Duration Of Remission Research Articles

Single-cell sequencing reveals the mechanisms of multiple myeloma progression: clarity or confusion?

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of myeloma cells and accumulation of genetic lesions. MM progression is accompanied by increased aggressiveness and drug resistance. Even the goal of "cure" remains hard to reach for most patients, advances in diagnosis and treatment have allowed some to achieve durable remissions and transition to plateau phase. Single-cell sequencing, with its powerful ability to analyze cellular heterogeneity and molecular patterns at ground-breaking resolution, is informative for deciphering tumors and their microenvironment. In this review, we summarize the new insights of studies facilitated by emerging single-cell sequencing into clonal evolution, myeloma-supported microenvironment transformation, epigenetic changes, and novel prognostic and therapeutic strategies for MM, revealing the key mechanisms underlying MM progression and the direction of future efforts. With the continuous expansion of the research scope and optimization of related technologies, single-cell sequencing is expected to revolutionize our understanding of the biology and evolutionary dynamics of MM and contribute to the radical and precise improvement of treatment.

Efficacy and safety of risankizumab for the treatment of patients with plaque type psoriasis.

Risankizumab (Skyrizi®, Abbvie, North Chicago, IL, USA) is a humanized immunoglobulin (Ig) G1 monoclonal antibody targeting the p19 subunit of IL-23, thereby inhibiting IL-23-dependent releasing of proinflammatory cytokines in plaque psoriasis. Risankizumab is licensed is most countries for the treatment of patients with moderate-to-severe plaque psoriasis, and in Japan for generalized pustular psoriasis, erythrodermic psoriasis and palmoplantar pustulosis. Risankizumab showed higher efficacy and favorable safety profiles in patients with moderate-to-severe plaque psoriasis, compared with adalimumab, secukinumab and ustekinumab in several randomized controlled phase 3 pivotal studies and among real-life data in large retrospective studies. Furthermore, its high efficacy even in patients with prior biologic failure, better drug survival, less need for biologic switch and longer drug-free remission durations have also been shown in real-life settings and in long-term follow up. In addition, reports of both reduced dosing and increased (bolus) dosing exist which increase our ability to use risankizumab more flexibly in an era of personalized medicine. Also, the use of risankizumab in several special population, such as elderly, Asian people, erythrodermic psoriasis, patients with high induction doses, pregnancy and human immunodeficiency virus group are discussed.

Evaluation of the Effects of systemic Therapy on Inflammatory Markers and Disease Severity in Patients With Pemphigus

Introduction: In recent years, various inflammatory markers that can change in inflammatory states have been investigated. On the basis of these, we thought that inflammatory markers could also be used in the treatment of pemphigus disease and monitoring its activity. Objective: In this study, our objective was to investigate changes in the inflammatory markers NLR, PLR, MPV, LMR, CRP and ESR, which are inflammatory markers, before treatment and during follow-up, and the correlation of disease severity with these markers in patients with pemphigus receiving IVIG and/or systemic immunosuppressant agents. Method: 76 pemphigus patients who received systemic treatment, and used these treatments for at least 6 months were included. Changes in NLR, PLR, LMR, MPV, CRP and sedimentation values were examined in patients who received systemic treatment for at least 6 months, before the start of treatment and 3 and 6 months after the start of treatment. Results: Significant changes in inflammatory markers and correlation values were found in all patients. Conclusions: We think that neutrophil, platelet, NLR and PLR values can be used to monitor the response to treatment in pemphigus, since they show a significant decrease with treatment and are significantly positively correlated with PDAI, which indicates the severity of the disease. LMR values were indicators of a poor prognosis. We found that the duration of remission was longer in the group receiving IVIg. Although there was no difference between the treatments in terms of disease recovery, only IVIg prolonged the duration of remission.

Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.

Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells. The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers. Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved. Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen. Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs.

Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study)

BackgroundEven though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2–3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma. However, prospective randomized trials including allogeneic stem cell transplantation as second-line therapy do not exist to date and therefore urgently needed to demonstrate the value of this therapy in the overall setting of patients with multiple myeloma.MethodsThis clinical trial is a national, multicenter, randomized, open labeled phase III study conducted in 30 hospitals spread all over Germany. After study inclusion, all patients will receive 3 cycles of salvage therapy with one of the currently approved triplet regimens for first relapse. After 3 cycles of salvage therapy, remission status will be assessed. If the patient achieves at least stable disease, partial or complete remission and an HLA compatible stem cell donor could be identified, he/she will be randomized (1:1) to the control or interventional study arm. Approximately 400 patients will be enrolled to enable a randomization of 280 patients. The primary endpoint is overall survival at five years after randomization. The main secondary objectives and endpoints are progression-free survival rate, time-to first occurrence of an infection with CTCAE grade 3–5, non-relapse mortality rate and incidence of acute and chronic graft-versus-host disease after allogeneic stem cell transplantation.DiscussionThe present clinical study is designed to evaluate the superiority of allogeneic stem cell transplantation compared to conventional therapy (triplet chemotherapy) for the difference in overall survival at 5 years, toxicity and quality of life in patients with multiple myeloma who have relapsed or progressed after first-line autologous stem cell therapy.Trial registrationClinicalTrials.gov (NCT05675319) registered on January 9, 2023.

Abstract IA02: Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy

Abstract The advent of the current cancer immunotherapy era based on the success of immune checkpoint blockade (ICB) inhibiting programmed death-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) has revolutionized the standard of care for cancer treatment. However, the limited response rates to ICB across multiple cancer types suggest that new approaches and treatment strategies are needed in order to achieve durable cancer remission. This includes re-examining the possibility that standard of care treatments, including surgery and chemo-radiation, may compromise the tumor response when delivered in concert with ICB. In particular, many cancer types, including head and neck squamous cell carcinoma (HNSCC), have a propensity to metastasize to locoregional lymph nodes, and standard oncologic management often involves elective ablation of tumor draining lymph nodes (tdLN). In a recent study, we have used tobacco-signature HSNCC syngeneic mouse models and showed that tdLN ablation by surgery or radiation therapy limits the tumor ICB response, thereby worsening overall survival and repolarizing the tumor- and peripheral-immune compartments. Mechanistically, we provided evidence that cDC1 dendritic cells in the tumor lesions and tdLN are required for an effective anti-tumor immune response. Recently, we have cross-integrated large single-cell RNA-sequencing datasets from intratumoral immune cells and identified a novel mechanism by which antigen-specific CD8+ T cells promote intratumoral cDC1 accumulation and T cell persistence, leading to improved overall survival. As a multipronged approach, we have also built on this computational pipeline to identify druggable oncogenic signaling networks that override cancer immune surveillance. Evidence will be presented that disruption of specific HNSCC driving signaling axes is sufficient to sculp the tumor immune microenvironment and disable their immune evasive mechanisms, thereby providing opportunities for the development of new precision therapies increasing the response ICB. The emerging information also provided a rationale for investigating the use of a new generation of radiation-sensitizing antibody drug conjugates targeting cancer-specific oncosignaling drivers, in combination with radiotherapy and ICB in the neoadjuvant setting, when tdLN are still intact. Ultimately, evidence will be presented supporting the future evaluation of spatially precise radiosensitizing antibody drug conjugate-directed chemo-radio-immunotherapy for precision cancer care in HNSCC and other malignancies. Citation Format: J. Silvio Gutkind. Preserving tumor-draining lymph nodes in the era of immuno-oncology: Opportunities for precision chemo-radio-immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA02

Phase I study of CD19 CAR T-cell therapy harboring a fully human scFv in CAR-naïve adult B-ALL patients.

CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971). Twenty-three patients received lymphodepletion chemotherapy and JCAR021 infusion. Nineteen patients developed CRS (any grade, 83%; grade 2, 61%) and 12 developed neurotoxicity (52%; grade ≥3, 35%). The overall response and CR/CRi rates were 82% and 64%, respectively. We observed MRD-negative marrow responses in 82% of those with marrow disease and extramedullary responses by PET-CT in 79% (CR, 50%) of those with measurable FDG-avid disease. The median duration of remission (DOR) was 10 months with a 4-year DOR probability of 29%. Four patients underwent allo-HCT while in CR/CRi after JCAR021. Durable remissions were observed in patients with low marrow disease burden. In contrast, the DOR was limited in those with high marrow burden, highlighting a remaining critical need to identify new strategies to prolong remissions. We observed similar outcomes in CAR-naïve adult B-ALL patients receiving CD19 CAR T-cells expressing a fully human or murine scFv-containing CAR.

Olutasidenib in combination with azacitidine induces durable complete remissions in patients with relapsed or refractory mIDH1 acute myeloid leukemia: a multicohort open-label phase 1/2 trial

BackgroundOlutasidenib is a potent, selective, oral, small molecule inhibitor of mutant IDH1 (mIDH1) which induced durable remissions in high-risk, relapsed/refractory (R/R) mIDH1 AML patients in a phase 1/2 trial. We present a pooled analysis from multiple cohorts of the phase 1/2 trial of patients with R/R AML who received combination olutasidenib and azacitidine therapy.MethodsAdult patients with mIDH1R132 AML received 150 mg olutasidenib twice daily plus standard-of-care azacitidine (OLU + AZA) and were evaluated for response and safety.ResultsSixty-seven patients with R/R mIDH1R132 AML received combination OLU + AZA. Median age was 66 years (range 28–82) and 54% were male. Most patients (83%) had 2 + prior regimens, including a hypomethylating agent in 40%, IDH1 inhibitor therapy in 31% (olutasidenib in 24%), and hematopoietic stem cell transplant in 10%. Cytogenetic risk was intermediate in 72%, poor in 18% and unknown in 10%. CR/CRh was achieved in 21/67 (31%; 95% CI 21–44) patients, with a median duration of 14.7 months (95% CI 4.6-not reached). CR was achieved in 18/67 (27%; 95% CI 17–39) patients, with median duration of 20.3 months (95% CI 3.7-not reached). Overall response (partial remission or better) was achieved in 34/67 (51%; 95% CI 38–63) patients. Median overall survival was 12.9 months (95% CI 18.7–19.3). In a subset analysis excluding patients who had prior OLU exposure (N = 51), CR/CRh was achieved in 19/51 (37%; 95% CI 24–52) patients, CR was achieved in 16/51 (31%; 95% CI 19–46), and overall response was achieved in 30/51 (59%; 95% CI 44–72). In patients who achieved CR/CRh and were transfusion-dependent at baseline, transfusion independence (RBC and platelets) was achieved in 64% (7/11) and 57% (4/7) of patients, respectively. The most common Grade 3 or 4 adverse events (> 20% patients) were decreased platelet count (37%), red blood cell count (25%), and neutrophil count (24%). Six patients (9%) experienced differentiation syndrome. Four (6%) discontinued treatment due to an adverse event.ConclusionsOlutasidenib plus azacitidine induced high response rates and durable remissions with a tolerable side effect profile in patients with R/R AML with diverse treatment histories. The results represent another therapeutic option for patients with mIDH1 AML who may benefit from a targeted therapy.Trial registrationNCT02719574.

Inferior Outcomes of Fludarabine-Cyclophosphamide-Rituximab Chemotherapy in Korean Chronic Lymphocytic Leukemia Patients with Concurrent Thrombocytopenia and Anemia.

Background/Objectives: Anti-CD20 monoclonal antibodies combined with alkylator-based chemotherapy enhance survival in chronic lymphocytic leukemia (CLL). However, the risks of infection and bone marrow suppression may mean that new, targeted therapies are more appropriate for some patients than fludarabine-cyclophosphamide-rituximab (FCR). In the Republic of Korea, where insurance limits coverage to novel agents, FCR therapy should be carefully considered for patients with CLL. Methods: Using clinical data from 144 FCR-treated patients with CLL, we retrospectively analyzed clinical characteristics impacting survival outcomes, the impact of cytopenia after FCR, and the durable remission status in terms of measurable residual disease (MRD). We compared the impact of bicytopenia with those of other hematologic conditions. Results: The 5-year overall survival (OS) and 5-year progression-free survival (PFS) for all patients were 84.4% and 68.3%, respectively. FCR-treated patients in the bicytopenia and TP53-positive groups exhibited poor OS and PFS; in particular, the bicytopenia group often experienced prolonged anemia and thrombocytopenia (6-12 months). The responder group achieved sustained remission for a median of 5 years for MRD negativity. Conclusions: In bicytopenia, FCR can induce prolonged cytopenia, making it difficult to switch to second-line therapy or complete cycles of chemoimmunotherapy, directly affecting poor survival outcomes. The cautious application of FCR therapy in CLL without bicytopenia or TP53 positivity can achieve long-term remission.

Guselkumab: A New Therapeutic Option for the Treatment of Moderately to Severely Active Ulcerative Colitis.

To summarize the evidence and pharmacologic profile of guselkumab for moderate to severe ulcerative colitis (UC). A PubMed search from inception to end of October 2024 using keywords guselkumab, UC, and interleukin (IL) was conducted. Additional information was obtained from abstracts and package insert. Phase 2/3 studies plus applicable literature on guselkumab pharmacologic and clinical profile were included. Approval was based on the QUASAR program, a multicenter, randomized, double-blind, placebo-controlled, phase 2b/3 trial assessing guselkumab's efficacy and safety in adults with moderately to severely active UC who had inadequate response or intolerance to conventional therapies, biologics (excluding IL antagonists), or Janus Kinase inhibitors. Results indicated that guselkumab led to higher clinical remission rates at week 12 and 44 compared to placebo, along with improvements in clinical response, symptomatic remission, endoscopic improvement, and histologic normalization. Common adverse effects included respiratory tract infections, injection site reactions, and arthralgia. Guselkumab is the fourth IL antagonist approved for UC, and the first to target CD64 (cells involved in IL-23 production). With its dual mechanism, guselkumab is hypothesized to neutralize IL-23 at production and reduce inflammatory response. The QUASAR findings suggest guselkumab can provide durable clinical remission and histologic normalization, addressing a significant gap in UC treatment. As the latest addition to UC therapies, guselkumab presents improved efficacy and dosing flexibility without introducing any new safety concerns compared to existing agents.

Eltrombopag for the treatment of refractory connective tissue disease-related thrombocytopenia: a pilot study of 52 cases

BackgroundThe objective of this study was to investigate the therapeutic effectiveness and safety profile of Eltrombopag, a thrombopoietin receptor agonist, as prolonged therapy in refractory CTD-ITP patients.MethodsWe conducted a pilot observational study of Eltrombopag in CTD-ITP patients who were unresponsive to or intolerant of conventional medications. Eltrombopag was administered orally at 25–75 mg/qd and adjusted on the basis of tolerance and efficacy until a minimum dosage of 25 mg/qd was reached. Clinical and laboratory data were collected and analysed monthly. The therapeutic response, relapse, and adverse events during the follow-up were also reviewed and evaluated.ResultsFifty-two patients were enrolled and followed monthly for a median of 6 months. Thirty-six (90%) patients achieved durable overall remission. The remission rates were 67.5% at month 1, 87.5% at month 2, 97.5% at month 3, and 95% at month 6. The platelet count of the patients improved significantly, with the median reaching 50 × 109/L within 2 weeks (p = 0.003). Disease activity indices were reduced in SLE and pSS patients (p = 0.016), allowing glucocorticoid tapering (p = 0.004). One patient had no response, four relapsed, and fifteen (28.8%) experienced clinically relevant adverse events. In the analyses, protopathy, comorbidity, and prior treatment were associated with efficacy.ConclusionsFor refractory CTD-ITP patients, Eltrombopag demonstrated significant clinical improvement, safety, and a steroid-sparing effect with prolonged use. Patient characteristics at baseline may affect treatment efficacy.

Durable remission after ileocolic resection for Crohn's disease is achievable in selected patients. Long-term results of a prospective multicentric cohort study of the GETAID Chirurgie.

Postoperative recurrence requiring medical treatment intensification or redo-surgery is common after ileocolic resection (ICR) for Crohn's disease (CD). This study aimed to identify a subgroup of CD patients for whom ICR could achieve durable remission. This retrospective follow-up study analyzed 592 CD patients who underwent ICR (2013-2015) in a nationwide prospective cohort. Patients with >36 months follow-up were included. Primary outcome was durable remission, defined as the absence of endoscopic recurrence and/or medical treatment intensification. Uni- and multivariate analyses identified predictive factors for durable remission. Among 268 included patients, 59% had B2 phenotype, 70% had a first ICR and 66% had postoperative medical treatment. After a median follow-up of 85(36-104) months, 52 patients (19%) experienced durable remission, of whom 24 (46%) didn't require medical treatment and 28 (54%) maintained the same postoperative treatment, including anti-TNF in 15/28 patients (54%). Surgery could stabilize the disease course in 112 patients (41.7%), including 22.4% endoscopic recurrence that didn't require CD treatment initiation or intensification. Durable remission rate was significantly increased in B1 phenotype vs. B2/B3 (n=7/18;39% vs n=45/250;18%, p=0.030) and in first ICR vs. redo ICR (n=43/184;23% vs n=9/80;11%, p=0.023). In multivariate analysis, B1 phenotype was the only independent predictive factor for durable remission (OR=3.59, IC95%[1.13-11.37], p=0.030). Surgery for CD achieved durable remission in 20%, rising to 40% in those with a B1 phenotype. These results support surgery as a viable alternative to medical treatment, offering treatment-free durable remission and preserving medical treatment options.

Long-Term and Sustained Remission of Advanced Triple-Negative Breast Cancer with Large Chest Wall Lesions after Transient Chemoimmunotherapy: A Case Report

Introduction: We report a case of advanced triple-negative breast cancer (TNBC) with special clinical manifestations, in which a durable remission was achieved after short-term administration of toripalimab combined with chemotherapy. The progress, advantages, and unique experience of chemoimmunotherapy in TNBC were examined. Case Presentation: A patient with TNBC with local recurrence 2 years following surgery, with inoperable large chest wall lesions and positive PD-L1 as the main manifestations, was treated with toripalimab plus paclitaxel (albumin-bound) for 5 months and achieved a partial remission. Twenty-five months after the discontinuation of treatment, the chest wall lesions exhibited a slow but continuous decline, until they achieved a nearly complete remission; however, the patient eventually died from cancer progression. Conclusion: Typically, chest wall recurrence in TNBC has a poor prognosis; however, recurrence was rapidly controlled, sustained remission was achieved after immunotherapy combined with chemotherapy, and the curative effect continued after drug withdrawal, which is a rare occurrence. Thus, the tailing effect of immune checkpoint inhibitors was confirmed in the treatment of TNBC.

In Reply: Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter Rapid Registry.

In Reply: Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter Rapid Registry.

Letter: Predictors of Durable Remission Following Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

Letter: Predictors of Durable Remission Following Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

Integrating different perspectives to define a concept of comprehensive remission in rheumatoid arthritis: The SUMAR project.

The SUMAR project aimed to establish a consensus on the concept of remission in patients with rheumatoid arthritis (RA) that takes into account the different perspectives of patients, health care professionals and health care managers. The scientific committee comprised a rheumatologist who acted as a national coordinator, 4 rheumatologists, 1 primary care physician, 1 nurse, 2 hospital pharmacists, 2 health care managers and 1 member of a patient advocacy group. The study was undertaken from 2020 to 2021 in three phases: (1) analysis of several perspectives on remission in RA with the participation of 275 patients, 160 rheumatologists and 31 health care managers; (2) an integrative definition of remission, which included two multidisciplinary workshops with 11 and 12 participants; and (3) extension and dissemination with up to 200 participants in 7 regional multidisciplinary meetings. The concept of remission in the different settings and by the different stakeholders was heterogeneous. It was agreed that, in addition to inflammatory activity, remission should include pain and functionality as well as the duration of remission. For the participants, the definition of remission varied depending on the clinical scenario, without or with structural damage, seeking to "normalize" the outcomes in the former and avoid progression in the latter. The implementation of the concept of comprehensive remission was considered less feasible, and the main barriers to implementation were the lack of time for consultation and the variability in information technology systems across the different autonomous communities. This definition of remission is not only based on the concept of the presence or absence of inflammatory activity based on existing indexes, but also includes variables directly reported by the patient that are related to their health and quality of life.

Predicting response to PD-1 Inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers

Immune checkpoint inhibitor (ICI) treatment has the potential to induce durable disease remission. However, the current combined positive score (CPS) is insufficient accurate for predicting which patients will benefit from it. In the present study, a real-world retrospective study was conducted on 56 patients of HNSCC who received ICI treatment. Then the treatment that patient received and levels of pre-treatment blood inflammatory markers (NLR, MLR and PLR) were identified to develop a model for predicting immunotherapy response. Notably, the model achieved an area under the curve (AUC) of 0.877 (95% CI 0.769-0.985) , providing a larger net benefit than the CPS marker (AUC=0.614, 95% CI 0.466-0.762). Furthermore, the internal validation of the prediction model showed a C-index of 0.835. Patients with high score of the model would get improved PFS than those with low score. Therefore, the prediction model for patients with local advanced or R/M HNSCC receiving ICI treatment, which represented an better efficient prediction of immunotherapy response than CPS marker.

Stimulation of future thinking in stimulant–depending patients using questionnaire–based structured interview

INTRODUCTION: Impaired future thinking (FT) a human ability to imagine and comprehend images and scenarios of the personal future may contribute to the severity of psychoactive substance dependence. Spontaneous mental images of the impacts of using psychoactive substances and/or of one’s own death (‘flash-forwards’), as well as impaired arbitrary modeling of future images (for example, overgeneralization and lack of reflection) interfere with adherence to treatment and stability of remission in addictions. AIM: To evaluate the influence of FT-activating intervention on treatment outcomes in patients with narcotic psychostimulant dependence. MATERIALS AND METHODS: A randomized prospective controlled clinical trial conducted in 2021–2023 involved 112 inpatients with stimulant dependence (F15.2). Of them, the main group consisted of 56 patients (age 24.0 [21.0; 27.0] years; 30.4% of men), who underwent FT stimulation in the form of semi-structured interview based on the Russian pilot version of the Impact of Future Events Scale (IFES). The control group consisted of 56 patients (age 23.5 [22.0; 26.0] years; 39.3% of men) who received a standard drug addiction conversation of equal duration. The treatment result parameters included the score on the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES); duration of remission, participation in long-term therapy, in outpatient rehabilitation, inpatient rehabilitation, confirmation of the fact of prescheduled discharge, infringement of regime, incarcerations. The test was conducted upon admission and after discharge. Hospitals stay period — 21 days, follow-up period — 6 months. RESULTS: At the hospitalization stage, the groups did not differ in socio-demographic and main clinical parameters (p 0.05). SOCRATES scores were higher in the control group 49.0 [47.0; 49.0] versus 48.0 [47.0; 49.0] (p = 0.040). At the stage of re-test before discharge, the main group showed an improvement in motivation according to SOCRATES and significantly outperformed the control group: 67.0 [65.3; 68.0] versus 50.0 [48.0; 53.8] points (p 0.001). The main group had a longer duration of remission — 3.3 [0.5; 5.4] months versus 0.5 [0.4; 1.0] months (p = 0.001); fewer prescheduled discharges — 12.5% versus 50.0% (p = 0.001); more frequent visits to long-term therapy — 30.4% versus 8.9% (p = 0.01) and outpatient rehabilitation — 21.4% versus 1.8% (p = 0.001) respectively. CONCLUSIONS: FT-activating intervention directed to stimulating reflection of anxious and positive aspects of the personal future, contributes to increase in duration of remission in the catamnesis, increases motivation and adherence to treatment in patients with addiction to narcotic psychostimulants.

