About

Eric Tam is an Assistant Professor of Clinical Medicine at the Keck School of Medicine of USC. His research focuses on the clinical integration of menin inhibitors in acute myeloid leukemia (AML), as well as exploring therapeutic perspectives and evolving data in this area. He has contributed to the understanding of various hematologic malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, and T-cell lymphoma, through his extensive publication record. His work involves investigating targeted therapies, resistance mechanisms, and treatment outcomes in hematologic cancers, aiming to improve clinical management and therapeutic strategies.

Research topics

• Medicine
• Immunology
• Internal medicine
• Pathology

Selected publications

• Pretransplant Blinatumomab Is Associated with Reduced Relapse and Improved Disease-Free Survival in Adults with B-Cell ALL Undergoing Allogeneic Hematopoietic Cell Transplantation

  Clinical Lymphoma Myeloma & Leukemia · 2026-05-01

  article
  PublisherDOI

• Pediatric-inspired USC ALL regimen vs hyper-CVAD in adults with ph-negative ALL: Real-world outcomes including blinatumomab in a predominantly hispanic cohort.

  Blood · 2025-11-03

  articleOpen access

  Abstract Introduction: Pediatric-inspired regimens have improved outcomes in adolescents and young adults with acute lymphoblastic leukemia (ALL), but the optimal frontline therapy for adults remains debated. The USC ALL regimen, a modified pediatric-based protocol with detailed composition established in prior institutional studies, incorporates PEG-asparaginase and multi-agent chemotherapy delivered sequentially across induction, consolidation, and maintenance phases. We retrospectively compared clinical outcomes and toxicities of USC ALL versus Hyper-CVAD in adult patients with newly diagnosed, Philadelphia chromosome (Ph)-negative ALL at our institution. Methods: This retrospective chart review included adults with newly diagnosed ALL treated with either Hyper-CVAD or USC ALL regimens at Norris Comprehensive Cancer Center (NCCC) between 2015 and 2024. The study was approved by the Institutional Review Board at the University of Southern California and conducted by the Declaration of Helsinki. Of 285 eligible patients (n=222 USC ALL, n=63 Hyper-CVAD), those with Ph-positive ALL (n=99) and those who did not receive PEG-asparaginase during either induction cycle (n=44) were excluded, leaving 158 patients for comparison. Demographic and clinical features were compared using Fisher's exact test for categorical variables and the Wilcoxon rank-sum test for continuous variables. Cumulative incidence of relapse (CIR) was assessed using competing risk regression (Fine-Gray method), with death as a competing outcome. Overall survival (OS) and disease-free survival (DFS) were analyzed using Cox proportional hazards models, with relapse and death as events for DFS. Patients treated with USC ALL served as the reference group. Results: Our predominantly Hispanic (75%) cohort (median age 35.5, range: 18-70) had a median follow-up of 43 months. Many patients were transplanted (n=83, 52.5%) and received blinatumomab (n=69, 44.8%) for measurable residual disease (MRD) or relapse. Most patients had Ph-negative B-ALL (n=89, 56.3%), followed by Ph-like B-ALL (n=50, 31.6%), T-ALL (n=18, 11.4%), and MPAL (n=1, 0.6%). Compared to those receiving Hyper-CVAD (n=43, 27.2%), patients given USC ALL (n=115, 72.8%) were younger (33 vs 44 years, P=0.036). While complete remission rates were similar, USC ALL patients were more often MRD-negative at CR (79.1% vs 56.7%, P=0.029). There were no differences in cytogenetics, sex, race/ethnicity, ALL/Ph subtype, CBC parameters, extramedullary disease, or refractory disease between groups. Within the USC ALL cohort, most patients received PEG during both induction cycles (n=84, 73.0%), with more receiving it in cycle 1 (n=108, 94.0%) than cycle 2 (n=91, 82.7%). The primary reason for withholding PEG in either cycle was transient hepatic dysfunction. The most common grade 3 or higher toxicities were hypofibrinogenemia (43.6%), febrile neutropenia (42.7%), elevated transaminases (18%), hyperbilirubinemia (13%), and thrombotic events (2.9%). For the entire cohort, 3-year OS, DFS, and CIR were 82.6% (95% CI: 75.9–89.9), 54.5% (95% CI: 46.4–64.0), and 42.4% (95% CI: 33.6–50.9), respectively. On univariate analysis, compared to USC ALL, Hyper-CVAD was associated with inferior DFS (3-year: 39.1% vs 61.0%; HR=2.00, 95% CI: 1.21–3.30, P=0.007) and increased CIR (56.0% vs 36.6%; HR=1.80, 95% CI: 1.07–3.05, P=0.028), but similar OS (76.2% vs 84.8%; HR=1.41, 95% CI: 0.63–3.16, P=0.40). After controlling for age, sex, and ALL/Ph type, Hyper-CVAD remained associated with significantly lower DFS (HR=2.06, 95% CI: 1.23–3.43, P=0.006) and higher CIR (HR=1.91, 95% CI: 1.07–3.35, P=0.023). In subgroup analyses by age (<40 vs ≥40), the younger cohort demonstrated persistently lower DFS (HR=2.56, 95% CI: 1.29–5.05, P=0.007) and higher CIR (HR=2.31, 95% CI: 1.17–4.58, P=0.016) with Hyper-CVAD relative to USC ALL, while outcomes were similar with both regimens in patients aged ≥40. Similar patterns were observed in Ph-like ALL: DFS (HR=2.94, 95% CI: 1.27–6.80, P=0.012), CIR (HR=2.91, 95% CI: 1.27–6.67, P=0.012), and no difference in OS (HR=3.54, 95% CI: 0.79–15.9, P=0.10). Conclusions: USC ALL was associated with improved disease-free survival and lower relapse compared to Hyper-CVAD in adults with Ph-negative ALL, particularly in patients under 40 and those with Ph-like disease. These findings support pediatric-inspired regimens as a preferred frontline regimen for select adult populations.

