Event-free Survival In Patients Research Articles

A randomized, multicenter, open-label, phase III trial comparing anthracyclines followed by taxane versus anthracyclines followed by taxane plus carboplatin as (neo) adjuvant therapy in patients with early triple-negative breast cancer: Korean Cancer Study Group BR 15-1 PEARLY trial.

LBA502 Background: Triple-negative breast cancer (TNBC) is known for its high risk of early relapse and poor prognosis. Platinum agents have shown to increase pathological complete response (pCR) rates when added to neoadjuvant chemotherapy for TNBC. However, evidence regarding the survival benefit of platinum in this setting remains inconclusive. The PEARLY trial is a multicenter, randomized, open-label, phase 3 study designed to assess the efficacy and safety of carboplatin in combination with anthracycline/taxane therapy compared to standard anthracycline/taxane alone as either neoadjuvant or adjuvant treatment in early-stage TNBC. Methods: Patients with stage II or III TNBC were randomly assigned to either the carboplatin arm or the standard therapy arm, stratified by nodal status, institution, treatment setting (neoadjuvant vs adjuvant), and germline BRCA status. The standard therapy involved doxorubicin and cyclophosphamide (AC) followed by taxane treatment. The experimental arm included carboplatin in addition to taxane following AC. The primary endpoint was event-free survival (EFS), defined as disease progression or inoperable status for neoadjuvant therapy group, local or distant recurrence, occurrence of a second primary cancer, or death from any cause, while secondary endpoints encompassed overall survival (OS), invasive disease-free survival (IDFS), distant recurrence-free survival (DRFS), pCR rate, and safety. With a planned enrollment of 878 patients, the trial aimed for 80% power to detect a hazard ratio of 0.70 for EFS at a two-sided alpha level of 0.05, anticipating 248 EFS events over a 5-year follow-up period. Results: Between Jan 2016 and Jun 2020, 868 patients across 22 institutions in South Korea were enrolled. At a median follow-up of 51.1 months, carboplatin significantly improved EFS compared to the control arm (hazard ratio [HR], 0.68; 95% confidence interval [CI]: 0.50 to 0.93; p=0.017). The 5-year EFS rates were increased from 74.4% to 81.9%, demonstrating a 7.5% difference. Subgroup analysis showed consistent benefits across various patient categories. Secondary endpoints like IDFS and DRFS also favored carboplatin arm. OS data were immature, a total of 43 patients (10.2%) in the carboplatin arm and 57 patients (13.1%) in the control arm died (HR 0.66; 95% CI: 0.42 to 1.01). Grade ≥3 treatment-related adverse event rates were 74.6% (1 death due to infection) in the carboplatin arm and 56.7% (2 deaths due to infection and suicide) in the control arm. Conclusions: The addition of carboplatin to standard anthracycline followed by taxane therapy significantly improved EFS in patients with early-stage TNBC. The safety profile was consistent with the known expectations for each regimen. Clinical trial information: NCT02441933 .

Abstract PO5-18-09: Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial

Abstract Background Anthracycline and taxane-based chemotherapy are the corner stone of neoadjuvant therapy in early breast cancer. Anthracycline-free regimens have been addressed widely because of cardiac toxicity especially in HER2-positive breast cancer when combining trastuzumab and pertuzumab. Aim of this trial was to assess the efficacy and safety of nab-paclitaxel combined with carboplatin in the neoadjuvant therapy of non-luminal breast cancer. Methods The Neopath trial was a prospective, single-arm phase II trial conducted in Comprehensive Breast Health Center, Ruijin Hospital between April 2019 and October 2021. Patients who had cT2-4NanyM0 or cTanyN1-3M0 triple negative breast cancer (TNBC) or HER2-positive breast cancer were enrolled. Patients were treated with neoadjuvant nab-paclitaxel (100 mg/m2) and carboplatin (area under the curve 2) on days 1, 8, and 15, for four 4-week cycles. Concurrent trastuzumab at 2 mg/kg (loading dose 4 mg/kg) and pertuzumab 420 mg (loading dose 840 mg) were given in patients with HER2-positive tumors. Surgery was performed after 4-6 cycles of neoadjuvant therapy. Trastuzumab and pertuzumab after surgery was continued every 3 weeks for a total duration of 1 year. The primary endpoint was pathological complete response (pCR) rate, defined as no invasive tumor in breast and axillary lymph nodes (ypT0/Tis N0) after neoadjuvant therapy. Secondary endpoints were pCR rate in predefined subgroups, pCR (ypT0 N0), objective response rate (ORR); event-free survival (EFS), breast conservation rate and toxicity. Results A total of 106 patients were enrolled in the study and 99 of them proceeded to surgery. The pCR (ypT0/is N0) rate was 41.41% in total, 33.78% in TNBC and 64.00% in HER2-positive breast cancer. Proportion of patients achieving pCR (ypT0 N0) was 38.38% in total, 31.08% in TNBC and 60.00% in HER2-positive tumors. In the ITT population, 93 patients were event-free at a median follow-up of 24 months, while 5 in TNBC group and 1 in HER2-positive group had relapse or distant metastasis. EFS in patients achieving pCR was higher than patients without pCR (HR=7.328, 95%CI=1.453-36.96, p=0.0158). ORR was 72.49% in total, 67.12% in TNBC and 88.00% in HER2-positive breast cancer. Total breast conservation rate was 10.1% and 12.2% in TNBC, 4.0% in HER2-positive subgroup. The most frequent grade 3 or higher adverse events were neutropenia (57%), vomiting (11%) and thrombocytopenia (8%). Conclusion Neoadjuvant anthracycline-free regimen of nab-paclitaxel combined with carboplatin in non-luminal breast cancer was an effective and well-tolerated regimen. Citation Format: Deyue Liu, Li Zhu, Jiayi Wu, Wei Wang, Shuning Ding. Anthracycline-free neoadjuvant therapy with nab-paclitaxel and carboplatin in non-luminal breast cancer: a single-arm phase II trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-18-09.

Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume

AbstractMetabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [median or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem cell transplantation in patients who had a response). All P values are descriptive. Within high- and low-MTV subgroups, event-free survival (EFS) and progression-free survival (PFS) were superior with axi-cel vs standard care. EFS in patients with high MTV (vs low MTV) was numerically shorter with axi-cel and was significantly shorter with standard care. PFS was shorter in patients with high MTV vs low MTV in both the axi-cel and standard-care arms, and median MTV was lower in patients in ongoing response at data cutoff vs others. Median MTV was higher in patients treated with axi-cel who experienced grade ≥3 neurologic events or cytokine release syndrome (CRS) than in patients with grade 1/2 or no neurologic events or CRS, respectively. Baseline MTV less than or equal to median was associated with better clinical outcomes in patients receiving axi-cel or standard care for second-line LBCL. The trial was registered at www.clinicaltrials.gov as #NCT03391466.

Local Treatment of Children Suffering From Parameningeal Rhabdomyosarcoma: A Retrospective Single-Center Study From China.

Treatment for parameningeal rhabdomyosarcoma (PM-RMS) has been a challenge since local control is difficult. The goal of this study was to analyse the impact of different local treatment approaches on childhood PM-RMS patients and help dispel the doubt that whether secondary radical surgery (SRS) should be encouraged in the management of PM-RMS. A total of 17 children with PM-RMS who received unified systemic chemotherapy and individualized local therapy such as radiotherapy (RT) and/or SRS were included in this retrospective study. The overall survival (OS) and event free survival (EFS) were compared between groups adopting different local strategies. The 3-year OS and EFS of our PM-RMS patients was 75.5% and 56.5% respectively. The OS and EFS of patients who received SRS were both significantly lower than that of the non-SRS group (3-year OS: 50.0% vs 90.0%, P = .031; 3-year EFS: 33.3% vs 60.6%, P = .020). The OS and EFS of the patients who received RT was higher than that of the patients of the non-RT group (3-year OS: 85.6% vs 0%, P = .001; 3-year EFS: 64.0% vs 0%, P = .011). This study illustrates that SRS was associated with poor prognosis of PM-RMS and should not be routinely performed. Optimized RT strategies along with more intensive chemotherapy may be alternative options to improve the survival of patients with PM-RMS. Multi-center, large sample and prospective studies are needed to further validate these findings.

Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

Validation of Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event-Free Survival in Intermediate and High-Risk Hodgkin Lymphoma

Background: Improving risk stratification of patients with Hodgkin lymphoma (HL) allows for optimization of treatment allocation and minimization of late effects when possible. The Childhood Hodgkin International Prognostic Score (CHIPS) was developed as a predictive model for event-free survival (EFS) in pediatric and adolescent HL using clinical data at diagnosis from patients with intermediate-risk HL treated on Children's Oncology Group protocol AHOD0031 (NCT00025259) with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and response-adapted radiation. Stage IV, large mediastinal mass, albumin &amp;lt;3.5 g/deciliter, and fever were identified as independent predictors of EFS and assigned one point each, resulting in CHIPS ranging from 0 to 4. CHIPS was highly predictive of EFS in this patient cohort, but has not been validated in high-risk patients or in patients treated with other therapeutic regimens. We aim to validate the CHIPS as a risk stratification tool for patients with intermediate or high-risk HL treated with Stanford V chemotherapy by the Pediatric Hodgkin Consortium (PHC). Methods: The PHC trial HOD99 (NCT00145600) enrolled patients on the high-risk arm with stage IIB, IIIB, or IV disease &amp;lt;22 years (n=123). HOD05 (NCT00352027) enrolled patients with intermediate-risk HL with stage IB, IA or IIA with “E” lesions, ≥3 nodal sites, or bulky mediastinal adenopathy, or IIIA disease &amp;lt;22 years (n=49). All patients received 12 weeks of Stanford V chemotherapy with doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone followed by low-dose, response-adapted radiation therapy. All patients with absent B symptoms were deemed afebrile; patients missing documentation of any elements of CHIPS were excluded from the analysis. Results: Our final analysis included a total of 164 patients, 116 with high-risk HL from HOD99 and 48 with intermediate-risk HL from HOD05. One patient was excluded for missing fever data and 7 were excluded due to missing albumin values. Patients were classified into 2 groups based on their CHIPS value: CHIPS 0-1 (n=88, 53.7%) and CHIPS 2-4 (n=76, 46.3%). The EFS for patients in the CHIPS 0-1 and CHIPS 2-4 groups was analyzed using Kaplan-Meier curves (Figure 1). The 2-year EFS estimates for patients with CHIPS 0-1 and CHIPS 2-4 were 95.5% (95% confidence interval (CI) 91.2%-99.9%) and 80.3% (95% CI 71.8%-89.7%), respectively, with a log-rank p-value of 0.003. Similarly, the 4-year EFS estimates for patients with CHIPS 0-1 and CHIPS 2-4 were 93.2% (95% CI 88.0%-98.6%) and 77.6% (95% CI 68.7%-87.6%), respectively, with a log-rank p-value of 0.004. The reduced EFS in patients with higher CHIPS is consistent across different stages and early response assessment (Table 1). Conclusions: CHIPS is highly predictive of EFS in pediatric and adolescent patients with intermediate and high-risk HL treated with Stanford V chemotherapy, as it identifies a subset (CHIPS 2-4) with significantly lower EFS compared to the other subset (CHIPS 0-1). Assessment of CHIPS alongside novel approaches such as circulating tumor DNA and total metabolic tumor volume should be analyzed across trials to allow for further enhancements to risk stratification for pediatric, adolescent and young adult HL.

