Myelodysplastic syndrome

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13 regimens on this page
23 variants on this page

Contents


Guidelines

International expert panel

NCCN

Untreated

Alemtuzumab (Campath)

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Indication: Intermediate-1 MDS (RAEB-I, RA, or RARS)

Regimen

Study Evidence
Sloand et al. 2010 Phase II

Chemotherapy

Supportive medications

11-day course of therapy

References

  1. Sloand EM, Olnes MJ, Shenoy A, Weinstein B, Boss C, Loeliger K, Wu CO, More K, Barrett AJ, Scheinberg P, Young NS. Alemtuzumab treatment of intermediate-1 myelodysplasia patients is associated with sustained improvement in blood counts and cytogenetic remissions. J Clin Oncol. 2010 Dec 10;28(35):5166-73. Epub 2010 Nov 1. link to original article contains verified protocol PubMed

Antithymocyte globulin (ATG)

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Regimen

Study Evidence
Molldrem et al. 1997 Phase II

Immunotherapy

References

  1. Molldrem JJ, Caples M, Mavroudis D, Plante M, Young NS, Barrett AJ. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol. 1997 Dec;99(3):699-705. link to original article PubMed
  2. Molldrem JJ, Leifer E, Bahceci E, Saunthararajah Y, Rivera M, Dunbar C, Liu J, Nakamura R, Young NS, Barrett AJ. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med. 2002 Aug 6;137(3):156-63. link to original article contains protocol PubMed
  3. Steensma DP, Dispenzieri A, Moore SB, Schroeder G, Tefferi A. Antithymocyte globulin has limited efficacy and substantial toxicity in unselected anemic patients with myelodysplastic syndrome. Blood. 2003 Mar 15;101(6):2156-8. Epub 2002 Oct 31. link to original article contains protocol PubMed
  4. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008 May 20;26(15):2505-11. Epub 2008 Apr 14. link to original article PubMed

Azacitidine (Vidaza)

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Regimen #1

Study Evidence Comparator Efficacy
Silverman et al. 2002 (CALGB 8421, 8921, & 9921) Phase III Best supportive care Seems to have superior OS
Fenaux et al. 2009 Phase III Best supportive care Superior OS

Chemotherapy

28-day cycles, given for at least 4 cycles, then depending on study, continued for 3 cycles beyond complete remission, or if there was progressive disease or unacceptable toxicity

Regimen #2

Study Evidence Comparator Efficacy
Fili et al. 2013 Phase II
Thépot et al. 2016 Randomized Phase II Azacitidine & Epoetin Seems not superior

Intended to be used for low-risk MDS patients who are symptomatic or intolerant to erythropoietin (Fili et al. 2013) or resistant to erythropoietin (Thépot et al. 2016).’’

Chemotherapy

Supportive medications

  • G-CSF or GM-CSF was allowed if ANC < 200 and/or systemic infection
  • Erythropoiesis-stimulating agents were not allowed
  • Antimicrobial and antifungal prophylaxis (agents not specified) given if ANC < 500

28-day cycle for 8 cycles (Fili et al. 2013) or up to 18 cycles (Thépot et al. 2016)

Regimen #3

Study Evidence
Grövdal et al. 2010 Phase II

Intended to be used for high-risk MDS patients in remission after induction therapy

