Prolonged Remission Research Articles

Multi-year recurrent pericarditis disease duration in Italian patients: clinical outcomes after cessation of long-term IL-1 pathway inhibition provide insights for chronic management

Abstract Background Recurrent pericarditis (RP) is a chronic disease mediated by IL-1 often lasting for years, and specific tools to guide treatment duration with IL-1 pathway inhibition at the individual patient (pt) level are limited. The Phase 3 trial RHAPSODY and 2-year long-term extension (LTE) demonstrated that rilonacept reduced risk of recurrence over long-term treatment (1,2). At the conclusion of the LTE, after a median of 28 months of rilonacept treatment (non-US pts), Italian pts returned to standard management because rilonacept was not commercially available. Clinical outcomes after rilonacept cessation and washout were followed to inform disease persistence and time to recurrence. Purpose Multicentric analysis of RP event rates in Italian pts after stopping long-term rilonacept. Methods Clinical records from Italian RHAPSODY pts were examined for the 18-month period post-LTE (To). Primary outcome: pericarditis recurrence (defined by tertiary-center experts as pericarditis pain plus c-reactive protein [CRP] elevation). Secondary outcomes: time to recurrence and proportion of pts requiring re-initiation of IL-1 pathway inhibition. Safety outcomes: serious adverse events (SAEs). Results 17 Italian pts were observed (Table 1). At To, median [Q1-Q3] disease duration (time from index episode) was 48 [41-56] months, during which pts had received a median 28 [27-30] months of continuous rilonacept treatment (all were in Clinical Response, i.e., no pain, normalized CRP, and on rilonacept monotherapy). After rilonacept cessation at To, no pts received prophylactic treatment. 82.4% (14/17) of pts experienced confirmed pericarditis recurrences, with time to recurrence 8 [6-9] weeks. Half of these pts (n=7) were given oral medications (NSAIDS, colchicine [n=3] and/or steroids [n=4], of whom 1 steroid-treated pt failed and resumed IL-1 pathway inhibition). The other half (n=7) resumed IL-1 pathway inhibition directly upon recurrence. The remaining 17.6% (3/17) of pts had no pericarditis recurrences after To and remained off treatment during the observation period. No pts experienced SAEs. Neither recurrence frequency nor time to recurrence was significantly related to baseline disease characteristics or demographics. Conclusions This exploratory analysis shows that in pts with RP of even 4-years’ duration (including a median 28-months’ rilonacept treatment), the 80% recurrence rate after treatment cessation was indicative of severe persistent underlying disease. Time to pericarditis recurrence after rilonacept cessation (median 8 weeks) was consistent with the predicted gradual pharmacokinetic washout and previously-reported 8.6-week time to flare in RHAPSODY (1). Pericarditis recurrences in these pts with long disease duration and systemic inflammation were severe enough to necessitate re-initiation of advanced therapy. Further studies could quantify optimal treatment duration for pts achieving prolonged remission on IL-1 pathway inhibition.

Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents

BackgroundAutologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT.MethodsThirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy.ResultsAHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function.ConclusionAHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.

Mechanisms of Action of Exclusive Enteral Nutrition and Other Nutritional Therapies in Crohn’s Disease

Background and Objectives: Crohn’s disease (CD) is an inflammatory bowel disease (IBD) characterized by transmural inflammation and intestinal fibrosis involving mostly the small intestine and colon. The pathogenic mechanisms of CD remain incompletely understood and cures are unavailable. Current medical therapies are aimed at inducing prolonged remission. Most of the medical therapies such as corticosteroids have substantial adverse effects. Consequently, many dietary therapies have been explored for the management of CD. Up to now, exclusive enteral nutrition (EEN) has been considered the only established dietary treatment for IBD, especially CD. In this article, we aim to give a concise review about the current therapeutic options and challenges in the management of CD and aim to compare the efficacy of EEN with other dietary therapies and update on the possible mechanisms of the benefits of EEN and other nutritional therapies. Methods: We searched the literature up to August 2024 through PubMed, Web of Science, and other sources using search terms such as EEN, nutritional therapy, IBD, Crohn’s disease, ulcerative colitis. Clinical studies in patients and preclinical studies in rodent models of IBD were included in the summary of the therapeutic benefits. Results and Conclusions: EEN involves oral or nasogastric tube feeding of a complete liquid diet with exclusion of normal foods for a defined period (usually 6 to 8 weeks). EEN treatment is demonstrated to have anti-inflammatory and healing effects in CD through various potential pathways, including altering gut bacteria and their metabolites, restoring the barrier function, direct anti-inflammatory action, and indirect anti-inflammatory action by eliminating mechanical stress in the bowel. However, efficacy of other nutritional therapies is not well established in CD, and mechanisms of action are largely unknown.

Dupilumab for refractory chronic rhinosinusitis in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is frequently associated with refractory chronic rhinosinusitis with nasal polyps (CRSwNP), despite current treatments. Dupilumab demonstrated efficacy in the treatment of severe and uncontrolled CRSwNP, with improvements in patient-reported outcome measures and in objective measurements. This study aims to evaluate efficacy and safety of dupilumab in refractory CRSwNP in EGPA patients. A prospective observational study was conducted on EGPA patients treated with dupilumab between 2021 and 2023. Patients in a phase of prolonged remission of vasculitis manifestations but still experiencing active CRSwNP were included. Clinical, biological, and rhinologic evaluations were performed, alongside with patient-reported outcomes measures (PROMs) and nasal cytology. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤ 4 mg/day, while partial response by BVAS = 0 and prednisone dose >4 mg/day. Nine EGPA patients were included. After 3 months, 55.6% achieved complete response, increasing to 83.3% at 12 months. Nasal symptoms and patient-reported outcomes improved significantly, with sustained efficacy over 12 months. An improvement in quality of life was also observed, with a significant reduction of the AAV-PRO score. Nasal cytology revealed reductions in eosinophils and neutrophils counts. Adverse events occurred in 44.4%, including hypereosinophilia in 2 cases, which led to dupilumab discontinuation. Dupilumab is an effective treatment option for severe and refractory ENT manifestations in EGPA, as it improves symptoms, reduces inflammation, and leads to better a quality of life. However, careful patient selection and monitoring are necessary to minimize adverse events and optimize outcomes.

Exploring Epidermodysplasia Verruciformis: A Case Report, Treatment Strategies, and Emerging Therapies

Abstract Introduction/Objective Epidermodysplasia verruciformis (EV) is a rare cutaneous disorder with both inherited and acquired forms. Inherited cases involve mutations in genes such as ERV1 and ERV2, crucial for HPV immunity, while acquired cases affect immunocompromised individuals. EV is linked to cutaneous squamous cell carcinoma (SCC), highlighting the need for prompt diagnosis and treatment. Methods/Case Report A 54-year-old HIV-positive man was referred with a persistent, itchy eruption on his forearms despite given ARV regimen, oral retinoids and topical therapies. Physical examination revealed hypopigmentation and hyperkeratotic plaques on both forearms. Histologic examination revealed large cells with blue-gray cytoplasm and perinuclear halo in the upper epidermis, consistent with EV. Although advised for papilloma virus vaccination and planned for a trial of topical cidofovir, the patient was lost to follow-up. Treatment strategies for EV vary depending on lesion severity. Severe keratinized or precancerous lesions typically require surgical removal as the first-line approach. For early-stage EV with few small lesions, 5-FU, cidofovir, glycolic acid, and imiquimod is recommended. Tazarotene 0.5% cream used twice weekly has shown success in resolving lesions within 14 days. Topical imiquimod’s efficacy appears variable. In HIV-positive patients with EV, topical 1% cidofovir showed success in some cases. Systemic and topical retinoids are advised for diffuse lesions, with electrocautery or cryotherapy as options if initial treatments fail. HPV vaccination combined with oral acitretin, topical tretinoin and imiquimod led to lesion flattening. Continuous low-dose isotretinoin achieved prolonged remission of EV, but its efficacy in acquired EV remains unclear. Topical methyl aminolevulinate followed by photodynamic therapy has also shown promise. Results (if a Case Study enter NA) NA Conclusion Since its discovery in the 1970s, Acquired EV has been observed across diverse demographics, including HIV patients and organ transplant recipients. Advanced HPV typing and sequencing techniques aid in predicting SCC risk. Emerging treatments like topical cidofovir and combination therapies show promise, necessitating larger clinical trials for validation.

No Effect of Low-Dose Glucocorticoid Maintenance Therapy on Damage in SLE Patients in Prolonged Remission: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone < 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual.

Long-term goflkicept therapy for patients with idiopathic recurrent pericarditis: results of the interim analysis of an ongoing open-label extension study

To evaluate the long-term safety and efficacy of goflkicept treatment in patients with idiopathic recurrent pericarditis (IRP). This report presents the interim analysis of an ongoing open-label extension (OLE) clinical trial of goflkicept in patients with IRP (NCT05673902), as a continuation of the core study (NCT04692766). The study assessed the frequency of pericarditis recurrence, time to recurrence after 12 and 60 weeks of goflkicept therapy, changes in C-reactive protein level, chest pain intensity, pericardial effusion size, and adverse events (AEs). All patients remained in clinical-laboratory remission during the 60 weeks of goflkicept treatment. The recurrence frequency was 31.3% (5/16) after 60 weeks and 90% (9/10) after 12 weeks of goflkicept treatment (p</i><</i>0.001). A total of 64 AEs were reported in 16 patients (94.1%), mostly of mild to moderate severity. The most common AEs were infections, occurring in 11 patients (64.7%). Nine serious adverse events were reported in 5 patients, none of which were considered drug-related. There were no deaths. Long-term goflkicept therapy resulted in a significant reduction in the risk of recurrence and prolonged remission without an increase in adverse events.

7884 Enigmatic Spontaneous Hypoglycemia During Prolonged Complete Remission in a Child with Autoantibody-Positive Diabetes: Possible Role of Coincidental GYS2 Heterozygous Mutation

Abstract Disclosure: S.S. Sundar: None. S. Shankar: None. M.S. Vaishnav: None. L. Lekkala: None. S.S. Srikanta: None. R.B. V: None. T.-. Kamala: None. C. Siddlingappa: None. C.D. Mandyam: None. P. Ravikumar: None. K. M: None. V. Nath: None. Introduction: Complete remission duration in type 1 diabetes is highly variable (few weeks to years, average 7 months in children). Non-diabetes hypoglycemia in children occurs due to metabolic/ endocrine/ congenital disorders [insulin-mediated (hyperinsulinism) or insulin-independent]. Clinical Case 2021 Sep T1D Diagnosis 13-year boy FTLSCS; 2.86 kg. Fatigue, sleepy, early morning headaches, weight loss, polyuria, polydipsia, headache. FPG 320 mg/dL; PPPG 596 mg/dL; Ketonuria++++; C Peptide fasting 0.42 ng/ml (1.1-4.4); TSH 2.44 (0.7-6.4); S Cortisol 27.2 mcg/dL (5-23); US abdomen normal. Treatment: IV fluids/ insulin; Regular 10 u tid; Glargine 20 u Family history: Diabetes adult onset++++; Hypothyroidism++ 2021 Oct T1D remission Hypoglycemia even with Glargine 2 U/day. Insulin discontinued. FPG 88; PPBG 159 2021 Dec Endocrinology work-up Weight 41.9 kg; Height 154 cm BMI 18.0 kg/m2 FPG 88; HbA1c 6.1 % (4.8-5.6); C-peptide fasting 1.26; Blood ketone 3.35 (0.2-2.8); TSH 2.66 Autoantibodies Islet cell IFL Positive; IA2 &amp;gt;280 IU/mL (&amp;lt;28); GAD65 0.5 U/mL (&amp;lt;10); TPO negative 2021-2023 T1D prolonged remission FPG 90; PPBG 140; HbA1c 5.5 2023 Nov 5 Hypoglycemia, coma and seizures Limited breakfast; skipped lunch; vomiting. 1.15 am: Unconscious seizures. CGM unable to record. Lab BG 39; Fingerstick BG 36. IV dextrose 25%. 4 am: Regained consciousness. BG 100 to 200; HbA1c 6.4%. Insulin fasting 8.9 µU/ml (2.6-24.9); Insulin post prandial 21.6; C Peptide fasting 2.0. S Cortisol 8 am 7.6. Imaging: MRI brain abdomen pelvis normal. EEG normal 2023 Nov 9 Hyperglycemia to hypoglycemia Holiday morning: BG unexpected 306 CGM. 8.30 pm: Symptomatic hypoglycemia with sweating and light headedness; BG 52 fingerstick. IV 25% dextrose. BG 140 “Coincidental” spontaneous hypoglycemia No intake of insulin/ oral hypoglycaemics / traditional medicines. 10 pm to 3 am low CGM BG upto 60; asymptomatic. FPG 103; PPPG 146; HbA1c 6.3 %; Insulin Fasting 2.85, 3.79; C-peptide fasting 1.18, 0.94; S Cortisol 8 am 12.5; TSH 2.66 Autoantibodies Islet cell IFL Positive; IA2 &amp;gt;280 IU/mL (&amp;lt;28); GAD65 0.5 U/mL (&amp;lt;10); ZnT8 50 AU/mL (&amp;lt;10); Insulin antibodies 3.7 (&amp;lt;10). TPO negative Whole genome sequencing No monogenic/ maturity onset/ mitochondrial diabetes mutations. Hepatic glycogen synthase 2 heterozygous mutation (c.1602+1G-T) detected (Glycogen Storage Disease Type 0 Autosomal recessive: Ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia in infancy or early childhood). Clinical Lessons Coincidental double metabolic glucose dyshomeostasis pathology? Susceptibility of heterozygous carriers of GYS2 mutations to glucose metabolism abnormalities (hypoglycemia and hyperglycemia) has been reported. Presentation: 6/2/2024

B-227 Customized molecular tests for minimal residual disease: a tool for therapeutic decisions in follicular lymphoma patients

Abstract Background Monitoring of minimal residual disease (MRD) is based on accurate laboratory tests which can recognize a small fraction of malignant cells that survived the course of treatment. Several studies of the B-non-Hodgkin lymphoma group have been presented that MRD positivity at the end of treatment is a negative prognostic index. Follicular lymphoma (FL) is a chronic indolent malignancy, which response highly to immuno-chemotherapy followed by prolonged remissions but with inevitable relapse in most patients. The GALLIUM study showed that immuno-chemotherapy combinations, 6 cycles of bendamustine-obinutuzumab (BO), is the most efficacious treatment, but with severe side effects .In addition, 90% of patients achieved negative MRD from peripheral blood (PB) or bone marrow (BM) after only 3 BO cycles. These findings raise the possibility for MRD based treatment approach, where the duration of chemotherapy could be decided according to MRD status at mid-induction (MI). Identification of a marker in the PB and/or BM of each FL patient which will be use to the design of a sensitive RQ-PCR test for MRD detection for follow-up. Methods Qualitative PCR for translocation 14:18 and for the VDJ rearrangement sequence of the immunoglobulin heavy chain was used for marker identification. MRD monitoring was done by RQ-PCR. MRD monitoring for VDJ was designed specifically to each patients based on his VDJ sequence. MRD was assessed on PB and BM at MI. Results Marker for monitoring was identified at 11/21 patients in this study. After 3 combined therapy cycles, 7 patients were found to have MRD negativity by RQ-PCR therefore continue with immuno-therapy only. MRD positivity was assessed in BM of 3 patients (0.11%, 0.022%, and 0.133%). These 3 patients continued with the combined therapy. RQ-PCR sensitivity was 10-4-10-5. Conclusions This study will reveal the ability to use sensitive and specific MRD that has to be designed for each patient according to his marker and enable the establishment of a treatment with a high safety profile for FL patients. Correlation between MRD status and clinical and safety parameters will be assessed at the end of the study, 30 months after the first treatment, taking into account MRD status from different time point of the follow-up period.