  PublisherOA PDFDOI

• Tuscany Study demonstrates safety and efficacy of tuspetinib plus standard of care venetoclax and azacitidine in patients with newly diagnosed AML ineligible for induction chemotherapy

  Blood · 2025-11-03 · 2 citations

  article

  Abstract BACKGROUND The combination of venetoclax (VEN) with azacitidine (AZA) improves response rates and overall survival in newly diagnosed AML patients. However, overall survival remains poor, particularly in cases harboring adverse FLT3-ITD, RAS, or TP53 mutations that drive VEN resistance and early relapse. The addition of a well-tolerated, broadly active, targeted agent to AZA/VEN is needed to enhance response, increase survival, and decrease therapeutic resistance. Tuspetinib (TUS) is a potent, once-daily oral kinase inhibitor that targets SYK, FLT3, JAK1/2, RSK1/2 of the RAS/MAPK pathway, and mutant KIT kinases that drive dysregulated proliferation in AML, and has been shown to indirectly inhibit MCL1 expression. In the prior APTIVATE study in relapsed/refractory (R/R) AML, both TUS monotherapy (93 pts) and TUS in combination with VEN (79 pts) produced objective responses in patients with diverse mutations with no dose-limiting toxicities (DLTs) observed at the 40-160 mg dose levels, supporting the combination of TUS with AZA/VEN in the TUSCANY study. OBJECTIVES To evaluate the safety, tolerability, response rates, measurable residual disease (MRD) status, and pharmacokinetics (PK) of TUS at various dose levels, in combination with VEN (APTIVATE), and in combination with AZA and VEN in newly diagnosed AML patients ineligible for induction chemotherapy (TUSCANY). METHODS The TUSCANY study investigates TUS in combination with standard doses of AZA (75 mg/m² daily for 7 days) and VEN (400 mg daily for 21 or 28 days) in each 28-day treatment cycle in patients with previously untreated AML, regardless of genotype. TUS is administered at dose levels of 40, 80, 120, and 160 mg daily for 21 or 28 days per cycle in a 3+3 dose-escalation design with 3–6 patients per cohort, followed by expansion of active dose levels. Safety, response rates, PK of VEN and TUS, and MRD status are systematically assessed. RESULTS Patient Demographics in the TUSCANY Frontline Study: Ten pts, aged 69 to 81 years received TUS (40, 80, or 120 mg once daily) in combination with VEN and AZA. Of these, 1 proceeded to transplant, and 8 remain on treatment. The cohort includes 2 pts with complex karyotypes (CK) and TP53 mutations, 2 with FLT3-ITD, one with RAS mutation, and 5 with myelodysplasia-related mutations. Safety: Treatment has been well tolerated with no DLTs, no Grade 4 myelosuppression observed past Day 42 in Cycle 1 in the absence of leukemia, and no treatment-related deaths or discontinuations. Grade ≥3 hematologic toxicity was observed in 9 pts (90%), with the most common being decreased platelet count (60%) and white blood cell count (60%). Febrile neutropenia was reported in only one patient. Non-hematologic adverse events were mostly Grade 1–2, with gastrointestinal symptoms such as constipation (50%), nausea (40%), and diarrhea (40%) being most frequent. Serious adverse events (SAEs) occurred in four patients (40%) with none leading to treatment discontinuation or death. Treatment modifications due to TEAEs occurred in 30% of patients for TUS, 40% for VEN, and 30% for AZA. PK: Plasma concentrations of TUS and VEN with AZA were consistent with levels observed for each agent as monotherapy, suggesting no meaningful PK interaction between them. Mean steady-state trough concentrations of TUS were 0.17 mM (40 mg), 0.34 mM (80 mg), and 0.55 mM (120 mg). Corresponding VEN concentrations were 0.83 mM, 1.31 mM, and 1.78 mM, respectively, supporting the combination of TUS with VEN and AZA without dose adjustment. Additionally, azole antifungal use did not appear to alter TUS exposure. Responses: CR/CRh rates were 90% across all TUS dose levels: 3 of 4 pts at the lowest dose of 40 mg, 3 of 3 pts at 80 mg, and 3 of 3 pts at 120 mg TUS. CR/CRh occurred in 2/2 (100%) FLT3-ITD pts, 7/8 (87.5%) FLT-WT pts, 1/1 (100%) RAS mutated pts, and 2/2 (100%) mutated TP53/CK pts. Marrow MRD by flow cytometry <0.1% was achieved in 5/9 (56%) of responding pts, including two with TP53-mutation/CK. CONCLUSIONS TUS has been well-tolerated, both as monotherapy and in combinations with VEN, with objective responses in diverse AML pts including those with FLT3-WT and mutated TP53, RAS, or FLT3. The combination of TUS with standard dosing of VEN/AZA in treatment-naïve AML demonstrates promising safety, tolerability, and efficacy, including MRD-negative remissions in a broad range of mutationally diverse pts. Additional enrollment and follow-up will be presented at the meeting.

