Introduction: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, representing ~25% of cancer diagnoses in children. Approximately 20% of childhood leukemias are of myeloid origin with the majority being acute. Isatuximab (Isa) is a monoclonal antibody that binds to a specific epitope of CD38 and exerts anti-multiple myeloma (MM) effects through several modes of action. Isa is approved for use in MM in adults. CD38 expression is high in some acute leukemia subsets in pediatric patients, making CD38 a potential target for acute leukemia treatment in children. Methods: ISAKIDS (NCT03860844) is a Phase 2, single-arm, multicenter, open-label study evaluating the antitumor activity, safety, and pharmacokinetics (PK) of Isa in combination with standard salvage chemotherapies in children with relapsed or refractory (R/R) leukemia in first or second relapse; including both T-ALL and B-ALL and acute myeloid leukemia (AML), conducted in 3 separate cohorts. Children from 2 years (yrs) to <18 yrs of age were eligible for inclusion. In all cohorts, participants received 20 mg/kg Isa as a single agent on Day 1 and then weekly for 5 weeks in the ALL groups or weekly for 3 weeks in the AML groups. Combination chemotherapy was added on Day 8 (modified UKALL R3 and fludarabine, cytarabine, G-CSF induction for ALL and AML patients (pts), respectively) unless it was judged necessary to start chemotherapy earlier than Day 8. The primary endpoint was complete response (CR) rate, defined as the proportion of pts with CR or CR with incomplete peripheral recovery (CRi). Secondary endpoints included duration of response, event-free survival, overall survival, and overall response rate. CD38 receptor density was assessed at baseline and CD38 occupancy was assessed at Day 15. Descriptive statistics were carried out on the evaluable population. Confidence intervals were computed using the Clopper-Pearson method. For this first interim analysis, PK parameters for Isa were assessed in the first 20 pts to confirm Isa dose and schedule in very young pts. Safety analyses included treatment-emergent adverse events (TEAEs) of all grades. Results: 24 pts were enrolled (10, B-ALL; 7, T-ALL; 7, AML) and treated. Baseline characteristics were comparable between cohorts; median age (range) B-ALL 6.5 (3-14) yrs; T-ALL 10.0 (7-16) yrs; AML 7.0 (2-17) yrs. Males (4/10 B-ALL; 6/7 T-ALL; 3/7 AML). Evaluable Lansky scores of 90 - 100 (9/10 B-ALL; 3/4 T-ALL; 4/6 AML). Mean (standard deviation) time from initial diagnosis to first dose of investigational medicinal product (IMP) was 2.6 (1.0) yrs, 1.2 (0.6) yrs, and 1.0 (0.3) yrs for the B-ALL, T-ALL, and AML groups, respectively. Number of prior regimens, median (range) was 6 (1-≥8), 3 (1-≥8), 4 (1-≥8) for the B-ALL, T-ALL, and AML groups, respectively, corresponding to inclusion of pts with very advanced disease. Three pts presented with hyperleukocytosis >20 x 10 9/L. Among 23 pts assessed for CD38 expression, all except 2 (1 B-ALL and 1 AML) were CD38 positive. There were 17 evaluable pts with valid response data collected up to the cutoff date (May 11, 2021). Of the evaluable participants, CR+CRi were observed for: 3/7 (42.9%) in the B-ALL cohort, 2/6 (33.3%) in the T-ALL cohort, and 2/4 (50.0%) in the AML cohort (Table). Safety data showed that Grade ≥3 TEAEs occurred in 17 pts (Table). Infusion reactions (majority Grade 1 or 2) occurred in 9/24 pts (2/10 B-ALL; 4/7 T-ALL; 3/7 AML). Three pts had Grade 5 TEAEs (deaths: 1 B-ALL and 2 AML). One subject in the AML cohort had cytokine-release syndrome (CRS) related to IMP with progressive disease as a confounding factor. The other 2 deaths were not treatment related. One subject in the AML cohort had cellulitis Grade 5 and 1 subject in the B-ALL cohort had septic shock Grade 5 as cause of death. Preliminary PK analysis on 18 pts (>2 yrs) showed that Isa PK parameters including exposure PK parameters in children with ALL or AML are consistent with those observed in adult ALL pts. PK modeling approaches predict a slightly lower exposure (<20%) in pts <2 yrs old (4-12 kg) compared with exposure achieved in adults (51-100 kg) at the same dose. Conclusions: In a poor prognostic relapsed population, 7/17 (41.2%) pts achieved CR+CRi. Safety profile and exposure is consistent with the available data for adults. Enrollment will be opened for pts <2 yrs of age with R/R ALL or AML. Figure 1 Figure 1. Disclosures Baruchel: Kite/Gilead: Other: Investigator; Novartis, Servier, Celgene, Jazz, Janssen, Sanofi, Amgen,Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: Satellite symposium; Shire Servier: Research Funding. Abrahamsson: wedish Children´s Cancer Foundation. Research grants and 50% senior research position for clinical research on pediatric leukemia: Research Funding. Nysom: Bayer, Y-mAbs, EUSA Pharma: Consultancy, Honoraria. Rizzari: Sobi: Other: personal fees; Jazz Pharmaceuticals: Other: Personal fees; Amgen: Other: Personal fees; Medac: Other: Grants and personal fees; Shire: Other: Grants and personal fees. Cesaro: Sobi: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau. Duarte: Amgen: Consultancy, Other: Advisory Board; Novartis: Consultancy; Jazz Pharma: Research Funding. Kang: Amgen Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cartexell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Korea: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kattamis: Agios Pharmaceuticals: Consultancy; IONIS: Consultancy; VIFOR: Consultancy; CRISPR/Vertex: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Chiesi: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy. Tøndel: Sanofi: Research Funding. Ivanina: Sanofi: Current Employment. Brillac: Sanofi: Current Employment. Wang: Sanofi: Current Employment. Oprea: Sanofi: Current Employment, Other: may have stock options . Abbadessa: Sanofi: Current Employment. Zwaan: Sanofi: Consultancy.