CD3xCD20 Bispecific Antibodies Yields Long-Term Survival in Relapsed/Refractory B Cell Lymphoma: A Follow-up Study of Patients Treated in Pivotal Phase 1/2 Trials

Introduction: T-cell engaging CD3xCD20 bispecific antibodies like glofitamab, mosunetuzumab and epcoritamab are a new group of immunotherapies with promising results in B-cell lymphomas. T-cell engaging antibodies might have milder adverse effect profile compared to chimeric antigen receptor T-cell therapy (CAR-T). However, the duration of response to these new agents is still uncertain and follow-up times for glofitamab and epcoritamab have been short. We performed extensive follow-up of all patients in Denmark who received CD3xCD20 bispecific antibodies in early pivotal phase 1 / 2 trials to map the response, adverse effects and long-term survival, and baseline correlates with these outcomes. Methods: Patients who received T-cell engaging CD3xCD20 bispecific antibodies from 2017 to 2023 as part of a clinical trial were included. The patients' electronic health records were assessed for sex, age, prior therapy, dose received, stage of disease, response according to Lugano criteria, target lesion response, Cytokine Release Syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity (ICANS) events, infections leading to hospitalization, event-free and overall survival. Kaplan-Meier estimates were provided for all time-to-event end points. Hazard ratios with two-sided 95% confidence intervals were calculated from a Cox proportional-hazards model. Results: A total of 130 patients with relapsed/refractory B cell lymphoma who received bispecific CD3xCD20 antibodies were analyzed. The median age of patients was 70 years (21 to 87 years) and 58% were male. The median number of prior lines of therapy was 3 and the median Ann Arbor stage was 4. B-symptoms were present in 18% of patients before treatment. The median follow-up time from first treatment was 14.8 months (4 to 74 months). Best overall response rate in all patients was 75% (95% CI, 67-83); 54 patients (45%) had complete response (CR), and 37 patients (31%) had partial response (PR). Among patients with a complete response (CR), the median duration of response was 22.5 months and 29.4 months in patients with DLBCL and follicular lymphoma, respectively. Among all patients, the most common adverse effects included CRS (max. grade 1 n=45, max. grade 2 n=28, max. grade 3 n=3 max. grade 4-5 n=0), Varicella Zoster infections (n=8), hypogammaglobulinemia (n=14), therapy-related leukemia (n=3) and autoimmune colitis or hepatitis (n=5). Two patients were diagnosed with ICANS, both grade 1. A total of 54 patients were hospitalized due to infections either during or after treatment. The most common infectious agents that lead to hospitalization were Sars-Cov2 (n=20) and Varicella zoster (n=8). Among patients who received the recommended phase two dose (R2PD) the incidence of CRS was 63% while patients who received doses lower than R2PD had an incidence of 53%. At 12 months after the first treatment, the rate of overall survival (OS) was estimated to 65% in all patients (95% CI, 57-74). (Figure 1), while it was 67% (95% CI, 56-68) in patients who received the recommended phase 2 dose (R2PD). The 24-month overall survival of all patients was estimated at 55 % (95% CI, 45-64), while the 24-month overall survival for patients who had received R2PD was 58% (95% CI, 45-70). The 24-month event free survival of all patients was estimated at 42% (95% CI, 33-51), while the 24-month event free survival for patients who had received the recommended phase 2 dose was 50% (95% CI, 39-62) Five patients died of disease progression within 30 days after first treatment. No deaths were attributed to bispecific antibodies or CRS. Among patients with a complete response (CR) the rate of PFS at 12 months was 84% (95% CI, 75-95). Of the patients who achieved complete remission, 73% (95% CI, 59-87) were still in complete remission after 36 months (Figure 1). Conclusions: We here present long-term national follow-up of heavily pre-treated patients who have received glofitamab or epcoritamab as part of early pivotal phase 1 / 2 trials. We found an overall response rate of 75% in all patients with 45% achieving complete remission. Most common adverse events were CRS and hypogammaglobulinemia, with the incidence of ICANS being notably low. Additionally, we found that CD3xCD20 bispecific antibodies can induce durable long-term responses with 73% of those who achieve complete remission still being in remission after 3 years.

