The patient is still continuing treatment with dasatinib, he has reached MR4.5. I chose dasatinib anhydrous because of the co-medication with PPI. So far, no adverse effects have occurred, the treatment is well tolerated.

Generally I agree with Susanne. The longer the DMR, the better the chance of TFR success. ENESTfreedom did show that with 2 years of DMR on nilotinib, TFR could be successful. Would I recommend a switch to NIL? Not with the AE record and no NIL-sensitive mutations. This has not been shown with other TKIs. A switch such as suggested is the best option.

First thank you for bringing a case incorporating one of the novel formulations of our available TKIs- if you can, might you share the path, approval/authorization and experience with the anhydrous 'dazatinib'? There are novel nilotinib formulations which limit or eliminate the variability and increased exposure related to nonfasting dosing or even suboptimal fasting conditions, and novel dasatinib formulations which minimize the dramatic effect of pH and limitations on co-administration with H2 blockers or moreover proton pump inhibitors. The noted ongoing use of PPI in this patient suggested to me that this was the reason to choose this novel formulation. Note the milligram dosing (79) is the 100 mg dosing equivalent (lower number milligram dosing is true of the nilotinib novel formulations as well).

I agree with Dr Saussele regarding longer and more conservative, ELN derived TKI treatment length versus shorterl length; note in the US this patient may have been counseled that 3y of therapy and 2y of deeper remission (>MR4) would suffice for TFR eligibiliy (per NCCN criteria). I would not advise TFR after only one year of deep MR for the record.

I personally don't view comorbidities including pulmonary disease as contraindications or reasons to switch TKI, but would certainly be vigilant in the care of this patient regarding potential for pleural and pericardial effusions from dasatinib; the further clarification and potential for reduction in adverse in overall event profile of the novel formulations of nilotinib and dasatinib are an area for current and future research I hope we will see.

The general recommendation from NCCN and ELN is for an optimal TFR attempt to have at least 5 year treatment of TKI of which 2-3 years should be in DMR. However, in case of adverse treatment the minimum criteria can be discussed in such a patient which should be 3 years of TKI with 1 year minimum in MR4. The chance to stay in TFR is raising then each year by approx 3%/year.

So for this patient I would recommend to switch TKI as dasatinib is probably not the best in COPD patients . An alternative would be bosutinib nilotinib or imatinib. I would go for TFR in this patient.

Location: Slovakia

46 years old patient was diagnosed with CML in CP in February 2024. His blood count was typical with leucocythosis of 41.8 x109/l with left shift, normal hemoglobin (144 g/l) and platelet level (266 x109/l). His risk score was low according to Sokal (0,6) and ELTS (1,07). He had typical cytogenetic finding: 46,XY,t(9,22)(q34,q11) [20], FISH: bcr::abl pozit. 96%, and typical transcript b2a2. In his medical history was asthma bronchiale and gastroezophageal reflux. His concomitant medication was ipratropium, antihistaminica and pantoprazol (PPI) as needed.

After initial cytoreductive treatment the question was, what´s the goal of the treatment: to prolong overall survival or to achieve treatment free remission? In this relatively young patient we decided to achieve treatment free remission, therefore he started treatment with second generation TKI - dazatinib anhydrous in a dose of 79mg since 21.3.2024. After 3 months of treatment, he achieved optimal cytogenetic and molecular response, his bcr::abl level decreased below 10%, after 6 months his bcr::abl level was below 1% and after 9 months he achieved major molecular response. He had no adverse events during treatment.

How long should TKI treatment last after achieving MR4 or MR4.5 before discontinuation?