scholarly journals Superior Outcomes in Hispanic Patients Compared to Non-Hispanic Patients with Ph-Negative Acute Lymphoblastic Leukemia Using the Modified Pediatric-Based University of Southern California Acute Lymphoblastic Leukemia (USC ALL) Regimen for Newly Diagnosed ALL Patients in the Era of Novel Agents; A Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3361-3361
Author(s):  
Vincent Louie Ramos Mendiola ◽  
Catherine Ly ◽  
Thuy Bui ◽  
Jennifer Wang ◽  
Jack Rodman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stock Options ◽  
Lymphoblastic Leukemia ◽  
Novel Agents ◽  
University Of Southern California ◽  
Publicly Traded ◽  
Free Survival ◽  
Hispanic Patients ◽  
Privately Held

Abstract INTRODUCTION: Hispanic patients with acute lymphoblastic leukemia (ALL) are historically known to have poor outcomes compared to non-Hispanic patients. Our institution, LAC-USC (LA County Hospital/University of Southern California) has shown a complete remission rate of 96% with use of pegasparagase at 2000 IU/m2 using the USC ALL regimen (based on CCG-1882) for patients aged 17-55 years with a 7-year OS of 51% reported in 2014. The modified USC ALL regimen now uses a single dose of cytarabine rather than fractionated doses and uses a single dose 3g/m 2 methotrexate compared to 1g/m 2 (2.5g/m 2 if T-cell) D1, 15 in original USC ALL regimen to improve compliance, while consolidation was increased to six cycles allowing for PEG holidays to improve toxicity (Table 1). Since our institution takes care of a large population of Hispanic patients with ALL, we now report outcomes in Hispanic and Non-Hispanic patients using the modified USC ALL regimen in the era of novel agents like blinatumomab and inotuzumab. METHODS : This retrospective, single institution chart review included adults >18 years old with newly diagnosed Ph-negative ALL (2016-2020). Primary objectives were 3-year over-all survival (OS), event-free survival (EFS), disease-free survival (DFS). Secondary objectives were complete remission/complete remission with incomplete recovery (CR/CRi), minimal residual disease (MRD) by flow cytometry, descriptive statistics of patients who were stratified into Hispanic and non-Hispanic cohorts and evaluated using Fisher's exact test. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p-value ≤0.05 was significant. RESULTS: 121 Ph-negative patients were reviewed. 87 were Hispanic patients (HP) and 34 non Hispanic patients (NHP). Median ages were 39 and 35 years (p=0.51) and median BMI were 29 and 26.9 kg/m 2 (p=0.42), respectively. There were about equal males and females in HP while NHP had 70.6% males compared to 29.4% females (p=0.076). Both HP and NHP were mainly of the Ph-negative ALL subtype, 50.6% vs 47.1%, followed by Ph-like, 25.4% vs 20.6%, respectively (p=0.884). Majority of the population were unfavorable risk by NCCN karyotypic risk stratification, 55.9% in HP compared to 56.0% in NHP (p=0.99). Over-all, no significant difference between baseline characteristics in both cohorts. After induction 1: CR/CRi was 85.9% in HP and 73.4% in NHP (p=0.09). MRD negativity by flow cytometry in HP was 41.4% compared to 26.4% in NHP (p=0.13). After induction 2: 83% of HP were in CR/CRi compared to 80% in NHP (p=0.99) and MRD negativity by flow was 35.6% in HP compared to 32.4% in NHP (p=0.73). Blinatumomab was given in 33.3% of HP and 32.3% of NHP (p=0.92) while only 5.7% of HP and 2.9% of NHP received inotuzumab (p=0.99). 34.5% of HP underwent allogenic hematopoietic stem cell transplant (allo-HSCT) versus 26.5% in NHP (p=0.40). 3-year OS was 92.2% in HP versus 67.4% in NHP (p=0.004). 3-year DFS was 92.8% in HP versus 60.7% in NHP (p=0.003). 3-year EFS was 54.1% in HP versus 32.3% in NHP (p=0.02) (Table 2). Rate of relapse for HP and NHP were 23.4% vs 29.4% (p=0.74) while rate of mortality for HP and NHP were 7.5% vs 28% (p=0.015), respectively. No clear difference in grade 3/4 PEG toxicities were found in HP and NHP except more hypertriglyceridemia in HP (p=0.019). CONCLUSIONS: We present comparison of outcomes in Hispanic and non-Hispanic patients using our modified USC ALL pediatric-based regimen in an era of novel agents. Our data shows significantly better outcomes in Hispanic patients compared to non-Hispanic patients [OS (92.2% vs 67.4%, p=0.004), DFS (92.8% vs 60.7%, p=0.003) and EFS (54.1% vs 32.3%, p=0.02)]. This study demonstrates that given equal access to care (eg. receiving blinatumomab, allo-HSCT), outcomes in HP with Ph-negative ALL are not worse, but rather superior to those in NHP. Utilization of novel immunotherapy like blinatumomab in the salvage setting to achieve deeper molecular response and increased utilization of haploidentical allo-HSCT have likely contributed to reducing ethnic disparities in Hispanic ALL patients. Future studies are needed to validate these findings with larger patient populations. Figure 1 Figure 1. Disclosures Chaudhary: Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Douer: Jazz: Consultancy; Amgen: Consultancy, Speakers Bureau; Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Servier: Consultancy, Speakers Bureau. Yaghmour: Takeda: Consultancy, Speakers Bureau; Astellas: Speakers Bureau; Alexion: Speakers Bureau; BMS: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