Similar Overall Survival and Event-Free Survival for Patients Under or over the Age of 14 Years, but More Chronic Graft Versus Host Disease and Non-Relapse Mortality in the “Older” Patients

Purpose: In the prospective, randomized, multinational FORUM trial, total body irradiation and etoposide were statistically more effective than chemoconditioning (Peters et al, JCO 2021; FORUM study; EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). The multivariate analysis in this cohort showed an inferior overall survival (OS) for patients (pts) over the age of 10 years, HR 1.8 (95% CI, p=0.048). To update these findings, we examine the impact of age at allogeneic hematopoietic stem cell transplantation (HSCT), we analyzed 791 FORUM pts who received TBI and etoposide as conditioning regimen between April 2012 and March 2022 and compared their outcomes according to different age categories. Patients and Methods: Almost all patients were transplanted in second or first complete remission (CR2) (47%, n=370; CR1: 46%, n=361, &amp;gt;CR3: 8%, n=59), from matched unrelated donors (MUD) 70%, n=552, HLA-identical sibling donors (MSD) 30%, n=239, bone marrow (BM) 70%, n=551, or cord blood (CB) 3%, n=26. Median age at HSCT was 10 years (4-21). Median observation time was 2.3 years (0.3 to 8) (Table 1: Basic Characteristics). The conditioning regimen consisted of total body irradiation (TBI) - 6 fractions of 2 Gy on 3 consecutive days followed by 60 mg/kg body weight etoposide (max 1800 mg/m2, total upper dose limit 3.6 g). GVHD prophylaxis was CSA only for MSD receiving bone marrow. ATG/CSA/MTX was used for the MUD HSCT group. Results: 127 evaluable pts were transplanted between 4-6 years (group 1), 249 between 6-10 years (group 2), 231 between 10-14 years (group 3), and &amp;gt; 14 years were 184 pts (group 4) (n.s.) By the 4 age groups, the 5-year OS was 0.83±0.04 (group 1), 0.75±0.04 (group 2), 0.75±0.04 (group 3), and 0.74±0.04 (group 4), respectively, p = 0.133. Five-year event-free survival (EFS) was also similar for all age groups: 0.71 ± 0.06, 0.72 ± 0.04, 0.66 ± 0.05, 0.69 ± 0.04 (p=0.611): Figure 1. The three-year cumulative relapse incidences (CIR) were 0.23±0.04, 0.19±0.03, 0.14±0.03, and 0.17±0.03, respectively (p=0.286). Non-relapse mortality (NRM) was significantly lower in the two younger age groups (0.02 ± 0.01 group 1 and 0.05 ± 0.02 group 2) compared to 0.11 ± 0.02 in both older age groups (p = 0.047). The primary causes of death in the 18/184 pts in group 4 were as follows: infections (fungal, viral, bacterial): n=8, acute and chronic graft versus host disease (aGVHD, cGVHD): n=3, sinusoidal obstruction syndrome, coagulopathies: n=4, multi-organ failure: n=3. Among the 767 evaluable pts, 503 (66%) had no or grade1 aGVHD, 188 (25%) had grade 2 aGVHD, and 76 pts (11%) had grade3 to 4 aGVHD; in patients &amp;gt; 14 years 22 (14%) had a grade 3 to 4 aGVHD (p = 0.624). The 3-year incidence of extensive cGVHD was significantly higher in pts older than 14 years (0.21±0.03 vs. 0.10±0.03, 0.11±0.02 and 0.14±0.03, respectively), which also translated into significantly better extensive cGVHD-free, relapse-free survival (cGRFS) for the younger cohorts (Table 1). To date, the overall incidence of secondary malignancies in this cohort is 0.01 (n = 11) with no significant differences in the 4 age categories. In the age group &amp;gt; 14 years, in 98 pts transplanted in first CR vs. &amp;gt; CR1 (n=86), 5-year OS is 0.83±0.04 and 0.63±0.06, respectively (p=0.005). Similarly, 5-year EFS was 0.79±0.05 and 0.56±0.07, respectively (p=0.002). In multivariate analysis, OS, EFS, CIR was not influenced by donor type and pts' age at transplant. However, NRM was higher in pts older than 14 years, the hazard ratio (HR) being 4.8 (1.4-16; p=0.012) as compared to patients aged 4-6 years. Remission status (CR1 vs. &amp;gt;CR1) had significant impact on EFS with HR of 1.6 (1.1-2.1; p= 0.004) and CIR (HR 1.7; 1.1-2.4; p= 0.012). Conclusions: In the FORUM trial, patients who underwent allogeneic HSCT from HLA-identical or HLA-matched unrelated donors older than 4 years and younger than 21 years who received myeloablative conditioning with TBI/etoposide had similar overall and event-free survival regardless of age at HSCT. The incidence of chronic GVHD and NRM was higher in patients &amp;gt; 14 years compared to younger patients.

Long-Term Outcome of 1296 Patients with Newly Diagnosed with APL: A Harmony Alliance Study

