resulted in long-term survival in a subset of patients. Early consideration of allo-HSCT may improve outcomes for patients with R/R PTCLs.

Efficacy and Safety of Venetoclax Plus Azacitidine for Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes.

Patients with higher-risk myelodysplastic syndromes (HR MDS) have a median survival of ~1.5 years with azacitidine, and hematopoietic stem cell transplantation is their only curative option. Therefore, improved therapies are needed. This phase 1b study investigated safety and efficacy of venetoclax, a selective BCL-2 inhibitor, at the recommended phase 2 dose (RP2D: 400 mg for 14 days/28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days/28-day cycle) for treatment-naive HR MDS (NCT02942290). Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). As of May 2023, 107 patients received venetoclax and azacitidine combination at the RP2D. Best response of CR or marrow CR was observed in 29.9% and 50.5% of patients (mOR, 80.4%). Median OS was 26.0 months, with 1-year and 2-year survival estimates of 71.2% and 51.3%, respectively. Of 59 patients who were red blood cell and/or platelet transfusion-dependent at baseline, 24 (40.7%) became transfusion-independent on study, including 11 (18.6%) who also achieved CR. Fifty-one (49.0%) of 104 evaluable patients achieved HI. Median TTNT excluding transplantation was 13.4 months. Adverse events reflected known safety profiles for venetoclax and azacitidine, including constipation (53.3%), nausea (49.5%), neutropenia (48.6%), thrombocytopenia (44.9%), febrile neutropenia (42.1%), and diarrhea (41.1%). Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes. A phase 3 study (NCT04401748) is ongoing to confirm survival benefit of this combination.