Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP

Abstract

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in chronic myeloid leukemia

“…The ELTS score has been validated several times for its ability to significantly discriminate risk groups regarding long-term survival outcome but mainly in patients first-line treated with imatinib [6,8,15,[24][25][26]28]. Despite significantly faster achievement of molecular reponses with second generation TKIs [10,13,[30][31][32][33], first-line treatment with imatinib and its generics is still widespread. Most physicians continue to see room for first-line treatment with imatinib depending on age, comorbidities, kinase domain mutations, treatment goal, costs, and availability of generic imatinib [1,[33][34][35][36][37].…”

“…Despite significantly faster achievement of molecular reponses with second generation TKIs [10,13,[30][31][32][33], first-line treatment with imatinib and its generics is still widespread. Most physicians continue to see room for first-line treatment with imatinib depending on age, comorbidities, kinase domain mutations, treatment goal, costs, and availability of generic imatinib [1,[33][34][35][36][37]. In prognostic support of first-line treatment selection, the ELTS score offers the most appropriate risk group classification.…”

“…In prognostic support of first-line treatment selection, the ELTS score offers the most appropriate risk group classification. This is also of interest as imatinib has fewer side effects than second generation TKIs, and it is perceived that a statistically significant overall superiority in long-term efficacy over imatinib has not yet been shown for another TKI [1,33,36,37]. There is indication that the ELTS score would also discriminate risk groups with respect to long-term survival if a second generation TKI were chosen as first-line treatment [24].…”

Tyrosine kinase inhibitors and pregnancy in chronic myeloid leukemia: opinion, evidence, and recommendations

“…The recently suggested criteria for safe TKI discontinuation and observation in TFR include TKI duration for >3-4 years for second generation TKIs or >5 years for imatinib; the recommended DMR duration is at least 1-2 years. 5,32 These patients have a ~50% chance of being able to remain off drug indefinitely. However, another 50% could lose response, the majority within 3-6 months, 38 and thus potentially before the end of first trimester, warranting caution when stopping treatment prior to conception.…”

Treatment Outcomes in Chronic Myeloid Leukemia: Does One Size Fit All?

“…ELTS has better prediction capacity in LRD because the weight of age is lower in this score. 23 Even though this score classifies patients more precisely, the Sokal score has historically been used in clinical trials and in some proposed optimal criteria for discontinuation. 3,17 Some guidelines 3,17 recommend non-high Sokal scores to attempt TFR, but this is a flexible point, depending on other factors that are further discussed later.…”