Characterization of Disparities, Diagnoses and Treatment Outcomes with Pemphigus Vulgaris

Pemphigus vulgaris (PV) and foliaceus (PF) are classified as rare autoimmune blistering disorders in which IgG antibodies destroy desmosome proteins desmoglein 1 and desmoglein 3 within the stratum spinosum of the epithelial layer of the skin. These disorders once used to be a fatal condition, but the advent of steroids and immunosuppressants has made these diseases manageable. Such treatments, however, only alleviate symptoms and have not been viable in allowing patients to achieve prolonged steroid-free remission. In 2018, the US Food and Drug Administration (FDA) approved the anti-CD20 monoclonal antibody rituximab as the first-line treatment for moderate to severe cases of pemphigus. While rituximab has been generally successful in treating this disease and has led to prolonged steroid-free remission in many patients, treatment disparities and differences in patient outcomes due to social determinants of health have not yet been studied in the context of PV and PF. Such studies have already been conducted with more common dermatological disorders such as hidradenitis suppurativa (HS), which show significant evidence of outcome disparities due to social factors such as race, ethnicity and socioeconomic status. However, such studies have yet to be conducted with pemphigus likely because of how rare the disease is and because the current first-line treatment was FDA approved recently in 2018. The aim of this study is to conduct a retrospective multivariable analysis of 100 patients with pemphigus from UT Southwestern Medical Center and Parkland County Hopital to determine which social factors are the most responsible for any discovered pemphigus treatment outcome disparities. The impacts of this study are far-reaching as any discovered disparities can alert dermatologists to place a special emphasis to address any social factors that may play a role in leading to treatment outcome differences for patients with pemphigus.

Relapsed mantle cell lymphoma manifesting with soft tissue tumors of the extremities: University of Miami experience and review of the literatur.

Mantle cell lymphoma (MCL) is frequently diagnosed at advanced stages and is characterized by multiple extranodal sites of disease, most notably the bone marrow, peripheral blood, and gastrointestinal tract. Historically the prognosis of mantle cell lymphoma has been poor with median survival of four to five years. With new treatment regimens, however, patients have been able to achieve prolonged remissions and require special attention while being evaluated for relapse. This report describes four patients treated for stage IV mantle cell lymphoma at the University of Miami who developed soft tissue relapse presenting as non-tender large masses of the extremities, including one patient who presented without associated nodal involvement. Average time to soft tissue relapse was 99 months (range: 28-240) following initial diagnosis. Providers who care for patients with mantle cell lymphoma should be aware of soft tissue lesions as a presentation of mantle cell lymphoma that merits evaluation for disease relapse.

Summary of Research: Ten-Year Safety and Clinical Benefit from Open-Label Etanercept Treatment in Children and Young Adults with Juvenile Idiopathic Arthritis.

This is a summary of the original article 'Ten-year safety and clinical benefit from open label etanercept treatment in children and young adults with juvenile idiopathic arthritis'. Juvenile idiopathic arthritis (JIA) usually appears before the age of 16. JIA causes pain, swelling, and stiffness in the joints. People with JIA receive treatment for several years until the disease goes into prolonged remission. Therefore, the long-term safety of these treatments is an important topic. Etanercept is a treatment for JIA, which acts on the body's immune system to reduce arthritis. This summary of research article describes safety and how well etanercept works in children with JIA taking it for up to 10years.

Diagnosis, management and follow-up of follicular lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance.

Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma subtype, accounting for 15-20% of all lymphoma diagnoses. Although typically slow-growing and responsive to frontline therapies, advanced-stage FL remains incurable with current treatments and typically follows a chronic relapsing/remitting course with increasingly shorter responses to subsequent lines of therapy. Outcomes are highly variable; some patients experience prolonged first remissions that may approximate a 'functional cure'. By contrast, a significant minority of patients experience disease progression shortly after frontline treatment resulting in high rates of lymphoma-related mortality. Reflecting on the heterogeneous natural history of FL, clinical practice varies widely, particularly in controversial areas, including appropriate disease staging, selection of management strategies and duration of clinical follow-up. This position statement presents an evidence-based synthesis of the literature for application in Australasian practice.

Comparative study of the efficacy of azathioprine, dapsone, and NB-UVB phototherapy as steroid-sparing modalities in generalised lichen planus.

Background Generalised lichen planus (GLP) is a chronic disease with an overall prevalence of 1% requiring longer treatment. Limited studies are available on GLP and its treatment in the literature, unlike oral lichen planus. Objective To determine the best steroid-sparing treatment modality for GLP by comparing the efficacy, response, safety, side effects, and remission with azathioprine, dapsone, and narrowband UV-B (NB-UVB) along with their impact on itching severity and life quality. Methodology Open-label, prospective, comparative, interventional study on generalised lichen planus patients treated with systemic steroids along with one of three steroid-sparing modalities. Totally 90 patients were studied including 30 patients each who received azathioprine (Group A), dapsone (Group B), and narrow band UVB (NB-UVB) (Group C), respectively, for 16 weeks. Itch severity index (ISI) and Dermatology life quality Index (DLQI) were assessed at baseline and week 24. All patients received oral prednisolone until there was no more active disease. Response was assessed in terms of occurrence of new lesions, flattening of lesions, post-inflammatory hyperpigmentation (PIH), and grading of lesions two weeks once for 6 months followed by six months of follow-up after treatment completion. Results Females outnumbered males in all 3 groups. Mean patient ages (34, 38, and 34) and the presence of one or more co-morbidities (50%, 42.3%, 37.5%) in Groups A, B, and C, respectively, were comparable. ISI and DLQI improvement at 24 weeks were greatest with NB-UVB, followed by azathioprine and dapsone in that order; the differences in improvement between groups showed high statistical significance. At week 24, occurrence of new lesions (0%, 0%, 3.8%), flattening (100% - all groups), PIH (100% - all groups), grade 3 lesions i.e. poor response, resolution of 20-50% of lesions (7.1%, 11.5%, 0%), grade 2 lesions i.e. partial response, resolution of 50-90% of lesions (35.7%, 76.9%, 8.3%) and grade 1 lesions i.e. complete response, resolution of >90% lesions (57.1%, 11.5%, 91.3%) were noted in Groups A, B and C, respectively; the differences in the extent of resolution of lesions between the groups were highly significant statistically. Remission was seen in 100%, 76.9%, and 87.5% in Groups A, B, and C, respectively, after six months. Limitations The sample size was small. Only 3 treatment options were compared in this study but many more options have been used for lichen planus. Long term follow-up is required. Conclusions NB-UVB with oral steroids showed a better response in terms of improvement in DLQI, ISI, disease control, and side effects than azathioprine and dapsone. Azathioprine showed a faster response and more prolonged remission. Dapsone showed poor response with multiple side effects.