Background: APL, a rare and aggressive subtype of acute myeloid leukemia (AML), is now curable in 75-90% of patients using targeted agents [All-trans retinoic acid (ATRA)/Arsenic Trioxide (ATO) or ATRA combined with chemotherapy (ATRA+Idarubicin, AIDA-based)]. Despite significant advances in survival, most reports are based on low patient numbers, which limit reliability of data. Aims: to study factors associated with outcome in a large patient cohort diagnosed with APL, and treated according to two European trials (UK AML-17 and GIMEMA APL0406), or recorded in national registries from 6 countries, enrolled in the HARMONY database. Methods: The Harmony platform includes to-date 1868 patients with APL, diagnosed between 2007 and 2020. The present analysis was performed on 1296 patients, who met the data quality requirements, by evaluating the list of variables shown in Table 1. Patients were treated according to APL0406 and AML17 clinical trials, or were included in the Study Alliance Leukemia (SAL), Swedish Cooperative Group or AML study Group (AML-SG) registries. After acquisition from the sources, data were harmonized and transformed using an Observational Medical Outcomes Partnership Common Data Model, and registered in the HARMONY Big Data Platform. Results: Of 1296 patients, 562 were treated with ATRA-ATO (median age 51 yrs, range 16-94; M:F ratio 1), and 605 with ATRA-Idarubicin (AIDA, median age 50 yrs, range 17-86; M:F ratio 1) (p for age groups according to treatment=0.3538). According to Sanz risk-score, 250 patients (44.4%) were low-risk (LR), 258 (45.9%) intermediate-risk (IR), and 50 (8.9%) high-risk (HR) in the ATRA-ATO cohort. The AIDA cohort included 191 LR (31.5%), 235 IR (38.8%), and 171 HR (28.3%) patients (p for risk groups according to treatment: &amp;lt; 0.001). Treatment data were not available in 8 patients (1.3%) The 10-year overall survival (OS) was 90% and 77% in ATRA-ATO vs AIDA groups, respectively (p&amp;lt;0.001, figure 1), while event-free survival (EFS) was 86% and 67%, respectively (p&amp;lt;0.001). At a median follow-up of 4.5 yrs (range 0.02 - 10.2), OS and EFS in patients treated with ATRA-ATO was similar in the three Sanz-risk classes (OS: LR: 94.6%, IR: 91%, HR: 85.6%, p=0.233, EFS: LR: 93.1%, IR: 88.7%, HR: 85.7%, p=0.319). The median follow-up of patients treated with AIDA was 6 yrs (range: 0-14.2). OS was 87.8% in LR, 83.5% in IR, and 74.8% in HR (p=0.004), while EFS was 72% in LR, 74.8% in IR, and 67.2% in HR (p=0.102). OS was significantly associated with age (&amp;lt;50 yrs: n=611, 50-69: n=516, &amp;gt;70: n=169), both overall (p&amp;lt;0.001), and within treatment groups (ATRA-ATO: p&amp;lt;0.001, AIDA: p&amp;lt;0.001). EFS also correlated with age subgroups, both overall (p&amp;lt;0.001) and according to treatment (ATRA-ATO: p&amp;lt;0.001, AIDA: p&amp;lt;0.001). No differences in OS were detected in between de-novo and secondary APL (p=0.746) both in ATRA-ATO (p=0.720) and in AIDA (p=0.766) cohorts. Patients treated outside the clinical trial context had inferior outcomes when compared to clinical trials, with a significant higher rate of early deaths (ED, 10% vs 2.8%, p&amp;lt;0.001), and inferior survival with major differences for the AIDA cohort (8-year OS: 73.6% vs 88.2%, p&amp;lt;0.001, EFS: 69.3% vs 71.7%, p=0.291), versus the ATRA-ATO cohort (8-year OS: 88% vs 93.3%, p=0.010, 8-years EFS: 80.6% vs 92.4%, p&amp;lt;0.001). The multivariate analysis for OS showed that age (50-69 vs &amp;lt;50 years, p&amp;lt;0.001, HR 4.2; &amp;gt;70 vs &amp;lt;50 years p&amp;lt;0.001, HR 8.9), Sanz-risk score (High vs Low/Intermediate p&amp;lt;0.001, HR 2), treatment type (AIDA vs ATRA-ATO p=0.001, HR 1.9) and treatment context (clinical trial vs non-clinical trial p=0.005, HR 1.7) were independent predictors of OS. The multivariate analysis for EFS showed an independent correlation with type of treatment (AIDA vs ATRA-ATO, p&amp;lt;0.001 HR 2.6), age (50-69 vs &amp;lt;50 years, p&amp;lt;0.001, HR 2.1; &amp;gt;70 vs &amp;lt;50 years p&amp;lt;0.001, HR 4.8) and Sanz-risk score (High vs Low/Intermediate p=0.005, HR 1.5), but not with treatment context. In multivariate analysis treatment type was the only predictive factor for early deaths (AIDA vs ATRA-ATO, p=0.047 HR 2.04). Summary/Conclusions: The analysis at long-term of the Harmony APL registry confirmed that patients treated with the ATRA-ATO chemo-free regimen present a significant survival advantage vs the AIDA regimen, with reduced ED rates and prolonged OS, independent of Sanz-risk score. Patients enrolled in clinical trials presented improved survival both in AIDA and in ATRA-ATO cohorts.

Abstract 15640: Long Term Event-Free Survival in Patients With Ischemic and Non-Ischemic Cardiomyopathy up to Thirteen Years Following Cell-Based Therapy: Results From the Hyperion Observational Cohort