  PublisherDOI

• Clinical Impact of Pretransplant Blinatumomab in Predominantly Hispanic Adults with B-Cell Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

  Transplantation and Cellular Therapy · 2025-02-01

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  PublisherDOI

• CAR t-cell therapy-related cytokine release syndrome and neurotoxicity: Real-world outcomes from a comprehensive cancer center

  Blood · 2025-11-03

  article

  Abstract Background: Chimeric Antigen Receptor T-Cell Therapy (CAR-T) is used in the treatment of relapsed/refractory hematologic malignancies, such as multiple myeloma, B-cell lymphoma, and acute lymphoblastic leukemia. Despite the durable, efficacious clinical responses, these therapies are associated with a serious adverse effect profile, most notably, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In the CAR-T clinical trials, rates of CRS and neurotoxicity have ranged from 50-90% and 20-80%, respectively, across different products. Given these concerns, more real-world studies need to be conducted to investigate the safety outcomes in broader, general populations. Objective: The purpose of this study was to compare real-world outcomes from a comprehensive cancer center to the pivotal trials that led to the FDA approvals of various CAR-T products. Methods: This is a retrospective cohort study conducted in adult patients (≥18 years old) with hematologic malignancies who received FDA-approved CAR-T therapy at USC Norris Comprehensive Cancer Center between January 2022 and December 2024. Treatment options included ciltacabtagene autoleucel, brexucabtagene autoleucel, and axicabtagene ciloleucel. Those enrolled on investigational protocols were excluded from the study. The primary outcome was the incidence of CRS and neurotoxicity/ICANS, graded and scored by the treating physician according to the American Society of Transplant and Cellular Therapy (ASTCT) criteria. Secondary outcomes included use of tocilizumab, corticosteroids, vasopressors, anakinra, intrathecal chemotherapy, dasatinib, and thiamine; length of stay; survival at 100 days and 1 year. Data were collected through chart review of the electronic medical record and analysis included descriptive statistics. Results: 53 patients were included in the study. Most patients receiving axi-cel experienced grade 1 or 2 CRS, with only three patients experiencing grade ≥3 CRS. The incidence of CRS was lower here compared to ZUMA-1 and ZUMA-5. Axi-cel had the highest rate of neurotoxicity in our study. The incidence of grade 1 or 2 neurotoxicity was similar to trials, but grade ≥3 was lower here. Most patients receiving brexu-cel experienced grade 1 or 2 CRS, with only one patient experiencing grade ≥3 CRS. The incidence of CRS was lower here compared to ZUMA-2 and ZUMA-3. Patients experienced a more diverse range of neurotoxicity, but the rates were still lower than in the trials. Patients receiving cilta-cel had a lower incidence of CRS than in CARTITUDE-1 and had no neurotoxicity. None of our patients experienced grade ≥4 CRS and only one patient experienced grade 4 neurotoxicity. For supportive care, approximately 75% of the patients received tocilizumab and 50% received dexamethasone, with a few patients needing anakinra and vasopressors. Discussion/Conclusion: CAR-T is associated with CRS and neurotoxicity/ICANS, though most cases were grade 1-2 and required minimal supportive care in our study. The incidences of CRS and ICANS were slightly more favorable than what was seen in the pivotal trials, possibly due to the higher and earlier utilization of tocilizumab and dexamethasone. These findings validate the safety profile of CAR-T outside of the clinical trial setting and showcase our institution's ability to provide safe outcomes in our patients.