scholarly journals An Update on Outcomes Using the USC ALL Frontline Regimen (based on CCG-1882) after Further Modification of Protocol in the Era of Novel Agents in Ph-Negative ALL Patients; A Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3362-3362
Author(s):  
Vincent Louie Mendiola ◽  
Catherine Ly ◽  
Thuy Bui ◽  
Jennifer Wang ◽  
Jack Rodman ◽  
...  
Keyword(s):  
T Cell ◽  
Complete Remission ◽  
Stock Options ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Novel Agents ◽  
Publicly Traded ◽  
Free Survival ◽  
Post Induction ◽  
Privately Held

Abstract INTRODUCTION: The use of pediatric inspired regimens in adolescent young adults and adults has improved outcomes in acute lymphoblastic leukemia (ALL). CALGB 10403 was prospectively tested in patients 17-39 years, showing a 3-year event free survival of 59%. In 2007, our institution reported outcomes after incorporating peg-asparaginase (PEG) dosed at 2000mg/m 2 in induction for patients aged 17- 55 years. This regimen was well tolerated and resulted in a complete remission (CR) rate of 96%. In 2014, we reported experience with the use of multiple doses of PEG (CCG-1882) for newly diagnosed ALL adult patients, with a 7-year overall survival (OS) of 51%. Since our last report, the USC ALL regimen consisting of 2 induction phases, has been further modified with a goal of maintaining good outcomes, and improving compliance and toxicities. Fractionated doses of cytarabine were changed to a single dose, the methotrexate dose of 1g/m 2 (2.5 g/m 2 if T-cell) given D1,15 of intensification phases was changed to 3g/m 2 (B and T cell) given in single doses, and consolidation was increased to six cycles allowing for PEG holidays (Table 1). Moreover, the approval and incorporation of novel agents such as blinatumomab and inotuzumab also changed outcomes in ALL. Therefore, this study reports an update of outcomes since further modification of the USC ALL pediatric-based regimen in the era of novel agents. METHODS: This is a retrospective review which included adults aged >18 with newly diagnosed Philadelphia negative ALL between 2016 and 2020 treated at USC/Norris Cancer Center and Los Angeles County Hospital (LAC). Primary objectives were over-all survival (OS), event-free survival (EFS), disease-free survival (DFS) at 3 years, and secondary outcomes were complete remission/complete remission with incomplete recovery (CR/CRi) rates and minimal residual disease (MRD) by flow cytometry. OS, DFS, EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 121 patients with Ph-negative ALL were identified (49.6% Ph-negative B-ALL, 24% Ph-like B-ALL, 0.8% B cell lymphoblastic leukemia (LBL), 9.1% T cell ALL, 4.1% T cell LBL, 4.1% early T-cell, 5.8% mixed phenotype acute leukemia (MPAL). Median age at diagnosis was 38.5 years and maximum age of patient to receive pegasparagase during induction 1 was 63 years. 71.9% Hispanic, 15.7% white, 9.9% Asian, 2.5% African American. 57.9% males, 42.1% females. 3.4% were favorable, 4.2% intermediate, 54.6% unfavorable and 37.8% unknown by karyotypic risk stratification. Median BMI was 28.9 kg/m 2.54.6% had hepatic steatosis either on history or imaging and 5.1% had CNS disease pre-induction. Post-induction 1, 81.4% of patients achieved CR/CRi and 50% MRD negative. Post induction 2, 82.2% achieved CR/CRi, 67.7% MRD flow negative. Post-consolidation 1, 90.9% were MRD flow negative. 33.1% subsequently received blinatumomab for MRD positive disease, 5% given inotuzumab for relapsed disease, 32.2% underwent allogenic hematopoietic stem cell transplant (allo-HSCT). Median number of pegasparagase doses received during treatment was 2, rate of relapse and mortality was 27.3% and 13% respectively. Median OS and DFS were not reached but median EFS was 35 months. 3-year OS was 85.3%, when stratified according to MRD post induction 2; 3-year OS was 91.7% for MRD positive patients and 91.2% for MRD negative patients (p=0.55). 3-year DFS was 83.2%; 88.2% for MRD positive patients and 97.4% for MRD negative patients (p=0.22). 3-year EFS was 47.3%; 51.3% for MRD positive patients and 50.6% for MRD negative patients (p=0.49) (Tables 2-3). Use of pegasparagase resulted in grade 3/4 toxicities including hypersensitivity (4.1%), transaminitis (21.5%), pancreatitis (5.4%), hypertriglyceridemia (49.5%), hypofibrinogenemia (45.5%), hyperbilirubinemia (21.5%) and thrombosis (16.5%). CONCLUSIONS: Pediatric-based modified USC ALL induction regimen led to a high 3-year OS (85.3%), DFS (83.2%) and EFS (47.3%) with predictable toxicity and compares favorably with original USC ALL regimen, CALGB 10407, GRAALL 2005 and USC/MSKCC regimen. Interestingly, MRD positivity after induction 2 did not adversely affect OS, DFS or EFS, which is likely due to incorporation of blinatumomab and inotuzumab. These agents could have allowed for deeper remissions allowing Ph-negative patients with residual disease to receive allo-HSCT. Figure 1 Figure 1. Disclosures Chaudhary: Oncotartis: Consultancy; Pancella: Consultancy; Moderna: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; TCR2: Current equity holder in publicly-traded company; Allogene: Current equity holder in publicly-traded company; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy . Douer: Servier: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Jazz: Consultancy. Yaghmour: Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Astellas: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Jazz: Speakers Bureau; Agios: Consultancy, Speakers Bureau.

scholarly journals Outcomes in Adult Philadelphia-Positive Acute Lymphoblastic Leukemia Patients Using Tyrosine Kinase Inhibitors Combined with the Modified University of Southern California (USC ALL) Regimen without Pegaspargase in the Era of Novel Agents; A Retrospective Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4372-4372
Author(s):  
Vincent Louie Ramos Mendiola ◽  
Catherine Ly ◽  
Thuy Bui ◽  
Jennifer Wang ◽  
Jack Rodman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Tyrosine Kinase ◽  
Stock Options ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Newly Diagnosed ◽  
Publicly Traded ◽  
Privately Held

