Session: 908. Outcomes Research: Myeloid Malignancies: Poster I
Hematology Disease Topics & Pathways:
Research, Combination therapy, Clinical Research, Health outcomes research, CML, Chronic Myeloid Malignancies, Diseases, Real-world evidence, Treatment Considerations, Registries, Myeloid Malignancies
Despite advent of multiple tyrosine kinase inhibitors (TKIs) and newer treatment methods for both AML and ALL, the outcomes of patients (pts) with chronic myeloid leukemia in blast phase (CML-BP) remain poor. Consensus guidelines on treatment of CML-BP are scarce. A recent study from the European leukemia network (ELN) blast phase registry reported outcomes of 240 CML-BP pts. They also reported marked heterogeneity in treatment patterns and lack of an accepted standard. Hence, we are undertaking this study through the H Jean Khoury Cure CML Consortium (HJKC3) to study the treatment patterns and outcomes of pts with CML-BP in the US.
Methods:
This is a multi-institution, retrospective study. IRB approval was obtained at each institution separately and data sharing agreements were executed. All pts diagnosed with CML-BP based on modified MD Anderson Criteria (≥30% blasts in the blood or bone marrow or extramedullary (EM) disease) from 2010 to 2024 were included. Categorical variables were compared using the Chi-square test. Overall survival (OS) was calculated from the time of diagnosis to death from any cause. Survival probabilities were computed using the Kaplan–Meier method and compared with the log-rank test.
Results:
Of the 72 pts with CML-BP included in this analysis, 29 (40.3%) were female and 43 (59.7%) were males. At the time of diagnosis, 36 (50%) had CML-CP (chronic myeloid leukemia in chronic phase), 11 (15.3%) pts were diagnosed with CML-AP (accelerated phase CML) and 25 (34.7%) pts with de-novo CML-BP. For the 47 pts that were initially diagnosed with CML-CP or CML-AP, the median time to progression to CML-BP was 26 months (1-207 months). Median age at diagnosis of CML-BP was 54 years (range 21-86 years). EM disease was present in 17 (23.6%) pts (7 myeloid sarcoma, 5 central nervous system and 5 skin) with 3 pts presenting with EM disease only. Blasts were of myeloid phenotype in 41 (56.9%), lymphoid in 29 (40.3%) and mixed in 2 (2.8%) pts. The bcr-abl protein was p210 in 59 (81.9%), p190 in 5 (6.9%) and p230 in 1 (1.4%) pt. Four pts had prior allogeneic stem cell transplant (alloSCT) for CML-CP. Of the pts who had an ABL kinase domain mutation tested, 42.9% (18/42) pts were found to have an ABL kinase domain mutation. The most common TKD mutation was T315I (n=6). Next generation sequencing was performed in 32 pts. The most common mutations were ASXL1 (n=10), RUNX1 (n=4), BCOR (n=2), BCORL1 (n=2), DNMT3A (n=2) and 1 each in CSF3R, KMT2A, EZH2, NF1 and TP53.
Of the 72 pts, 68 underwent CML-BP directed therapy. While only 9 (13.2%) pts were treated with TKI alone (4 dasatinib, 2 imatinib, 2 ponatinib and 1 asciminib), 54 (79.4%) pts were treated with a combination of chemotherapy with TKI (24 dasatinib, 13 ponatinib, 9 imatinib, 6 nilotinib, 1 bosutinib and 1 asciminib), and 5 (7.4%) pts were treated with chemotherapy alone. The response rate after CML-BP directed therapy was 72.1% (n=49). Best response was return to CML-CP in 17 pts, CHR with PCyR in 1 pt, CCyR in 11 pts, MMR in 5 pts, MR4 in 4 pts, MR4.5 in 5 pts and MR5 in 6 pts. Rate of response with third and second generation TKI was significantly better than first generation TKI (80% and 77.1% vs 36.3%; p=0.02287). 30 (44.1%) pts proceeded to alloSCT. Of the 49 pts that responded, 16 (32.6%) relapsed. The median time to relapse was 5 months (range 1-46 months). At a median follow up of 57 months, the median OS for all pts was 18 months. There was no difference in OS based on blast phenotype (14 months for myeloid, 21 for lymphoid and 7.5 for mixed; p=0.1185), initial diagnosis (38 months CP-CML, 13 for CML-AP and 16 for de-novo BP pts; p=0.6380), or TKI (13 months for first generation, 20 for second and not reached for third generation TKI; p=0.1729). The OS of pts that were treated with a combination of TKI and chemotherapy was significantly longer compared to pts treated with TKI or chemo alone (28 vs 13 or 4.5 months; p=0.0003). Of the 32 pts that responded, OS for pts that underwent alloSCT was significantly longer compared to pts that did not (not reached vs 14 months; p= 0.0022).
Conclusion:
CML-BP continues to have a dismal prognosis. Treatment is heterogenous involving various combinations of TKI and chemotherapy. In our analysis, treatment with second or third generation TKI led to better responses. In addition, treatment with chemotherapy in combination with TKI and alloSCT led to improved OS. Updated results from further multi-institution analysis will be presented at the meeting.
Disclosures: Jain: Rigel: Other: Teaching and Speaking. Yang: Novartis: Consultancy, Research Funding; Puretech: Research Funding; Pfizer: Research Funding. Ritchie: Novartis: Consultancy, Other: Travel Expenses; Incyte: Consultancy, Research Funding, Speakers Bureau; NS Pharma: Research Funding; Ariad: Speakers Bureau; Pfizer: Consultancy, Other: Travel Expenses, Research Funding; Astellas: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy. Mims: Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees. Tantravahi: GSK: Consultancy, Honoraria; CTI Biopharma: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Partnership for Health Analytic Research LLC: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Karyopharm Therapeutics: Consultancy, Honoraria, Research Funding. Badar: Morphosys: Other: Advisory Board; Takeda: Other: advisory board ; pfizer: Other: Advisory board. Rein: Incyte: Consultancy, Other: Site Principal Investigator for clinical trial, Research Funding; Sobi: Consultancy; DAVA Oncology: Other: Speaker, conference participant; Karyopharm: Other: Site Principal Investigator for clinical trial, Research Funding; PharmaEssentia: Other: Site Principal Investigator for clinical trial, Research Funding; Merck: Other: Site Principal Investigator for clinical trial, Research Funding; Morphpsys: Consultancy; Geron: Other: Site Principal Investigator for clinical trial, Research Funding; Blueprints Medicine: Other: Site Principal Investigator for clinical trial, Research Funding; Protagonist: Other: Site Principal Investigator for clinical trial, Research Funding; Cogent Biosciences: Consultancy, Other: Site Principal Investigator for clinical trial, Research Funding; Sumitomo Dainippon Pharma Oncology: Consultancy, Other: Site Principal Investigator for clinical trial, Research Funding; Novartis: Consultancy, Honoraria, Other: Site Principal Investigator for clinical trial, Research Funding; Abbvie: Consultancy; Telios Pharma: Research Funding; Silence Therapeutics: Research Funding. Oehler: Novartis: Consultancy; Terns Pharmaceuticals: Consultancy; Pfizer: Research Funding. Radich: ThermoFisher: Honoraria. Kota: Novartis: Honoraria; Kite Pharma: Honoraria; Pfizer: Honoraria. Cortes: Sun Pharma: Consultancy, Research Funding; Biopath Holdings: Consultancy, Research Funding; Takeda: Consultancy; Pfizer: Consultancy, Research Funding; Abbvie: Research Funding; Novartis: Consultancy, Research Funding; Nerviano: Consultancy; Rigel: Consultancy. Hunter: GSK: Consultancy, Honoraria; PharmaEssentia: Consultancy, Honoraria; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Sobi (formerly CTI biopharma): Consultancy, Honoraria; Incyte: Consultancy, Honoraria, Research Funding; Cogent Biosciences: Research Funding; Ascentage Pharma: Research Funding; Syntrix Biosystems: Research Funding; Novartis: Research Funding; PharmaEssentia: Research Funding. Chan: Syndax: Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Research Funding; Aptitude Health: Honoraria; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding. Pinilla-Ibarz: Bristol Meyers Squibb: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pfizer: Consultancy; Eli Lily: Consultancy, Speakers Bureau; Sanofi: Consultancy, Speakers Bureau; Novartis: Honoraria; Janssen: Consultancy, Speakers Bureau; Secura Bio: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Deininger: SPARC: Research Funding; Leukemia & Lymphoma Society: Research Funding; Fusion Pharma: Consultancy; DisperSol: Consultancy; Takeda: Honoraria, Other: Part of a study management committee, Research Funding; Sangamo: Consultancy, Honoraria; Medscape: Honoraria, Other: Case Author ; Incyte: Honoraria, Research Funding; Blueprint Medicines Corporation: Consultancy, Honoraria, Other: Part of a study management committee, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Grants, Travel, , Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Grants, travel, clinical trial support, Research Funding. Sweet: Novartis: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria, Other: travel accommodations/expenses ; Nkarta: Consultancy; Incyte: Research Funding; Jazz: Consultancy, Other: travel accommodations/expenses , Research Funding; BeiGene: Current Employment, Current equity holder in publicly-traded company; Nelson Mullins: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Atallah: Novartis Pharmaceuticals Corporation: Honoraria.
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