Safety and activity of lenalidomide in combination with obinutuzumab in patients with relapsed indolent non-Hodgkin lymphoma: a single group, open-label, phase 1/2 trial

Rituximab and lenalidomide is a preferred option for relapsed indolent B cell non-Hodgkin lymphoma. Obinutuzumab may be a superior combination partner with lenalidomide given enhanced antibody dependent cellular cytotoxicity and phagocytosis compared to rituximab. Our aim was to determine the recommended phase 2 dose, safety, and activity of lenalidomide in combination with fixed dose of obinutuzumab in relapsed and refractory indolent B cell non-Hodgkin lymphoma. In this single-arm, open-label, phase 1/2 trial, we enrolled patients with relapsed or refractory WHO Grade 1-3A follicular lymphoma, marginal zone lymphoma and small lymphocytic lymphoma and adequate performance status (ECOG 0-2) at the MD Anderson Cancer Center. We excluded patients with evidence of ongoing transformation to aggressive lymphoma. During phase 1, 1000mg intravenous obinutuzumab was administered with three predefined levels of oral lenalidomide in a 3+3 dose escalation design to establish lenalidomide 20mg as the recommended phase 2 dose. During phase 2, patients received induction therapy with six 28-day cycles of lenalidomide 20mg with intravenous obinutuzumab 1000mg. In accordance with our prior experience with lenalidomide plus rituximab, patients who were responding to the combination could receive up to 6 additional cycles (up to 12 cycles in total) of combination therapy. Dosing of obinutuzumab was continued in all responding patients after cycle 6 every 2 months for a total of 30 months from the start of therapy. The decision of number of cycles of combination therapy beyond 6 was at discretion of the investigator and was included to allow individualisation of therapy to maximise response while minimising exposure. The co-primary objectives were to evaluate the safety and overall response, defined as the proportion of patients who achieved a complete or partial response in relapsed and refractory indolent non-Hodgkin lymphoma at the end of induction therapy, according to Cheson and colleagues (2007 criteria). The secondary endpoints were complete response after induction therapy and time to event endpoints including time to progression, progression free survival, and overall survival. Analyses were intent to treat in the efficacy cohort and per-treated in the safety population in all patients who received at least one dose of either investigational agent. This trial is registered with ClinicalTrials.gov, NCT01995669. Between June 03, 2014, and 07 March 2019, we completed planned enrolment, and 66 patients started therapy including 9 patients in phase 1 and 57 patients in phase 2. All patients were evaluated for safety and the 60 patients treated at the recommended phase 2 dose of lenalidomide 20mg were evaluable for activity. Grade 3-4 haematological toxicities included neutropenia 21% (14/66) and thrombocytopenia 11% (7/66) with no cases of febrile neutropenia. Grade 3-4 non-haematological toxicities included lung infection 8% (5/66), fatigue 8% (5/66) and rash 6% (4/66). By Cheson 2007 criteria, 90% (54/60, 95% CI: 79-96) achieved an overall response at the end of induction meeting the prespecified activity endpoint. Complete responses were seen in 33% (20/60, 95% CI: 22-47) at the end of induction. Median progression free survival, time to progression and overall survival have not been reached after median follow-up of 41.7 months. Estimated 4-year progression free survival rates were 55% (95% CI: 42-73), time to progression of 56% (95% CI: 43-74) and overall survival of 84% (95% CI: 74-95). Our findings suggest that oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration. The study is limited by the lack of a control arm leading to cross-trial comparisons to evaluate activity. Future randomised trials comparing this regime to rituximab and lenalidomide are warranted. Genentech and an MD Anderson Core grant.

Identifying Candidates for Effective Utilization of Stored Autologous PBSCs in Salvage Transplantation for Multiple Myeloma: Who Benefits Most?

Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT's efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.

Rituximab in Steroid-Dependent Podocytopathies

Plain Language SummaryRituximab (RTX) seems to be an effective treatment alternative in primary forms of MCD and FSGS, particularly in cases of steroid dependence and frequent relapses. Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.

The impact of continuous lenalidomide maintenance treatment on people living with multiple myeloma—a single-centre, qualitative service evaluation study

PurposeContinuous lenalidomide maintenance treatment after autologous stem cell transplantation delivers improvement in progression free and overall survival among newly diagnosed multiple myeloma patients and has been the standard of care in the UK since March 2021. However, there is scant information about its impact on patients’ day-to-day lives. This service evaluation aimed to qualitatively assess patients receiving lenalidomide treatment at a cancer centre in London, in order that the service might better align with needs and expectations of patients.MethodsWe conducted 20 semi-structured interviews among myeloma patients who were on continuous lenalidomide maintenance treatment at a specialist cancer centre in London. Members of the clinical team identified potentially eligible participants to take part, and convenience sampling was used to select 10 male and 10 female patients, median age of 58 (range, 45–71). The median treatment duration was 11 months (range, 1–60 months). Participants were qualitatively interviewed following the same semi-structured interview guide, which was designed to explore patient experience and insights of lenalidomide. Reflexive thematic analysis was used for data analysis.ResultsFour overarching themes were as follows: (i) lenalidomide: understanding its role and rationale; (ii) reframing the loss of a treatment-free period to a return to normal life; (iii) the reality of being on lenalidomide: balancing hopes with hurdles; (iv) gratitude and grievances: exploring mixed perceptions of care and communication. Results will be used to enhance clinical services by tailoring communication to better meet patients’ preferences when making treatment decisions.ConclusionThis study highlights that most patients feel gratitude for being offered continuous lenalidomide and perceive it as alleviating some fears concerning relapse. It reveals variations in side effects in different age groups; younger patients reported no/negligible side effects, whilst several older patients with comorbidities described significant symptom burden, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. Future research should prioritise understanding the unique needs of younger patients living with multiple myeloma.

A Review of CAR-T Combination Therapies for Treatment of Gynecological Cancers.

CAR-T cell therapy offers a promising way for prolonged cancer remission, specifically in the case of blood cancers. However, its application in the treatment of solid tumors still faces many limitations. This review paper provides a comprehensive overview of the challenges and strategies associated with CAR-T cell therapy for solid tumors, with a focus on gynecological cancer. This study discusses the limitations of CAR-T therapy for solid tumor treatment, such as T cell exhaustion, stromal barrier, and antigen shedding. Additionally, it addresses possible approaches to increase CAR-T efficacy in solid tumors, including combination therapies with checkpoint inhibitors and chemotherapy, as well as the novel approach of combining CAR-T with oncolytic virotherapy. Given the lack of comprehensive research on CAR-T combination therapies for treating gynecological cancers, this review aims to provide insights into the current landscape of combination therapies for solid tumors and highlight the potential of such an approach in gynecology.

Surgical Debulking Modifies Notch Signaling and May Improve Vismodegib Effectiveness for Locally Advanced Basal Cell Carcinoma

Smoothened inhibitors, such as vismodegib, exhibit remarkable success in treating patients with locally advanced basal cell carcinoma (LaBCC). Yet, vismodegib efficacy is hindered by notable side effects, which often lead to treatment discontinuation and subsequent relapse in patients with LaBCC. Prolonged remission was previously reported in patients with LaBCCs who underwent surgical debulking before starting vismodegib. In this study, we enrolled 4 patients with LaBCC who underwent debulking followed by vismodegib therapy to assess their clinical outcomes and analyze the cutaneous molecular changes occurring as a result of surgical intervention. After LaBCC debulking, patients underwent a punch biopsy of residual basal cell carcinoma tissue 1 week later. RT-qPCR analysis of 24 Notch and Wnt signaling-associated genes revealed elevated PTCH1, HEY2, LGR6, FZD2, LEF1, ALCAM, and RUNX1 expressions in follow-up biopsies compared with those in patient-matched debulked tissue. Immunoblot and immunostaining further confirmed elevated Notch signaling in follow-up biopsy tissue compared with that in patient-matched debulked tumor tissue. Patients 1, 3, and 4 displayed a clinical response to debulking followed by vismodegib, whereas patient 2 was lost to follow-up after debulking. These findings suggest that surgical manipulation of LaBCCs is correlated with molecular alterations in signaling pathways associated with cellular reprogramming.