I have been on Imatinib 10 months now on Spirit 2 trial, and responding slowly. I have today been told no mutation, which is very good news.At 10 months in to treatment my PCR has risen to 28% BCR ABl (the lowest it has been was 17.3% at 6 months). I am very worried, trying to not think about it, but my consultant still insists this is an ok result, no need to worry, and no need to change from 400g Imatinib as i have not reached a failure or sub optimal response yet, within current ELN guidelines. Everything i read on here though seems to indicate i am not doing very well. Trying my hardest to not worry but its impossible! He has contacted the professor in charge of the trial for advice, but he says he is happy with my results as all my other blood counts are excellent. Has anyone else been at this point and what happened?
You are here
PCR result 28% at 10 months
Definitions, methodological and statistical issues for phase 3 clinical trials in chronic myeloid leukemia: a proposal by the European LeukemiaNet
http://bloodjournal.hematologylibrary.org/content/119/25/5963.full.pdf
I have taken a look at this article to see where the current thinking on this is. I do understand why you are worried, just because your BCR-ABL1 transcripts have risen to 28%.
If you consultant is not concerned, then you might ask him to explain why. From the above article, the ELNet guidelines for imatinib state the following:
..."1. No response and insufficient response.
“No response” and “insufficient response” are not events per se. Because it takes time to obtain a response, the time at which “no response” or “insufficient” level of response is considered as a failure must be predefined.
It depends on the treatment that is tested and on the study design.
For patients treated by imatinib at standard dose or by imatinib-based regimens, definitions were published by the ELN1,20,21 in which timelines at
3, 6, 12, and 18 months are recommended;
no CHR (complete haematological response) at 3 months,
no cytogenetic response (CgR) at 6 months,
less than PCgR (partial CyR is less than 35% Ph+ cells) at 12 months
and
less than CCgR (0.1%) at 18 months
are unfavourable events."
Given you have had a negative result for an IM resistant mutation (good) you might ask your doctor if there is any evidence that you have additional clonal abnormalities.
Otherwise, if it were me, I would be looking for an explanation of why there is the rise in BCR-ABL to 28%..... and then if it is possible in the SPIRIT 2 trial, a switch to dasatinib at some point very soon.
I really hope you get some answers,
Sandy
Suboptimal Responses in Chronic Myeloid Leukemia
Elias Jabbour, MD,1 Giuseppe Saglio, MD, PhD,2 Timothy P Hughes, MD,3 and Hagop Kantarjian, MD1
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3412948/
NCCN Guidlines for response criteria in CP CML -table 1.
ELNet criteria for sub-optimal response -table 2.
Table 1
Response Criteria in Chronic Phase Ph+ CML According to National Comprehensive Cancer Network Guidelines 17
Response Criteria
Hematologic
Complete: Complete normalization of peripheral blood counts (leukocyte <10 × 109/L)
Platelet count <450 × 109/L
No immature cells (eg, myelocytes, promyelocytes, or blasts) in peripheral blood
Partial: No signs or symptoms of disease; no palpable splenomegaly
Same as complete hematologic response, except for:
Presence of immature cells
Platelet count <50% of pretreatment count but >450 × 109/L
Persistent splenomegaly but <50% of pretreatment enlargement
Cytogenetic a
Complete No Ph+ metaphases
Partial 1%-35% Ph+ metaphases
Major 0%-35% Ph+ metaphases (complete + partial)
Minor >35% Ph+ metaphases
Molecular
Complete BCR-ABL mRNA undetectable by qRT-PCR
Major ≥3-log reduction of BCR-ABL mRNAb
Abbreviations: CML, chronic myeloid leukemia; Ph, Philadelphia chromosome; RT Q-PCR, real-time qualitative polymerase chain reaction.
(< means less than; > means more than)
a Examination of ≥20 metaphases.
b European LeukemiaNet guidelines define major molecular response as a ratio of BCR-ABL1 to
ABL1 or other housekeeping genes of ≤ 0.1% on the International Scale (IS).
Table 2
ELN Criteria for Defining a Suboptimal Response
Testing Time ELN Criteria-a
3 months No cytogenetic response
6 months
Thank you Sandy for the tables and link you provided. After reading all this I think I have to agree with my Consultant's opinion that I am still within guidleines (at least for Essex Health authority), as I am still below 35%. The other problem is the rise in PCR to 28%, I am hoping this is a blip. I have to accept what my consultant says that i am ok, and carry on with the Imatinib until at least a year has passed before I can be classed as a sub optimal responder. It still worries me but I will just wish the next 2 months away and see where I am at a year, and then change treatment as I am still certain that I will need to, but at the hospital I am at (Colchester) they will not change until the year has passed unfortunately and i am tired of the worry and doubt.I find it very unfair that others with far lower pcr than mine have been changed treatment,and it feels like a postcode lottery, but you can't beat the system! Sorry to sound so negative to anyone reading this and I hope this does not happen to anyone else as its horrible enough to have CMl without having to feel you are getting inferior treatment too.
Hi Sandy, great news today, I am now on Nilotinib as they think i have resistance to Imatinib. I am so pleased, thank you for all your info and giving me the push to try for this change. It has been a brilliant day and i look forward now to seeing a decreasing pcr. They are going to monitor me on the Spirit trial still, even though I am not on Dasatinib or Imatinib they will still have an interest in how I respond.
That's really great news...you must be so relieved. I am glad you found the strength to push for the change - your research paid off!
I think it is also good that SPIRIT 2 lab will still monitor your PCR results and presumably advise your doctor. Good news all round ;o)
Best wishes, Sandy
