-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1464 Achievement of Undetectable BCR::ABL1 (uBCR::ABL1) Is Predictive of Improved Survival in Philadelphia Chromosome Positive (Ph+ve) Acute Lymphoblastic Leukemia (ALL) Patients Not Receiving Allogeneic Stem Cell Transplantation

Program: Oral and Poster Abstracts
Session: 612. Acute Lymphoblastic Leukemias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Diseases, Lymphoid Malignancies, Minimal Residual Disease
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Talha Badar, MD1, Ravi Narra, MD2*, Alice Mims, MD3, Rory M. Shallis, MD4, Guilherme Sacchi De Camargo Correia, MD5, Cameron Hunter6, Vamsi K. Kota, MD7, Shreya Desai, MD8, Anand Ashwin Patel, MD9, Adam S Duvall, MD10, Neil Palmisiano, MD, MS11, Emily K Curran, MD12, Omer Zulfa, MD13,14*, Anjali S. Advani, MD15, Ehab L. Atallah, MD16 and Mark R. Litzow, MD17

1Division of Hematology-Oncology, Blood and Marrow Transplantation Program, Mayo Clinic, Jacksonville, FL
2BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
3Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH
4Section of Hematology, Department of Internal Medicine, Yale School of Medicine and Yale Cancer Center, Killingworth, CT
5Mayo Clinic, Jacksonville, FL
6Section of Hematology, Department of Internal Medicine, Yale School of Medicine - Yale Cancer Center, New Haven, CT
7Georgia Cancer Center, Augusta University, Augusta, GA
8Georgia Cancer Center at Augusta University, Augusta, GA
9Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL
10Department of Medicine, University of Chicago, Chicago, IL
11Department of Medical Oncology, Thomas Jefferson University Hospital, Philadelphia, PA
12Division of Hematology/Oncology, University of Cincinnati Cancer Center, Cincinnati, OH
13University of Cinncinati, Cincinatti, OH
14Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
15Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
16Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
17Division of Hematology, Mayo Clinic, Rochester, MN


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.


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.


Baseline characteristics

The median age of the pts was 53 years (range [R] 19-85), median white blood cell count (WBC) was 17.6 (109/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 2nd 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).


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).


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.

Disclosures: Mims: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Shallis: Rigel: Consultancy; Curio Science: Consultancy; Bristol Myers Squibb: Consultancy; Gilead Sciences: Consultancy; Servier: Consultancy. Kota: Novartis: Honoraria; Kite: Honoraria; Incyte: Research Funding; Pfizer: Honoraria. Patel: BMS: Honoraria; AbbVie: Honoraria; Kronos Bio: Research Funding; Pfizer: Research Funding. Palmisiano: Rigel: Consultancy; Genentech: Research Funding; Abbvie: Consultancy, Research Funding. Curran: Amgen: Other: Advisory board; Kite: Other: Advisory board; Incyte: Other: Advisory board; Pfizer: Honoraria, Other: Advisory board; Jazz: Other: Advisory board; Servier: Consultancy, Other: Expert consensus panel. Advani: Incyte: Research Funding; Kite: Honoraria, Other: consulting, Research Funding; Immunogen: Research Funding; Glycomimetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Macrogenics: Research Funding; Servier: Research Funding; OBI: Research Funding; Pfizer: Honoraria, Research Funding; Kura: Honoraria; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Other: advisory board, Research Funding; Beam: Honoraria; Taiho: Honoraria, Membership on an entity's Board of Directors or advisory committees; Nkarta: Honoraria; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Atallah: Takeda: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding.

*signifies non-member of ASH