half of the patients were previously treated with IFN leading to a non-homogenous cohort of patients
80% of relapses (relapse being loss of MMR) occurred in the first 3 months
39 of 100 (39%) remained treatment free
100 CML patients who had a sustained PCRU (UMRD) for at least 2 years started the STIM study. Only 16 maintained continuous PCRU all six years. Another 23 never lost MMR but lost PCRU. So 39 remained treatment free for all six years.
treated only with imatinib; MR4.5 DMR of at least 2 years duration;. median age 61, 62 men. 62 women
76 of 124 (61%) remained treatment free ... However 41 experienced a BCR-ABL RQ-PCR fluctuation without clear molecular relapse. In this so-called-fluctuation group of patients, 7 were found positive once, 6 twice, 12 patients between 3 and 5 times, 10 patients between 6 and 10 times and 6 patients more than 10 times confirming that BCR-ABL reappearance does not mean automatically clinical relapse.
half of the patients were previously treated with IFN leading to a non-homogenous cohort of patients.
a minimum of 3 years of imatinib and a minimum of 2 years of UMRD
a prospective study of 40 patients with UMRD by using a qRT-PCR assay with a sensitivity of 4.5 log.
18 of 40 (45%) remained treatment free
The 200 patients on EURO-SKI had a median treatment duration of 8 years (range 3-13 years), and 5 years of MR4 before stopping TKI (range 1-12 years).
111 of the 200 patients (56%) remained treatment free
TKI therapy was stopped in 498 people who had maintained MR4 for at least one year
Most started treatment with Gleevec, but some had switched to Sprycel or Tasigna. The median duration of a deep molecular response (4-log reduction or better) was five years.
Overall, 61.5% maintained good disease control for six months after stopping treatment. However, the amount of time previously spent on treatment appeared to make a difference.
Among those on a TKI for eight years or more, only 26% lost their major molecular response (MMR) within six months of stopping treatment, compared to 47% of those on a TKI for fewer than eight years.
The duration of a deep molecular response was also important. Loss of MMR was 32% in those with a sustained 4-log reduction for more than five years, compared to 46% for those with a 4-log reduction for a shorter time.
The 868 study participants were in the chronic phase of CML, had received TKI treatment for at least 3 years, and had achieved a deep molecular response for at least 1 year. The median time from the diagnosis of CML to the first day of stopping TKI therapy was 7.7 years (range, 3.1 - 22.6 years), and the median duration of molecular remission prior to stopping TKIs was 4.7 years (range, 1.0 - 13.3 years).
Patients had a median age at diagnosis of 51.9 years, and median age at the discontinuation of TKIs was 60.3 years.
390 patients had been pretreated with hydroxyurea prior to TKI therapy, and 87 patients received interferon before TKI.
At a median follow-up of 10 months, 62% of patients continued to have deep molecular remission 6 months after discontinuing TKI therapy. At 12 months, 56% still had deep remission, as did 52% at 24 months and 49% at 36 months.
Of the 348 patients who did have molecular relapse, 37% relapsed 6 months after TKI discontinuation, 43% relapsed at 12 months, 47% relapsed at 24 months, and 50% relapsed at 36 months. Five patients died in remission.
Of patients who resumed TKI treatment, the median time for restarting was 4.1 months, and the therapy appears to be effective in those patients, despite the interruption.
In terms of duration of treatment, the rate of molecular relapse-free survival at 6 months was 65.5% in patients treated with imatinib for at least 5.8 years and 42.6% for those treated with the drug for 5.8 years or less.
was conducted in five countries (including Canada) and used a new digital PCR test which is reportedly 100-fold more sensitive than conventional PCR testing (Mori and colleagues. ASH 2014; abstract 813).
The 112 people enrolled in the study were required to be in CMR for at least 18 months. The median time on imatinib (Gleevec) was 8-9 years, and the median duration of CMR was 26 months. In the first 16 months off treatment, 43.5% of people relapsed, typically within the first nine months.
All of those who relapsed were able to regain MMR or CMR with two months of re-starting treatment.
In this study, the amount of time on Gleevec didn't have an impact on the risk of relapse.
However, a person's age was inversely related to the risk of relapse. Relapses occurred in 90% of people aged 45 years or younger, compared to 37.5% in those aged 45-64, and 27.5% in those aged 65 years or older.
I'm liking the odds.
Data were analysed for 115 people. The median age was much younger (44 years) than in the other Stop trials.
The median time on a TKI was seven years; and the median duration of deep molecular response was 3-4 years
The estimated probability of maintaining MMR for one year off treatment was 67%.
52 patients required prior 2nd generation TKI treatment (Dasatinib, Nilotinib, Bosutinib) with a median of 6.5 years of TKI treatment and a median duration of MR4.5 of 2.3 years ...
28 of 52 (54%) remained treatment free
All 63 patients (42 male, 21 female) had been treated with imatinib before the start of the dasatinib treatments.
Median age, 59.5
from an initial 63 with confirmed deep molecular response for at least 1 year
after 6 months, 31 (49%) treatment free
after 20 months, 30 (47.6%) still treatment free
LAST: From December 2014 to December 2016, 208 patients were screened and 173 patients were enrolled from 14 sites in the US. The median age was 61 (range, 50-68) and 90 (52%) were females. Median duration of TKI prior to enrollment was 79 months (range, 51-117). At the time of enrollment, 60%, 23%, 15%, and 2% were on imatinib, nilotinib, dasatinib, and bosutinib respectively. With a median follow up of 12.3 months (range, 0.9-27) and a minimum follow up of 6 months for all patients remaining on study, 115 (66%) patients remain in a treatment-free remission (TFR). Of the 58 who restarted TKI, 46 patients restarted based on loss of MMR by central lab, and 12 restarted by patient choice. Of the 46 patients who restarted drug based on loss of MMR by central lab, 38 (82%) again achieved MMR by central lab, 3 withdrew consent before confirmation of MMR, 4 patients have had less than 6 months follow up, and one patient died (from causes unrelated to CML) before confirmation of MMR. PROs will be reported separately. Of note, 3 patients restarted TKI because of withdrawal syndrome. The proportion of patients who remained in TFR at 6 and 12 months is 73% (127/173) and 60% (76/127) respectively.
Managing chronic myeloid leukemia in the elderly with intermittent imatinib treatment http://bit.ly/1OJMAPq
For the benefit of yourself and others please add your CML history into your Signature
02/2010 Gleevec 400mg
2011 Two weakly positives, PCRU, weakly positive
2012 PCRU, PCRU, PCRU, PCRU
2013 PCRU, PCRU, PCRU, weakly positive
2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR
2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000
2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17
At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.
In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.
longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation. GFR and creatinine vastly improved after stopping Gleevec.
Cumulative Gleevec dosage estimated at 830 grams
Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.
Trey's CML Blog - Stopping - The Odds - Stop Studies - Discussion Forum Cessation Study
Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt