Rash Research Articles

A Cross-Sectional Study To Assess Knowledge of Monkeypox Among Medical Students and Graduates in India.

Background and aim Monkeypox outbreaks in several nations have brought focus to the emerging virus. The clinical presentation of monkeypox is less severe than smallpoxbut is fairly comparable, presenting with fever, headache, lymphadenopathy, back discomfort, myalgia, and skin rashes. The misinformation spread on social platforms had a major impact on the effectiveness of outbreak control measures. The clinical management of breakouts depends on the adequate knowledge of the healthcare personnel about the disease. This study aims to assess the knowledge of medical students and graduates regarding monkeypox in India. Methods A cross-sectional survey was conducted by circulating a predesigned questionnaire with 20 questions to collect information regarding the demographic characteristics of the study participants, source of knowledge about monkeypox disease, self-perceived knowledge, and number of correctly answered questions regarding the disease. The responses obtained from the questionnaire and teleconsultation were recorded and analyzed. Results Out of 404 medical students and graduates who participated in the study, the mean age of participants was 23.17±2.14 years, and only 156 students learned about monkeypox in medical colleges. Only 72 (17.82%) participants reported that their medical college or hospital organized an educational class to teach about monkey pox disease. A majority of respondents (n=350, 86.63%) received their knowledge from online sources, which were the first most used source, followed by Instagram. Conclusions The knowledge assessment about monkeypoxrevealed that the average correct responses of participants who perceived to beknowledgeable were significantly lower than those who perceived to have good knowledge.

Design and development of air ventilated air bed for hospitalized patients

Proper ventilation is a critical consideration for the comfort of hospitalized patients. Dry skin, skin rashes, weariness, poor sleep, and other concerns caused by insufficient ventilation can all be avoided with proper ventilation. Air-Ventilated Air Beds are used to supply air to the major parts of the patient’s body. This air bed is constructed in such a way that air is circulated con-tinually throughout the body of the hospitalized patient. It is especially beneficial for people who are bedridden and need to spend a significant amount of time in bed due to illness. Exces-sive heat generated between the bed and the patient is perhaps the common cause of bedsores. Sweating is the leading cause of bedsores. Air ventilation is included in the system to prevent sweating and reduce the incidences of bedsores. Dual compressors, rubber tubes, flow control valves, and anti-decubitus mattresses are among the components used. The rubber tubes are used to ventilate the space between the body of the patient and the upper surface of the air bed. Above the mattress, the rubber tube mesh is positioned. The air is first compressed in two compressors before passing through the distribution manifold and through the meshing. The tubes are altered by drilling holes at certain intervals. The air from the compressor is circulated through the pipes before passing through the openings in the pipes. The unrestricted passage of compressed air via a capillary tube lowers the temperature of the air. The air exhausted through the capillary tubes maintains the patient’s body temperature stable for a while before lowering it. The air is ventilated throughout the bed in this manner. Bedsore can be avoided by reduction of sweat by using the air in close contact with the patient.

Quetiapine-Induced Reversible Skin Rash: A Case Report

Çeşitli psikiyatrik bozuklukların tedavisinde kullanılan ketiapin deri döküntüsüne neden olabilir. Bu olgu sunumunda, ketiapin kullanımı ile ilişkili deri döküntüsünü sunduk. Yaygın anksiyete bozukluğu tanısıyla takip edilen ve uykusuzluk şikâyetine yönelik olarak ketiapin 200 mg/gün başlanan 43 yaşındaki erkek hastada tedavinin yedinci gününde yüz, saçlı deri ve boyun bölgesiyle sınırlı deri döküntüsü ortaya çıktı. İlaç başlanmasınu takiben ortaya çıkan bu yan etki ketiapin kullanımı ile ilişkilendirildi ve ilaç kesildi. Ketiapin kesilmesini takiben deri döküntüsü giderek azaldı ve üç haftanın sonunda tamamen ortadan kayboldu. Hastanın yaygın anksiyete bozukluğu ile ilişkili tedavisi tamamlandı ve taburcu edildi. Takiplerinde deri döküntüsü gözlenmedi. Deri ile ilişkili yan etkiler ketiapin kullanımı ile ilişkili olabilir. Klinisyenler, ketiapinin deri döküntüsü yan etkisine karşı uyanık olmalıdır.

Optimization of RT-PCR methods for enterovirus detection in groundwater

Enteroviruses (EVs), which belong to the Picornaviridae family, infect individuals asymptomatically or cause mild symptoms (fever, runny nose, cough, skin rash, sneezing, mouth blister). Severe cases can cause various diseases, such as acute hemorrhagic conjunctivitis, aseptic meningitis, or myocarditis, especially in infants. These viruses can be transmitted via the fecal-oral route via contaminated water. In this study, we established a polymerase chain reaction (PCR) method for detecting EVs in water sample using Coxsackievirus B5 (CV-B5) and Echovirus 30 (E-30), which belong to species B of the four species of EVs (EV-A to D). Several methods have been investigated and compared for the detection of EVs, including real-time reverse transcription (RT) polymerase chain reaction and conventional RT-PCR. The most sensitive primer sets were selected, and the PCR conditions were modified to increase sensitivity. We also quantified the detection limits of real-time and conventional RT-PCR. The detection limits of conventional RT-PCR were detected in 105–106 copy/mL for CV-B5 and 106–107 copy/mL for E-30, respectively. This optimized method for detecting EVs is expected to contribute substantially to the investigation of EV outbreaks in water samples.

Congenital Rubella Syndrome-a Case Report with Clinical Manifestation and Management Approach

Congenital rubella syndrome (CRS) is an illness in infant resulting from maternal infection with rubella virus during pregnancy. Patients suffer from some complications included deafness, cataract, heart defects, mental retardation, bone alterations, liver and spleen damage. Purpose of this study is to create attention, early identification and keep special concern in management of such case. A 15 years old girl presented with dimness of vision since childhood. Her mother had a history of fever and skin rash during prenatal period. She had mental retardation, deafness, dumbness, thin stature, microchephaly. Unaided vision fixed and follows in both eyes. Anterior segments showed bilateral microphthalmos, nystagmus, microcornea, aphakia. Intraocular pressure was 40 mm of Hg in each eye. Color fundus photograph showed myopic crescent with tessellated fundus. Echocardiogram showed pulmonary stenosis. Ultrasonography whole abdomen revealed chronic hepatitis. LDH level was 380 units/L. She had hyperthyroidism. Her sensory neural hearing loss was detected by audiometry. She was referred to glaucoma clinic for raised ocular pressure; low vision clinic for visual rehabilitation; medicine specialist for cardiac problem, liver problem and hormonal imbalance. All presenting features revealed that it was a case of congenital rubella syndrome as the girl had deafness, cardiac problem and ocular abnormality which are triad of CRS. Early diagnosis, timely management and proper counseling to patient and guardian will consequently increase life quality of this patient. National awareness should be increased for full coverage of antenatal check up with MMR vaccination in all health care centers of developing countries. J.Natl.Inst.Ophthalmol.2023;6(1): 54-59

Post-marketing safety surveillance and re-evaluaiton of Shu-Xue-Ning injection: a real-world study based on 30,122 cases