  PublisherDOI

• Outcomes and Toxicities of Total Body Irradiation-Based Conditioning for B-ALL in a Predominantly Hispanic Patient Population Undergoing Hematopoietic Stem Cell Transplantation: A Ten-Year Experience from an NCI-Designated Comprehensive Cancer Center

  International Journal of Radiation Oncology*Biology*Physics · 2025-09-01

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  PublisherDOI

• Prognostic impact of TP53 mutation status and variant allele frequency in myelodysplastic syndromes: A meta-analysis of prognosis and transplant outcomes

  Blood · 2025-11-03

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  Abstract Background: TP53 mutations are among the most clinically significant genetic alterations in myelodysplastic syndromes (MDS), frequently associated with complex karyotypes, therapy-related MDS, and adverse outcomes. Recent studies suggest that TP53 allelic status (mono- vs. multi-hit) and variant allele frequency (VAF) influence prognosis. VAF serves as a marker of clonal dominance and may help define disease risk. Although allogeneic stem cell transplantation (HSCT) is the only curative option for MDS, outcomes remain poor for TP53-mutated patients. We conducted a meta-analysis to evaluate the prognostic implications of TP53 allelic status and VAF in MDS, including outcomes after HSCT. Methods: A comprehensive meta-analysis was conducted to investigate the prognostic impact of TP53 mutation status and variant allele frequency (VAF) in patients with myelodysplastic syndromes (MDS), including post–stem cell transplant outcomes. Eligible studies were identified through a systematic search and included those reporting hazard ratios (HRs) for overall survival (OS) stratified by TP53 status (wild-type, single-hit, multi-hit) and VAF thresholds (<30% vs. ≥30%). In total, data was extracted from 33 unique studies, comprising 2,526 participants in the exposure group and 8,428 in control group. HRs and corresponding 95% confidence intervals (CIs) were extracted from studies. A random-effects model using inverse-variance weighting was applied to calculate pooled HRs. Heterogeneity between studies was assessed using the I² statistic. Four primary analyses were performed: (1) OS comparison between TP53-mutated and wild-type patients. (2) OS analysis within TP53-mutated patients based on VAF (<30% vs. ≥30%). (3) Comparison of outcomes between wild-type and multi-hit TP53 subtypes. (4) Post-transplant OS stratified by TP53 mutation status immediately at time of transplant. Subgroup analyses further evaluated the interaction between TP53 allelic state, VAF, and transplant outcomes. All statistical analyses were performed using R (packages: meta, survival), with statistical significance defined as α = 0.05. Results: Across included studies, patients with any TP53 mutation had significantly inferior overall survival (OS) compared to wild-type, with a pooled HR of 2.34 [95% CI: 1.92–2.86] (p<0.001). When stratifying by allelic complexity, patients with single-hit mutations exhibited a HR: 1.59 [1.08–2.33] (p=0.018). Multi-hit mutations exhibited aHR: 1.53 [1.15–2.05] (p=0.004). Variant allele frequency (VAF) was also associated with differential outcomes: patients with high VAF (≥30%) showed significantly reduced OS (HR: 2.16 [1.79–2.61]) versus those with low VAF (<30%) (HR: 1.60 [1.29–1.97]), with statistically significant subgroup differences (p=0.035). Among the transplant cohort, TP53-mutated patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) had worse post-transplant survival compared to wild-type counterparts (HR: 1.99 [1.68–2.35], p<0.001). These findings highlight the independent prognostic significance of TP53 mutation status, allelic complexity, and VAF in both general and transplant-eligible MDS populations. Conclusions: This meta-analysis confirms that both TP53 mutation status and VAF independently predict poorer outcomes in MDS, including among HSCT recipients. Elevated VAF reflects clonal dominance and is associated with more aggressive disease. VAF should be incorporated into MDS risk stratification models and may guide transplant decisions and future therapeutic strategies.

