scholarly journals A Report on 114 Patients Who Experienced Treatment Free Remission in a Single Institution during a 15 Years Period: Long Term Follow-up, Late Molecular Relapses and Second Attempts

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 27-27 ◽  
Author(s):  
Philippe Rousselot ◽  
Clémence Loiseau ◽  
Marc Delord ◽  
Caroline Besson ◽  
Jean-Michel Cayuela ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Median Duration ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Molecular Response ◽  
Single Institution ◽  
Long Term Follow Up

Background. The A-STIM (According to Stop IMatinib, NCT1038732) observational study established the loss of major molecular response (loss of MMR, BCR-ABL1 IS >0.1%) as a practical and safe criterion for restarting therapy in patients with CML who had stopped tyrosine kinase inhibitors after a prolonged (≥2 years) and sustained deep molecular response (J Clin Oncol. 2014;32(5):424-30). We focus now on the long-term prospective follow-up of a cohort of 114 patients from a single institution included in the A-STIM observatory in order to describe late events (late molecular relapses after 2 years or more in TFR and second TFR attempts). Methods: Adult chronic phase CML patients treated with tyrosine kinase inhibitors and in sustained (≥2 years) MR4.5 (BCR-ABL1 IS ≤0.0032%) were eligible. Patients with a previous history of resistance or mutations of the BCR-ABL tyrosine kinase domain were excluded. Molecular relapses were defined by loss of MMR. After TKI discontinuation, BCR-ABL transcripts were monitored monthly during the first 12 months, every 2-3 months during the 2nd year and every 3-6 months thereafter. Median follow-up from diagnosis of CML was 15.9 years. Results. Over a 15 years period, 114 patients followed at the Centre Hospitalier de Versailles were registered. Median age at diagnosis was 48.2 years, sex ratio was 0.5 and Sokal score distribution was 54%, 26% and 20% for the Low, intermediate and high-risk categories respectively. Median duration of TKIs before the first TFR attempt was 7.4 years. Thirty-six patients (31%) were previously treated with interferon, 62 (54%) received imatinib only and 52 (46%) were on 2G-TKIs at the time of discontinuation (13 as first line therapy and 39 after a switch for sub-optimal response or intolerance). Median follow-up in TFR1 was 5.4 years. TFR1 rates were 57.6% at 1 year, 53.8% at 3 years, 51.6% at 5 years and 44.5% after 7 years. The longest duration of ongoing TFR1 is 14.9 years. The duration of TKIs and the duration of MR4.5 were associated with a higher TFR1 rate; a trend was observed for previous exposure to interferon. Patients on 2G-TKIs (first or second line) had similar TFR1 rates as compared to patients on imatinib. Fifty-seven patients relapsed including 8 patients (14%) experiencing late molecular relapses. Of those, 4 patients relapsed after 5 years. The latest molecular relapse was observed after 6.4 years. In late relapsing patients, MR4.5 was lost after 10 months in median and MR4 after 22 months with a long-lasting period of fluctuations of the BCR-ABL1 ratio in-between MR4 and MR3 (a focus on patients with fluctuations of the BCR-ABL1 ratio will be presented at the congress). Out of the 57 patients who restarted a TKI, 31 patients (54%) experienced a second attempt. Median duration of TKIs between TFR1 and TFR2 was 2.9 years and total exposure to TKIs before TFR2 was 9 years. Fifteen patients (48%) were on imatinib before TFR2 whereas 16 where on 2G-TKI (52%). Median follow-up in TFR2 was 3.4 years. TFR2 rates were 53.9% at 1 year, 45.6% at 3 years and 39.9% after 5 years. The longest TFR2 is 9 years. No factor was associated with TFR2 duration, a switch to 2G-TKIs did not provide any advantage. Seventeen patients relapsed including 3 patient (17%) experiencing late molecular relapses. Anecdotally, 5 patients went to a third TFR attempt and 1 is in TFR3 for 5.2 years. Conclusion. Based on a 15 years' experience we were able to report on long term follow-up in TFR1 and in TFR2. Among patients experiencing molecular relapses, we observed 14% and 17% late relapses after more than 2 years after TFR1 and TFR2 respectively, suggesting that a long-term molecular follow-up is mandatory for CML patients in TFR. Figure Disclosures Rousselot: Incyte: Research Funding; Pfizer: Research Funding. Cayuela:Incyte: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau.

scholarly journals Prognostic Implication of Early Molecular Response at 3 Months in Chronic Myeloid Leukemia Patients: A Comparison of Imatinib and Second Generation Tyrosine Kinase Inhibitors

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3017-3017
Author(s):  
Dong-Wook Kim ◽  
Sung-Eun Lee ◽  
Soo Young Choi ◽  
Dae Young Zang ◽  
Won-Sik Lee ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Research Funding ◽  
Kinase Inhibitors ◽  
Molecular Response ◽  
Long Term Outcomes ◽  
Free Survival ◽  
Frontline Therapy ◽  
The Impact

Abstract Background: Although several studies have demonstrated that BCR-ABL1 transcript levels at 3 months were prognostically significant in patients treated with frontline imatinib (IM) and second-generation tyrosine kinase inhibitors (2G-TKIs), the decision to change treatment based on early molecular response (EMR) status remain under investigaiton. Because CML patients currently have multiple treatment options, the impact of early molecular milestones on long-term outcomes needs to be determined in each agent treated patients. Aims: The aim of this study is to evaluate the impact of 3-month early molecular response (EMR) on long-term outcomes of CML patients treated with IM and different 2G-TKIs, as additional information to guide clinical decisions on switching to a different TKI. Methods: 734 new CP CML patients who were treated with frontline IM (n = 366) or 2G TKIs (n = 368) were analyzed. Molecular responses were monitored using qRT-PCR assay in 3 month intervals by achieving major molecular response (MMR), and then 6 month intervals after achieving MMR. Main study objectives were to evaluate the long-term outcomes, including failure-free survival (FFS), progression-free survival (PFS), and overall survival (OS), according to 3-month EMR. FFS was measured from the date of treatment start until death, progression to AP or BP, or ELN failure on treatment, whichever came first. PFS and OS collected survivals on patients who were treated with other TKIs after frontline therapy discontinuation. Results: A total of 734 patients were treated with imatinib (IM; n = 366), dasatinib (DAS; n = 141), nilotinib (NIL; n = 89), and radotinib (RAD; n = 138). The median age was 43 years (range, 11-87). The percentages of patients with low, intermediate, and high Sokal risk scores were 37%, 38% and 23%, respectively, with 2% unknown risk. With a median follow-up of 85.6 (IM; range, 4.4-207.5) and 38.9 (2G-TKIs; range, 11.6-130.2) months, 460 (62.7%; 182 IM and 218 2G-TKIs) patients continue on the frontline therapy and 274 (37.3%) patients were permanently discontinued or changed to other TKIs due to intolerance (73 IM, 38 DAS, 2 NIL, 28 RAD), ELN failure (32 IM, 3 DAS, 2 NIL, 3 RAD), progression (3 IM, 1 DAS, 1 RAD), and others (60 warning, 3 pregnancy, 14 treatment-free remission study, and 9 follow-up loss). In 366 patients treated with IM, patients achieving BCR-ABL1 ≤ 10% at 3 months (n = 275, 75.1%) had a better outcomes in terms of 8-y OS (97.4% vs 89.7%, P <0.001), 8-y PFS (96.3% vs 88.6, P=0.002), and 8-y FFS (91.5% vs 74.6%, P<0.001) compared with those of the patients with BCR-ABL1 >10%. In 368 patients treated with 2G-TKIs, achievement of 3-month EMR (n = 331, 90.0%) was associated with a higher 8-y OS (98.6% vs 91.9%, P <0.001), 8-y PFS (98.2% vs 91.7, P=0.001), and 8-y FFS (96.5% vs 82.7%, P<0.001). The prognostic impact of 3-month EMR was observed in both IM and 2G-TKIs treated groups. Conclusions: Our data showed that EMR failure at 3 months could translate into poor survival outcomes in patients treated with frontline IM and 2G-TKIs.However, to confirm the benefit of an early switch of therapy, further investigations in a larger patient population with longer follow-up are needed. Disclosures Kim: Pfizer: Research Funding; BMS: Research Funding; Novartis: Research Funding; Ilyang: Research Funding.

scholarly journals The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up

Blood ◽  
2009 ◽  
Vol 114 (20) ◽  
pp. 4361-4368 ◽  
Author(s):  
Ravin J. Garg ◽  
Hagop Kantarjian ◽  
Susan O'Brien ◽  
Alfonso Quintás-Cardama ◽  
Stefan Faderl ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Treatment Options ◽  
Chronic Phase ◽  
Best Response ◽  
Long Term Follow Up ◽  
New Treatment