Introduction: The long-term clinical outcomes of cell-based therapies to treat ischemic (ICM) and non-ischemic dilated cardiomyopathy (NIDCM) are unknown. We therefore prospectively followed patients (pts) with ICM/NICDM treated by targeted transcatheter endocardial mesenchymal stromal cell (MSC) injections (TESI). Methods: Of the 155 pts enrolled in prior MSC TESI studies, 111 were eligible to be contacted. Of these, 47 (42%) agreed to participate and have periodic follow-up assessments (Cardiac MRI/CT, 6MWT, labs, PE, EKG, and MLHFq) for up to 13 years following their index procedure. Time-to-event information was captured from all 155 former participants. Endpoints included event-free survival, changes in left ventricular ejection fraction (EF), and ventricular remodeling. Clinical endpoint events were defined as the composite of: Death (all-cause mortality), Left Ventricular Assist Device (LVAD) placement, or Heart Transplant. Descriptive statistics were used to classify the sample, and Kaplan-Meier survival analysis was generated to examine time-to-event trends. Results: There were 134 men and 21 women, mean age 60.0±11.0 years, including 121 (78%) with ICM, and 34 (22%) with NIDCM. In pts with ICM, mean EF at baseline was 31 %±10.8% and after 1 year was 32.6%±11.8% (P=0.08). In pts with NIDCM baseline EF was 27%±10% and increased to 34%±13% after 1 year (P=0.002). Overall, 40% of pts had a decrease in LVEF, 26% had &lt;5% increase, 34% had a ≥5% increase, and 17% had a ≥10% increase in LVEF after 1 year. Increases of ≥5% LVEF post-therapy were associated with longer event-free survival in NIDCM (OR: 2.57; 95% CI: 0.6, 11.1) but not ICM (OR: 1.25; 95% CI: 0.4, 3.6). Conversely, reductions in LVEDV were associated with longer event-free survival in ICM (OR: 7.23; 95% CI: 1.9, 27.1) but not NIDCM (OR: 1.88; 95% CI: 0.4, 10.0). Conclusion: In this long-term observational cohort analysis, improvement of EF and/or reduction in LVEDV was associated with survival benefits among pts with NIDCM and ICM respectively. Future studies are needed with placebo controls to determine which pts are most likely to respond to MSC therapy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov.; Unique ID: NCT03071835.

Event-free survival in patients with polycythemia vera treated with ropeginterferon alfa-2b versus best available treatment

Event-free survival in patients with polycythemia vera treated with ropeginterferon alfa-2b versus best available treatment

Impact of BRAFV600E Mutation on Event-Free Survival in Patients with Papillary Thyroid Carcinoma: A Retrospective Study in a Romanian Population.

We aimed to evaluate the prognostic value of BRAFV600E mutation in a series of 127 papillary thyroid carcinoma (PTC) cases as a single factor, and in synergic interaction with other standard risk factors. BRAFV600E mutation was assessed by real-time PCR. Event-free survival (EFS) was calculated between the date of the first evaluation and the date of occurrence of an adverse event or the date of the last known status. The prevalence of BRAFV600E mutation was 57.2%. The Kaplan-Meier analysis showed a significant reduction of EFS among cases harboring BRAFV600E mutation compared to non-mutated cases (p = 0.010). In addition, BRAFV600E mutation was found to better predict adverse outcomes when associated with the following risk factors: age ≥ 55 years old (p < 0.001), male gender (p < 0.001), conventional (p = 0.005) and tall cell (p = 0.014) histology, tumor size > 40 mm (p = 0.001), extrathyroidal extension (p = 0.001), multifocality (p = 0.001) and lymph node metastasis (p < 0.001). In univariate analysis, a 3.74-fold increased risk for a reduced EFS (p = 0.018) was found for BRAFV600E-mutated cases, but no increased risk was further confirmed by multivariate analysis. Our results highlight that BRAFV600E mutation cannot be used alone as an independent predictive factor in PTC patients, but is prognostically valuable if integrated in the context of other clinicopathological risk factors.

Prospective use of molecular minimal residual disease for risk stratification in children and adolescents with acute lymphoblastic leukemia : Long-term results of the AIEOP-BFM ALL 2000 trial in Austria.

Since 1979 Austrian children and adolescents with acute lymphoblastic leukemia (ALL) have been treated according to protocols of the Berlin-Frankfurt-Münster (BFM) study group. The Associazione Italiana di Ematologia eOncologia Pediatrica and BFM (AIEOP-BFM) ALL 2000study was designed to prospectively study patient stratification into three risk groups using minimal residual disease (MRD) on two time points during the patient's early disease course. The MRD levels were monitored by detection of clone-specific rearrangements of the immunoglobulin and T‑cell receptor genes applying aquantitative polymerase chain reaction-based technique. The 7‑year event-free survival (EFS) and overall survival rates for all 608 Austrian patients treated between June 1999 and December 2009 within the AIEOP-BFM 2000study were 84 ± 2% and 91 ± 1%, respectively, with amedian observation time of 6.58years. Event-free survival for patients with precursor B‑cell and T‑cell ALL were 84 ± 2% (n = 521) and 84 ± 4% (n = 87; p = 0.460), respectively. The MRD assessment was feasible in 94% of the patients and allowed the definition of precursor B‑cell ALL patients with alow, intermediate or high risk of relapse even on top of clinically relevant subgroups.A similar finding with respect to MRD relevance in T‑ALL patients was not possible due to the small number of patients and events. Since this pivotal international AIEOP-BFM ALL 2000 trial, molecular response to treatment has been continuously used with additional refinements to stratify patients into different risk groups in all successive trials of the AIEOP-BFM ALL study group.

Treatment with idelalisib in patients with chronic lymphocytic leukemia – real world data from the registry of the German CLL Study Group

Idelalisib in combination with rituximab is an efficacious treatment for patients suffering from chronic lymphocytic leukemia (CLL) with known limitations due to toxicities. However, the benefit after prior Bruton tyrosine kinase inhibitor (BTKi) therapy remains unclear. For this analysis, 81 patients included in a non-interventional registry study of the German CLL study group (registered at www.clinicaltrials.gov as # NCT02863692) meeting the predefined criteria of a confirmed diagnosis of CLL and being treated with idelalisib containing regimens outside clinical trials were considered. 11 patients were treatment naïve (13.6%) and 70 patients (86.4%) pretreated. Patients had median of one prior therapy line (range 0–11). Median treatment duration with idelalisib was 5.1 months (range 0–55.0 months). Of 58 patients with documented treatment outcome, 39 responded to idelalisib containing therapy (67.2%). Patients treated with the BTKi ibrutinib as last prior treatment prior to idelalisib responded in 71.4% compared to a response rate of 61.9% in patients without prior ibrutinib. Median event free survival (EFS) was 15.9 months with a 16 versus 14 months EFS in patients with ibrutinib as last prior treatment or not, respectively. Median overall survival was 46.6 months. In conclusion, treatment with idelalisib appears to have a valuable impact in patients being refractory to prior ibrutinib therapy even though there are limitations in our analysis due to the low number of patients included.

