Long-Term Follow-Up of the French Stop Imatinib (STIM1) Study in Patients With Chronic Myeloid Leukemia

2017 ◽  
Vol 35 (3) ◽  
pp. 298-305 ◽  
Author(s):  
Gabriel Etienne ◽  
Joëlle Guilhot ◽  
Delphine Rea ◽  
Françoise Rigal-Huguet ◽  
Franck Nicolini ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Treatment Discontinuation ◽  
Molecular Response ◽  
Long Term Follow Up ◽  
Study Population ◽  
Analysis Point

Purpose Imatinib (IM) can safely be discontinued in patients with chronic myeloid leukemia (CML) who have had undetectable minimal residual disease (UMRD) for at least 2 years. We report the final results of the Stop Imatinib (STIM1) study with a long follow-up. Patients and Methods IM was prospectively discontinued in 100 patients with CML with UMRD sustained for at least 2 years. Molecular recurrence (MR) was defined as positivity of BCR-ABL transcript in a quantitative reverse transcriptase polymerase chain reaction assay confirmed by a second analysis point that indicated an increase of one log in relation to the first analysis point at two successive assessments or loss of major molecular response at one point. Results The median molecular follow-up after treatment discontinuation was 77 months (range, 9 to 95 months). Sixty-one patients lost UMRD after a median of 2.5 months (range, 1 to 22 months), and one patient died with UMRD at 10 months. Molecular recurrence-free survival was 43% (95% CI, 33% to 52%) at 6 months and 38% (95% CI, 29% to 47%) at 60 months. Treatment was restarted in 57 of 61 patients with MR, and 55 patients achieved a second UMRD with a median time of 4 months (range, 1 to 16 months). None of the patients experienced a CML progression. Analyses of the characteristics of the study population identified that the Sokal risk score and duration of IM treatment were significantly associated with the probability of MR. Conclusion With a median follow-up of more than 6 years after treatment discontinuation, the STIM1 study demonstrates that IM can safely be discontinued in patients with a sustained deep molecular response with no late MR.

scholarly journals Concomitant essential thrombocythemia with JAK2 V617F mutation in a patient with chronic myeloid leukemia with major molecular response with imatinib and long-term follow-up

2016 ◽  
Vol 12 (1) ◽  
pp. 485-487 ◽  
Author(s):  
KATIA BORGIA BARBOSA PAGNANO ◽  
MÁRCIA TORRESAN DELAMAIN ◽  
MARIANA MUNARI MAGNUS ◽  
JOSÉ VASSALLO ◽  
CARMINO ANTONIO DE SOUZA ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Essential Thrombocythemia ◽  
Myeloid Leukemia ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Molecular Response ◽  
Major Molecular Response ◽  
Long Term Follow Up

scholarly journals Long-Term Follow-up Results after Imatinib Discontinuation in Chronic Myeloid Leukemia Patients with Undetectable Minimal Residual Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4553-4553
Author(s):  
Ho-Young Yhim ◽  
Na Ri Lee ◽  
Eun-Kee Song ◽  
Chang-Yeol Yim ◽  
So Yeon Jeon ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Adverse Events ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Molecular Response ◽  
Front Line ◽  
Sokal Score ◽  
Minimal Residual

Abstract Introduction Imatinib (IM) is an effective treatment in patients with chronic phase chronic myeloid leukemia (CML-CP). In the previous report (Leukemia research, 2012;36:689-693), we demonstrated that IM could be discontinued in CML patients achieved undetectable minimal residual disease (UMRD) after the treatment of front-line IM therapy. These observations were confirmed by prospective STIM1 and TWISTER studies. However, in both studies, approximately half of patients were treated with front-line interferon therapy, which might be a confounding factor when considering the impact of prior interferon on treatment free remission (TFR) in the previous IM discontinuation studies. Thus, the aim of this study was to investigate the long-term outcomes of IM discontinuation in patients with CML-CP, who have treated with front-line IM therapy and achieved UMRD. Patients and methods We consecutively enrolled patients with CML-CP, discontinued IM therapy after achieving UMRD for at least 12 months in 2 Korean institutions from June 2009 to Jan 2013. Patients with a prior history of any other treatment (>1 months) for CML before IM administration were excluded. UMRD was defined by undetectable levels of BCR-ABL transcript by RQ-PCR with sensitivity of at least 0.0046%IS. After discontinuation, BCR-ABL/ABL ratio was monitored by RQ-PCR monthly during the first 6 months and every 3 months thereafter, and molecular relapse was defined by detectable levels of BCR-ABL transcript in two successive assays. Results Nineteen patients (8 male, 11 female) with a median age of 52 years (range, 29-78) were included. The reasons for discontinuing IM were shared decision between physicians and patients with long undetectable BCR-ABL transcript (n=9), chronic adverse events of IM (n=6), patient’s request (n=3), and wish for pregnancy (n=1). At initial diagnosis, the Sokal score was low to intermediate in 11 patients and high in 8 patients. All patients started IM at a dose of 400mg/day and median interval between IM initiation and UMRD was 21.5 months (range, 7.0-61.9). IM therapy was then maintained during a median of 34.8 months (range, 12.1-72.4). With a median follow-up of 52.1 months (range, 17.5-60.5), the overall probability of UMRD persistence at 4-year was 22.1% (95% CI, 11.6-32.6). Fourteen patients (73%) lost UMRD after a median of 4.0 months (range, 1.1-22.8). 12 patients relapsed within first 9 months and 2 late relapse were identified at 20.5 and 22.8 months, respectively. No patients included in this analysis were progressed to advanced stage CML or died. IM therapy was resumed in all patients with molecular relapse, but 2 patients were switched to dasatinib owing to chronic adverse events of IM. At the time of this analysis, all patients were still sensitive to IM and dasatinib therapy. 12 patients re-achieved UMRD and 2 patients maintained stable major molecular response. In univariate analysis for molecular relapse, high risk of Sokal score (P<0.001), ≥24 months of interval between IM initiation and UMRD (P=0.016), and <34.8 months of duration of IM therapy after UMRD achievement (P=0.029) were significantly associated with frequent molecular relapse. Conclusion This study represents that IM discontinuation in patients who have received front-line IM therapy and achieved UMRD would be feasible, as approximately one-fourth of these patients could enjoy long-term TFR. Moreover, no molecular relapse was observed after 2 year of IM discontinuation. Although the Sokal score, time to deep molecular response, and duration of IM therapy were suggested as clinical factors for predicting molecular relapse in this analysis, further studies would be necessary to confirm the results in this population. Disclosures No relevant conflicts of interest to declare.

Imatinib Mesylate Therapy in Late Ph+ Chronic Myeloid Leukemia Patients in Stable Complete Cytogenetic Response after Interferon-Alpha Results in a Very High Complete Molecular Response Rate.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2158-2158
Author(s):  
Giuliana Alimena ◽  
Massimo Breccia ◽  
Luigia Luciano ◽  
Fabrizio Quarantelli ◽  
Daniela Diverio ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Copy Number ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Complete Cytogenetic Response ◽  
Complete Molecular Response

Abstract Imatinib mesylate was given to 26 Philadelphia positive (Ph+) chronic myeloid leukemia (CML) patients who were in late chronic phase (CP) and in stable complete cytogenetic response (CCR) after interferon-alfa (IFN-α), but showed persistent positive residual disease at PCR analysis under this treatment. At diagnosis median age was 40 years (range 21–64) and according to Sokal’s score, 18 patients were low risk and 8 were intermediate risk. Median IFN treatment was 88 mo.s (range 15–202) and median CCR duration was 73 mo.s (range 10–148). Imatinib was administered at the standard dose of 400 mg/die, after stopping IFN for 1 week. Residual disease was measured on bone marrow (BM) cells at baseline, before starting Imatinib, at 3, 6, 12, 18 mo.s and at the last follow-up (median 32 mo.s, range 21–49), by assaying BCR-ABL transcripts using quantitative PCR (RQ-PCR). The copy number (CN) of BCR/ABL and ABL transcript were derived by the interpolation of CT values to the appropriate standard curve, and the result, for each sample, was expressed as ratio of BCR/ABL mRNA copies to ABL mRNA x 100 (normalized copy number - NCN). Imatinib treatment resulted in a progressive and consistent decline of residual disease in all but one patient, from a median of 0.89 at baseline to 0.01 at the end of follow-up. Major molecular response (BCR/ABL levels <0.1) was reached in 20 patients (77%) and BCR/ABL transcripts were undetectable in 13 (50%). Achievement of molecular response was significantly correlated with post-IFN baseline transcript level (mean 1.194 for patients achieving complete molecular response vs 18,97 for those who did not; p<0.001), but not with other clinical/biological patient characteristics. In all patients, imatinib was well tolerated with no side effects requiring drug dose reduction or dose discontinuation. Albeit obtained from an unusual subset of selected patients with favourable prognosis, and likely particularly sensitive to imatinib, present results confirm the efficacy of combining Imatinib and IFN-α and further support investigating treatment approaches employing these two drugs.

Long-Term Follow-up Results Over 7 Years for Survival, and Safety with Imatinib Mesylate Accompany with Allogeneic Transplantation for Chronic Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4529-4529
Author(s):  
Jun Wang ◽  
Aining Sun ◽  
Wu Depei ◽  
Huiying Qiu ◽  
XiaoWen Tang
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Imatinib Mesylate ◽  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Allogeneic Transplantation ◽  
Cytogenetic Response ◽  
Hematopoietic Stem ◽  
Long Term Follow Up

Abstract Abstract 4529 Objective: To observe the efficacy and safety of imatinib mesylate (IM) accompany with allogeneic transplantation for chronic myeloid leukemia (CML). Methods: During the period from January 2003 to August 2011,we retrospectively observed 95 patients with CML receiving IM for a minimum of 4 months before allogeneic hematopoietic stem cell transplantation (HSCT). Patients with advanced CML received IM from 3 month after transplantation for 12 months. Results: Among 95 enrolled patients (CML-CP 76, CML-AP 10, CML-BP 9), types of transplantation: sib-matched HSCT 64, unrelated-HSCT 19, haplo-HSCT 12. For the whole patients, 7 year overall survival (OS) is 80.5%, and disease free survival (DFS) is 74.5%. Complete hematologic response (CHR) is 93.6%, complete cytogenetic response (CCR) is 84.5%, major cytogenetic response (MCR) is 60.3% at 7 year. For CML-CP1, OS is 83.2% and CML-AP/BC is 33.3% (P<0.05). Compared patients of advanced CML achieving CP2 after IM and with no CP2,the former has better results of CCR or MCR, OS and PFS (P<0.05). The total treatment related mortality (TRM) is 16.8%. Cox multivariate regression analysis of prognostic factors indicates that status of CML and severe acute graft-versus-host disease (aGVHD III-‡W) retain independent predictive value. No increase in rates of serious adverse events was observed with continuous use of IM for up to 7 years. Conclusions: For chronic myeloid leukemia, combining with imatinib mesylate and allogeneic transplantation is a good strategy, with favorable long-term follow-up results and acceptable TRM, especially for the patients with advanced CML. Disclosures: No relevant conflicts of interest to declare.

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