Background: The GATLA Collaborative Group has a 50 year (y) long experience of running cooperative trials for lymphomas in Argentina. Aim: Describe the outcome of pediatric patients(pts) treated according to the international cooperative work with AHOPCA and St. Jude Children's Research Hospital (11-EHP-12) adopting OEPA/COPDAC strategy for High Risk (HR) pts and ABVD for Intermediate (IR) and Low Risk (LR) pts. Methods: 11-EHP-12: Risk assignment according Stanford/Danna Farber/ SJCRH Consortium classification. LR: ABVD x 4± IFRT (20 Gy). IR: ABVD x 6 ± IFRT (20 Gy). HR: OEPA-COPDAC+IFRT (20/25 Gy). Response evaluation: LR after 4th cycle, IR and HR after the 2nd cycle. Complete Remission (CR): response > 80% reduction and PET negative. Partial Remission (PR): response >50% and <80% reduction and/or PET positive. 170 pediatric patients (pts) were enrolled since November 2012. 133 evaluable pts. 37 on treatment and/or a follow up of less than 5 years. Sex: M/F: 85 (63,9%) /48. Median age: 13 y (range 4-18 y). Histology: nodular sclerosis 91 (68,4%), mixed celularity 31 (23.3%), lymphocyte rich 1 (0,7%), lymphocyte depleted 1 (0,7%), nodular lymphocyte predominant 8 (6,9%). Stage: I :16 (12%), II: 51 (38.4%), III: 27 (20.3%), IV: 39 (29.3%). B Symptoms: 66 (49.6%). Interim evaluation: PET/TC: 109/133 (82%), TC: 24. Distribution by risk groups: HR pts.: 77 (57,9%), IR: 35 (26,3%), LR: 21 (15,8%). Results: 5 y OS was 94% (100% for LR and IR, and 91% HR) and 5y EFS was 88% (100% for LR, 91% IR, and 84% HR). 95% of the LR pts and 72% of the IR pts did not undergo radiotherapy. 70% of the HR pts achieved CR after the 2nd OEPA and received 20 Gy IFRT. According PR or CR after 2nd OEPA, the 5y EFS in HR pts was 84% and 90% respectively. Conclusion: Thanks to this international cooperation We could significantly improve the results in Argentina compared to our previous experience (7-PHD-96: COPP-ABV x 6 + IFRT Bulky disease or PR (20/25Gy): 5yOS:85%, 5yEFS:67%), reduce the number of patients who required radiotherapy and reproduce the Euronet experience for HR pts in a different context. Figure Disclosures No relevant conflicts of interest to declare.
