Session: 632. Chronic Myeloid Leukemia: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Clinical Practice (Health Services and Quality), Adverse Events
This study assesses the Downgrading Impact (D-IMPACT) in CML patients, the reasons behind this strategy, and clinical outcomes. Data were collected via a Google Forms survey distributed in July 2024 to CML Campus Centers. Inclusion criteria were: i) CML patients on 2nd-generation or higher TKI therapy; ii) Patients who switched from a higher to a lower potency inhibitor; iii) Patients with documented side effects from high-potency TKIs.
The survey collected demographic data, treatment start and dosage, TKI before and after downgrading, therapy line, reasons for downgrading, and outcomes. It also investigated dosage de-escalation before downgrading and TFR attempts afterward. Response was assessed by qRT-PCR-IS for BCR::ABL1 at downgrading, and at 3, 6, 12 months, and the last follow-up.
We identified 137 eligible CML patients diagnosed between 1996 and 2022 in 31 centers. Median age at diagnosis was 52 years [IR 17-81], with 91 males (66.4%) and 46 females (33.6%). Sokal score: Low 48 (35%), Intermediate 55 (40.1%), High 24 (17.5%), not available 10 (7.3%). EUTOS score: Low 71 (51.8%), Intermediate 17 (12.4%), High 11 (8%), not available 38 (27.7%). TKIs before downgrading: Imatinib (IMA) 800 mg (n=8; 5.8%), Bosutinib (BOS)(n=4; 2.9%), Nilotinib (NIL) (n=58; 42.3%), Dasatinib (DAS) (n=52; 38%), Ponatinib (PON) (n=14; 10.2%), ASC (n=1; 0.7%), in first 77 (56.2%), second 40 (29.9%), third 13 (9.5%), 4th-6th 7 (5.1%) line. Treatment duration with last TKI before downgrading: 3-162 months (median 44 months). Dosage de-escalation before downgrading in 71 (51.8%) patients due to extra-hematological (n=65; 91.5%) or hematological (n=6; 8.5%) toxicity.
The TKIs used for downgrading were IMA 84 (62.2%), BOS 34 (25%), NIL 4 (2.9%), DAS 6 (4.4%), ASC 4 (2.9%), PON 3 (2.2%), Interferon 1 (0.7%). At downgrading molecular response was: MR1 in 22 (16.7%), MR2 in 37 (28%), MR3 in 29 (22%), MR4 in 26 (19.7%), MR4.5-5 in 18 (13.7%). Downgrading reasons: adverse events in 113 (89.6%), elective choice to avoid/reduce adverse events in 13 (10.4%), pregnancy in 1.
Adverse events included gastrointestinal side effects, bone-joint pain, headache, cutaneous reactions, cardiovascular events, pleural and pericardial effusions, and pulmonary hypertension. Post-downgrading molecular response at 3, 6, 12 months, and last follow-up showed BCR::ABL1 trending down in 68 (58.6%), stable in 34 (29.3%), worsened in 14 (12%). The impact of adverse events also improved. Imatinib and Bosutinib were the most chosen drugs for downgrading, with . There was no consensus on ASC and PON potency as 4 patients downgraded from PON to Asciminib and 3 from ASC. Most common switch was NIL -IMA (33%), DAS- IMA (29%), NIL-BOS (13%).
The survey also examined TFR attempts post-downgrading. Twenty-six patients (18.9%) entered TFR, with 20 (76.9%) remaining free of treatment at a median follow-up of 37 months (IR 3-320).
In conclusion, this exploratory survey shows that a downgrading approach can be safely considered in CML patients, especially for long-term treatment. In 58.6% of cases, molecular response improved without higher-generation treatment, reducing toxicity. Patients who lessen therapy can attempt a TFR: although the number of patients is limited, the relapse rate is only 23.1%.
These interesting results stimulate the expansion of the case series and warrant the introduction of future prospective studies.
Envisaging a broader context to the years to come, the introduction of generic drugs and new therapies, emphasizes the need for sustainable pharmaceutical spending. Documenting the transition from potent inhibitors to lower-impact, lower-cost options could improve resource management, ensuring access to necessary treatments without compromising care.
Disclosures: Abruzzese: MorphoSys: Consultancy; BMS: Consultancy; Ascentage: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Incyte: Consultancy. Trawinska: glaxo: Consultancy; novartis: Consultancy. Galimberti: AbbVie: Honoraria, Other: support for attending meetings; AstraZeneca: Honoraria, Other: support for attending meetings; Jazz: Honoraria, Other: support for attending meetings; Novartis: Honoraria, Other: support for attending meetings; Incyte: Honoraria; Roche: Honoraria, Other: support for attending meetings; Celgene: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. D'Adda: Novartis, BMS, Pfizer, Incyte: Membership on an entity's Board of Directors or advisory committees. Bonifacio: Amgen: Honoraria; Incyte: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Bocchia: Novartis: Honoraria, Other: travel grant; Incyte: Honoraria, Other: travel grant; Abbvie: Honoraria, Other: travel grants. Crugnola: BMS: Speakers Bureau; Novartis: Speakers Bureau.
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