  PublisherDOI

• Philadelphia‐like B‐cell acute lymphoblastic leukaemia: Disease features and outcomes in the era of immunotherapy

  British Journal of Haematology · 2024-09-18 · 5 citations

  article

  Philadelphia chromosome (Ph)-like acute lymphoblastic leukaemia (ALL) is a high-risk subtype with a gene expression profile similar to Ph-positive ALL, due to activation of tyrosine kinase signalling. To understand the clinical implications of Ph-like ALL, this single-centre retrospective study evaluates outcomes in 268 adults, largely Hispanic ALL patients treated between 2013 and 2024, with a subgroup analysis of 139 haematopoietic stem cell transplantation (HSCT) patients. ALL subtypes included 68 (25.4%) Ph-like, 89 (33.2%) Ph-positive, and 111 (41.4%) Ph-negative. Ph-like patients were the youngest age at diagnosis (p = 0.007), most likely to have refractory disease (p < 0.001), and least likely to achieve minimal residual disease (MRD) negativity after induction (p = 0.031). Relative to Ph-negative ALL, Ph-like achieved worse event-free survival (EFS) (HR = 1.66; 95% CI 1.12-2.46; p = 0.012), whereas Ph-positive had improved EFS (HR = 0.60; 95% CI 0.38-0.93; p = 0.024) and cumulative incidence of relapse (CIR) (HR = 0.59; 95% CI 0.35-0.99; p = 0.046). Within the transplant subgroup, Ph status did not impact disease-free survival (DFS), CIR, or overall survival (OS). However, patients who received blinatumomab within 1-year pre-HSCT had improved DFS (HR = 0.43; 95% CI 0.20-0.94; p = 0.034) and CIR (HR = 0.26; 95% CI 0.09-0.75; p = 0.13). In conclusion, our data suggest that Ph-like is less likely to respond to standard induction therapy and HSCT may result in similar survival outcomes to Ph-negative ALL.

  PublisherDOI

• Clinical Impact of Pretransplant Blinatumomab in Predominantly Hispanic Adults with B-Cell Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

  Blood · 2024-11-05 · 1 citations

  articleOpen access

  Introduction: Adult B-cell acute lymphoblastic leukemia (B-ALL) remains a challenging disease, particularly in Hispanic patients who often present with unfavorable cytogenetics. Allogeneic hematopoietic stem cell transplantation (HSCT) serves as a potentially curative treatment. Blinatumomab, a bispecific T-cell engager targeting CD19, has shown promise in improving B-ALL outcomes. Our aim is to evaluate the clinical impact of pretransplant blinatumomab. Methods: This is a retrospective study includes 145 B-ALL adults who received allogeneic HSCT at Norris Comprehensive Cancer Center from 2014 to 2024. Incidence of severe chronic graft versus host disease (cGVHD), grade 3-4 acute GVHD (aGVHD), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) were evaluated using competing risk regression (Fine-Gray method), with death as a competing outcome. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) were analyzed with Cox proportional hazards model. Results: Demographics Our cohort was predominantly male (n=85, 58.6%), Hispanic (n =111, 76.6%) with a median age of 42 years (range 20-69) and underwent a pediatric-based regimen (USC ALL 61.1%, Hyper-CVAD 20.8%, Other 18.1%). Most were Philadelphia (Ph) neg (Ph-negative 40.4%, Ph-positive 35.3%, Ph-like 24.8%) and had unfavorable (51.4%) or intermediate (40.0%) risk cytogenetics according to CALGB criteria. Patients most often received haploidentical (haplo) HSCT (haplo 36.4%, MSD 32.9%, MUD 25.9%, MMUD 4.9%) with myeloablative conditioning (93.6%) while in CR1 (CR1 68.3%, CR2/CR3 31.7%) and achieved measurable residual disease (MRD) negativity (89.7%). GVHD prophylaxis consisted of posttransplant cyclophosphamide (PTCy) with tacrolimus (tac) and mycophenolate mofetil (58.2%), methotrexate (MTX)/tac(37.6%), or PTCy alone (4.3%). Within six months pretransplant, 36 patients (24.8%) received blinatumomab (median cycles = 2, range 1-5) for positive MRD (75.0%) or relapse/refractory disease (25.0%). When comparing patients by pretransplant blinatumomab, age, sex, cytogenetics, induction regimen, donor type, stage, donor age, and transplant risk index (TRI) did not differ between groups. The blinatumomab group more frequent Ph-like status(38.9% v. 20.2%; p=0.041), and trended towards having fewer MRD-positive patients pretransplant (2.9% v. 12.9%; p=0.115). Survival/Relapse: At 3 years post-transplant, our OS, DFS, CIR, and NRM were 83.3% (76.2-91.0), 69.1% (61.1-78.1), 22.8% (15.6-30.8), and 8.15% (4.09-14.0), respectively. Patients who received blinatumomab had improved DFS (93.7% v. 61.5%, HR 0.24, 95%CI 0.07-0.76, p=0.016) and CIR (3.3% v. 29%, HR 0.22, 95%CI 0.05-092, p=0.038), but similar OS (93.5% v. 80.0%, p=0.16) and NRM (2.9% v. 9.7%, p=0.31). Relative to CR1, patients transplant in CR2/3 had worse OS(HR 3.47, 95% CI 1.43=8.42, p=0.006), DFS(HR 2.19, 95% CI 1.16-4.15, p=0.016) and CIR(HR 2.26, 95% CI 1.09-4.67, p=0.028), while pretransplant MRD positivity predicted worse OS(HR 3.63, 95% CI 1.32-10.0, p=0.013) and DFS (HR 2.35, 95% CI 1.04-5.34, p=0.041) on univariate analysis. Higher TRI, absence of radiation, and MTX/tac GVHD regimen were univariate predictors of worse OS, DFS or CIR (data not shown). When controlling for disease status and MRD status at transplant, the blinatumomab group continued to have improved CIR (HR 0.22, 95% CI 0.05-0.92, p=0.039) and DFS (HR 0.24, 95% CI 0.07-0.80, p=0.019) on multivariate analysis. Subgroup analysis of Hispanic patients demonstrated improved DFS with blinatumomab (HR 0.22, 95% CI 0.05-0.94, p=0.041). GRFS/GVHD: Our 6-month incidence of grade 3/4 aGVHD was 9.90% (5.67-15.5) while 3-year GRFS and moderate/severe cGVHD was 44.7% (35.8-55.9) and 39.5% (29.9-48.9) respectively. There were no differences in grade 3/4 aGVHD (17.3% v. 7.49%, p=0.1), moderate/severe chronic GVHD (43.0% v. 38.0%, p=0.440), or GRFS (43.3% v. 45.1%, p=0.488) by blinatumomab administration. Conclusion: This study demonstrates that pretransplant blinatumomab therapy in adult B-ALL patients undergoing allogeneic HSCT is associated with improved DFS and reduced CIR despite having higher-risk cytogenetics without increasing the risk of GVHD. These findings suggest incorporating blinatumomab into pretransplant treatment strategies may enhance outcomes for adult B-ALL patients undergoing allogeneic HSCT.

  PublisherOA PDFDOI

• Phase 1 Safety and Efficacy of Tuspetinib Plus Venetoclax Combination Therapy in Study Participants with Relapsed or Refractory Acute Myeloid Leukemia (AML) Support Exploration of Triplet Combination Therapy of Tuspetinib Plus Venetoclax and Azacitidine for Newly Diagnosed AML

