Purpose of Review Clinical factors alone do not enable us to differentiate which patients will maintain treatment-free remission (TFR) from those who are likely to relapse. Thus, patient-specific factors must also play a role. This review will update the reader on the most recent studies presenting biological factors that can help predict tyrosine kinase inhibitor (TKI) discontinuation success. Recent Findings Cellular and molecular factors with a suggested role in TFR include immune factors and leukemic stem cell (LSC) persistence; the BCR::ABL1 transcript type, halving time, and BCR::ABL1 DNA and RNA positivity; as well as other molecular factors such as somatic mutations, RNA expression, and telomere length. Summary Our review presents several biomarkers with predictive value for TFR but also highlights areas of unmet need. Future discontinuation guidelines will likely include biological factors for the personalization of TFR prediction. However, it will be important that such advances do not prevent more patients from making a TKI discontinuation attempt.

No abstract

Our prior (EB08 Abs.738.4) cross sectional study suggested that bilateral chronic aortic baroreceptor denervation (AD) induces salt‐sensitive normotension in rats. To assess this in depth, mean arterial pressure (MAP) was measured intra‐arterially over time (3 times) in two groups of conscious Wistar rats. The first time (PreDen) was measured in caudal artery before random sham (SH, n = 7) or real AD (n = 10); the second one was measured in left femoral artery after 7 days on low sodium diet (PostDen LNaD = 0.04% Na) and the third time was measured in right femoral artery after 21 days on high sodium diet (PostDen HNaD = 8% Na). The effectiveness of AD was judged by Box‐Cox transformation of PHE(1) and SNP (2) slope [((( [3 ‐ (HR2‐HR1/ MAP2‐MAP1)] −0.4) ‐1) / ‐0.046)] obtained in conscious state. Salt Sensitivity = SS = (PostDen HNaD MAP ‐ PostDen LNaD MAP, mmHg). Delta of MAP (PostDen MAP ‐ PreDen MAP, mmHg) on both LNaD and HNaD were calculated too. &p = 0.05, *p <0.003 vs SH and + p < 0.01, # p < 0.009 vs LNaD.PreDen PostDen PostDen SS Delta MAP DeltaMAPLNaD HNaD LNaD HNaDSH 105.0 114.0 122.0+ 7.7 9.0 16.7+±2.7 ±1.8 ±1.7 ±2.5 ±2.6 ±2.3AD 101.0 123.2& 134.5*# 11.3 22.2* 33.5*#±2.0 ±2.4 ±2.8 ±2.6 ±2.0 ±2.4ConclusionsWistar rats show salt‐sensitive normotension that chronic AD switches to salt‐sensitive hypertension. Supported by: CONACYT 62282

Background:In February of 2009 the Canarian registry of chronic myeloid leukemia (CML) was created in order get a better insight of treatment response, behavior and outcome in our region. For that purpose data from patients (pts) treated in the 7 hospitals of the Canary Islands was collected.Aims:Analyze Overall survival and responses to the tyrosine kinase inhibitor (TKI) treatment on real life CP‐CML pts.Methods:Our series consisted of 262 pts with CP‐CML diagnosed between 2000 and 2019 and treated with TKIs, 138 (52.7%) were males and 124 (47.3%) females with a mean age at diagnosis of 52.66 ± 17.36. The median follow‐up for the whole series is 6.26 years (0.02‐19.21). We analyzed overall survival (OS), cumulative incidence (CI) of major molecular response (MMR) and deep molecular response (DMR) on 2 first lines with Kaplan‐Meier test (KM) and compared the molecular response of different treatments on first and second line of treatment using the Jonckheere‐Terpstra test (JT). For the statistics we used SPSS V.23 and the p‐value was 0.05.Results:We have an OS at 8 years of 88.8%. Totally 39 pts died from which 3 (7.7%) were clinically related to CML. 183 (69.85%) pts received only 1 line of treatment, 55 (20.99%) 2 lines of treatment, 16 (6.1%) 3 lines of treatment and 8 (3.05%) 4 or more lines of treatment. At this moment 87 (39.01%) pts are on Imatinib (IM), 63 (28.25%) on Nilotinib (NI), 34 (15.25%) on Dasatinib (DA), 3 (1.35%) on Bosutinib, 2 (0.89%) on Ponatinib and 30 (13.45%) on Treatment free remission (TFR). All pts on TFR are on DMR with a median follow up of 6 months (0.5‐64). 172 (77.13%) pts are on DMR, 30 (13.45%) pts are on MMR, 9 (4.03%) pts are on cytogenetic response, 10 (4.45%) pts are on complete hematologic response and only 2 (0.89%) did not achieve any response.In 1st line 193 (86.54%) pts were treated with IM, 51 (22.87%) with NI and 18 (8.07%) with DA. By the JT test we found that there is a statistically significant difference between the medians of BCR/ABL levels at 3 (IM = 1.00, NI = 0.06, DA = 0.14), 6 (IM = 0.06, NI = 0.003, DA = 0.021) and 12 (IM = 0.014, NI = 0.0006, DA = 0.022) months between the different drugs (p < 0.001). We also found statistically significant difference for the CI of MMR between NI and IM (p < 0.001) and between NI and DA (p = 0.029) with a median of time till MMR of 3.27 months NI, 9.53 for IM and 7.9 for DA (Fig1a). We found a statistically significant difference for the CI of DMR between IM and NI (p = 0.004) with a median of time till DMR of 23.33 months for DA, 19.8 for IM and 11.2 for NI.We treated 79 pts with a TKI in 2nd line with a median follow‐up of 4.34 years (0‐11.37). 3 (73.66%) pts were treated with IM, 52 (19.47%) with NI and 24 (6.87%) with DA. By the JT test we found no statistically significant difference between the medians of BCR/ABL levels at 3 (IM = 0.14, NI = 0.02, DA = 0.10), 6 (IM = 1.00, NI = 0.06, DA = 0.00) and 12 (IM = 0.04, NI = 0.01, DA = 0.00) months between the different drugs (p = 0.979, p = 0.31 and p = 0.54 respectively). There is no statistically significant difference for the CI of MMR between the three treatment groups with a median of time till MMR of 5.13 months NI, 4.3 for IM and 6.7 for DA (Fig1b).Summary/Conclusion:Our OS is comparable to the one presented on the IRIS study 8‐year follow‐up (85%). When we analyzed the responses on 1st line we found that NI reaches faster the MMR than IM and DA. We also found differences reaching DMR between NI and IM but no with DA and we think the reason for not finding it is due to the small sample of pts with DA. The differences between 2nd generation TKIs are not present on 2nd line.image