2605 Introduction: The outcome in pediatric patients with relapse-refractory acute leukemia (acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)) is very poor. Clofarabine is an active agent in this high risk group. Purpose: Report the GATLA experience in patients with relapse-refractory acute leukemia treated with clofarabine based regimens. Methods: Between June 07 and April 12, 66 patients from 15 GATLA centers were enrolled. 61 ALL (52 B/9 T): 23 first relapse (20 BM, 1 CNS, 2 combined), 33 second relapse (28 BM, 1 CNS, 4 combined), 5 with refractory disease. 5 AML (4 first relapse, 1 refractory disease). Median age 10,5 years (1–20 ys). Gender: 44 boys and 22 girls. 60 patients received chemotherapy combined clofarabine-etoposide-cyclophosphamide (CLO 218), 4 patients received clofarabine plus ara-c therapy and 2 patients were treated with clofarabine alone (52mg/m2). 63.7% (42/66) of the patients were treated with 2 therapeutic lines prior to clofarabine regimens, 22.7% (15/66) received only 1 prior treatment, 13.6% (9/66) got 3 or more therapies and 5 patients undergone prior HSCT (Hematopoietic Stem Cell Transplantation). Results: Complete remission (CR) was achieved in: 36/66 patients (54,5 %). Early toxic death rate was 7/66 (10,6%). No response occurred in 22/66 (33,3%) patients. 1 patient is on induction, not evaluable at the moment. Of the 36 responders, 19 patients (52,7 %) proceeded to HSCT: 6 (31,5 %) remain alive post-transplantation with a median follow up of 55 weeks ( range 6–156 w), HSCT related death: 7 (37 %), relapse after HSCT: 6 (31,5%) at a mean of 20 weeks( range 8–56 weeks). Among the 61 ALL patients, 18/23 (78%) in first relapse achieved CR, 12/18 (66,6%) needed only one course to achieved CR, of them, 3/12 (25%) relapsed at 8, 8 and 14 weeks and died for progressive disease. 1/12 (8,3%) died in CR at week 8. 2/12 (16,6%) patients are on treatment. 6/12 (50%) proceeded to HSCT: 1/6 relapsed 56 weeks after. 3/6 patients died in CR after HSCT at 12, 15 and 24 weeks. 2/6 remain in CR at 6 weeks follow up. 6/18 (33,3%) of the patients in first relapse needed 2 courses to achieved CR. 1/6 (16,7%) relapsed at week 8. 2/6(33,3%) died in CR at week 9 and 16. 3/6 ( 50%) proceeded to HSCT, 1 is alive at 36 weeks, 1 relapsed at week 26 and 1 died in CR at week 14. 13/33 (39%) ALL patients in second relapse achieved CR and 8/13 (61,5%) needed only one course to CR. 3/8 (37,5%) relapsed at 6,8 and 16 weeks and died for progressive disease. 5/8(62,5%) proceeded to HSCT, of them 3 (60%) relapsed after HSCT at 8,8 and 12 weeks. 1/5 (20%) is alive and disease free at 6 weeks after HSCT. 1/5 (20%) died in CR. 5/13 (38%) needed 2 courses to achieved CR, 1/5 relapsed after 4 weeks. 1/5 died in CR at week 6, 1/5 is alive 40 weeks after CR. 2/5 proceeded to HSCT and died in CR at 10 and 22 weeks after HSCT. 2/5 ALL patients with refractory disease achieved CR with 2 and 3 courses of clofarabine, one proceeded to HSCT and is alive with a follow up of 156 weeks, the other relapsed at 8 weeks. 3/5 did not response and died. AML patients: 3/5 received clofarabine as 3rd therapeutic line: 1 patient achieved CR after one course but died of toxicity, 1 patient did not response and 1 died during induction. 2/5 received clofarabine as 2ndline ( 1 with refractory disease and 1 who undergone prior HSCT), they achieved CR with 2 courses of chemotherapy and proceeded to HSCT, one relapsed after 16 weeks and the other is alive and disease free after 120 weeks. Conclusion: In our series, Clofarabine was well tolerated and shows significant antileukemic activity in heavily pretreated children. The response rate and the durability of remission observed is better when clofarabine regimens are used earlier (first relapse). Responses allowed several refractory patients to proceed to HSCT. Levels of pre transplant MRD (Minimal Residual Disease)should be taken into account in order to follow this procedure. Disclosures: No relevant conflicts of interest to declare.
10074 Background: Studies comparing survival between adult and paediatric population with osteosarcoma are scarce and contradictory. Generally adults were excluded from analysis in historical series. End Point: evaluate age as prognostic factor in ostosarcomas IIb treated exclusively by a multidisciplinary group in a single institution. Methods: 132/278 patients with histological diagnosis of osteosarcoma IIb were selected. All were treated exclusively in our hospital from July 1988 until December 2010. Patients 17 years old or younger were considered paediatric. They all received presurgical chemotherapy with the same scheme: ifosfamide + doxorrubicin + high dose methotrexate. Univariate analysis was made (Fischer exact test). Survival was calculated wih Kaplan-Meier actuarial method. Curves were compared with log rank test. Multivariate Cox analysis was made. Results: Median age was 19.6 years (std: 9,1; range 5-58). Adults: 77, children: 55. No differences were detected between the two age groups regarding: elevated alkaline phosphatase, kind of surgery (amputation vs. limb sparing), relapse site (lung, local, other), necrosis greater than 90% or number of lung resections. There was a tendency towards axial localization in adults (p=0.05). No paediatric patient had inadequate medical intervention, but it was present in 14.3% of adults (p=0.002). 5 year Overall survival (5y OS) in children was 85,2% compared with 61,8% in adults (p=0.005); Disease free survival (DFS) had a non significant tendency to be better in children (69.6% vs. 51,3%). Variables associated with worse OS were: axial location (p=0.01), elevated alkaline phosphatase (0.003), amputation (p=0.008), local relapse or systemic non-lung metastasis (p= 0.001), necrosis less than 90% (0.001). Multivariate Cox analysis showed association between OS and paediatric population (p=0.01) and necrosis greater than 90% (p=0.001), while DFS was associated with necrosis greater than 90% (p=0.01) and elevated alkaline phosphatase (p=0.05). Conclusions: Paediatric population presents better survival compared to adults in our institution. Differences in tumour biology and in the mode of presentation related to age may be the explanation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.