Issues in current management of chronic myeloid leukemia: Importance of molecular monitoring on long term outcome

Hari Menon

doi:10.4103/2278-330X.105893

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Review Article

02 (

); 038-043

doi:

10.4103/2278-330X.105893

Issues in current management of chronic myeloid leukemia: Importance of molecular monitoring on long term outcome

Hari Menon^1,

1 Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India

*Corresponding author: Dr. Hari Menon. menontata@yahoo.in

Published: 2020-12-31

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Abstract

Monitoring of CML patients while on therapy is vitally important and ENL has come up with specific guidelines for the same. Since we are currently talking about operational cure, this review shall focus on evaluating the emerging data to optimize response. This requires attention to all outstanding controversial issues. Only careful, accurate and regular monitoring with specific attention to grey areas will help us select first line therapy, decide when to discontinue TKIs and also move to second line TKIs in a timely manner.

Keywords

References

Vaid A. Nilotinib as first line therapy for CML. Indian J Cancer 2011;48: 438-45.
Kurkure AP, Koyande SS, Thorat V. Cancer incidence and mortality in greater Mumbai. Publisher Indian Cancer Society. 2008. p. 28.
Raja T. Optimizing second line therapy for CML. Indian J Cancer 2012:49;46-56.
Baccarani M, Castagnetti F, Gugliotta G, Palandri F, Soverini S. Response definitions and European Leukemianet Management recommendations. Best Pract Res Clin Haematol 2009;22:331-411.
Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-35.
Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ: Targeted therapy for advanced renal cell cancer (RCC): A Cochrane systematic review of published randomised trials. BJU Int 2011;108:1556-63.
Escudier B. Sorafenib for the management of advanced renal cell carcinoma. Expert Rev Anticancer Ther 2011;11:825-36.
Jänne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: A randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2012. [Epub ahead of print].
Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med 2006;125:69-92.
Pavlu J, Szydlo RM, Goldman JM, Apperley JF. Three decades of transplantation for chronic myeloid leukemia: What have we learned? Blood 2011;117:755-63.
de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukaemia: Incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358-63.
C0 ortes JE, J0 ones D, O′0 brien S, J0 abbour E, K0 onopleva M, F0 errajoli A, 0 et al . 0 Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol. 2010;28:392.
Saglio G, Kim DW, Issaragrisil S, Le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9.
Larson RA, Kim D, Rosti G, Stenke L, Pasquini R, Hoenekopp A, et al. Comparison of nilotinib and imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 24-month follow-up. J Clin Oncol 2011;29(suppl 15):6511.
Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, et al. Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia. Blood 2009;114:4933.
Martinelli G, Castagnetti F, al. PAe. Molecular responses with nilotinib 800 mg daily as first-line treatment of chronic myeloid leukemia in chronic phase: Results of a Phase II trial of the GIMEMA CML WP. J Clin Oncol [Abstract]. 2009;27.
Signorovitch JE, Wu EQ, Betts KA, Parikh K, Kantor E, Guo A, et al. Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a0 matching-adjusted indirect comparison of randomized trials. Current Medical Research and Opinion 2011;27:1263-71.
Available from: http://www.fda.rog/safety/medwatch/safetyinformation/ucm218929.htm. [Last accessed on 2011 Sep 12].
Available from: http://www.fda.rog/safety/medwatch/safetyinformation/ucm223728.htm. [Last accessed on 2011 Sep 12].
Metcalfe P, Gray E, Hawkins R, Rigsby P. A Proposed 1st WHO International Genetic Reference Panel for the quantitation of BCR-ABL translocation by RQ-PCR, NIBSC code 09/138, EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION, WHO/BS/09.2106, 2009.
Balasubramanian P, Chendamarai E, Markose P, Fletcher L, Branford S, George B, et al. International reporting scale of BCR-ABL1 fusion transcript in chronic myeloid leukemia: First report from India. Acta Haematol 2012;127:135-42.
Mattarucchi E, Spinelli O, Rambaldi A, Pasquali F, Curto FL, Campiotti L. Molecular monitoring of residual disase in chronic myeloid leukemia by genomic DNA compared with conventional mRNA analysis. J Mol Diagnostics 2009;11:482-7.
Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Bartley PA, et al. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia. 2010;24:1719-24.
Deininger M. Hematology: Curing CML with imatinib-a dream come true? Nat Rev Clin Oncol 2011;8:127-8.
Mahon FX, Rea D, Guilhot J, et al. Discontinuation of Imatinib in Patients with Chronic Myeloid Leukemia Who Have Maintained Complete Molecular Response: Update Results of the STIM Study. Blood 2011;118: Abstract #603.
Rea D, Rousselot P, Nicolini F, Legros L, Tulliez M, Giraudier S, et al. Discontinuation of Dasatinib or Nilotinib in Chronic Myeloid Leukemia Patients with Stable Undetectable BCR-ABL Transcripts: Blood 2011;118:632.
Ibrahim AR, Eliasson L, Apperley JF, Milojkovic D, Bua M, Szydlo R, et al: Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood 2011;117:3733-6.
Darkow T, Henk HJ, Thomas SK, Feng W, Baladi JF, Goldberg GA, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25:481-96.
Awidia A, Ayeda AO, Bsoula N, Magablaha A, Mefleha R, Dweirib M, et al. Relationship of serum imatinib trough level and response in CML patients: Long term follow-up. Leuk Res 2010;34:1573-5.
Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 2007;109:3496-9.
Moon JH, Sohn SK, Kim SN, Park SY, Yoon SS, Kim IH, et al. Patient counseling program to improve the compliance to imatinib in chronic myeloid leukemia patients. Med Oncol 2012;29:1179-85.
M0 ilojkovic D, A0 pperley J. M0 echanisms of r0 esistance to i0 matinib and s0 econd -g0 eneration t0 yrosine i0 nhibitors in c0 hronic m0 yeloid l0 eukemia . C0 lin C0 ancer R0 es 2009;15:7519.
0 Hughes T, Saglia G, Branford S, Soverini S, Kim DW, Muller MC, et al. Impact of baseline bcr-able mutations on response to nilotinib in patients with CML in chronic phase. J Clin Oncol 2009;27:4204-10.
Marin D, Ibrahim AR, Lucas C, Gerrard G, Wang L, Szydlo RM, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 2012;30:232-8.
Etienne G, Dupouy M, Costaglioli P, Chollet C, Lagarde V, Pasquet JM, et al: á-defensin 1-3 and á-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients. Dis Markers. 2011;30:221-7.
J Valentin Garcia-Gutierrez JV, Maestro B, Casado LF, Perez-Encinas M, Massague I, De Paz R, et al. Switching to a Second Generation TKI in Chronic Myeloid Leukemia Patients with Late Suboptimal Response with Imatinib Obtained Better Molecular Responses That the "Watch and Wait" Approach. An Experience of a Multicenter Registry in Patients Outside Clinical Trials. Blood 2012;XX:abstract 3768.
Cortes JE, Kim D, Pinilla-Ibarz J, Paquette R, Coutre PD, Chuah C, et al. PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. J Clin Oncology 2012;abstract 6503. http://www.asco.org/ASCOv2/Meetings/Abstracts?andvmview=abst_detail_viewandconfID=114andabstractID=97216. [Last accessed on 2012 Nov 20].
Crews LA, Jamieson CH. Selective elimination of leukemia stem cells: Hitting a moving target. Cancer Lett 2012 PMID: 22906415.
Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res 2010;16:338-47.
Liao HF, Su YC, Zheng ZY, Jhih Cai C, Hou MH, Chao KS, et al. Sonic hedgehog signaling regulates Bcr-Abl expression in human chronic myeloid leukemia cells. Biomed Pharmacother 2012;66:378-83.
Parikh PM, Charak BS, Banavali SD, Koppilar S, Giri NK, Kumar A, et al. Retrospective analysis of 224 cases of CML. Ind J Hematol 1988;6:85-7.

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[1] Vaid A. Nilotinib as first line therapy for CML. Indian J Cancer 2011;48: 438-45.

[2] Kurkure AP, Koyande SS, Thorat V. Cancer incidence and mortality in greater Mumbai. Publisher Indian Cancer Society. 2008. p. 28.

[3] Raja T. Optimizing second line therapy for CML. Indian J Cancer 2012:49;46-56.

[4] Baccarani M, Castagnetti F, Gugliotta G, Palandri F, Soverini S. Response definitions and European Leukemianet Management recommendations. Best Pract Res Clin Haematol 2009;22:331-411.

[5] Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: The prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-35.

[6] Coppin C, Kollmannsberger C, Le L, Porzsolt F, Wilt TJ: Targeted therapy for advanced renal cell cancer (RCC): A Cochrane systematic review of published randomised trials. BJU Int 2011;108:1556-63.

[7] Escudier B. Sorafenib for the management of advanced renal cell carcinoma. Expert Rev Anticancer Ther 2011;11:825-36.

[8] Jänne PA, Shaw AT, Pereira JR, Jeannin G, Vansteenkiste J, Barrios C, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: A randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol 2012. [Epub ahead of print].

[9] Branford S, Hughes T. Diagnosis and monitoring of chronic myeloid leukemia by qualitative and quantitative RT-PCR. Methods Mol Med 2006;125:69-92.

[10] Pavlu J, Szydlo RM, Goldman JM, Apperley JF. Three decades of transplantation for chronic myeloid leukemia: What have we learned? Blood 2011;117:755-63.

[11] de Lavallade H, Apperley JF, Khorashad JS, Milojkovic D, Reid AG, Bua M, et al. Imatinib for newly diagnosed patients with chronic myeloid leukaemia: Incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol 2008;26:3358-63.

[12] C0 ortes JE, J0 ones D, O′0 brien S, J0 abbour E, K0 onopleva M, F0 errajoli A, 0 et al . 0 Nilotinib as front-line treatment for patients with chronic myeloid leukemia in early chronic phase. J Clin Oncol. 2010;28:392.

[13] Saglio G, Kim DW, Issaragrisil S, Le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9.

[14] Larson RA, Kim D, Rosti G, Stenke L, Pasquini R, Hoenekopp A, et al. Comparison of nilotinib and imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd 24-month follow-up. J Clin Oncol 2011;29(suppl 15):6511.

[15] Rosti G, Palandri F, Castagnetti F, Breccia M, Levato L, Gugliotta G, et al. Nilotinib for the frontline treatment of Ph+ chronic myeloid leukemia. Blood 2009;114:4933.

[16] Martinelli G, Castagnetti F, al. PAe. Molecular responses with nilotinib 800 mg daily as first-line treatment of chronic myeloid leukemia in chronic phase: Results of a Phase II trial of the GIMEMA CML WP. J Clin Oncol [Abstract]. 2009;27.

[17] Signorovitch JE, Wu EQ, Betts KA, Parikh K, Kantor E, Guo A, et al. Comparative efficacy of nilotinib and dasatinib in newly diagnosed chronic myeloid leukemia: a0 matching-adjusted indirect comparison of randomized trials. Current Medical Research and Opinion 2011;27:1263-71.

[18] Available from: http://www.fda.rog/safety/medwatch/safetyinformation/ucm218929.htm. [Last accessed on 2011 Sep 12].

[19] Available from: http://www.fda.rog/safety/medwatch/safetyinformation/ucm223728.htm. [Last accessed on 2011 Sep 12].

[20] Metcalfe P, Gray E, Hawkins R, Rigsby P. A Proposed 1st WHO International Genetic Reference Panel for the quantitation of BCR-ABL translocation by RQ-PCR, NIBSC code 09/138, EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION, WHO/BS/09.2106, 2009.

[21] Balasubramanian P, Chendamarai E, Markose P, Fletcher L, Branford S, George B, et al. International reporting scale of BCR-ABL1 fusion transcript in chronic myeloid leukemia: First report from India. Acta Haematol 2012;127:135-42.

[22] Mattarucchi E, Spinelli O, Rambaldi A, Pasquali F, Curto FL, Campiotti L. Molecular monitoring of residual disase in chronic myeloid leukemia by genomic DNA compared with conventional mRNA analysis. J Mol Diagnostics 2009;11:482-7.

[23] Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Bartley PA, et al. Patients with chronic myeloid leukemia who maintain a complete molecular response after stopping imatinib treatment have evidence of persistent leukemia by DNA PCR. Leukemia. 2010;24:1719-24.

[24] Deininger M. Hematology: Curing CML with imatinib-a dream come true? Nat Rev Clin Oncol 2011;8:127-8.

[25] Mahon FX, Rea D, Guilhot J, et al. Discontinuation of Imatinib in Patients with Chronic Myeloid Leukemia Who Have Maintained Complete Molecular Response: Update Results of the STIM Study. Blood 2011;118: Abstract #603.

[26] Rea D, Rousselot P, Nicolini F, Legros L, Tulliez M, Giraudier S, et al. Discontinuation of Dasatinib or Nilotinib in Chronic Myeloid Leukemia Patients with Stable Undetectable BCR-ABL Transcripts: Blood 2011;118:632.

[27] Ibrahim AR, Eliasson L, Apperley JF, Milojkovic D, Bua M, Szydlo R, et al: Poor adherence is the main reason for loss of CCyR and imatinib failure for chronic myeloid leukemia patients on long-term therapy. Blood 2011;117:3733-6.

[28] Darkow T, Henk HJ, Thomas SK, Feng W, Baladi JF, Goldberg GA, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25:481-96.

[29] Awidia A, Ayeda AO, Bsoula N, Magablaha A, Mefleha R, Dweirib M, et al. Relationship of serum imatinib trough level and response in CML patients: Long term follow-up. Leuk Res 2010;34:1573-5.

[30] Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA, et al. Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 2007;109:3496-9.

[31] Moon JH, Sohn SK, Kim SN, Park SY, Yoon SS, Kim IH, et al. Patient counseling program to improve the compliance to imatinib in chronic myeloid leukemia patients. Med Oncol 2012;29:1179-85.

[32] M0 ilojkovic D, A0 pperley J. M0 echanisms of r0 esistance to i0 matinib and s0 econd -g0 eneration t0 yrosine i0 nhibitors in c0 hronic m0 yeloid l0 eukemia . C0 lin C0 ancer R0 es 2009;15:7519.

[33] 0 Hughes T, Saglia G, Branford S, Soverini S, Kim DW, Muller MC, et al. Impact of baseline bcr-able mutations on response to nilotinib in patients with CML in chronic phase. J Clin Oncol 2009;27:4204-10.

[34] Marin D, Ibrahim AR, Lucas C, Gerrard G, Wang L, Szydlo RM, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol 2012;30:232-8.

[35] Etienne G, Dupouy M, Costaglioli P, Chollet C, Lagarde V, Pasquet JM, et al: á-defensin 1-3 and á-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients. Dis Markers. 2011;30:221-7.

[36] J Valentin Garcia-Gutierrez JV, Maestro B, Casado LF, Perez-Encinas M, Massague I, De Paz R, et al. Switching to a Second Generation TKI in Chronic Myeloid Leukemia Patients with Late Suboptimal Response with Imatinib Obtained Better Molecular Responses That the "Watch and Wait" Approach. An Experience of a Multicenter Registry in Patients Outside Clinical Trials. Blood 2012;XX:abstract 3768.

[37] Cortes JE, Kim D, Pinilla-Ibarz J, Paquette R, Coutre PD, Chuah C, et al. PACE: A pivotal phase II trial of ponatinib in patients with CML and Ph+ALL resistant or intolerant to dasatinib or nilotinib, or with the T315I mutation. J Clin Oncology 2012;abstract 6503. http://www.asco.org/ASCOv2/Meetings/Abstracts?andvmview=abst_detail_viewandconfID=114andabstractID=97216. [Last accessed on 2012 Nov 20].

[38] Crews LA, Jamieson CH. Selective elimination of leukemia stem cells: Hitting a moving target. Cancer Lett 2012 PMID: 22906415.

[39] Smith BD, Kasamon YL, Kowalski J, Gocke C, Murphy K, Miller CB, et al. K562/GM-CSF immunotherapy reduces tumor burden in chronic myeloid leukemia patients with residual disease on imatinib mesylate. Clin Cancer Res 2010;16:338-47.

[40] Liao HF, Su YC, Zheng ZY, Jhih Cai C, Hou MH, Chao KS, et al. Sonic hedgehog signaling regulates Bcr-Abl expression in human chronic myeloid leukemia cells. Biomed Pharmacother 2012;66:378-83.

[41] Parikh PM, Charak BS, Banavali SD, Koppilar S, Giri NK, Kumar A, et al. Retrospective analysis of 224 cases of CML. Ind J Hematol 1988;6:85-7.

Issues in current management of chronic myeloid leukemia: Importance of molecular monitoring on long term outcome

Abstract

Abstract

Keywords

References

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