Objective: This study aims to investigate the safety of Shu-Xue-Ning injection (SXNI) in real-world clinical applications.Methods: A prospective, multi-center, large-sample intensive monitoring method was used to monitor the use of SXNI in several medical institutions across China while collecting patients’ dosing and adverse event information. Patients who suspected as adverse reactions made comparisons with patients who did not report adverse reactions to calculate the correlation between relevant risk factors and suspected adverse reactions. Statistical analysis software SAS 9.1 was used for data analysis.Results: A total of 48 hospitals participated in this intensive monitoring study of SXNI, and 30,122 patients were monitored from July 2015 to December 2018. A total of 1,908 adverse events were reported during the use of SXNI, with an adverse event rate of 6.33% and a 95% confidence interval (CI) of 6.06%–6.61%. Association assessment showed that 54 cases presented with SXNI-related adverse reactions with an incidence of 0.18% and a 95% CI of 0.13%–0.23%, thereby indicating that the incidence of SXNI-related adverse reactions was occasional. SXNI-related adverse reactions involved 9 systems-organs with 20 clinical manifestations, and the most common adverse reactions were rash, pruritus, and other damages of skin and its appendages. No serious adverse reactions were observed; 27.78% of the adverse reactions occurred within 30 min of drug administration and more than half of them occurred within 2 h of drug administration; 96.3% of the adverse reactions were cured or improved. Causal analysis showed that women, long dispensing time, and slow dripping speed rate were considered as risk factors.Conclusion: The incidence of SXNI-related adverse reactions in real-world clinical applications is occasional and in a reasonable range with a good prognosis.

Mycosis fungoides presenting as suspected allergic reaction

Mycosis Fungoides (MF) and Sezary Syndrome are the most common subtypes of cutaneous T cell lymphoma. MF is a mature T cell non-Hodgkin lymphoma with initial involvement of the skin, but as the disease progresses can involve lymph nodes, blood and viscera as illustrated in this case. Diagnosis is difficult due to the disease presenting similarly to benign allergic skin rashes. The median age of presentation for MF is between 50-60 years and affects males more than females. African Americans are more at risk although the exact reason is unknown.

Engraftment Syndrome Incidence after Immune Checkpoint Inhibitor Therapy in Pts with Classical Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplantation: A Single Institutional Review

Introduction: After receiving frontline chemotherapy for classical Hodgkin lymphoma, up to 30% of patients (pts) relapse. Salvage chemotherapy and autologous stem cell transplantation (ASCT) are the standard of care. Immune Checkpoint inhibitors (ICIs) have become essential to salvage therapy with improved complete response (CR) rates. However, ICIs have been linked to an increased risk of engraftment syndrome (ES), reported in as many as 68-78% of cases (Moskowitz et al. 2021; Park et al. 2021), while others have reported lower rates 3-12% (Bryan et al. 2023; Mei et al. 2022). The variability is connected to the definition of ES. The more stringent Spitzers criteria require 3 major (non-infectious fever (NIF), skin rash, pulmonary edema, or hypoxia) or 2 major and 1 minor criteria within 96 hours of engraftment, while the more lenient Maiolino criteria require a NIF with skin rash, pulmonary infiltrates, or diarrhea. Early diagnosis of ES and early intervention with corticosteroids is important to minimize toxicity during the ASCT. Here, we evaluate ES incidence at our institution during ASCT with or without the inclusion of ICI during salvage therapy. Method: The institutional database was queried for pts with relapsed/refractory cHL who underwent ASCT between 2018 and 2023. ES is broadly defined as the presence of non-infectious fever with skin rash, diarrhea, or pulmonary infiltrates (Maiolino Criteria) or clinical suspicion requiring corticosteroids. Results: A total of 47 pts underwent ASCT during this period and were included in the final analysis. Twenty-nine pts received ICI during salvage therapy (72%). Regarding basic patient characteristics: the median age at ASCT was 31 [19-72], 27 pts were female (57.5%), 35 pts were white (74.5%), the most common subtype was nodular sclerosis (n=42; 89.4%), with 23 pts (50%) initially presenting with advanced-stage disease. The most common initial therapy was ABVD (n=42, 89.4%), with one patient being treated with an ICI-based therapy on clinical trial (SWOG 1826). Thirty pts (63.8%) had a CR after frontline treatment and 16 pts with primary refractory disease. For the CR pts, the median time to progression was 159 [13-3864] days. Thirty-five pts achieved a CR after salvage therapy (74.5%), 25 receiving ICI (71.4%), most commonly pembrolizumab. Regarding conditioning regimens, the most used and our institutional standard is total lymphoma irradiation (TLI) followed by high-dose chemotherapy (CCV) (n=34; 72.3%), which we have reported having high and durable response rates (10-yr PFS 68.5% and OS 68.0%). (Paudel et al. 2019) The median time to neutrophil engraftment is 10 days [7-30]. The rate of post-ASCT relapse was higher in the chemotherapy-only conditioning group (31%) compared to TLI-CCV (3.3%). All pts who received TLI-CCV are still alive, with two deaths in the chemotherapy only conditioning group (Total OS 95.7%). Out of 47 evaluable pts, no pts qualified with a diagnosis of ES using the stringent Spitzers criteria. However, 17 received corticosteroids using the broader diagnosis criteria for ES (36%). Looking specifically at pts who received ICI (n=29), 14 pts had ES (48.3%), while of the 18 pts who did not receive ICI, 3 had ES (16.7%). Of the pts who did develop ES (n=17), 16 pts received TLI-CCV (94%), the median time to onset was 9 [2-11] days, the median time to resolution was 6 [2-19] days, the median time to neutrophil engraftment was 10 [8-12] days. When evaluating pts who received TLI-CCV conditioning, 24 pts received ICI during treatment before ASCT, with 13 pts having ES (54.2%). By comparison, 3 (33%) of the 9 ICI-naïve pts who received TLI-CCV were diagnosed with ES. The incidence of ES with or without ICI exposure was not statistically significant (p = 0.2549). Overall, the median time to ES onset is 9 days, and the duration of 6 days. There was no recorded mortality from ES. Only 3 pts relapsed post-ASCT (8.8%), with two receiving ICIs. Even with the small number of pts in this retrospective study, there was an increase in ES incidence between the use of ICI during salvage therapy (p=0.0279). Conclusions: In this single-institution retrospective analysis, we found that the addition of ICI during salvage therapy increased the incidence of a broadly defined ES, with an increase in corticosteroid use. ES must be recognized early and treated with corticosteroids aggressively.

An Acute Gvhd Classification Based on the Dynamic of Gvhd Skin Involvement from Its Appearance to Start of Systemic Treatment

The currently used classifications of acute GVHD are based on signs and symptoms in the skin, gut and liver, graded at the start of first-line therapy. However, they do not consider the rate at which these symptoms developed. Since skin aGVHD is the most frequent initial sign, we conducted a prospective observational study aimed at investigating the prognostic value of the dynamic of skin involvement such as the rate at which aGVHD progresses from cutaneous involvement to visceral involvement. One hundred and eight consecutive patients who underwent allogeneic hematopoietic transplantation in our centre were registered for this observational study, their aGVHD episodes were classified according to both the modified Glucksberg classification and according to a “GHVD skin dynamic” proposed by us. Our classification “GVHD skin dynamic” classified acute GVHD based on the time interval between rash initial appearance to time when treatment using corticosteroids (CS) was started. In patients left untreated, we considered the change in skin rash extension shown during the first week without treatment. Median age of treated patients was 49 years, 69% were affected by Acute Leukemia, 64% had an alternative donor type (MUD, HAPLO). Primary aGVHD treatment was started in all patients in the case of progression to Glucksberg Overall Grade 2 or a persisting Overall Grade 1, no local corticosteroids were used on the skin. Eighty-two presented a skin rash as a first sign of a-GVHD (80.3%) and were classified according both to Glucksberg classification and our scheme; 18/82 started CS within 48 hours (Group 1); 13/82 started CS within days 3-7 (Group 2). Fifty-one patients (62.2%) were left untreated for 7 days (Group 3) and subclassified 3a and 3b. Group 3a (n 31) was defined when Skin GVHD Overall Grade 1, left untreated for 1 week, showed an absolute increase in involved body surface area <5 %. Group 3b (n 20), was defined when Skin GVHD Overall Grade 1, left untreated at 1 week, had an absolute increase in involved body surface area >5% (Fig 1). Demographic, disease-related and transplant features (Age, Donor type, Disease status, HSC Source, ATG use, Conditioning RIC, Diagnosis) in the four groups were not significantly different. The four groups, identified by “GVHD skin dynamic”, had distinctive 2-y OS, (Fig 2). In Group 1 (patients who were started on CS within 48 h) the OS at 2y was 50.1% and TRM 41.6%. In Group 2 (patients who started on CS after 2 days and within 7 days) the OS at 2 y was 64.8% and TRM 16.8%. In Group 3a (patients who were started on CS after 7 days and had no increase of skin rash during days 1-7) the OS was 75.1% and TRM 10.4%. In Group 3b (patients who were started on CS after 7 days and had an increase of skin rash during days 1-7) the OS was 39.8% and TRM 39.2%. Patients were then grouped based on “GVHD skin dynamic” into “Dynamic type poor risk” (Group 1 and Group 3b) and “Dynamic type good risk” (Group 2 and Group 3a). Such grouping was found statistically important using Cox proportional hazard univariate analysis for OS (p=0.04). Such grouping “Dynamic type poor risk” and “Dynamic type good risk” retained importance for OS when evaluated in Cox proportional hazard multivariate analysis (HR 2.222 ; 95% CL 1.017-4.875; p=0.04) together with age, status of the disease and conditioning. Patients who were left untreated because of skin-only acute GVHD and who during a week had a worsening skin extension (Group 3b) were compared to those who when left untreated for one week showed a stable skin-only involvement (Group 3a). Overall Survival at 2 y in Group 3b was significantly inferior compared to Group 3a: 39.8% vs 75.1% (log-rank: p= 0.03). Group 3b had also increased Treatment-Related Mortality: 39.2% versus 10.4% vs (Gray test: p=0.05) and increased rate in need of secondary anti-GVHD treatment: 76.4% vs 46.6% (chi-test p=0.002). The dynamic of skin aGVHD during the first week from appearance may be used to classify acute GVHD and this proposed acute GVHD classification has good prognostic value. Further, patients who have a skin-only acute GVHD and who, when left untreated for one week show an increase in skin involvement, have inferior prognosis and should start systemic CS promptly.

Addition of Acalabrutinib to Lenalidomide and Rituximab Induces High Complete Response Rates in Patients with Previously Untreated Follicular Lymphoma: Results of a Phase II Study

Background. We previously reported pro-tumoral macrophages may be associated with resistance to lenalidomide and rituximab (R 2) treatment in follicular lymphoma (FL) ( Marques-Piubelli, Blood Adv 2022). As pre-clinical studies suggest that BTK inhibition can mitigate the crosstalk between monocyte/macrophages and FL B cells, we hypothesized that acalabrutinib, a specific BTK inhibitor, may synergize with R 2 without increasing toxicity. In agreement with this, the combination of acalabrutinib and R 2 (aR 2) was shown to be safe and effective in patients with relapsed FL ( Strati P et al, ASH 2022). Here, we investigated the safety and efficacy of aR 2 in previously untreated FL patients and analyzed the biological effects of this combination on peripheral blood immune cells. Methods. This phase 2 single arm study (NCT04404088) was conducted between 09/2020 and 09/2021 (data cutoff 06/2023). Adult patients with previously untreated FL, grades 1 to 3A, stage 3-4, and meeting indication for treatment per GELF criteria were included. Treatment consisted of acalabrutinib lead-in at 100 mg PO twice a day for one 28-day cycle and continued for total of 13 cycles, lenalidomide 20 mg PO daily on days 1-21, during cycle 2-13, and rituximab 375 mg/m 2 IV weekly during cycle 2, and on day 1 of cycle 3-13. The primary endpoint was best complete response (CR) rate per Lugano 2014 criteria. Bulk RNA sequencing with deconvolution to characterize circulating immune cells was performed on peripheral blood collected at baseline, and on day 1 of cycles 2 and 6. Results. We enrolled and treated 24 patients. Baseline characteristics are shown in the Table. Median number of cycles was 13 (range, 6-13) and 15 (62.5%) patients experienced a cycle delay, due to COVID19 in 11 (46%) cases; 6 (25%) patients required dose reduction of lenalidomide, but none discontinued, and 2 (8%) required dose reduction of acalabrutinib and 1 discontinued. The most common (>5% of patients) grade 3-4 adverse events were neutropenia (58%), liver function test elevation (17%), infection (12.5%; 2 out of 3 related to COVID19), anemia (8%) and skin rash (8%). Best ORR was 100%, best CR rate was 92%, and median time to CR was 3 months ( Figure). After a median follow-up of 26.8 months (95% CI 24.6-29.6 months), 6 (25%) patients had disease progression, including 2 who transformed at 5 and 7 months. The 2-year PFS rate was 79.2% (95% CI, 64.5-97.2%). At data cutoff, 2 patients have died, 1 due to COVID19 (while in CR, at 14 months) and 1 due to transformed lymphoma (at 10 months). The 2-year OS rate was 91.7% (95% CI, 81.3-100%). While the frequency of circulating immune cells were unchanged after single agent acalabrutinib, its use associated with a significant decrease in the expression of VMO1 (FDR 0.001), a gene encoding for a protein expressed on extra-cellular exosomes derived from non-classical monocytes, and a significant increase in gene signatures of monocyte proliferation (p=0.01), TNF response (p=0.01), anti-viral (p=0.006) and anti-tumoral activity (p=0.009), consistent with the expected effect of BTK inhibition in monocytes. After 5 cycles of aR 2, we observed a decrease in the frequency of circulating B cells (p=0.003) and regulatory NK cells (p=0.01), and an increase in the frequency of circulating naive T cells (p=0.004), CD4+ T cells (p=0.005) and classical monocytes (p=0.003). Conclusion. Our results indicate that the addition of acalabrutinib to R 2 is a safe and effective frontline non-chemotherapy regimen for FL patients, resulting in high CR rates, and induces favorable biological changes in multiple circulating immune cells. Since CRs occurred early, the study has been amended to include 26 additional patients who will be treated with only 6 cycles of aR2.

A Phase I/II Study of Combination of ASTX727, Gilteritinib and Venetoclax in Patients with Relapsed/Refractory FLT3 Mutated Acute Myeloid Leukemia (AML)

Background Activating mutations in FLT3 occur in approximately 30% of patients (pts) with AML. Gilteritinib (GILT), a second-generation type I oral FLT3 inhibitor, has been approved in pts with relapsed/refractory (R/R) FLT3-mutated AML. We conducted a phase I/II study to evaluate the combination of decitabine/cedazuridine (ASTX727), venetoclax (VEN), and GILT in pts with FLT3-mutated R/R AML or intermediate-2/high risk MDS/CMML. Methods This phase I/II study included pts with 1) R/R FLT3-mutated AML or R/R intermediate-2/high risk MDS/CMML or 2) newly diagnosed FLT3-mutated AML unfit for intensive chemotherapy (eligible for phase II only). Here we report the initial data from the R/R cohort. In the phase I portion there was no restriction to the number of prior therapies received; however, in the phase II portion pts who had received ≥3 prior therapies were excluded. Pts with FLT3-ITD and/or TKD mutations were eligible. Pts were required to have a performance status ≤3, total bilirubin ≤2.5 x ULN, ALT/AST ≤3 x ULN, and creatinine clearance ≥30 mL/min. In cycle 1 (C1), pts received decitabine/cedazuridine (35mg/100mg) orally on days 1-5, VEN (ramp-up to 400mg with adjustment for concomitant azole) orally on days 1-28, and GILT orally continuously. The GILT dose ranged from 80mg to 120mg daily during the phase I dose escalation (3+3 design). A bone marrow biopsy was performed on day 14, and if blasts were <5% or the marrow was insufficient/aplastic, the VEN was held. For C2 and beyond, ASTX727 was given for 5 days, VEN was given for 14-21 days and GILT was given continuously. The primary endpoint for the phase I was the MTD; and for the phase II, the overall response (defined as CR, CRh, CRi, or MLFS within 2 cycles of therapy). Results The phase I portion is complete with 12 pts enrolled (11 AML, and 1 high-risk CMML). Nine pts received GILT 80mg and 3 received 120mg. No DLTs at either dose level were observed. However, 80mg of GILT was selected for the phase II portion of this study based on the more favorable safety/efficacy profile and better count recovery observed in a parallel study of azacitidine combined with VEN and GILT in AML. In the combined phase I/II cohort of pts with R/R AML or MDS/CMML, 15 pts have been treated. The median age was 65 years (range 38-83 years). Thirteen pts had a FLT3-ITD mutation (including 2 with a concomitant TKD mutation), and 1 pt had a FLT3-TKDmutation alone. Among pts with a FLT3-ITD, the median allelic ratio was 0.21 (range, 0.09 - 10.6). Among pts with a FLT3-TKD, the median allelic ratio was 0.05 (range, 0.02-0.09). Nine pts had diploid karyotype, 2 had adverse risk karyotype, and 4 had miscellaneous, intermediate-risk cytogenetic findings. The median number of prior therapies was 1 (range 1-9). Among the 15 pts treated, 8 (53%) responded: 1 (6%) with CRh, 3 (20%) with CRi, and 4 (27%) with MLFS. The pt with an isolated FLT3-TKD mutation (along with del7q) did not respond. The pt with high-risk CMML achieved a CRi. Six of 12 pts who received prior HMA + VEN responded (2 CRi and 4 MLFS), and 2 of 3 pts without prior HMA + VEN responded (1 CRh and 1 CRi). The median number of cycles received by pts was 2 (range 1-8). Best response was achieved by the end of C1 in 50% of responders, and by the end of C2 in the other 50% of responders. Of the 8 responders, 1 proceeded to alloSCT (with flow positive MRD at 0.3% but FLT3 negative by PCR), 1 is still receiving treatment on protocol with continued response, 5 relapsed without HSCT (median time to relapse 2 months [range, 0.5-7 months]), and 1 died in MLFS. The transplanted pt remains in MRD-negative remission 5 months after alloSCT and is receiving maintenance GILT off protocol. With a median follow-up of 3.8 months (range, 1-18 months), the median overall survival for the cohort was 6.1 months. There were 3 pts with grade 1-2 toxicities (1 with elevated liver enzymes, 2 with skin rash), 9 pts with grade 3 toxicities (9 with neutropenic fever, 4 of which became septic), no pts with grade 4 toxicities, and 2 patients with grade 5 toxicities (both had neutropenia and died from sepsis while on trial). Conclusion In this poor-risk population of pts with R/R FLT3-mutated AML or MDS/CMML, many of whom received prior HMA + VEN, the combination of ASTX727, VEN, and GILT was active, with an ORR of 53%. The trial continues to enroll to the R/R cohort, and is now open for patients with newly diagnosed FLT3-mutated AML who are unsuitable for intensive chemotherapy.

Ixazomib, Pomalidomide and Dexamethasone (IxaPD) Pan-Oral Regimen in the Treatment of Refractory and Relapsed Multiple Myeloma

Aim To analyze the efficacy and safety of Ixazomib, pomalidomide and dexamethasone (IxaPD) regimen in patients with refractory and relapsed multiple myeloma（RRMM）. Methods Clinical data of RRMM patients were collected from 5 centers in north China from Jan 2021 to Aug 2023, who were treated by IxaPD regimen for at least two courses. Response, time to next treatment and overall survival were analyzed as end points. Results A total of 34 patients were enrolled, including 21 in multicenter real-world study and 13 in investigator initiated IxaPD trial (NCT04989140) who were naïve to ixazomib or pomalidomide with previous treatment of 1 to 3 lines. There were 18 males and 16 females with the median age 65.5 (range 41-81) years old. The median duration from diagnosis to enrollment was 31 months (range 1-117), including 23/34 (67.3%) of patients were in first relapse. Thirteen in 24 (54.2%) patients had high-risk cytogenetic abnormalities. Regarding previous history, 20.6% presented renal insufficiency, 3 cases (8.8%) had extramedullary diseases, and 5 cases (14.7%) received autologous hematopoietic stem cell transplantation. After median 5 courses (range 2-24) of IxaPD chemotherapy, the overall response rate (ORR) was 64.7%, with 47.1% VGPR or better. The median time to achieve the best response was 2 months (range 1-6). After a median follow-up of 13 months (range 2-28), 52.9% of patients progressed and the median time to next treatment was 7 months (range 3-21). The mortality rate was 17.6%, and the median overall survival was not reached. In the multivariate analysis, response to first-line induction therapy significantly affected the time to next treatment(P<0.05), while age, first relapse, R-ISS stage, high-risk cytogenetics abnormalities, and renal insufficiency did not impact significantly. Neither did those factors also have significant impact on overall survival. Most of the adverse effects (AEs) were grade 1-2, mainly skin rash, peripheral neuropathy, constipation, diarrhea, edema, arthralgia, herpes zoster, and shortness of breath. Only one case of grade 3 pulmonary infection occurred. Conclusion The pan-oral IxaPD regimen showed anticipated effect and good tolerance for RRMM patients, especially appropriate for patients achieving deep response in first-line therapy. More patients are being enrolled and update data will be reported.

Responses to Combination Chemotherapy with MAPK Pathway Inhibition in Relapsed and Refractory LCH

MAPK pathway inhibition (MAPKi) is associated with high response rates in patients with Langerhans cell histiocytosis (LCH), but monotherapy may not be curative and efficacy in LCH-associated neurodegeneration (LCH-ND) is not known. Based on upregulation of Bcl-xL by MAPK activation, we hypothesize that MAPKi may render LCH cells more sensitive to chemotherapy-induced cytotoxicity. We assessed the safety and efficacy of combination therapy in 10 patients with refractory systemic disease and LCH-ND. Records of patients treated with combination therapy at Texas Children's Hospital from October 2018 to July 2023 were reviewed for clinical responses as well as peripheral blood/tissue BRAFV600E mutation status, ataxia rating scores, and toxicity. The median age at the start of combination therapy was 6.82 years (range, 0.48-20.45 years) with a median of 4 treatments prior to this therapy regimen (range, 1-14). Almost all Clofarabine was administered outpatient (typical starting dose 25 mg/m2/day x 5 days). MAPK inhibitors included BRAFV600E inhibitors (50%) and MEK inhibitors (50%). Overall response was 8/10 (80%), with 5/5 (100%) objective response rate (ORR) for systemic disease. Further, 5/6 (83%) demonstrated reduced or extinguished peripheral BRAFV600E+ fraction by the end of combination therapy. Ataxia rating scores were improved in 2/3 (67%) individuals with clinical neurodegeneration. Common toxicities during treatment included fever, skin rash, arthralgia, and cytopenia. Combining therapy was well-tolerated and associated with clinical and molecular improvement in most patients with highly refractory systemic LCH and LCH-ND. Further prospective multi-center trials are required to optimize this approach, determine potential for combination therapy to achieve cure, and compare risks and benefits to chemotherapy or MAPK inhibitor monotherapy.

The Impact of Continuous Lenalidomide Maintenance Treatment on People Living with Multiple Myeloma - a Single-Centre Qualitative Service Evaluation

Background: Randomised trials examining continuous lenalidomide maintenance after autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) have demonstrated progression free survival (PFS) and overall survival benefit compared to placebo. In 2021 the UK National Institute of Clinical Excellence (NICE) approved lenalidomide maintenance for all newly diagnosed National Health Service (NHS) patients receiving ASCT after induction chemotherapy. Patient-reported outcomes from observational studies suggest lenalidomide causes tolerable adverse effects. However, clinical trial data demonstrate that neutropenia, fatigue, neuropathy, and gastrointestinal issues are common, particularly in the first six months of treatment, and that lenalidomide increases the risk of secondary malignancies. Before lenalidomide maintenance was used in this setting, individuals would typically enter a treatment-free phase after ASCT, where they might experience a reasonable quality of life (QoL) without treatment burden. Studies suggest that medication breaks allow patients to detach from the ‘illness’ experience, but with continuous lenalidomide that opportunity is lost. Whilst the PFS benefit of lenalidomide maintenance is proven, both short- and longer-term toxicities reported in clinical trials suggest the trade-off between efficacy and harm should be considered. In-depth information about how continuous lenalidomide impacts individuals' QoL is scant. The overall objective of this qualitative service evaluation was to examine patients' experience of lenalidomide maintenance, including perceived impact on QoL and experience of side-effects. It was anticipated that findings would result in clinical service improvement through the delivery of communication better suited to patients' needs and priorities when facing treatment choices. Methods: We conducted 20 one-to-one semi-structured interviews with purposively selected patients (10 female and 10 male) from a specialist MM center in London. All participants had undergone induction chemotherapy followed by ASCT and were receiving continuous lenalidomide. Ages ranged from 45 to 71 years (median 58). The sample comprised 12 White British, 2 Black Caribbean, 1 Black African, 1 Asian Indian, 2 from other ethnic groups and 2 with undisclosed ethnicity. Lenalidomide treatment duration varied; seven patients had received lenalidomide for 1-6 months, five for 7-12 months, five for 13-18 months, one for 19-24 months, and two for over 24 months. Reflexive thematic analysis was used for data analysis. Results: Four themes were developed from the data: 1) Lenalidomide: understanding its role and rationale, 2) Reframing the loss of a treatment-free period to a return to normal life, 3) The reality of being on continuous lenalidomide maintenance: balancing hopes with hurdles, 4) Gratitude and Grievances: Exploring patients' mixed perceptions of care and communication. Most patients believed lenalidomide maintenance would double remission time and were compelled by the relative certainty it offered, which contrasted with the unpredictability of MM. Many participants reported that lenalidomide helped to diminish fears about relapse, and thus most did not feel they were missing out on a treatment break. The impact of lenalidomide maintenance on patients' QoL varied; younger patients reported no/negligible side-effects, while several older patients with comorbidities described significant symptom burden, such as skin rashes, debilitating fatigue, unpredictable gastric disturbances and bone pain, occasionally leading to treatment discontinuation which caused distress at the perceived loss of prolonged remission. The transition from frontline to maintenance treatment required a return to greater patient autonomy as medical support was reduced. Some patients described anxiety and depression in this period, suggesting the need for greater support. The study also highlighted specific challenges that younger patients experience, such as concerns about sexual transmission and fertility, which merits further research. Conclusions: Understanding the real-world symptom burden in MM is key as continuous treatment becomes routine. Qualitative research on the impact of treatment could lead to a more comprehensive understanding, helping patients cope with the increasingly chronic nature of this disease.

Safety and Efficacy of Bortezomib-Pomalidomide-Dexamethasone (VPD) As Novel Induction Therapy in Newly-Diagnosed Multiple Myeloma: Updated Data from an Ongoing Single Arm Phase-II Investigator- Initiated Clinical Trial (PRIME Study)

Introduction: Pomalidomide is a third-generation immunomodulatory drug approved for relapsed and/or refractory Multiple Myeloma (RRMM). In a phase 3 OPTIMISMM trial, Pomalidomide, Bortezomib, and Dexamethasone demonstrated superior efficacy in patients with RRMM. PRIME study (CTRI/2019/10/021618) is testing Bortezomib, Pomalidomide and Dexamethasone combination in Newly Diagnosed Multiple Myeloma (NDMM). Initial data of 26 patients was presented as abstract in 63rd ASH Annual Meeting and Exposition. Current abstract is reporting the results of 46 patients with a longer follow up of this ongoing study. Objectives: Primary objective is to determine the efficacy of VPD regimen by measuring Minimal Residual Disease (MRD) assessment by flow-cytometry after 9 cycles of VPD. Secondary objectives are to determine response rates, PFS and safety of the regimen Methods: A prospective, single arm, phase II study from a tertiary care center. Both transplant eligible and ineligible patients with NDMM aged between 18-70 years as defined by the International Myeloma Working Group (IMWG) are being recruited in the study. The regimen consists of weekly Bortezomib 1.3mg/sq m, Pomalidomide 2 - 4mg once daily for 21days and Dexamethasone 20mg twice weekly, in a 28 days cycle for 9-12 cycles. Transplant patients planned for 9 cycles and non-transplant patients for 12 cycles of VPD. Eligible patients underwent High dose chemotherapy followed by Autologous HCT after 4-6 cycles of VPD. After Auto HCT 3-5 cycles of VPD given as consolidation therapy. After 9-12 cycles of VPD maintenance treatment given as per institutional practice. A 2-tube 8-colour antibody panel was used for MRD analysis using Flowcytometry (BD FACS CANTO-II) and analysed on Kaluza version. 1.3 software. A valve of < 0.001% was considered as MRD negative. Results: In this ongoing study, out of the proposed 50 patients, 46 patients were enrolled between April 2020 to June 2023. Median follow up is 24.5 months. The median age was 55 years (38-70), and gender ratio 1:1. At disease presentation, bone lesions was the commonest (91.3%, n 42) finding. The most common myeloma subtype was IgG Kappa in 43.5% (n 20). High risk cytogenetics were seen in 43.5% (n 20) and 43.5% (n 20) of patients were in RISS stage III (Table 1). Out of 46 patients 41 (89.1%) have completed 4 cycles and 30 (65.2%) patients have completed 9 cycles of VPD till last follow up (June, 2023). One patient had withdrawn consent, two patients were out of study due to increasing peripheral neuropathy (Grade 3). Five deaths occurred, 2 post cycle 8 and 3 after cycle 9. Four deaths were due to infections (COVID 19 and bacterial) and one due to progressive disease. Five patients underwent auto HCT (between Cycle 4 to 6). No patient failed stem cell mobilization, 2 patients required plerixafor in addition to G-CSF for mobilization. Table-1 shows drug-induced toxicity and response rates. Hematological toxicities were the commonest followed by fever, infections and skin rash. Majority of nonhematological adverse events were grade 1 to 2 and protocol was well tolerated. Protocol adherence was 97.8% (45/46 patients). After 4 cycles (n 43), 13 (30.2%) patients were in stringent complete response (sCR), 2(4.7%) in CR, 24 (55.8%) in very good partial response (VGPR) and 2 (4.7%) in partial response. After 9 cycles (n 35), 16 (45.7%) patients were in sCR, 2(5.7%) in CR and 11 (31.4%) in VGPR. Two (5.7%) patients had progressive disease (PD) and 3 patients were out of study due to consent withdrawn and toxicity. After 4 cycles of VPD 21 (48.8%) patients were MRD negative and MRD negative rate improved after 9 cycles to 74.3% (26 patients). Two years Progression Free survival (PFS) was 77.2% +/- 7.7% (Figure 1), disease free survival was 90.3% +/- 5.3% and overall survival (OS) was 83.1% +/- 7%. Conclusion: Safety data from the PRIME study demonstrates that VPD regimen has a favorable tolerance profile in patients with NDMM and no clinically significant impact on stem cell mobilization or engraftment. Early efficacy signals are encouraging, and recruitment continued. VPD has shown improved depth of response (MRD negativity) and overall response rate. Early follow up results shows promising PFS and OS results. VPD may be a promising induction regimen instead of Dara VRD in resource constrain setting where Daratumumab is not readily accessible. Phase 3 randomized trials are the way forward to its clinical use in frontline setting.

The Updated Results of Asciminib Managed-Access Program (MAP) in Patients with Chronic Myeloid Leukemia in Russia

Background: Therapy choice in chronic myeloid leukemia (CML) patients (pts) with ≥2 lines of tyrosine kinase inhibitors (TKIs) failure or in pts with T315I mutationis a relevant problem. Efficacy and good tolerability of a first-in-class BCR::ABL1 allosteric inhibitor Asciminib (ASC) in chronic phase (CP) CML pts were confirmed in clinical trials. The out-study world data of ASC use in Managed Access Program (MAP) is of particular interest. Aim: to report the updated results of the ASC use within MAP in 3 clinical centers of Russia. Methods : Adult (≥18 years) CML pts with the lack of efficacy or intolerance to ≥2 lines of TKIs or T315I-positive pts after ≥1 prior TKI were included into a MAP. Inclusion criteria for our analysis were: CML-CP, ASC therapy for >3 months (mo). Two dosing regimen were used: 40 mg BID in BCR::ABL1 T315I-negative pts (40BID group) and 200 mg BID in BCR::ABL1 T315I-positive pts (200BID group). Complete cytogenetic response (CCyR, equivalent of MR2 or BCR::ABL1≤1%), major molecular response (MMR) and deep molecular response (MR4) achievement was assessed by cumulative incidence function (CIF) with Gray's test for comparison. Survival analysis was performed by Kaplan-Meier method according to “intention-to-treat” principle. Results: A total 82 pts received ASC in the MAP, 68 of them met the criteria for analysis (baseline characteristics are in table 1), while 14 were excluded. The median follow-up was 26 mo (range 4-49). The 2-year overall survival was 93% and 83%, the progression free survival was 90% and 70% in 40BID and 200BID groups, respectively. In 40BID group 17/43 pts discontinued ASC: 2 progressed to AP/BP, 2 - for bone marrow transplantation (BMT), 13 - failure (3 pts died due to CML after ASC discontinuation). In 200BID group 12/25 pts discontinued ASC: 2 developed AP, 3 -BMT, 7 - failure (one pt died). CIF of CCyR/MMR/MR4 by 24 mo was 58%/68%/19% in 40BID group and 65%/56%/32% in 200BID group. The achieved CCyR was preserved in 93% (14/15) and 77% (10/13) pts in 40BID and 200BID group, respectively. CIF of MMR in ponatinib-naïve pts was higher in both groups than in ponatinib-pretreated pts (picture). Dose escalation to 80-100 mg BID in 8/43 pts of 40BID group (due to lack of efficacy) resulted in achieving MMR for 2/8 pts with no MMR before escalation. Dose reduction in two groups was done both for adverse events (AEs) grade 3-4 (n=8) and stable MR4,5. In 4 pts (200BID) with no AEs and having a stable MR4,5 for >1 year, no MR4,5 loss was observed after ASC dose reduction to 100 mg BID. Subclone with emerging a new mutation was detected in 3 pts of 40BID group (A337T, G250A, T315I) while no new mutations were found in 200 mg BID group. AEs associated with ASC have been identified in 27/43 pts and 13/25 pts in 40BID and 200BID group, respectively, with no significant difference in AE spectrum and frequency. Most common (≥5%) AEs in two groups were: thrombocytopenia (29%), neutropenia (18%), cholesterol high (13%), anemia (6%), skin rash (5%). AEs grade 3-4 were detected in 13 (30%) and 4 (16%) pts in 40BID and 200BID group, respectively, and mostly presented by hematologic/cytopenic AEs (24%). No pt discontinued ASC due to toxicity, no arterial occlusive AEs were observed. Conclusion: ASC shows effectiveness and good safety profile in pts after prior failure to TKIs and those with T315I mutation. The CIF of any response was higher in ponatinib-naive pts at any dose. Different mutational subclones evolution was observed, including emergence of myristoyl-site mutation in 1 pt. ASC half dose reduction was safe in pts with previous MR4,5 stable response.

Predictive Value of Elevated Tryptase and Mediator Symptoms in Systemic Mastocytosis - a Single Center Experience

Background: Systemic mastocytosis (SM) is a rare clonal hematologic disorder primarily driven by the KIT D816V mutation in almost all (95%) patients. These patients most often have elevated serum tryptase levels and can present with a wide spectrum of symptoms caused by mediator release from clonal mast cell degranulation (e.g., skin rash, anaphylaxis, diarrhea, and neurocognitive symptoms). However, these symptoms are similar in other non-clonal mast cell disorders such as idiopathic mast cell activation syndrome (MCAS) and hereditary alpha-tryptasemia (HaT). As such, many patients are referred to hematology for SM work-up based on elevated serum tryptase and mediator release symptoms. We evaluated a real-world single-center experience determining whether elevated serum tryptase, mediator release symptoms, and/or a history of anaphylaxis correlated with a diagnosis of SM. Methods: We conducted a retrospective chart review of patients referred to the Mastocytosis Clinic at Huntsman Cancer Institute at the University of Utah for a year between August 2022 and July 2023. Data were collected by chart review and analyzed for disease characteristics, laboratory values, and diagnostic outcomes. Findings/Results: There were a total of 37 patients referred to us during the designated time period with either a tryptase value greater than 10.9 ug/L or abnormal mast cells found on tissue biopsy (e.g., skin, colon, etc) with or without systemic mediator release symptoms. Patients did not have to have a history of anaphylaxis to be seen. Of these, 7 patients already had a known diagnosis of SM and had bone marrow biopsy at an outside institution. Of the 30 remaining patients, 19 (63%) patients reported a history of at least one mediator release symptom, defined as pruritus, flushing, syncope, bloating, nausea, vomiting, or diarrhea. The median serum tryptase level was 17.4 ug/L. (Range 2 - 317 ug/L). KIT D816V mutation was detected in the peripheral blood by digital droplet PCR in 7 (23.3%) patients. Diagnostic bone marrow was done in 19 patients wherein 6 (31.5%) of them met the WHO diagnostic criteria for SM. Of these patients, 5 patients tested positive for KIT D816V mutation on peripheral blood and 1 patient had KIT wild type. Two patients with KIT D816V mutations did not receive bone marrow biopsy as they had no mediator release symptoms. The remaining 13 patients had a bone marrow biopsy but did not have a diagnosis consistent with SM, although some had rare scattered mast cells identified in the marrow. They were all KIT D816V mutation negative and serum tryptase ranged from 2.7 - 43 ug/L. As of the date of data analysis, 4 (30.7%) patients tested positive for HaT; serum tryptase ranged from 20 - 26 ug/L in this cohort. Conclusion: While SM can have a variety of clinical manifestations, including elevated tryptase level and mediator release symptoms, the presence of KIT D816V in the peripheral blood is a strong predictor of SM diagnosis. Persistently elevated serum tryptase without the KIT D816V mutation may suggest the likelihood of HaT, while only mediator release symptoms with normal serum tryptase and without the KIT mutation is a strong negative predictor of SM and HaT.

Subcutaneous (SC) Mosunetuzumab (mosun) As First-Line Therapy for Patients (pts) with High Tumor-Burden Follicular Lymphoma (FL): First Results of a Multicenter Phase 2 Study

Introduction: Cytotoxic chemotherapy plus anti-CD20 antibodies is the current standard of care for pts with newly diagnosed high-burden FL. While effective, this approach is burdened by toxicities, including infections and second cancers, and up to 20% of pts progress within 2 years and have poor outcomes. Intravenous (IV) mosun is a CD20xCD3 bispecific antibody recently approved for the treatment of pts with relapsed or refractory FL based on remarkable efficacy data, and its activity may be even greater in chemotherapy-naïve patients. Furthermore, SC mosun proved as effective as, and possibly better tolerated than, the IV formulation while increasing administration efficiency and convenience. Here, we present the first results of a phase 2 multicenter trial of SC mosun in patients with untreated high-burden FL. Methods: Key eligibility criteria included: Age ≥18 years, stage 2-4 FL in need of therapy per GELF criteria, being fit for chemoimmunotherapy, adequate bone marrow and organ function. SC mosun was administered at the dose of 5 mg on D1 and 45 mg on D8 and D15 of C1, and 45 mg on D1 of each subsequent 21-day cycle. Premedication consisted of dexamethasone, diphenhydramine, and acetaminophen before each mosun dose during C1 and on C2D1 if cytokine release syndrome (CRS) occurred in C1. Subjects with ≥3 CRS risk factors (stage 3-4, bulky disease, bone marrow (BM) involvement, elevated LDH) received dexamethasone 10 mg for 3 days with each mosun dose in C1 and C2. Prophylactic hospitalization was not required. Treatment lasted 8 cycles in pts who achieved complete response (CR), and up to 17 in those with partial response. Response was assessed per the Lugano 2014 and LYRIC 2016 criteria. BM evaluation was mandated in pts with baseline BM involvement who achieved radiographic CR. CRS and neurotoxicity were graded per the 2019 ASTCT criteria. Results: Between July 2022 and July 2023, 43 pts were enrolled. Median age was 55 years (range 26-77), 40% of pts had bulky disease (≥7 cm), 25% had grade 3A FL, and 27% had a FLIPI score ≥3. The median SUV max was 11.5 (range 3.7-41.1)(Table). At the cutoff date of 07/21/2023, 4 pts were in screening, 22 were on treatment, and 13 completed treatment. Four pts discontinued therapy early due to progressive disease (1), or adverse events (AE) (3, one related to study drug). Out of 230 patient-cycles administered, 9 (4%) were delayed due to AEs, by a median of 13 days (range 7-17). Among 39 safety-evaluable pts, the most common treatment-emergent AE were injection site reaction (72%, all G1), CRS (51%), fatigue (33%), dry skin (33%), skin rash (26%), ALT elevation (23%), and AST elevation (21%). G≥3 neutropenia occurred in 4 pts (10%), while infections occurred in 10 pts (26%), and were G1-2 in 8 cases and G3 in 2 cases. One pt died of cardiac arrhythmia in the setting of COVID19-associated pneumonia. CRS occurred most commonly after C1D1 and was G1 in 18 pts (90%) and G2 in 2 (10%). Median time to onset of the first CRS episode was 31h (2-91). Hospitalization and tocilizumab were only required in the two pts who experienced G2 CRS. Twenty-six pts were evaluable for response (1 had concurrent neoplasm at first response assessment, 1 had indeterminate response (IR)3 per LYRIC criteria, and 15 are yet to be evaluated). The best overall response rate was 96% and the CR rate was 81%. All 22 CR were seen at the first response assessment (Figure). Similar response rates were observed among higher-risk subgroups, including pts with high-risk FLIPI (figure), grade 3A FL (ORR 100%, CR 75%), bulky disease (ORR 100%, CR 82%), or SUVmax ≥13 (ORR 83%, CR 83%)). At a median follow-up for response-evaluable pts of 6.0 months, 2 pts have experienced progression, one with CD20-negative FL at the end of therapy, the other with DLBCL diagnosed 6 weeks after treatment initiation on a left axillary lymph node with baseline SUV 41 and not previously biopsied. Conclusion: SC mosun demonstrated a manageable safety profile and highly encouraging efficacy in pts with newly diagnosed high-burden FL, including those with higher-risk disease. Assessment of durability of responses will require additional follow-up. Enrollment continues and updated data will be presented.

Real-World Experience of Ropeginterferon-Alfa Treatment of PV and ET - Two Centers Experience

BACKGROUND AND AIM: Interferon alpha is an effective treatment for Polycythemia Vera (PV) and Essential Thrombocythemia (ET) and is the only treatment known to induce sustained molecular responses by decreasing JAK2 mutation allelic burden. Long-acting pegylated interferons are better tolerated. Ropeginterferon-alfa is a monopegylated interferon with a longer half-life and is the first interferon to be FDA-approved for the treatment of PV. It is not yet approved for ET, but clinical trials are ongoing. Given the similar disease biology between PV and ET and the efficacy of pegylated interferon-alfa in both PV and ET, this study aims to look at a real-world experience of treating PV and ET with ropeginterferon-alfa since its approval. METHODS: We conducted a retrospective chart review of all our PV and ET patients treated with ropeginterferon-alfa at Huntsman Cancer Institute, University of Utah (SLC cohort), and at the University of North Carolina at Chapel Hill (UNC cohort), since the drug's approval for PV from November 2021 through June 2023. The complete hematologic response (CHR) was defined as the normalization of blood counts within the reference range of the local lab standards. Prior to ropeginterferon-alfa, the participants were managed with therapeutic phlebotomies, or cytoreduced with either hydroxyurea, pegylated interferon-alpha 2a ( Pegasys), JAK2 inhibitors, or were newly diagnosed and previously untreated. RESULTS: A total of 120 patients (76 in SLC cohort and 44 in UNC cohort) were included in this study. Of those, 75 (62.5%) were diagnosed with PV, 37 (31%) with ET, and 1 with congenital polycythemia due to germline JAK2 mutation. Twenty-three (19%) patients had a prior history of thrombosis. JAK2 mutation was present in 100 (83%) patients, while 9 (7.5%) were CALR mutated, 1 with MPL mutation, and 1 with triple-negative ET. Extended myeloid gene panel sequencing was available in 64 (53.3%) patients and 35 of them (54.6%) patients had additional somatic mutations. Most common somatic mutations include TET2 (11 patients) and DNMT3A (8 patients) and CBL (3 patients), among others. Of the cohort, 15 (12%) patients discontinued ropeginterferon-alfa due to various adverse events, which included: fatigue, joint aches, skin rash, and increased anxiety and depression. Of the 105 patients who are on ropeginterferon-alfa, 9 patients were previously untreated patients while 96 (91.4%) were pretreated with other therapies and switched to ropeginterferon-alfa. In many patients, the switch to ropeginterferon-alfa was done because of the increased frequency and aggressivity of squamous cell skin cancers while on hydroxyurea treatment. All of them started ropeginterferon-alfa at a dose of either 50 mcg or 100 mcg every two weeks and were increased at an increment of 50 mcg to achieve a goal of CHR. As most of the patients were switching from prior therapies, 51 (49%) were already in CHR at the time of initiating ropeginterferon-alfa. The median ropeginterferon-alfa dose to maintain CHR was 50mcg in the SLC cohort and 100mcg in the UNC cohort. (See table for more details). We have 6 patients with DNMT3A mutation, 4 (66.6%) have achieved CHR at a median ropeginterferon-alfa dose of 100 mcg (range 50 mcg - 150 mcg), and 2 patients are undergoing dose titration. Of the 11 patients with TET2 mutation, 7 (63.3%) achieved CHR at a median ropeginterferon-alfa dose of 150 mcg (range 50 mcg - 500 mcg). The analysis of JAK2 V617F and CALR allelic burden, transcripts of inflammatory, prothrombotic, and hypoxia-regulated (HIFs) genes, and evaluation of females for reversal of clonal to polyclonal myelopoiesis is ongoing. CONCLUSION: Ropeginterferon-alfa is effective in PV and ET, however, the dose that achieves CHR is highly individualized, necessitating an incremental titration approach. The patients already in CHR from prior therapy needed relatively lower doses of ropeginterferon-alfa to maintain CHR. Clinical trials are ongoing with an alternate accelerated dosing scheme and results are awaited.

Efficacy of Consolidation Therapy with Ponatinib 15mg on Treatment-Free Remission Rate in Patients with Chronic Myeloid Leukemia. Results of the Ponazero Trial

Introduction: Discontinuation of tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has become part of routine clinical practice in recent years, thanks to growing evidence on their feasibility and safety. However, and despite adequate patient selection based on current recommendations, loss of response is observed in approximately 50% of patients. In this scenario, efforts are focused on finding strategies to increase the rate of successful discontinuations. Ponatinib has shown to induce deeper molecular responses compared with imatinib, but its risk of arterial occlusive events (AOE) limits its use in first line at its standard dose of 45mg. The risk of AOEs appears to be dose-related and following the results of the OPTIC study, dose reduction to 15mg in patients with good response is an increasingly popular strategy. Under these premises it has been postulated that a consolidation with ponatinib 15mg may increase the proportion of patients who could discontinue treatment successfully. Our aim is to evaluate the efficacy and safety of one year of consolidation therapy with ponatinib 15mg on treatment-free remission (TFR) rate in patients with CML who have achieved a deep molecular response with imatinib. Material and Methods: A multicenter open-label, single-arm, phase II, exploratory, prospective clinical trial (NCT 04043676) was conducted including patients with philadelphia-positive CML who met discontinuation criteria according to European LeukemiaNet recommendations, had received 4 years or more of imatinib therapy, with a documented grade 4 molecular response (MR4) at least 12 months prior to study entry. Uncontrolled arterial hypertension, active cardiovascular disease, or concomitant medication with potential for QTc prolongation were exclusion criteria. The study has two main phases: ponatinib consolidation (48 weeks), and ponatinib TFR phase (48 weeks); where patients remain without treatment. During the TFR phase, patients with a confirmed loss of MR4 or a single value above major molecular response (MMR) were scheduled to restart treatment with a TKI at investigator's discretion. The present abstract reports the results of the primary endpoint of the study; the proportion of patients with no loss of MR4 at the end of the TFR phase. Results: A total of 23 patients started treatment with ponatinib 15mg. One patient subsequently failed screening due to a major protocol deviation. Baseline patient characteristics were as follows: median age was 51.8 years (range 26-74), 65.2% were male. Ninety-five percent were Caucasian and 5% were Hispanic, ECOG was 0 in 83% and 1 in 17%, Sokal was low in 69.5%, intermediate in 17.5% and unknown in 13%. Eighteen patients were receiving imatinib 400mg daily (82%) at study entry, 2 patients 800mg and two 200mg. Median time on prior imatinib was 10 years (range 4-17), with a median time on MR4 of 3.6 years (range 1.9-13.3). Prior to initiation 13 patients (56.5%) had a grade 5 molecular response, 4 had a 4.5 molecular response (26%) and the remainder had a MR4. The adverse events (AEs) reported with ponatinib are summarized in Table 1, the most frequent being constipation (30%), asthenia (26%), myalgias and arthralgias (26% respectively) and skin rash (17%). A high rate of SARS-CoV2 infections was reported during the treatment period (26%), which should be interpreted considering that the study took place during the COVID-19 pandemic. Three patients out of 22 (13.6%) had serious AEs with ponatinib leading to treatment discontinuation; thrombophlebitis, erectile dysfunction, and intermittent claudication. Of the patients who entered the TFR phase, 14/19 (74%) continue with MMR without requiring treatment after a median follow-up of 12 months (68% with MR4) (table 1). Six patients (31%) lost MR4, five of them required reintroduction of an TKI (4 imatinib, 1 dasatinib; median time to reintroduction 5.4 months). All patients with MR4 loss were receiving the 400 mg dose of imatinib at study entry. All patients who restarted treatment recovered MMR. The sixth patient lost MR4 while maintaining an MMR without requiring treatment reinduction to date. Conclusions: Consolidation with 12 months of ponatinib 15mg in this study shows a high discontinuation success rate with an adequate safety profile, although not free of AEs. The results make this approach attractive for the design of further randomized clinical trials.