Atallah, Ehab

Introduction: Based on a donor versus no-donor analysis, UKALLXII/E2993 showed a survival benefit for adults with acute lymphoblastic leukemia (ALL) who underwent allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR1) compared to consolidation/maintenance chemotherapy alone. The follow-up phase 3 E1910 trial (NCT02003222) randomized BCR::ABL1-negative B-lineage ALL patients (pts) aged 30-70 years in measurable residual disease (MRD)-negative CR1 after intensification to conventional chemotherapy (CC) +/- blinatumomab (blin) and demonstrated significantly improved overall survival (OS) with blin (Litzow, NEJM 2024). The current exploratory subgroup analysis evaluates outcomes of MRD-negative pts randomized on E1910 who underwent alloHCT on trial. Methods: Among pts enrolled on E1910, pts in MRD-negative CR1 by 6-color flow cytometry after intensification who were randomized to CC +/- blin and subsequently underwent alloHCT were identified. We compared baseline characteristics, MRD status post induction, relapse-free survival (RFS) and OS using the Kaplan-Meier method and the two-sided log-rank test and Cox model. A multivariable analysis was performed with alloHCT included as a time-varying covariate as well as a landmark analysis comparing the outcome of pts with unfavorable risk on the CC + blin arm who underwent alloHCT versus those who did not. Results: Of 224 MRD-negative randomized pts, 44 underwent alloHCT on trial: 22 in each arm. The median time from randomization to transplant was 3.2 months (mos). The median follow-up from initial registration was 57.8 mos. Baseline demographics including age (median 55 years), gender (53% male), race (89% white) and ethnicity (89% non-Hispanic/Latino) were equally distributed. Compared to CC + blin, the median peripheral blood white cell (WBC) count and blast percentage at diagnosis were higher in the CC arm at 6,640 vs 3,740/uL and 55 vs 9%, respectively, while median marrow blast percentage and overall unfavorable risk as defined in E1910 (55% vs 64%) were similar. Of the 44 MRD-negative pts who proceeded to alloHCT on study, 77% in the CC arm and 64% in the CC+ blin arm were MRD-negative after induction. Myeloablative conditioning was given to the majority of pts (68% CC arm and 73% CC+blin arm) and the most common graft versus host disease prophylaxis was tacrolimus-based on both arms. Among the 44 pts who underwent alloHCT, the observed hazard ratio (HR) comparing relative risk of death between pts randomized to CC+blin or CC only was 0.59 (95% CI: 0.12-2.11) with a 3-year OS rate of 82% versus 71% and the HR comparing relative risk of relapse/death was 0.52 (CI: 0.15-1.79) with a 3-year RFS rate of 82% versus 67%. For patients with unfavorable risk, 3-year OS and 3-year RFS in each treatment arm were both 71% versus 65%. Among 50 pts with unfavorable risk in MRD-negative CR after intensification who were randomized to CC + blin, a landmark analysis performed at 5 mos post randomization showed 3-year OS and RFS rates of 71% versus 90% and 71% versus 86% between the 14 pts who underwent alloHCT and those who did not, respectively. Receipt of alloHCT was a time-varying covariate in a multivariable analysis with gender, WBC count, platelets, hemoglobin, peripheral blood blasts, bone marrow blasts, performance status, and combined molecular risk category. Age, CD20 status, rituximab use, and intention to receive alloHCT were used as stratification factors. In the entire cohort of MRD-negative pts who were randomized, there was a significant association between improved OS and the receipt of CC+blin vs CC alone (HR 0.46, 95% CI: 0.26 - 0.82; p=0.009), better performance status of 0-1 vs ≥2 and favorable vs unfavorable risk ALL. In contrast, the receipt of alloHCT had no significant effect on OS (HR 1.00, 95% CI: 0.49 - 2.01). Conclusions: Within the constraints of small numbers, this exploratory subgroup analysis demonstrates that in pts with newly diagnosed BCR::ABL1-negative B-ALL treated on E1910 who achieved MRD-negativity after intensification, alloHCT outcomes did not appear to be different with or without blin in consolidation. In a multivariate analysis of all MRD-negative pts, receipt of blin but not alloHCT was associated with improved OS. Further investigation is warranted to characterize the relative benefit of blinatumomab in pts receiving alloHCT in frontline consolidation.

Background: Acute promyelocytic leukemia (APL) is one of the most treatable leukemias in the current era, with cure rates upwards of 90%. Early mortality due to coagulopathies often seen at diagnosis is a major driver of adverse outcomes. Prompt initiation of all-trans retinoic acid (ATRA) is crucial for suspected APL, as it is known to reverse these coagulopathies. Chemotherapy-free protocols consisting of arsenic trioxide (ATO) and ATRA have become the standard of care for low-risk APL with high cure rates and reduced hematologic toxicities. For high-risk disease, there are multiple treatment options that have not been compared. Since APL is rare, there is a lack of real-world data for this disease. This retrospective review aimed to assess the outcomes of APL patients (pts) across multiple institutions and to examine the most common induction regimens, characteristics linked to early (30-day) mortality, and supportive care strategies. Methods: This retrospective study involved 9 institutions in the US and was conducted through the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND). Data included pts admitted from 8/5/2006 through 2/3/2024 with a confirmed diagnosis of APL. Each institution received a data-collection form and contributed data on APL pts from presentation to last follow-up. Key data categories included patient demographics, presenting laboratory and molecular data, treatment regimen, supportive care, and patient outcomes. Results: Data for 412 pts were identified with a median age of 51 (range 17-90) and 49% were female. Cardiovascular comorbidities were present in 44% of pts and 16% had a known pulmonary comorbidity. At presentation 109 (27%) had high risk-disease, defined as a white blood cell count (WBC) greater than 10 x 109/L. A FLT3 mutation was seen in 50% of tested pts, WT1 (22%), KRAS (3.6%), and NRAS (6.5%). The median WBC at presentation was 2 x 109/L (range: 0-166 x 109/L) and the median platelet count was 27 x 109/L (range: 2.0-315 109/L). Twenty-six percent presented with grade 2+ thrombosis, bleeding, or both. A higher percentage of pts with high-risk vs. low-risk disease presented with grade 2+ thrombosis, bleeding, or both (43% vs. 20%), DIC (60% vs. 36%), and mutated FLT3 (81% vs. 37%). The majority of pts received a chemotherapy-free induction regimen consisting of ATRA plus ATO. It was determined that 36 (8.7%) pts received induction with intermittent ATO plus ATRA (Burnett AK, Lancet Oncol 2015), 276 (67%) received daily ATO plus ATRA (Ravandi F, J Clin Oncol 2009 and Lo Coco, NEJM 2013), and 70 (17%) received a regimen inclusive of an anthracycline plus ATRA. Eleven pts did not start an induction regimen other than single-agent ATRA due to early death, while 19 had their regimen classified as “other” because they did not follow a conventional induction path. In total, 295/358 (82%) received ATRA within 24 hours of admission. At least 1 dose of gemtuzumab ozogamicin was given to 58 (14%) pts, of which 35 (60%) were considered high risk. The incidence of differentiation syndrome (DS) was 37% (n=154). Among the 243 pts who received steroid prophylaxis, 30% developed DS, compared to 52% of those who did not receive prophylaxis. Among the 360 pts with at least 1 available PCR result after starting induction, 94% achieved PCR-negativity. The 30-day mortality rate was 6.6%. On univariate analysis, presenting variables associated with a higher 30-day mortality include older age, diabetes, cardiovascular comorbidities, thrombosis or bleeding, DIC, eGFR < 60, elevated total bilirubin and D-dimer levels, and high-risk disease. The median overall survival (OS) of the cohort was not reached, and the 5- and 10-year OS was 88% (95% CI: 84-91%) and 79% (95% CI: 72-87%) respectively. The cumulative incidence of relapse at 3 years was 2.7% (95% CI: 1.4 - 5.1%), with no additional relapses observed. The incidence of CNS relapse at 3 years was 0.9% (95% CI: 0.3% - 2.8%), with 2 of the 4 pts classified as high-risk. Conclusion: This is the largest real-world evidence data collection in the US evaluating the outcome of pts with APL in the current era, inclusive of ATO as front-line induction. Outcomes for this disease remain extremely positive, with low 30-day mortality rates noted in this study along with durable OS rates and low incidence of relapse. Additional information on outcomes, safety, and supportive care will be presented at the meeting.

Background: Randomized studies in newly diagnosed (ND) AML patients with a FLT3 mutation show that adding 14 days of a FLT3 inhibitor to each intensive chemotherapy cycle improves overall survival. For patients unsuitable for intensive chemotherapy due to older age or comorbidities, the presence of a FLT3-ITD mutation is associated with high rates of early relapse and short remission duration. There is a limited survival benefit of venetoclax (ven) plus azacitidine (aza) compared to aza alone among patients with AML with a FLT3-ITD mutation. Accordingly, there is significant interest in adding FLT3-targeted therapy to lower intensity chemotherapy for patients with ND AML and FLT3 mutations, but to date no randomized data have demonstrated a survival benefit for this approach.Gilteritinib (gilt) is a highly potent and FLT3-selective oral tyrosine kinase inhibitor that is the standard therapy of relapsed/refractory FLT3-mutated AML, based upon superior survival in randomized studies. Gilt can also be combined safely with ven and/or aza, though myelosuppression remains a concern. Despite this, single institution studies of ven, aza, and gilt therapy of ND AML patients with FLT3-mutations show that this three-drug regimen is associated with near-universal complete remission rates (CR 90%, CRi 6%) and a majority of studied patients eliminate detectable FLT3-ITD (<1 x10-5) within four cycles by an ultrasensitive, amplicon-based NGS assay (Short, et al. JCO 2024). Rates of CR with full count recovery and survival appear superior to historical comparisons, but myelosuppression is potentially increased with the triplet regimen. These data demonstrate a need for multi-institutional comparative trials, not only to determine whether adding FLT3-inhibitors to ven and aza improve deep remission rates, but also to refine schedules of the triplet combination that improve tolerability for widespread use.Methods: This tier 1 MyeloMATCH substudy is an open-label, randomized phase 2 trial that will enroll ND AML patients older than age 60 or individuals judged by their treating physician to be best served by azanucleoside + ven-based therapy due to comorbidity. Subjects provide samples to the central MyeloMATCH Master Screening and Reassessment Protocol (MSRP, NCT05564390 ) and are assigned to the MM1OA-EA02 substudy (NCT06317649) based upon the presence of a FLT3-ITD or FLT3-TKD (D835) mutation by NGS. Subjects are randomized to one of three arms (regimens 1, 2, or 3), stratified by age (<70 years vs. older) and FLT3-ITD burden (ITD VAF>33% vs. lower VAF or D835). All study arms contain aza and ven administered in 28-day cycles with two study arms also including gilt. Regimen 1 is ven and aza administered as per the pivotal VIALE-A study. Regimen 2 adds gilt 80 mg once daily on days 1-28 and regimen 3 adds gilt on days 8-21 only. A marrow biopsy is performed during the first cycle (day 14-21, depending on study arm) and all chemotherapy is held until count recovery if a morphologic leukemia-free state or aplasia is seen. Patients receive up to two induction cycles to achieve remission and then receive ongoing consolidation cycles of therapy with a similar pattern of gilt administration up to 2 years. To minimize risk of cumulative myelosuppression, during consolidation azacitidine administration is reduced to days 1-5 on regimens 2 and 3 and ven limited to days 1-7 on regimen 2 and days 1-14 on regimen 3. For all arms, treatment-related adverse events prompt further reduction in ven, aza, or gilt dose or duration. Response will be measured after cycles 2 and 4, including centrally-performed MRD by flow cytometry. The primary endpoint is the rate of MRD(-) CR (<1 x 10-3) after up to 4 cycles. Key secondary endpoints include safety data, response rate, EFS, and OS. The study is powered to detect a 25% absolute improvement in MRD(-) CR rate in either triplet arm from a target accrual of 147 patients. A safety run-in for regimens 2 and 3 to confirm tolerability and feasibility will be performed after 20 subjects enroll to these arms; an interim futility analysis will be performed once response assessment of 50% of all planned accrual occurs. Study was activated on June 6, 2024 and is expected to continue until December 2025.

AbstractIntroductionRelapsed or refractory (r/r) acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) remains a therapeutic challenge. Preclinical data in both B‐ and T‐ALL suggests synergy of venetoclax (VEN) with vincristine (VCR). We designed a phase I/II trial (EA9152) of the combination of L‐VCR and VEN for patients with r/r B‐or T‐cell ALL or LL. Here, we report the safety and efficacy outcomes of the phase I portion of this trial (NCT03504644).MethodsIn a 3+3 dose escalation design, r/r ALL subjects were given single‐agent VEN doses reaching 400, 600, or 800 mg for the three respective dose levels. Weekly L‐VCR at 2.25 mg/m2 IV was started on D15 of cycle 1. The primary phase I objective was to determine the maximum tolerated dose (MTD) of the combination.ResultsAmong the 18 patients in phase I, grade ≥ 3 treatment‐related adverse events were reported in 89% of treated patients. Two patients (two of three) at dose level 3 experienced dose‐limiting toxicities. Therefore, the MTD of the combination was determined to be dose level 2 (VEN 600 mg). Twenty‐two percent of evaluable patients (N = 4) achieved a complete response, with two of them showing no evidence of measurable residual disease (MRD).ConclusionThe combination of VEN and L‐VCR was found to be safe for patients with r/r ALL and encouraging preliminary efficacy, including MRD negative responses. With the removal of L‐VCR from the US market, the phase 2 portion of this trial is actively enrolling with vincristine sulfate.

AbstractVenetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real‐world data published on HMAs plus VEN have been either single‐center studies or using community‐based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real‐world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85–13.5), with OS significantly worse among patients with TP53‐mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30‐day and 60‐day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE‐A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.

Background: First-line therapies for chronic-phase (CP) CML include the tyrosine kinase inhibitors(TKIs) dasatinib, nilotinib, bosutinib or imatinib, while ponatinib and asciminib are indicated only in later lines. There are typically high response rates to first-line therapy in CP-CML, with responses to second- and third-line therapy lower and highly dependent on the specific TKI. Our goal in this study is to evaluate the role of ponatinib in the treatment of patients with CML using data from routine clinical practice. Study design and methods: Data will come from the H. Jean Khoury Cure CML Consortium (HJKC3) CML registry, a North American multi-site research database. Participating sites include the HJKC3 members (curecml.org). Patient inclusion criteria include a diagnosis CML in chronic phase, receiving second line therapy after initial therapy with a second generation TKI (dasatinib, nilotinib, or bosutinib) or receiving third or later line TKI therapy for CML. Participating patients provide consent to collect their data both retrospectively and prospectively for 1 year. Clinical data, including toxicities and complications of TKI therapy, are abstracted from the electronic health record. Participating patients are invited to complete a questionnaire to assess health-related quality of life. Data are managed using REDCap, a secure web application. Study Objectives: The primary objective is to compare the outcome of patients treated with ponatinib vs. other TKIs as second or later line therapy. Secondary objectives are to evaluate patient-reported outcomes (PRO) for CML treated with second or later line therapy and to determine if there are any patient or disease characteristics that can predict outcomes. Statistical plan for clinical outcomes: Descriptive statistics will be used to compare baseline demographic characteristics. Categorical variables will be compared using the Chi-square test. Continuous variables will be compared using ANOVA. Overall survival will be calculated from the time of diagnosis to death from any cause and patients will be censored if they were alive at the last follow-up. Survival probabilities will be computed using the Kaplan-Meier method and compared with the log-ranktest. Cox regression analyses will be used to determine significant factors that influence survival, and hazard ratios with 95% confidence intervals will be presented. Event free survival (EFS) and transformation free survival (TFS) will be calculated for patients. For EFS, loss of complete hematologic remission, loss of major cytogenetic response, progression to accelerated or blast phase, or death from any cause at any time will be considered an event. For TFS, transformation to accelerated or blast phase while on therapy or death on study will be considered an event. Statistical plan for PRO: Different PRO domains will be analyzed separately (for example, depression separate from fatigue, etc.). Descriptive statistics for each PRO measure will be reported and compared to previously published studies. Differences by treatment type will be evaluated.

Background and significance: There are typically high response rates to first line TKI therapies in chronic phase chronic myeloid leukemia (CP-CML). However, responses in later lines (second line and beyond) are diminished and highly dependent on the specific tyrosine kinase inhibitors (TKIs) used. Asciminib received FDA approval in October 2021 for the treatment of adult patients with Philadelphia chromosome-positive (Ph+) CML-CP who were previously treated with two or more TKIs, and in patients with Ph+ CML-CP with the T315I mutation. Our goal in this study is to evaluate the role of asciminib therapy for patients with CML beyond clinical studies, in routine clinical practice. Study Design and methods: Data for this study will be abstracted from the HJKC3 (H. Jean Khoury Cure CML Consortium) CML registry project (HJKC3-0005); the HJKC3 CML Registry is a collaborative academic multi-site registry. Patients will be consented to allow collection of both retrospective and prospective data for the HJKC3 CML Registry. The data forms and surveys will be built and managed through the Research Electronic Data Capture (REDCap), a secure web application managed by the Clinical & Translational Science Institute. Participating sites include members of the HJKC3 (curecml.org). This study will be an opportunity to evaluate asciminib usage in ‘real-world’ academic practices across the United States. This observational study will include cohorts of patients diagnosed with CP-CML previously treated with two or more tyrosine kinase inhibitors and/or receiving asciminib and/or those with a T315I mutation, not currently enrolled in a randomized controlled trial. The HJKC3 CML Registry intends to collect clinical and patient reported outcome (PRO) data. After obtaining patient consent, patients will be invited to complete PRO assessments. The study will attempt to collect PRO data regardless of disease or treatment status. PRO assessments will be primarily administered online, though study staff will offer alternatives (e.g., phone) for participants without internet access. Study subjects will be emailed a link to access a secure platform hosted by one of the study sites, Medical College of Wisconsin (MCW), using the REDCap platform. Study Objectives: The primary objective of the study is to describe characteristics of patients who were previously treated with two or more TKIs and treated with asciminib or with any other TKIs. The secondary objectives are to describe the clinical outcomes and PRO of those patients. Exploratory objectives include description of characteristics, treatment outcome and PRO for patients with T315I mutation. Statistical plan: The sample size of approximately 225 participants during the 5-year recruitment period is based on the available clinical expertise and ongoing recruitment data in the HJKC3 CML registry in lieu of statistical power analysis. We estimate that 150 patients in the HJKC3 CML registry will be treated with other TKI and 75 treated with asciminib. Among a total of 225 patients, we estimate that 75 patients with the T315I mutation will be enrolled in the registry. No formal statistical inference will be drawn to compare the outcomes between these two groups. Bayesian predictive probability (PP) will be utilized for the exploratory analysis of Major Molecular Response (MMR). Survival probabilities will be computed using the Kaplan-Meier method, and the p-values from the log-rank test will be provided. Different PRO domains of the patient's symptoms and functioning will be analyzed separately (e.g., depression separate from fatigue, separate from GI symptoms, etc.) since combining them into a summary score may dilute the effects of the individual (and not necessarily related) components and mask actual change. The main objective for the analyses of PRO data from the registry is to describe any differences by treatment type in patients treated with asciminib and other TKIs.

Background With the advent of tyrosine kinase inhibitor (TKI)-based therapy the outcome of Philadelphia chromosome-positive (Ph +) acute lymphoblastic leukemia (ALL) has significantly improved. Moreover, patients (pts) who achieved undetectable (u) BCR::ABL1 at 3 months (mo) from the time of initiating therapy, tend to have improved outcomes (Short et al. Blood 2016; 128 [4];504-507). We conducted a retrospective multicenter study to analyze the predictors of achieving uBCR::ABL1 in adult (> 18 years) Ph + ALL pts. Methods A total of 458 adult Ph + ALL pts from 10 US academic institutions, who were diagnosed between May 2003 and April 2023, were evaluated to assess the rates of uBCR::ABL1 at 3 mo after initiating therapy and factors that predict the achievement of molecular response. Continuous variables were summarized as median (range), while categorical variables were reported as frequency (percentage). Unadjusted comparisons of patient/ treatment related characteristics and molecular response were made using a non-parametric test (continuous variables) or Fisher's exact test (categorical variables). Survival curves were estimated using the Kaplan-Meier method and compared between molecular responses via the log-rank test. Results Baseline characteristics The median age of the pts was 53 years (range [R] 19-85), median white blood cell count (WBC) was 17.6 (10 9/L) (R, 1.2-571), 249 (55%) pts had additional cytogenetic (CG) abnormalities, 98 (22%) pts had p210 fusion protein, and 35 (8%) pts had CNS disease at diagnosis. A higher proportion of pts received TKI in combination with intensive chemotherapy (IC) (69%), than TKI + steroids (15%), TKI + low intensity chemotherapy (LC; combination of vincristine, steroids +/- rituximab) (9%), TKI + blinatumomab (3%) and IC without TKI (4%) during induction. During induction, the highest proportion of pts received 2 nd generation TKI combinations (67%; majority dasatinib 98%), compared to imatinib (19%) or ponatinib (10%): 4% of pts did not receive TKI with induction. The complete remission (CR) rate was 94%; measurable residual disease (MRD) negative by flow cytometry 51% (181/352 evaluable pts) and 58.5% (209/354 evaluable pts) of pts had uBCR::ABL1 by PCR at 3 mo from induction. A total of 212 (46%) pts received allogeneic stem cell transplantation (allo-HCT) in CR1, among them 61% of pts received TKI maintenance post allo-HCT. Predictors of uBCR::ABL1 at 3 months Predictors for uBCR::ABL1 at 3 mo are summarized in Table 1. The proportion of pts with WBC > 100 (45% vs 60%, p= 0.04), p210 fusion protein (35% vs 85%, p= <0.001), additional CG abnormality with monosomy 7 (40% vs 61%, p= 0.03), additional somatic myeloid co-mutation (39% vs 61%, p= 0.09; 94 pts evaluable), received induction with steroid plus TKI (41% vs 63%, p= 0.002) or received imatinib based induction (47% vs 61%,p= 0.07) had inferior uBCR::ABL1 rates at 3 mo. Conversely pts who received ponatinib based induction had significantly better uBCR::ABL1 rates (79% vs 57%, p= 0.009). Survival The median relapse free survival (RFS) was 72.3 mo (95% CI; 50.1-94.4), RFS was numerically higher among pts who achieved uBCR::ABL1 at 3 mo but not statistically significant (84.2 mo vs 62.9 mo, p= 0.20). The median overall survival (OS) was 129.2 mo (95% CI; 81.2-177.2), OS was not significantly different among pts who achieved uBCR::ABL1 at 3 mo (129.2) versus no uBCR::ABL1 (not reached; 50% alive at 94 mo), p= 0.47. In sub-set analysis, among non-transplanted pts, RFS was not statistically significant between those who achieved uBCR::ABL1 vs those who did not (38.9 vs 22.0 mo, respectively p= 0.24). However, the median OS was significantly higher in pts who achieved uBCR::ABL1 at 3 mo compared to pts who did not achieve uBCR::ABL1 at 3 mo: 149.3 vs 77.5 mo, p= 0.04 ( Figure 1). Conclusion In this large multicenter study, we observed significantly inferior uBCR::ABL1 rates among pts with WBC > 100, p210 fusion protein, monosomy 7 CG abnormality, pts receiving induction with steroid plus TKI or imatinib based induction. Conversely, uBCR::ABL1 rates were significantly better in pts receiving ponatinib based induction therapy. Overall, we did not see significant impact of uBCR::ABL1 at 3 mo, on RFS or OS. It is likely subsequent therapies and allo-HCT abrogates the negative impact of not achieving uBCR::ABL1 at 3 mo. However, among non-transplanted pts achievement of uBCR::ABL1 at 3 mo showed a significantly improved OS.