Abstract Responses can be achieved with dasatinib or nilotinib after failure of 2 prior tyrosine kinase inhibitors (TKIs). We report on 48 chronic myeloid leukemia patients sequentially treated with 3 TKIs: 34 with dasatinib after imatinib/nilotinib failure and 14 with nilotinib after imatinib/dasatinib failure. Before the third TKI, 25 patients were in chronic phase (CP), 10 in accelerated phase (AP), and 13 in blast phase (BP). Best response to third TKI in CP was 5 major molecular responses (MMR), 3 complete cytogenetic (CCyR), 2 partial cytogenetic (PCyR), 3 minor cytogenetic (mCyR), 6 complete hematologic responses (CHR), and 6 with no response (NR). In AP, 1 patient achieved MMR, 1 CCyR, 2 PCyR, 1 mCyR, 4 CHR, and 1 NR. In BP, 1 achieved MMR, 2 CCyR, 1 PCyR, 1 mCyR, 2 returned to CP, and 6 NR. Median CCyR duration was 16.3 months; 3 CP patients achieving CCyR had a response more than 12 months. Median failure-free survival was 20 months for patients in CP, 5 months in AP, and 3 months in BP. Use of second-generation TKI after failure to 2 TKIs may induce responses, but these are usually not durable except in some CP patients. New treatment options are needed.

scholarly journals Long term term follow-up of tyrosine kinase inhibitors treatments in inoperable or relapsing diffuse type tenosynovial giant cell tumors (dTGCT)

PLoS ONE ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. e0233046 ◽  
Author(s):  
Mehdi Brahmi ◽  
Philippe Cassier ◽  
Armelle Dufresne ◽  
Sylvie Chabaud ◽  
Marie Karanian ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Giant Cell ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Diffuse Type ◽  
Giant Cell Tumors

Molecular Response to Tyrosine Kinase Inhibitors (TKIs) for Chronic Myeloid Leukemia (CML), the Experience At Tawam Hospital, Abudhabi, UAE

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4458-4458
Author(s):  
Arif Alam ◽  
Sabir Hussain ◽  
Amar Lal ◽  
Donna Lee ◽  
Jorgen Kristensen
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Chronic Phase ◽  
Molecular Technique ◽  
Molecular Response ◽  
Female Ratio

Abstract Abstract 4458 Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative disorder characterized by the presence of a balanced reciprocal translocation involving the long arms of chromosomes 9 and 22. The fusion gene that is created by this translocation (BCR-ABL1) encodes for a constitutively active protein tyrosine kinase that is primarily responsible for the leukemic phenotype. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) has become the recommended first-line treatment for patients with CML. Monitoring of the CML is done with quantification of the BCR-ABL transcripts by RQ-PCR–based molecular technique. Twenty nine patients were diagnosed with CML in chronic phase between January 2009 till June 2012. The median age was 32 years (range 22–68 years). Male to female ratio was4.14:1. Three patients were lost from follow up after diagnosis and are excluded. Molecular response is available for 16 patients. Nine patients were treated with Imatinib 400 mg daily, four with Dasatinib 100 mg daily and three with Nilotinib 400 mg BID daily as upfront therapy. Twelve patients have achieved MMR/CMR (75 %) within 18months of starting therapy. Four patients have failed to achieve MMR by 24 months. All non responders were on Imatinib. Interestingly six (37.5%) patients achieved MMR/CMR within 9 months of starting TKIs. Of these only 1 was on Imatinib while the rest were on 2nd generation TKIs (Nilotinib 3 and Dasatinib 2). MMR report from Enestnd trial is 67–71% in favor of Nilotinib as compared to Imatinib 44%, while the Dasision trial reported a MMR of 44 % in favor of Dasatinib with faster rate to response. Our results mirror the results of these phase 3 randomized trial with MMR/CMR of 75 %. Until today there has been no case of progressive disease. Our data is limited but shows that the median age is much lower compared to Western countries, just reflecting differences in the age distribution of the population in the UAE with 80% being below the age of 65 years. Expatriates accounts for approximately 80% of the population in the UAE and many are temporary employed, having limited health care coverage, limited financial means as well as limited possibilities to attend regular follow-ups. This leads to compliance problems, loss from follow-up and suboptimal management and monitoring of their disease. Disclosures: Alam: BMS/Novartis: Consultancy, Honoraria. Hussain:BMS: Consultancy, Honoraria.

Discontinuation of Maintenance Tyrosine Kinase Inhibitors in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia outside of Transplant

2020 ◽  
pp. 1-8
Author(s):  
Bachar Samra ◽  
Hagop M. Kantarjian ◽  
Koji Sasaki ◽  
Ahmad S. Alotaibi ◽  
Marina Konopleva ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Median Duration ◽  
Kinase Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Tki Discontinuation

<b><i>Background:</i></b> The addition of tyrosine kinase inhibitors (TKIs) to chemotherapy has dramatically improved outcomes of patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). When allogeneic hematopoietic stem cell transplant (HSCT) is performed, maintenance TKI is generally given for a fixed duration. However, the optimal duration of TKI outside of HSCT remains unknown, and the common practice is to continue indefinitely. Here, we report characteristics and outcomes of 9 patients treated with chemotherapy + TKI without HSCT and later discontinued TKI. <b><i>Methods:</i></b> Among 188 patients with Ph-positive ALL who did not undergo HSCT, 9 of them discontinued maintenance TKI mainly due to side effects. Patients were closely monitored with serial PCR testing for the BCR-ABL1 transcript. Major molecular response (MMR) was defined as BCR-ABL1 transcript ≤0.1% on the international scale for p210 transcripts and a 3-log reduction from baseline for p190 transcripts. Deep molecular remission (DMR) was defined as the absence of quantifiable BCR-ABL1 transcripts with a sensitivity of 0.01%. Molecular relapse was defined as loss of MMR. Treatment-free remission (TFR) was defined from time of TKI discontinuation to molecular relapse, last follow-up, or death from any cause. <b><i>Results:</i></b> At the time of TKI discontinuation, transcript level was undetected in 6 patients, &#x3c;0.01% in 2 patients, and 0.01% in another patient. Prior to discontinuation, the median duration of TKI therapy and of DMR was 70 and 47 months, respectively. No morphological relapse occurred. Three patients (33%) had molecular relapse at a median of 6 months. All 3 resumed TKI therapy, and 2 of them regained DMR after a median of 13 months. After a median follow-up of 49 months, the median TFR was not reached, and the 4-year TFR rate was 65%. The median duration of DMR in patients with and without molecular relapse was 22 and 58 months, respectively (<i>p</i> = 0.096). <b><i>Conclusion:</i></b> TKI discontinuation outside of HSCT in Ph-positive ALL in the setting of compelling toxicity may be safe only among a highly selected group of patients with deep and prolonged DMR undergoing close and frequent monitoring. Validation of these findings in prospective clinical trials is highly needed.

Transient Massive Lymphoid Bone Marrow Infiltrate Developing during Therapy with the Tyrosine Kinase Inhibitors Imatinib and Nilotinib: Report of 2 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4577-4577
Author(s):  
Ester Pungolino ◽  
Silvia Cantoni ◽  
Cecilia Del Curto ◽  
Livio Gargantini ◽  
Marianna Caramella ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Clinical Relevance ◽  
Kinase Inhibitors ◽  
Progressive Increase ◽  
Lymphoid Cells ◽  
Molecular Response

Abstract Clinical use of tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML) has highlighted uncommon side effects of this group of novel anti-cancer agents. One of these peculiar side effects observed with imatinib (IM) is the occurrence of a bone marrow (BM) polyclonal lymphoid (Ly) infiltrate, usually accounting for 15–30% of total BM cellularity, sometimes taking the form of mature lymphoid follicles. No such effect has so far been described with nilotinib (NIL). We report on 2 CP-CML pts, one on IM and the second one on NIL, who developed transient massive BM Ly infiltrate without any clinical modification and with stable disease. Case1 A 40 yr old male pt was started on IM 400 mg/day as first line therapy in July 2003. Complete Cytogenetic Response (CCyR) and complete molecular response (CMoR) were obtained at 3 and 12 mos respectively. Routine BM monitoring showed progressive increase of the Ly infiltrate coincident with CCyR, up to 30%. In March 2007, BM examination disclosed massive infiltration with mature lymphocytes accounting for 60% of total BM cellularity; cytogenetic and molecular monitoring for CML were negative and peripheral blood count (PBC) was normal. The BM examination repeated a month later showed a spontaneous regression of Ly infiltrate to 25%; the remaining lymphocytes were prevalently B, polyclonal by molecular biology; cariotype was normal; FISH showed non specific abnormality (18% of 45 nuclei positive for del 17p13). Subsequent follow up disclosed normal BM with stable lymphocyte infiltrate and persistent CCyR and CMoR. Case2 A 60 yr old female pt resistant to IM was switched to NIL on November 2005. CCyR were obtained at 12 mos. BM monitoring showed progressive increase of the Ly infiltrate coincident with CCyR, up to 25%. The pt was mildly leucopenic throughout treatment. In March 2007, BM examination disclosed a 50% infiltration of mature lymphocytes; cytogenetic, molecular analysis and PBC were invariate. BM examination was repeated and the Ly infiltrate had spontaneously regressed to 20%. Considering the paucity of residual lymphoid cells, no further analysis was performed. Subsequent follow up showed normal BM with stable Ly infiltrate and persistent CCyR. Discussion. Data from the literature support the correlation between clinical efficacy of IM and increased BM Ly infiltration. Such correlation has also been found in our pts receiving IM and NIL. What has not yet been described is the massive transient polyclonal Ly infiltrate observed in our pts with both IM and NIL. This finding are of uncertain clinical relevance: PBCs were unaffected and molecular studies did not disclose presence of other hematological disorders. However, the known possibility of chronic lymphoproliferative disorders developing during CML needs to be kept in mind. An environmental factor - e.g. a subclinical viral infection - can not be excluded considering that both pts developed the same BM changes concomitantly. The role of TKIs is still unclear, in this case, and the clinical relevance of this event is uncertain. However, the similar mechanism of action of IM and NIL may suggest that a similar mechanism underlies the development of the BM massive Ly infiltrate observed in our pts.

scholarly journals Long-Term Outcomes of Chronic Myeloid Leukemia Patients Who Lost Undetectable Molecular Residual Disease (UMRD) after Imatinib Discontinuation: Korean Imatinib Discontinuation Study (KIDS)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1643-1643 ◽  
Author(s):  
Sung-Eun Lee ◽  
Joon Seong Park ◽  
Hyeoung-Joon Kim ◽  
Sung-Hyun Kim ◽  
Dae Young Zang ◽  
...  
Keyword(s):  
Median Time ◽  
Research Funding ◽  
Residual Disease ◽  
The Other ◽  
Risk Scores ◽  
Late Relapse ◽  
Molecular Response ◽  
Long Term Follow Up

Background The recent discontinuation clinical trials have demonstrated that IM discontinuation can be employed based on clinical study in patients who had enough IM therapy and undetectable molecular residual disease (UMRD) durations prior to IM discontinuation. Moreover, treatment rechallenge in patients with molecular recurrence lead a second deep molecular response, suggesting that IM discontinuation is safe. However, the issues on the definition of molecular relapse requiring treatment resumption and the occurrence of late relapse with a long-term follow-up after IM discontinuation are important. Therefore, here we analyzed the long-term follow-up results of the patients who lost UMRD after IM discontinuation Methods CP CML patients who were treated with IM for more than 3 years and had undetectable levels of BCR-ABL1 transcripts determined by quantitative reverse transcriptase polymerase chain reaction (PCR) for at least 2 years were eligible for KID study and in cases of MMR loss after 2 consecutive assessments, IM treatment was re-introduced. After IM resumption for MMR loss, the molecular response was evaluated every month until MMR was re-achieved and every 3 months thereafter. The second stop was permitted in the patients who were in second UMRD for at least 2 years. Results Between October 2010 and June 2015, a total of 126 patients (70 females, 56 males) were enrolled on KID Study, with a median age of 47 years (range, 18-82), the percentages of patients with low, intermediate and high Sokal risk scores were 33%, 25% and 15%, respectively with unknown Sokal risk scores in 27%. And the median time on IM therapy and the median duration of sustained UMRD prior to discontinuation were 83 months (range, 32-141) and 41 months (range, 22-131), respectively. After a median follow-up of 62.6 months (range, 4.9-100.8 months) after IM discontinuation, 83 patients (65.9%) lost UMRD. Among them, 56 (67.5%) patients lost MMR in 2 consecutive analyses. The other 27 (32.5%) patients who lost UMRD but not MMR exhibited different patterns of BCR-ABL1 kinetics: 8 patients spontaneously re-achieved UMRD after a median time of 2.8 months (range, 0.9-3.0 months), and 19 patient showed fluctuation of BCR-ABL1 transcript under the level of 0.1% on IS for a median 19 months (range, 3-34), and then spontaneously returned and maintained UMRD for a median 31 months (range, 2-64). Of 73 patients who lost MR4.0, the rate of MMR loss was 76.7%. Out of 56 patients with molecular relapse, 54 patients (except two patients who restart radotinib) were re-treated with IM, all patients (except one patient lost follow-up) re-achieved MMR at a median of 1.9 months (range, 0.0 - 5.4 months) after resuming treatment. Among them, two patients who re-achieving of MMR after resuming IM therapy lost MMR again; One patient who relapsed at 53.2 months after IM discontinuation, despite re-achieving MMR 1.4 later after IM restarting, suddenly progressed to blast crisis at 6 months after restarting IM and in spite of switching to dasatinib and ponatinib, she died. Another patient lost MMR at 7.4 months after IM discontinuation and re-achieved MMR 1.7 later after IM restarting, but progressed to AP on the assessment 32 months later. The patient switched to dasatinib and lost follow-up. Among the patients who maintained a second UMRD for at least 2 years after IM resumption, 23 patients entered into a second IM stop. With a median follow-up of 29.5 months (range, 9-63 months) since second IM stop, 15/23 patients (65%) lost MMR after a median 2.9 months (range, 1.8-30.7 months), which was similar to those of the first IM discontinuation [median 3.7 (range, 1.8-20.8 months)]. The patients who lost MMR were retreated with IM for a median of 24.5 months (range, 1.2-49.7 months); 14 patients re-achieved MMR and one patient was in therapy for 1.2 months. Conclusions Our results showed that 67.5% and 76.7% of patients who lost UMRD and MR4.0, respectively resulted in MMR loss, and the other patients were below MMR without re-treatment, suggesting loss of MMR can be chosen for treatment re-challenge. Overall, IM discontinuation could be applied with approximately 55% of probability of sustained MMR in the long term. In addition, we demonstrated that a second attempt might be possible. Further studies on the predictors to select patients for a trial of second stop are warranted. Disclosures Kim: Il-Yang co.: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; BMS: Research Funding; Novartis: Research Funding.

Screening practices for late effects in pediatric patients on tyrosine kinase inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22527-e22527
Author(s):  
Stephanie M Smith ◽  
Himalee S. Sabnis ◽  
Rebecca Williamson Lewis ◽  
Karen Elizabeth Effinger ◽  
Daniel John Bergsagel ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Late Effects ◽  
Kinase Inhibitors ◽  
Bone Age ◽  
Cell Transplant ◽  
Screening Practices ◽  
Target Effects

e22527 Background: BCR-ABL tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) and chronic myeloid leukemia (CML). The off-target effects of long-term TKI use in children are poorly understood. We evaluated institutional screening practices for cardiac and endocrine late effects in those who had received TKIs at two large pediatric cancer centers. Methods: This retrospective cohort included patients diagnosed with Ph+ALL (post completion of frontline therapy) or CML at age < 21 years with ≥1 years of follow-up. Patients were censored at stem cell transplant, blast crisis, secondary neoplasm, death, or last contact. Demographics, clinical features, and incidence of screening echocardiogram (ECHO), electrocardiogram (EKG), dual-energy x-ray absorptiometry (DXA), bone age, and thyroid function (TSH) were abstracted. Descriptive statistics and incidence of screening are presented by diagnosis. Results: The cohort (n = 68) was 50% female, 28% non-Hispanic white, 24% non-Hispanic black, 24% Asian, and 19% Hispanic. CML: Patients were diagnosed at 12.9±4.6 years of age and had 6.3 (0.9-15.6) years of TKI exposure and 6.3 (0.9-15.6) years of follow-up. Imatinib was most commonly used (80%) followed by dasatinib (59%); 48% were exposed to > 1 TKI. Excluding tests at diagnosis, 48% had an ECHO and 48% had an EKG during the follow-up period. TSH, DXA and bone age were measured in 50%, 9% and 11% patients, respectively. Ph+ALL: Patients were diagnosed at 10.8±5.1 years of age and had 2.8 (0.6-11.6) years of TKI exposure and 5.7 (2.1-11.8) years of follow-up. Dasatinib was most commonly used (73%) followed by imatinib (64%); 36% were exposed to > 1 TKI. All received anthracyclines and steroids. Excluding tests at diagnosis, 91% had an ECHO and 77% had an EKG. TSH, DXA and bone age were measured in 82%, 68% and 36% patients, respectively. Conclusions: We note inconsistent cardiac and endocrine screening in patients receiving TKIs for CML and Ph+ALL. Evidence-based guidelines for long-term follow-up and structured monitoring for potential off-target effects are needed. A prospective screening study is in progress and may enhance our understanding of the prevalence of late effects of TKIs. [Table: see text]

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