Chemotherapy

28-day cycles

References

  1. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15;20(10):2429-40. link to original article contains verified protocol PubMed
    1. Update: Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL, Larson RA; Cancer and Leukemia Group B. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006 Aug 20;24(24):3895-903. link to original article contains protocol PubMed
  2. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. Epub 2009 Feb 21. link to original article contains protocol PubMed
  3. Grövdal M, Karimi M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P, Engström LM, Kjeldsen L, Linder O, Nilsson L, Olsson A, Holm MS, Tangen JM, Wallvik J, Oberg G, Hokland P, Jacobsen SE, Porwit A, Hellström-Lindberg E. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy. Br J Haematol. 2010 Aug;150(3):293-302. Epub 2010 May 20. link to original article contains verified protocol PubMed
  4. Filì C, Malagola M, Follo MY, Finelli C, Iacobucci I, Martinelli G, Cattina F, Clissa C, Candoni A, Fanin R, Gobbi M, Bocchia M, Defina M, Spedini P, Skert C, Manzoli L, Cocco L, Russo D. Prospective phase II Study on 5-days azacitidine for treatment of symptomatic and/or erythropoietin unresponsive patients with low/INT-1-risk myelodysplastic syndromes. Clin Cancer Res. 2013 Jun 15;19(12):3297-308. link to original article contains verified protocol PubMed
  5. Thépot S, Ben Abdelali R, Chevret S, Renneville A, Beyne-Rauzy O, Prébet T, Park S, Stamatoullas A, Guerci-Bresler A, Cheze S, Tertian G, Choufi B, Legros L, Bastié JN, Delaunay J, Chaury MP, Sanhes L, Wattel E, Dreyfus F, Vey N, Chermat F, Preudhomme C, Fenaux P, Gardin C; Groupe Francophone des Myélodysplasies (GFM). A randomized phase II trial of azacitidine +/- epoetin-β in lower-risk myelodysplastic syndromes resistant to erythropoietic stimulating agents. Haematologica. 2016 Aug;101(8):918-25. Epub 2016 May 26. link to original article contains verified protocol PubMed

Azacitidine & Lenalidomide

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Regimen

Study Evidence
Sekeres et al. 2012 Phase II

Chemotherapy

28-day cycle for up to 7 cycles, with option to continue single agent azacitidine per MD discretion

References

  1. Sekeres MA, Tiu RV, Komrokji R, Lancet J, Advani AS, Afable M, Englehaupt R, Juersivich J, Cuthbertson D, Paleveda J, Tabarroki A, Visconte V, Makishima H, Jerez A, Paquette R, List AF, Maciejewski JP. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012 Dec 13;120(25):4945-51. Epub 2012 Aug 22. link to original article contains protocol PubMed

Azacitidine & Vorinostat

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Regimen

Study Evidence
Verma et al. 2013 Phase II

Three different schedules were evaluated; a randomized trial is underway using the doses from schedule two.

Schedule One

Schedule Two

Schedule Three

28-day cycles

References

  1. Abstract: Amit Verma, Rosalie Odchimar-Reissig, Eric J. Feldman, Shyamala C. Navada, Erin P Demakos, Maria R. Baer, Vesna Najfeld, Joseph A Sparano, Richard Piekarz. A Phase II Trial Of Epigenetic Modulators Vorinostat In Combination With Azacitidine (azaC) In Patients With The Myelodysplastic Syndrome (MDS): Initial Results Of Study 6898 Of The New York Cancer Consortium. Blood Nov 2013,122(21)386 link to original abstract

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Silverman et al. 2002 (CALGB 8421, 8921, & 9921) Phase III Azacitidine Seems to have inferior OS
Kantarjian et al. 2006 Phase III Decitabine Inferior ORR
Fenaux et al. 2009 Phase III Azacitidine Inferior OS
Lübbert et al. 2011 (EORTC LSG/GMDSSG 06011) Phase III Decitabine Inferior PFS
Santini et al. 2016 Phase III Lenalidomide Inferior RBC transfusion independence ≥ 8 weeks

No active antineoplastic therapy; included here because it was a comparator arm in several studies.

References

  1. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, Stone RM, Nelson D, Powell BL, DeCastro CM, Ellerton J, Larson RA, Schiffer CA, Holland JF. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002 May 15;20(10):2429-40. link to original article contains verified protocol PubMed
    1. Update: Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL, Larson RA; Cancer and Leukemia Group B. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006 Aug 20;24(24):3895-903. link to original article contains protocol PubMed
  2. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006 Apr 15;106(8):1794-803. link to original article contains protocol PubMed
  3. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. Epub 2009 Feb 21. link to original article contains protocol PubMed content property of HemOnc.org
  4. Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pflüger KH, Coens C, Hagemeijer A, Eckart Schaefer H, Ganser A, Aul C, de Witte T, Wijermans PW. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011 May 20;29(15):1987-96. Epub 2011 Apr 11. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Becker H, Suciu S, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Muus P, Pflüger KH, Hagemeijer A, Schaefer HE, Fiaccadori V, Baron F, Ganser A, Aul C, de Witte T, Wijermans PW, Lübbert M. Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Ann Hematol. 2015 Dec;94(12):2003-13. Epub 2015 Sep 24. link to original article PubMed
  5. Santini V, Almeida A, Giagounidis A, Gröpper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Cañizo C, Gattermann N, Ozawa K, Risueño A, MacBeth KJ, Zhong J, Séguy F, Hoenekopp A, Beach CL, Fenaux P. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. J Clin Oncol. 2016 Sep 1;34(25):2988-96. Epub 2016 Jun 27. link to original article PubMed