Molecular profile &amp; clinical outcome in 121 cases - experience from a tertiary referral centre in South India

Ewing sarcoma is the second most common sarcoma involving the bones in children and adolescents. Published data on the clinical features, morphology, translocation and follow-up of patients with Ewing sarcoma from India, is sparse. Objectives of this study were to analyse the clinico-pathologic features of Ewing sarcoma and compare with translocation status, BCoR immunohistochemistry, treatment and survival. 406 cases of Ewing sarcoma were diagnosed in the Department of Pathology, Christian Medical College, Vellore during the period 2008-2015. 135 patients underwent molecular testing for common translocations by RT-PCR and were included in this study.Mean age of patients at diagnosis was 22 years. Most common location of tumour was appendicular skeleton (31.4%) and 19% had solid organ involvement. Distant metastasis was present in 21.5% patients. Translocation was seen in 63 (46.7%) cases, EWS-FLI1 type I (87%), EWS-FLI1 type II(11%) and one patient had EWS-ERG translocation. Seven out of 30 patients were classified as “Sarcoma with BCOR genetic alteration”. Patients who underwent 6 cycles of chemotherapy had a better mean survival. Mean follow-up was 13.72 months and 3 year event free survival of patients was 93.8%.Percentage of viable tumour &amp;#60;10% was the only significant histologic parameter predicting survival. Age at diagnosis ≤15yrs, female sex, size ≤12cm, extra-osseous site, chemotherapy and translocation positivity predicted an improved survival. This study has analysed the type of mutations/translocations seen in a subset of Indian patients with Ewing sarcoma and correlated the clinical and pathological factors affecting survival.

Survival and prognostic factors in pediatric patients with medulloblastoma treated at a national pediatric hospital in Peru: a retrospective cohort.

The objectives of this study were to determine the overall survival (OS) and event-free survival (EFS) rates of patients with medulloblastoma treated in a national pediatric hospital in Peru, as well as to identify demographic, clinical, imaging, postoperative, and histopathological characteristics and prognostic factors associated with OS and EFS. The authors conducted a retrospective study analyzing information from the medical records of children with a diagnosis of medulloblastoma who underwent surgical treatment at the Instituto Nacional de Salud del Niño-San Borja, a public hospital in Lima, Peru, from 2015 to 2020. Clinical-epidemiological variables, degree of disease extension, risk stratification, extent of resection, postoperative complications, status of oncological treatment received, histological subtype, and neurological sequelae were taken into account. The Kaplan-Meier method and Cox regression analysis were used to estimate OS, EFS, and prognostic factors. Of the 57 children evaluated with complete medical records, only 22 children (38.6%) underwent complete oncological treatment. OS was 37% (95% CI 0.25-0.55) at 48 months. EFS was 44% (95% CI 0.31-0.61) at 23 months. High-risk stratification-meaning patients with ≥ 1.5 cm2 of residual postoperative tumor, those younger than 3 years, those with disseminated disease (HR 9.69, 95% CI 1.40-67.0, p = 0.02), and those who underwent subtotal resection (HR 3.78, 95% CI 1.09-13.2, p = 0.04)-was negatively associated with OS. Failure to receive complete oncological treatment was negatively associated with OS (HR 20.0, 95% CI 4.84-82.6, p < 0.001) and EFS (HR 7.82, 95% CI 2.47-24.7, p < 0.001). OS and EFS of patients with medulloblastoma in the author's milieu are below those reported in developed countries. Incomplete treatment and treatment abandonment in the authors' cohort were also high compared with high-income country statistics. Failure to complete oncological treatment was the most important factor associated with poor prognosis, both in terms of OS and EFS. High-risk patients and subtotal resection were negatively associated with OS. Interventions are needed to promote the completion of adjuvant oncological therapy for medulloblastoma in the disadvantaged Peruvian population.

Perioperative toripalimab + platinum-doublet chemotherapy vs chemotherapy in resectable stage II/III non-small cell lung cancer (NSCLC): Interim event-free survival (EFS) analysis of the phase III Neotorch study.