Abstract Introduction: Prior to the introduction of tyrosine kinase inhibitors (TKIs), the presence of BCR-ABL1 conferred a poor prognosis in patients with acute lymphoblastic leukemia (ALL). We published in 2017 in Br J Haematology our analysis comparing the survival of Ph-Positive (Ph+) and Ph-negative ALL during the period when TKIs were universally available in the United States for Ph+ ALL using a Surveillance, Epidemiology, and End Results (SEER) Database analysis. Despite using TKIs, we have continued to remain reliant on cytotoxic chemotherapy regimens and allogeneic hematopoietic stem cell transplant (allo-HSCT) to achieve the best long-term outcomes. However, with the introduction of more potent TKIs and other novel agents, as well as better methods for monitoring minimal/measurable residual disease (MRD) the best approach is yet to be determined. In this study we present data from our institution with incorporation of TKIs in our modified USC ALL pediatric-based regimen without pegaspargase (PEG) (Table 1). Methods: This retrospective, single institution chart review included adults aged >18 with newly diagnosed Ph+ ALL between 2016 and 2020. Primary objectives were Overall survival (OS) and event-free survival (EFS) at 3 years for Ph+ ALL patients and secondary objectives were rates of complete remission/complete remission with incomplete recovery (CR/CRi), minimal residual disease (MRD) by flow cytometry and presence of BCR-ABL1 fusion transcript by real time polymerase chain reaction. Descriptive statistics of patients were reported and evaluated using Fisher's exact test. OS and EFS were reported through Kaplan Meier curves and Log-rank tests. Two-sided p value ≤0.05 was significant. RESULTS: 26 Ph+ ALL patients were identified. Median age at diagnosis was 42.5 years, with 42.3% males and 57.7% females. Median BMI was 31.1 kg/m 2, 42.3% had hepatic steatosis and 34.6% had CNS disease pre-induction. After induction 1, 91.3% of patients achieved CR/CRi, 8.7% were refractory, and 64.3% were MRD flow negative with 24% of patients with undetectable BCR-ABL1. After induction 2, 94.1% had achieved CR/CRi, 64.3% were MRD flow negative with 44.4% of patients with undetectable BCR-ABL1. After consolidation I, 78.6% were MRD flow negative. 50% of patients had received blinatumomab for MRD flow positivity early in the course and 34.6% underwent allo-HSCT. Of note, 65.4% of patients received Dasatinib only and 30.8% received at least 2 TKIs. Overall, 11.5% had known relapse, 12.5% died. 3-year OS was 83.3% and 3-year EFS was 86.6% (Table 2). When survival was stratified by transplant status, 3-year OS with allo-HSCT was 100% versus 70% without allo-HSCT (p=0.15) and 3-year EFS with allo-HSCT was 100% compared to 77.9% without allo-HSCT (Table 3). CONCLUSIONS: The use of the modified USC ALL regimen without PEG for the treatment of newly diagnosed Ph+ ALL combined with TKI at our institution led to an excellent 3-year OS (83.3%) and 3-year EFS (86.6%). All patients received TKI, half of the patients received blinatumomab and at least one third received allo-HSCT which likely led to higher OS even without PEG. We also observed a trend towards improved OS in recipients of allo-HSCT compared to patients who did not receive allo-HSCT (100% vs. 70%, p=0.15) although statistically not significant, it highlights the role of allo-HSCT in the management of Ph+ ALL patients. Figure 1 Figure 1. Disclosures Chaudhary: TCR2: Current equity holder in publicly-traded company; Celldex: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Pancella: Consultancy; Oncotartis: Consultancy; Athelas: Consultancy, Current holder of stock options in a privately-held company; Angeles Therapeutics: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Founder, Patents & Royalties: Cell therapy ; Allogene: Current equity holder in publicly-traded company. Douer: Adaptive: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Speakers Bureau; Jazz: Consultancy; Servier: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. Yaghmour: Agios: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; BMS: Speakers Bureau; Alexion: Speakers Bureau; Astellas: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Jazz: Speakers Bureau.

scholarly journals No difference in outcome between children and adolescents transplanted for acute lymphoblastic leukemia in second remission

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6683-6690 ◽  
Author(s):  
Giorgio Dini ◽  
Marco Zecca ◽  
Adriana Balduzzi ◽  
Chiara Messina ◽  
Riccardo Masetti ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Confidence Interval ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Disease Recurrence ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Total Body ◽  
Related Mortality

Abstract Acute lymphoblastic leukemia (ALL) in second complete remission is one of the most common indications for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. We compared the outcome after HCST of adolescents, aged 14 to 18 years, with that of children (ie, patients < 14 years of age). Enrolled in the study were 395 patients given the allograft between January 1990 and December 2007; both children (334) and adolescents (61) were transplanted in the same pediatric institutions. All patients received a myeloablative regimen that included total body irradiation in the majority of them. The donor was an HLA-identical sibling for 199 patients and an unrelated volunteer in the remaining 196 patients. Children and adolescents had a comparable cumulative incidence of transplantation-related mortality, disease recurrence, and of both acute and chronic graft-versus-host disease. The 10-year probability of overall survival and event-free survival for the whole cohort of patients were 57% (95% confidence interval, 52%-62%) and 54% (95% confidence interval, 49%-59%), respectively, with no difference between children and adolescents. This study documents that adolescents with ALL in second complete remission given HSCT in pediatric centers have an outcome that does not differ from that of patients younger than 14 years of age.

Is It Better to Treat Adolescents with Acute Lymphoblastic Leukemia as Old Children or as Young Adults?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3968-3968 ◽  
Author(s):  
Marta Alves ◽  
Liane Daudt ◽  
Karina L. M. Mazzucco ◽  
Adriano Taniguchi ◽  
Tiago Nava ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Poor Risk ◽  
Wbc Count

Abstract PURPOSE: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. PATIENTS AND METHODS: From January 1997 to December 2007, 34 and 11 adolescents (10 to 20 years of age) were treated according to German pediatric BFM 90 and 95 and adult BFM 84 protocols, respectively. Age, B/T lineage, WBC count, complete remission, cytogenetics, and response to steroids were analyzed. Age, B/T lineage and WBC count were similar. Poor risk-cytogenetics (t (9;22),t(4;11) and hypodiploidy less than 45 chromosomes were present only in BFM 90 and 95 group. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving overall survival (OS) and event-free survival (EFS). RESULTS: OS in 10 years and EFS was, respectively, 68.6% and 68.7% for the pediatric protocol and 31.4% and 21.6% for the adult protocol. CONCLUSION: This study’s findings were similar to others in USA, UK, France, Italy and Holland that clearly demonstrate that current pediatric regimens are more effective for adolescents and may contribute to indicate that adolescents should be included in intensive pediatric protocols. Keywords: leukemia, survival, adolescent.

scholarly journals A Comparison of Clinical Outcomes from Updated Zuma-5 (Axicabtagene Ciloleucel) and the International Scholar-5 External Control Cohort in Relapsed/Refractory Follicular Lymphoma (R/R FL)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3543-3543
Author(s):  
M. Lia Palomba ◽  
Paola Ghione ◽  
Anik R. Patel ◽  
Kevin Deighton ◽  
Caron Jacobson ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Clinical Outcomes ◽  
Odds Ratio ◽  
Stock Options ◽  
Research Funding ◽  
External Control ◽  
Control Cohort ◽  
Publicly Traded ◽  
Free Survival ◽  
Privately Held