PREDICTORS OF RHEUMATOID ARTHRITIS FLARE AFTER GLUCOCORTICOIDS WITHDRAWAL WHILE RECEIVING CONVENTIONAL SYNTHETIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS

Summary: Predictors of rheumatoid arthritis (RA) flare after glucocorticoid (GC) withdrawal while receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The aim of this study is to investigate predictors of RA flare following GC withdrawal despite the continuation of csDMARDs in the Ukrainian cohort of patients with different disease durations. Materials and methods: One hundred twenty-six patients with early (56.3%) and advanced (43.7%) RA who newly started GC as bridging therapy with concomitant csDMARDs were included in the study. Most were female – 107 (84.9%), seropositive (RF: 60.3%; ACCP: 60.9%), with a mean age of 51.0±11.4 and disease duration of 42.1±57.6 months. Results: During the 3-year study, 89 patients managed to quit GC without further disease aggravation over a period of 3 to 30 months. Exacerbation of RA was observed in 29.4% of patients. Patients with RA flare had 1.7 times longer duration of GC exposure (ꭓ 2 =4.17, p < 0.05), a shorter duration of remission (ꭓ 2 =10.9, р < 0,01), higher disease activity after 12 months of therapy (р < 0,01), a cumulative GC dose (p < 0.001) and a higher proportion of dissatisfied control of RA (ꭓ2=45,5, р < 0,001) compared to the alternative group. In multivariate and ROC analysis, a higher cumulative GC dose (OR 17.4[2.62-116.4]; regression criterion >1.37), RA activity after 12 months (OR 4.06 [1.36-12.0]; regression criterion > 4.37) and dissatisfied control of RA activity were independently associated with the risk of RA flare after GC discontinuation. Conclusions: The flare following GC withdrawal is observed in one-third of patients with RA undergoing csDMARD therapy. Indicators of dynamic monitoring, rather than baseline data, affect the risk of RA exacerbation. Independent predictors of increased RA activity after GC withdrawal are a higher cumulative GC dose, dissatisfied control of RA activity and a higher DAS28 (ESR) after 12 months of treatment.

Comparison of HiDAC Versus FLAG-IDA in the Treatment of Relapsed Acute Myeloid Leukemia and High-Risk Myelodysplastic Syndrome.

Relapsed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (HR-MDS) are associated with a poor prognosis. It is unknown which re-induction therapy provides the highest chance of durable remission. Commonly used therapies are high dose cytarabine (HiDAC) and triple therapy consisting of fludarabine, cytarabine, and idarubicin combined with granulocyte colony-stimulating factor (FLAG-IDA). Two patient cohorts with relapsed AML or HR-MDS treated with HiDAC or FLAG-IDA between October 2015 and December 2021 in two academic hospitals in the Netherlands were retrospectively analyzed. Patients were treated with either HiDAC (n=22) or FLAG-IDA (n=25). Rates of CR (71% vs. 74%, P=0.85), 1-year OS (47% vs. 51%, P=0.99) and EFS (38% vs. 35%, P=0.71) were comparable between HiDAC and FLAG-IDA. Durations of neutropenia (median 24 days (IQR 20-26) vs. 30 days (IQR 22-39), P=0.014) and thrombocytopenia (22 days (IQR 17-26) vs. 36 days (IQR 26-53)) were significantly shorter in the HiDAC group than in the FLAG-IDA group. While remission rates and survival outcomes were similar, FLAG-IDA was associated with longer periods of myelosuppression and transfusion dependency compared to HiDAC in these two cohorts. HiDAC can be considered as a salvage chemotherapyfor relapsed AML/HR-MDS based on our study.