Outcomes of Accelerated and Blast Phase Chronic Myeloid Leukemia at a Tertiary Center

• Published in: Blood Vol. 144; no. Supplement 1; p. 6610
• Main Authors: Mohamed, Ahmed N, Zureigat, Hadil, Alsabbagh Alchirazi, Muaz, Dhakal, Aastha, Mushtaq, Ali, Rehman, Naveen, Berube, Bryan, Govande, Sneha, Zabor, Emily C., Jain, Akriti G., Molina, John C., Balderman, Sophia, Singh, Abhay, Gerds, Aaron T., Advani, Anjali S., Carraway, Hetty E., Kalaycio, Matt, Mukherjee, Sudipto, Mustafa Ali, Moaath K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 05.11.2024
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2024-210152

Background: Around 90% percent of patients with chronic myeloid leukemia (CML) present at a chronic phase (CP) (CML-CP), which is a slow-progressing disorder that responds well to treatment with tyrosine kinase inhibitors (TKI). The incidence of accelerated phase (AP) and blast phase (BP)-CML at diagnosis is 3.5% and 2.2%, respectively. Because of the rarity of CML-AP and CML-BP, less is known about their response and long-term survival. Methods: We conducted a single-center retrospective study to investigate the outcomes of CML-AP and CML-BP in comparison to CML-CP. Advanced CML (CML-Adv) included both CML-AP and CML-BP. Patients included were all consecutive adult patients (≥18 years) diagnosed with CML and treated at Cleveland Clinic from 7/2007-12/2022. CML phases were defined using the 2022 International Consensus Classification of Myeloid Neoplasms. We collected the following variables: demographics, Cytogenetics, comorbidities, all treatment lines and responses, and follow-up data. Responses to TKI were determined using overall survival (OS), calculated from the initiation of therapy to the time of death and response at the 12-month (mo) mark. Because response criteria to TKI varied throughout the years, we used the following criteria for 12-mo response: 1. Latest years (≥2010): rate of achieving major molecular response three or more, 2. Middle years (~2008-2010): rate of achieving a total of 3 log reductions or more in BCR:-ABL1 PCR transcript or 3, Earliest years (~2007): rate of achieving a complete cytogenetic response on bone marrow (BM) exam. The 12-mo response rate was the intention to treat, and no patients were excluded if the drug was discontinued for any reason (i.e., death less than 12 mo or intolerance...etc.). The Kaplan-Meier and log rank were used for survival analysis Multivariable regression was used to adjust outcomes for confounders. Results: A total of 361 patients were included in this study, of those 345/361 (95%) had CML-CP, 6/361 (1.5%) had CML-BP, and 10/361 (2.7%) had CML-AP. 13 with CML-CP evolved into CML-Adv (CML-CP or CMP-BP) at a median time of 18 mo (range 15-41). Among the CML-BP, 2 patients had a lymphoblastic crisis. The median ages for CML-CP, BP and AP were 57, 45, and 57 years, respectively. High-risk cytogenetics (i.e., + 8, i(17q), second Ph, +19, and complex karyotype) were seen in 1%, 33%, and 10% of CP, BP, and CML-AP groups, respectively. The average BM blast at diagnosis was 1%, 44.5%, and 12.5% in the CP, BP, and CML-AP groups, respectively. Allogeneic transplant was administered in 29 (8.4%), 2 (33%), and 3 (30%) of CML-CP, CML-BP, and CML-AP, respectively. Imatinib was given as the first line in 177 (51%), 1 (17%), and 3 (30%) of CML-CP, CML-BP, and CML-AP, respectively. In the CML-myeloid BP, 2 patients were treated with induction 7+3+TKI and the 2 patients with CML-lymphoblastic BP were treated with modified CALGB 19802+ TKI. The median follow-up time for the study groups was 85.22 mo (range: 0.2 - 205.9). The 2-year (yr) (95% CI) OS probability was 93% (90-96), 50% (22-100), and 90% (73-100) in CML-CP, BP, and AP, respectively (long rank P=0.015). On the multivariable Cox proportional hazards model, CML-BP was associated with higher mortality compared to CML-CP (reference) (HR: 9.68, 95%CI: 3.30, 28.4) (P<0.01). In contrast, CML-AP showed no difference in OS compared to CML-CP (HR: 1.11, 95%CI: 0.76-1.81). In the CML-CP patients who evolved into CML-Adv, the 2-yr OS was 46% (95%CI 26-83) since evolution. The 12-mo intention-to-treat response rate was 13%, 0% and 10% in the CML-CP, CML-BP, and CML-AP, respectively. When comparing CML-CP with CML-Adv (AP+BP), the 2-yr OS (95% CI) probability was 93% (90-96) and 73% (54-100) (long rank P=0.2). In subgroup analysis, the 2-yr OS (95% CI) probability among accelerated/blast type were 67%, 75%, and 73% in patients treated with imatinib, dasatinib+ nilotinib+ bosutinib, and others, respectively (P=0.9). Conclusion: In our long-term follow-up study, we found the incidence of CML-BP and CML-AP at diagnosis and as evolution are rare. Our study showed that patients with CML-BP exhibit significantly worse OS. Patients with de-novo CML-AP had similar long-term OS compared to CML-CP, however our sample size is limited. Furthermore, patients who transform to blast/accelerated phase CML from the CML-CP demonstrated even lower OS compared to those diagnosed with blast or accelerated phase CML at baseline (i.e., de novo). Jain:Rigel: Other: Teaching and Speaking. Molina:Autolus: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Gerds:Agios: Consultancy; Disc Medicine: Consultancy; PharmaEssentia: Consultancy; Rain Oncology: Consultancy; GSK: Consultancy; AbbVie: Consultancy; BMS: Consultancy. Advani:Servier: Research Funding; Seattle Genetics: Research Funding; Kura: Research Funding; Macrogenics: Research Funding; Immunogen: Research Funding; Incyte: Research Funding; Novartis: Consultancy; OBI: Research Funding; BEAM: Other: Research support, Research Funding; Amgen: Research Funding; MD Education: Honoraria; Springer: Honoraria; Glycomimetics: Research Funding; Pfizer: Other: Manuscript help, Research Funding; Wiley: Honoraria; American Society of Hematology: Honoraria; Emmes: Honoraria; PER: Honoraria; Web MD: Honoraria; Wolters Kluwer: Honoraria; Kite: Consultancy, Research Funding; MJH Life: Honoraria. Carraway:Daiichi: Membership on an entity's Board of Directors or advisory committees; Stemline: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees.