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To share and enhance best practice management of CML, experts and interested clinicians can discuss difficult or interesting CML patient cases here. Clinicians submit a brief history of the patient and the case for discussion (no more than 200 words) by posting it in this forum ("+ NEW TOPIC" button below).

Each clinical case will be forwarded to the iCMLf expert clinical panel for a brief independent response. Consideration should be given to patient confidentiality. Details that are not critical to the case can be changed to preserve anonymity.

As a full clinical history is necessary for accurate comment, cases and comments on the Forum are only accepted from clinicians. If individual patients have a specific question we encourage them to contact their healthcare provider.

DISCLAIMER: The iCMLf does not recommend or endorse any specific tests, physicians, products, procedures, or opinions, and disclaims any representation, warranty, or guaranty as to the same. Reliance on any information provided in this Forum is solely at your own risk.

TOPIC: Poor response to TKI therapy

Poor response to TKI therapy 3 weeks 6 days ago #1700

  • Ruth Spearing
  • Ruth Spearing's Avatar
I would be grateful for your advice on this 32 year old man who was diagnosed with CML in April 2016. He has had a poor response in terms of reduction of BCR-ABL and his present level is 0.3% with no mutation of the ABL kinase binding domain. He initially started on imatinib but changed after four months to dasatinib because of poor response (BCR-ABL 138% at diagnosis, 35% at 3 months) and then a year later changed to nilotinib 400mg bd because of again, a poor response (1.3% at 12 months and 2% at 15 months). His BCR-ABL at the present time is 0.3 and has never dropped below 0.18. The last result which was two weeks ago was 0.3. Do I simply at this stage increase the nilotinib to 600mg twice daily? He is on treatment for hypertension having a significantly labile blood pressure. His full blood count remains normal. We have tissue-typed him and one brother who is not a match. We are awaiting tissue-typing on his second brother at this stage.

Planned follow up: For bone marrow examination at this stage
Repeat BCR-ABL monitoring at end of June

Poor response to TKI therapy 3 weeks 6 days ago #1701

  • Tim Hughes
  • Tim Hughes's Avatar
Hi Ruth,

His response to nilotinib 400 mg bd has been slow but steady – he has fallen from 2% in Aug 2017 to 0.3% May 2018. It is now over 2 years since he started TKI therapy so his risk of transforming to BC is quite small. The outcome for patients who are in CCyR at 2 years compared to the subset who are in MMR is fairly similar. So I would be reluctant to switch or dose increase at the moment. We know the 400 mg bd dose of nilotinib doubles the risk of vascular events compared to 300 mg bd so I would be worried about the vascular risk of 600 mg bd, plus there is limited data on improving efficacy with this dose. Ponatinib is worth considering, but given the vascular risk profile, probably only if his BCR-ABL increases to over 1%. I agree a marrow study would be reasonable to reassure you that he remains in CCyR. I wouldn’t consider an allograft unless he transforms or subsequently fails ponatinib therapy.

Tim
Last Edit: 3 weeks 6 days ago by Nicola.
Moderators: Melissa Davis-Bishop
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