  Blood · 2024-11-05 · 4 citations

  articleOpen access

  INTRODUCTION: Combination therapy with a hypomethylating agent (HMA) and venetoclax (VEN) has improved response rates and overall survival of newly diagnosed AML patients. However, long-term outcomes remain poor, particularly in those with adverse clones harboring FLT3-ITD, RAS, or TP53 mutations. Since the emergence of VEN resistance is associated with a dismal prognosis, addition of a well-tolerated and active agent to the HMA/VEN combination is needed to improve response rates, increase survival, and prevent emergence of resistant AML clones. Tuspetinib (TUS) is a potent once daily oral kinase inhibitor of SYK, FLT3, JAK1/2, RSK1/2, mutant KIT, and TAK1-TAB1 kinases that mediate dysregulated cellular proliferation in AML. Development of TUS as a combination agent with HMA/VEN is supported by early phase safety and efficacy results in R/R AML, both as a monotherapy and in combination with VEN. AIMS: To assess the safety, tolerability, and pharmacokinetics (PK) of TUS and TUS/VEN to support selection of appropriate doses for monotherapy and combination (doublet and triplet) therapy. METHODS: TUS was administered to study participants (pts) with R/R AML as a single agent in dose escalation, exploration, and expansion (20-200 mg once daily dose levels), and at once daily dose levels of 40 and 80 mg in combination with VEN (400 mg once daily dose). Cycles were planned to be 28 days, with a C1D15 marrow assessment in the combination arm. RESULTS: As of July 02, 2024, 93 pts have been treated with TUS monotherapy: pts were mostly Asian (47.3%) and White (41.9%) with a median age of 63 years (range 18-84 years). No TUS-related non-hematologic SAEs, QTc prolongation, differentiation syndrome, deaths, or discontinuations were observed. Clinical responses with TUS were observed across the 40-160 mg dose levels including the recommended Phase 2 dose of 80 mg (n=19, CRc=26.3%) among all evaluable pts. Clinical response was superior in VEN-naïve (n=30, CRc=30.0%) vs prior-VEN treated pts (n=35, CRc=5.7%), with CR/CRh=35.7% (n=14) for VEN-naïve pts receiving 80 mg TUS. Among pts with FLT3 mutated (FLT3-MUT) treated with TUS 80 mg, CRc=37.5% (n=8), with 33.3% (n=3) in prior-FLT3i exposed. Dose cohorts higher than 80 mg TUS had a greater proportion of prior-VEN treated pts, which likely impacted their response rate, motivating study of the TUS/VEN combination. Seventy-nine pts were treated with TUS/VEN combination therapy: pts were largely White (77.2%) with a median age of 69 years (range 31-86 years); with 73.4% having wild-type FLT3 (FLT3-WT). Participants received a mean of 2.3 prior lines of therapy (range 1-7); 74.7% were prior-VEN treated. The most frequent TEAEs were those typically associated with VEN, including febrile neutropenia (26.6%; lower than expected for a VEN-containing regimen in R/R AML), nausea (26.6%), and pneumonia (22.8%). Objective responses were observed (overall CRc=18.5%) in pts receiving 80 mg TUS/400 mg VEN: FLT3-WT (n=49, CRc=16.3%); FLT3-MUT (n=15, CRc=26.7%), including pts with prior-FLT3i treatment (n=13, CRc=30.8%); prior-VEN treated (n=48, CRc=18.8%); and VEN-naïve (n=17, CRc=17.6%) pts. One response (n=14; 7.1%) was observed at 40 mg TUS/400 mg VEN. PK data showed no clinically meaningful interactions between TUS and VEN. Available data from the frontline triplet study will be presented at the meeting. CONCLUSIONS: Tuspetinib as monotherapy and in combination with VEN has been well- tolerated with objective responses among diverse AML patient groups including those with FLT3-WT and mutated TP53 or RAS, and in prior-VEN and prior-FLT3i treated pts. These safety and efficacy results support the upcoming combination of TUS/VEN plus azacitidine as a triplet in newly diagnosed AML pts ineligible for intensive chemotherapy, independent of FLT3 mutation status.

  PublisherOA PDFDOI

Frequent coauthors

• George Yaghmour

  University of Southern California

  78 shared

• Abdullah Ladha

  University of Southern California

  76 shared

• Karrune Woan

  University of Southern California

  72 shared

• Preet M. Chaudhary

  USC Norris Comprehensive Cancer Center

  72 shared

• Jack Rodman

  Southern California Clinical and Translational Science Institute

  47 shared

• Amir Ali

  40 shared

• Thuy Bui

  Society of Hospital Pharmacists of Australia

  26 shared

• Dan Douer

  University of Southern California

  24 shared

Education

• MBA, Business

  University of Southern California

  2025

• MD

  Saint George's University

  2013

• BS, Chemical Engineering

  University of California Los Angeles

  2007