425126 Background: Adjuvant and neoadjuvant immunotherapy have been approved by US FDA to treat early-stage NSCLC. However, the optimal neoadjuvant and adjuvant treatment, including duration of treatment, are unknown. We present the interim results of a randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy in resectable stage III NSCLC. Methods: Patients with stage II/III resectable NSCLC, without EGFR/ALK alterations for non-squamous NSCLC, were randomly assigned 1:1 to receive 240 mg toripalimab or placebo combined with chemotherapy Q3W for 3 cycles before surgery and one cycle after surgery, followed by toripalimab or placebo monotherapy Q3W for 13 cycles. Stratification variables for randomization included disease stage, histopathologic subtype, PD-L1 expression and surgical procedure. Primary endpoints were EFS by investigator and major pathological response (MPR) rate by a blinded independent pathologic review (BIPR) in the stage III and the ITT populations. Secondary endpoints included overall survival (OS), pathologic complete response (pCR) rate, EFS by independent review committee (IRC), and safety. A planned interim analysis was performed on the primary endpoint of EFS in the stage III subjects. Results: A total of 404 patients with stage III NSCLC were randomly assigned to toripalimab (n=202) or placebo (n=202). By the data cutoff date (November 30, 2022), the median follow-up was 18.3 months. Baseline characteristics were well balanced between the two arms. EFS was significantly improved in the toripalimab arm, HR=0.40, 95% CI (0.277-0.565), P&lt;0.0001, and crossed the pre-specified efficacy boundary. The median EFS was not reached in the toripalimab arm and 15.1 months in the placebo arm. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups. The MPR and pCR rates per BIPR were also higher in the toripalimab arm, 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The OS results showed a trend favoring toripalimab. The incidence of Grade ≥3 adverse events (AEs) (63.4% vs 54.0%), fatal AEs related to toripalimab/placebo (0.5% vs 0%) and AEs leading to discontinuation of toripalimab/placebo (9.4% vs 7.4%) were comparable between the two arms. However, the incidence of immune-related AEs (42.1% vs 22.8%) was more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to perioperative chemotherapy showed statistically significant improvements in EFS for patients with stage III NSCLC with a manageable safety profile. Patients will be followed for overall survival. Clinical trial information: NCT04158440 .

Haematopoietic cell transplantation for children with acute megakaryoblastic leukaemia without Down syndrome.

Patients with acute megakaryoblastic leukaemia of Down syndrome (DS-AMKL) have an excellent survival rate; however, patients with non-DS-AMKL experience poor outcomes. Therefore, this study retrospectively analysed 203 children with non-DS-AMKL who underwent their first haematopoietic cell transplantation (HCT) from 1986 to 2015 using a nationwide Japanese HCT registry data to assess HCT outcomes for non-DS-AMKL. The 5-year overall survival (OS) and event-free survival (EFS) rates were 43% and 38% respectively. The 5-year OS rate was significantly higher for patients who underwent HCT in the first complete remission (CR1, 72%) than for those in the second CR (CR2, 23%) and non-CR (16%) (p < 0.001), and for those from a human leukocyte antigen (HLA)-matched (52%) than for those from an HLA-mismatched donor (27%) (p < 0.001). Multivariate analysis for OS revealed that HCT in CR2 and non-CR was a significant risk factor (hazard ratio, 5.86; 95% confidence interval, 3.56-9.53; p < 0.001). The 3-year EFS in patients who received HCT in CR1 using reduced-intensity conditioning (RIC, 35%) was significantly lower than in those using myeloablative conditioning (busulfan-based, 71%; total body irradiation-based, 58%) (p < 0.001). Risk stratification in patients with non-DS-AMKL should be established to determine HCT indication in CR1.

Ga-68-Edotreotide Positron Emission Tomography/Computed Tomography Somatostatin Receptors Tumor Volume Predicts Outcome in Patients With Primary Gastroenteropancreatic Neuroendocrine Tumors.

We retrospectively aimed to assess the prognostic significance of somatostatin receptor (SSTR) standardized uptake value (SUVmaxsstr), SSTR representative tumor volume (RTVsstr) and total lesion SSTR expression (TLsstr) obtained by [68Ga]Ga-edotreotide PET/CT ([68Ga]Ga-SSTR PET/CT) in patients with primary gastroenteropancreatic neuroendocrine tumors (GEP-NET) before surgery. We analyzed patients who underwent [68Ga]Ga-SSTR PET/CT 3-6weeks before surgery from February 2020 to April 2022. The mean SUVmaxsstr value, the RTVsstr (cm3; 42% threshold) and the TLsstr (g) were registered. Thereafter the patients were followed up 10.3 months (range 3-27). The PET/CT results were compared to the event free survival (EFS). Forty-two patients (61 ± 13years) have been enrolled. At multivariate analysis only RTVsstr values were predictive. The Kaplan-Meier survival analysis for RTVsstr showed a significant better EFS in patients presenting lower values as compared to those having greater (P = .003, log-rank test). SUVmaxsstr was not suitable for predicting EFS, TLsstr mildly. RTVsstr represents a valuable volumetric parameter able to predict the outcome in GEP-NET patients who underwent surgery. The magnitude of the SSTR representative tumor burden holds a predominant value for determining the response to therapy in GEP-NET patients before surgery, rather than the maximal SSTR representation at single voxel.

Prolonged use of eltrombopag in patients with severe aplastic anemia in the real world.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6months.Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6months. Patients not achieving complete remission (CR) at 6months were treated with EPAG for another 6months.At 1, 3, 6 and 12months after IST, the cumulative response rates were 31%, 61%, 82% and 90%, and the cumulative CR rates were 0, 14%, 27% and 45%, respectively. The cumulative effect curve showed that 93% and 53% of all remission and CR occurred within 6months, while 98% and 83% of all remission and CR occurred within 12months. Thirty-seven percent of patients (11 of 30) with partial remission (PR) at 6months continuously exposed to EPAG improved to CR within 3 (1-5) months of the extended median time. Six patients failing at 6months continued to use EPAG. Three patients showed improved responses with an extended median time of 6 (1-6) months. The 2-year event-free survival (EFS) was better in those continuing with EPAG (89% vs. 49%, P = 0.006) for patients with PR or non-remission at 6months.Continuous administration with EPAG could improve the hematologic response and EFS in patients without achieving CR at 6months.This trial has been registered at the Chinese Clinical Trial Registry (ChiCTR2100045895).