Abstract Background: In the pivotal ZUMA-5 (Z-5) trial, axicabtagene ciloleucel (axi-cel; an autologous anti-CD19 chimeric antigen receptor T-cell therapy) demonstrated high rates of durable response in r/r FL patients, including those with high-risk disease such as patients who progressed within 24 months of initiating first-line chemoimmunotherapy (POD24). Aims: To compare clinical outcomes from updated 24-month Z-5 to a weighted sample from the international SCHOLAR-5 (S-5) external control cohort. Methods: The international S-5 cohort data were extracted for r/r FL patients from 7 institutions in 5 countries who initiated a third or higher (3L+) line of therapy (LOT) after July 2014. Data from the pivotal idelalisib DELTA trial was also included in the S-5 cohort. Z-5 trial eligibility criteria were applied to the S-5 cohort, with patients excluded or censored upon transformation. The S-5 and Z-5 cohorts were balanced for patient characteristics through propensity scoring on prespecified prognostic factors and standardized mortality ratio weighting. Characteristics with a standardized mean difference (SMD) &lt;0.1 were deemed balanced. Overall response rate (ORR) was compared using odds ratio. Overall survival (OS), progression-free survival (PFS) and next treatment-free survival (NTFS) were evaluated using Kaplan-Meier analysis. Subgroup analysis was conducted on patients who initiated a fourth or higher (4L+) LOT. Results: 143 patients were identified in S-5, reducing to 85 patients after applying propensity score weights, versus 86 patients in Z-5. Median follow-up time for Z-5 and S-5 were 29.4 and 26.2 months respectively. Variables that were successfully balanced (SMD&lt;0.1) included POD24, number of prior LOT, relapsed vs refractory, prior stem cell transplant, size of largest nodal mass, response to prior LOT, time since last therapy and age (Table 1). Despite weighting, the S-5 cohort had a higher proportion of ECOG 1 vs 0 (66.9% vs 40.7%) at baseline. In 3L+ patients, the ORR was 42/85 (49.9%) in S-5 compared to 81/86 (94.2%) in Z-5 for an odds ratio of 16.2 (95% confidence interval [CI]: 5.6-46.9). The median OS was not reached in Z-5 while median PFS was 39.6 months. In S-5 median OS and PFS were 59.8 months and 12.7 months, respectively (Table 2). The hazard ratios for OS and PFS were 0.52 (95%CI: 0.28-0.95) and 0.28 (0.17-0.45) (Figure 1). In sub-group analysis of 4L+ patients, which compared 60 patients from Z-5 to 59 patients from S-5, improvements in OS and PFS outcomes were more pronounced (Table 2). Summary/Conclusion: Compared to currently available therapies in r/r FL patients, axi-cel demonstrated a substantial and statistically significant improvement in meaningful clinical endpoints including ORR, PFS, NTFS and OS, highlighting the durable treatment effect of axi-cel. These findings suggest that axi-cel addresses an important unmet medical need for r/r FL patients. Figure 1 Figure 1. Disclosures Palomba: PCYC: Consultancy; BeiGene: Consultancy; Juno: Patents & Royalties; Pluto: Honoraria; Wolters Kluwer: Patents & Royalties; Kite: Consultancy; Notch: Honoraria, Other: Stock; Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding; Priothera: Honoraria; Nektar: Honoraria; Lygenesis: Honoraria; Magenta: Honoraria; Rheos: Honoraria; WindMIL: Honoraria; Ceramedix: Honoraria; Novartis: Consultancy. Patel: Kite, A Gilead company: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company. Deighton: Delta Hat: Current Employment. Jacobson: Lonza: Consultancy, Honoraria, Other: Travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; AbbVie: Consultancy, Honoraria; Nkarta: Consultancy, Honoraria; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Clinical Care Options: Speakers Bureau; Axis: Speakers Bureau; Humanigen: Consultancy, Honoraria, Other: Travel support; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel support. Nahas: Kite: Current Employment; Gilead: Current equity holder in publicly-traded company. Jung: Kite, a Gilead Company: Current Employment; Amgen, Kura, Gilead, and Turning Point: Current equity holder in publicly-traded company. Hatswell: Delta Hat: Current Employment. Kanters: RainCity Analytics: Current Employment. Limbrick-Oldfield: RainCity Analytics: Current Employment. Wade: Kite, A Gilead Company: Consultancy; Amgen: Consultancy; Allergan: Consultancy. Thornton Snider: Kite, a Gilead Company: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Gilead: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Neelapu: Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding. Gribben: Abbvie: Honoraria; AZ: Honoraria, Research Funding; BMS: Honoraria; Gilead/Kite: Honoraria; Janssen: Honoraria, Research Funding; Morphosys: Honoraria; Novartis: Honoraria; Takeda: Honoraria; TG Therapeutis: Honoraria. Radford: ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Current holder of individual stocks in a privately-held company; BMS: Honoraria. Bobillo: Gilead: Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Speakers Bureau. Ghesquieres: Gilead Science: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Roche: Consultancy; Mundipharma: Consultancy, Honoraria; Janssen: Honoraria.

scholarly journals Allogeneic Stem Cell Transplantation from Unmanipulated Haploidentical Donors Versus Matched or Mismatched 9/10 Unrelated Donors in Acute Lymphoblastic Leukemia in First Complete Remission: On Behalf of the ALWP of the EBMT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2174-2174
Author(s):  
Noga Shem-Tov ◽  
Christophe Peczynski ◽  
Myriam Labopin ◽  
Maija Itälä-Remes ◽  
Didier Blaise ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Free Survival ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
First Complete Remission

Abstract Background: Unmanipulated T-cell replete haploidentical allogeneic stem cell transplantation has become an attractive alternative choice for patients with no HLA matched sibling or unrelated donors. However data of outcome in patients with Acute Lymphoblastic Leukemia (ALL) is still scarce. The Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) conducted this study to compare the outcome of allogeneic transplantation (Allo-SCT) from haploidentical donor (Haplo) versus matched (MUD 10/10) or mismatched (MMUD 9/10) unrelated donor for patients with ALL in first Complete Remission (CR1). Methods: The outcomes of 1,234 adult patients with Philadelphia positive or negative (Ph+ / Ph-) B ALL or T ALL in CR1 who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was made between Haplo (136 patients), MUD 10/10 (809 patients) and MMUD 9/10 (289 patients). Multivariate analyses were performed using the Cox proportional-hazard model. To control potential confounding factors between treatments that could influence outcome, propensity score matching was also performed between Haplo and the 2 other groups. Results: Main population characteristics are depicted in Table 1. Recipients of Haplo, MUD 10/10 and MMUD 9/10 were comparable concerning median age, time from diagnosis to Allo-SCT and myeloablative versus reduced intensity conditioning (MAC/RIC). However, Haplo transplants cohort differed in several characteristics from the MUD and MMUD patients groups. The percentage of female donors was higher in Haplo transplants and female to male mismatch was higher accordingly, CMV matched negative status was lower in Haplo. The source of stem cells was bone marrow (BM) versus peripheral blood (PB) stem cells in significantly higher percentage of Haplo transplants (53.7% vs 15.1% and 16.6% for MUD and MMUD respectively, p<0.0001). Most Haplo patients received post-transplant cyclophosphamide for graft versus host disease (GVHD) prophylaxis (77%) while this regimen was rarely used in the other groups (about 3%, p=0.0005). Univariate analysis showed similar results in Haplo, MUD and MMUD. Disease free survival (DFS) at 3 years was 49±11%, 53±4% and 55±7%, respectively (p=0.67) (Figure 1). Overall survival (OS) was 54±11%, 62±4% and 62±6%, respectively (p=0.11) (Figure 2). Relapse incidence (RI) and non-relapse mortality (NRM) at 3 years were not different either, RI was 28±9%, 28±4% and 25±6%, respectively (p=0.7) and NRM was 23±8%, 19±3% and 20±6%, respectively (p=0.6). Acute GVHD (AGVHD), either grade II-IV or grade III-IV and chronic GVHD (CGVHD) did not differ between the 3 groups (p=0.1, p=1.0 and p=0.6 respectively). The GVHD-relapse free survival (GRFS) was also not statistically different between the groups, 43±10%, 43±4% and 46±7%, respectively (p=0.7). After adjustment for center effect, patient age, donor/patient gender, donor and patient CMV serostatus, ALL type (B Ph- vs B Ph+ vs T), time from diagnosis to SCT, type of conditioning and cell source (PB vs BM), the multivariate Cox model showed that Haplo recipients did not experience worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the Hazard Ratio (HR) for DFS was 1.1 for MUD (p=0.7) and 1.1 for MMUD (p=0.8). The HR for OS in MUD and MMUD did not differ from Haplo either (HR=0.9, p=0.4 and HR=1.0, p=1.0 respectively). Moreover, compared to Haplo, SCT from MUD and MMUD were not associated with lower hazards for RI (HR=0.9, p=0.8 and HR=0.7, p=0.2 respectively), NRM (HR=0.7, p=0.2 and HR=0.8, p=0.4 respectively), AGVHD II-IV (HR=1.1, p=0.8 and HR=1.2, p=0.3 respectively) and CGVHD (HR=0.8, p=0.2 and HR=0.9, p=0.6 respectively). Propensity matching confirmed the results of the multivariate Cox analysis with no difference in outcome between Haplo, MUD and MMUD. Compared to Haplo the HR for DFS and OS were 1.04 (p=0.84) and 0.85 (p=0.50) for MUD and 0.9 (p=0.66) and 0.82 (p=0.48) for MMUD. Conclusions: Outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as an additional option for patients lacking a matched sibling donor. Disclosures Tischer: Jazz Pharmaceuticals: Other: Jazz Advisory Board. Mohty:MaaT Pharma: Consultancy, Honoraria.

scholarly journals Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 57-63
Author(s):  
KK Hussein ◽  
S Dahlberg ◽  
D Head ◽  
CC Waddell ◽  
L Dabich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Complete Response ◽  
Good Prognosis ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Remission Duration

The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan- Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis.

scholarly journals Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 57-63 ◽  
Author(s):  
KK Hussein ◽  
S Dahlberg ◽  
D Head ◽  
CC Waddell ◽  
L Dabich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Complete Response ◽  
Good Prognosis ◽  
Cancer Center ◽  
Significant Prognostic Factor ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Remission Duration

Abstract The Southwest Oncology Group conducted a study of acute lymphoblastic leukemia (ALL) in adults over a 5-year period, testing the utility of the L-10M regimen initially described by the group from Memorial Sloan- Kettering Cancer Center. One hundred sixty-eight eligible patients were treated with this intensive combination chemotherapy regimen. One hundred fifteen (68%) achieved complete remission. With the current median follow-up time of 34.5 months, the median durations of remission, relapse-free survival, and overall survival were 22.9, 20.9, and 17.7 months, respectively. Only 35% of the patients over 50 years of age achieved a complete remission. Age was a significant prognostic factor for complete response, survival, relapse-free survival, and remission duration. In addition, a low initial WBC count was found to have a statistically significant association with longer remission duration. Responders between the ages of 20 and 49 years with WBC counts of less than 15,000 appear to have an exceptionally good prognosis.

General Outcome of Four Years Experience in the Treatment of Acute Lymphoblastic Leukemia in the National Hospital Edgardo Rebagliati Martins. Lima- Peru.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4105-4105
Author(s):  
Mariela Moreno ◽  
Sergio Murillo ◽  
Jackeline Rodriguez ◽  
Juan Ramon JN Navarro ◽  
Lourdes Aranda ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
National Hospital ◽  
Free Survival ◽  
Disease Free ◽  
Very High

Abstract Abstract 4105 Considering our Pediatric Hematology Unit (PHU), as a social security national reference Unit, one third of the hospitalized children population have acute leukemia in the Pediatrics Department of the National Hospital Hospital Edgardo Rebagliatti Martins- ESSALUD, Lima - Perú. PURPOSE: To analyze survival outcome and behavioral of the disease in children with acute lymphoblastic leukemia (ALL) in a Social Security Hospital of a Developing country. PATIENTS AND METHODS: We analyze 100 pediatrics patients (less than 14 years old) diagnosed with acute lymphoblastic leukemia (ALL) since 2005 to 2008. Disease-free survival (DFS) was computed according to the Kaplan-Meier method and long rank test, using the SPSS 15.0. RESULTS: A total of 100 children were evaluated. The major incidence according to age was in the group of children between 1 and 9 years old (76%); there were no difference between gender: 51% females and 49% males. The B type was the most common diagnosed leukemia: The B CALLA positive (CD10, CD19, HLA, DR) was the most frequent inmunophenotype, present in 87 children (87%). T-cell ALL was seen in 7%, bi-phenotype and Pro B in 3%. According to our risk stratification protocol, 34 patients were in the very high risk group (VHR), 47 patients in the high risk (HR) group and 19 patients in the intermediate-low risk (ILR) group. About Kariotype evaluation, the most common presentations were normal and hyperdiploid kariotype (67%). We achieved Complete Remission in 95% of our patients post 4 weeks Induction therapy (“A” Induction period). The Total 4th year disease free survival was 48.9% (36.3% VHR, 50.4% HR and 75.9% ILR); of these 61.8 ± 6.2% had DFS after 2 years of therapy and 55.9±6.9 % after 3 years. The Disease Free Survival was significantly increased on those with the following risk factors at diagnosis: white blood cell count &lt; 100 000/mm3 (P= 0.002), normal or hyperdiploid kariotype (P&lt;0.0001). However age, gender and type of ALL in our small group do not have statistical significance. The groups of patients not responding to prednisone have identical DFS than the Responding patients, but the no responding patients received treatment as an immediately superior group (High or Very High Risk). All the patients that have more than 1% of Minimal Residual Disease after a 4 week Induction therapy and achieved a Complete Remission with other chemotherapy treatment, had a poor DFS of less than 10 months (P = 0.015). CONCLUSION: The Total DFS was 48.9%. WBC count below 100,000 mm3; normal and hyperdiploid kariotypes, correlate with best DFS. The MDR &gt;1%, was correlated with poor DFS (less than 10 months). The no responding prednisone group must receive a more intensive chemotherapy (the treatment of the immediately superior risk group). The poor DFS at 4 years explain the reason of our therapeutic decision to perform a sibling stem cell Transplant, in those pediatric patients with HR or VHR Acute Lymphoblastic Leukemia (BMT with a 12 year disease free survival of 59.8%). Disclosures: No relevant conflicts of interest to declare.

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