Clofarabine (Clolar)

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Regimen #1

Study Evidence Comparator Efficacy
Faderl et al. 2012 Randomized Phase II Clofarabine 30 mg/m2 dosing Seems not superior

This randomized trial tested two doses of clofarabine, 15 mg/m2 and 30 mg/m2. Lower dose was less toxic and clinical activity was comparable

Chemotherapy

Supportive medications

  • "Supportive care measures such as antibiotic prophylaxis (eg, levofloxacin, valacyclovir, and itraconazole or voriconazole), hematopoietic growth factors, and transfusions were provided as necessitated for optimal medical care of the patients." In order to decrease risk of liver function abnormalities, no antifungals were given on the days where clofarabine was given.

4 to 8 week cycle for up to 12 cycles

Regimen #2

Study Evidence
Faderl et al. 2010 Non-randomized

Initial dose was too toxic; 20 mg/m2 was final dose level

Chemotherapy

Supportive medications

  • "Supportive care included anti-infectious prophylaxis (eg, levaquin, valacyclovir, and itraconazole or voriconazole), hematopoietic growth factors, and transfusions as judged indicated by the treating physician." In order to decrease risk of liver function abnormalities, no antifungals were given on the days where clofarabine was given.

4 to 8 week cycle for up to 12 cycles

References

  1. Faderl S, Garcia-Manero G, Estrov Z, Ravandi F, Borthakur G, Cortes JE, O'Brien S, Gandhi V, Plunkett W, Byrd A, Kwari M, Kantarjian HM. Oral clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. J Clin Oncol. 2010 Jun 1;28(16):2755-60. Epub 2010 Apr 26. link to original article contains verified protocol PubMed
  2. Faderl S, Garcia-Manero G, Jabbour E, Ravandi F, Borthakur G, Estrov Z, Gandhi V, Byrd AL, Kwari M, Cortes J, Kantarjian HM. A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher-risk myelodysplastic syndrome. Cancer. 2012 Feb 1;118(3):722-8. Epub 2011 Jul 12. link to original article contains verified protocol PubMed

Cyclosporine modified (Neoral)

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Regimen

Study Evidence
Jonásova et al. 1998 Pilot, <20 pts

Immunotherapy

  • Cyclosporine modified (Neoral) 5 to 6 mg/kg/day, divided into two equal doses PO BID, adjusted to maintain therapeutic cyclosporine level of 100 to 300 ng/mL

References

  1. Jonásova A, Neuwirtová R, Cermák J, Vozobulová V, Mociková K, Sisková M, Hochová I. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol. 1998 Feb;100(2):304-9. link to original article contains protocol PubMed
  2. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008 May 20;26(15):2505-11. Epub 2008 Apr 14. link to original article PubMed

Decitabine (Dacogen)

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Regimen #1, IV x 5 days per cycle

Study Evidence Comparator Efficacy
Kantarjian et al. 2007 Randomized Phase II Decitabine IV x 10 days per cycle Seems to have superior CR rate
Decitabine SC x 5 days per cycle Seems to have superior CR rate
Issa et al. 2014 Randomized Phase II Decitabine & Valproic acid Seems not superior

Chemotherapy

4- to 6-week cycles

Regimen #2, IV x 3 days per cycle

Study Evidence Comparator Efficacy
Kantarjian et al. 2006 Phase III Best supportive care Superior ORR
Lübbert et al. 2011 (EORTC LSG/GMDSSG 06011) Phase III Best supportive care Superior PFS

Chemotherapy

6-week cycle for up to 10 cycles, depending on the protocol

Regimen #3, SC x 5 days per cycle

Study Evidence Comparator Efficacy
Kantarjian et al. 2007 Randomized Phase II, <20 pts in this arm Decitabine IV x 5 days per cycle Seems to have inferior CR rate
Decitabine IV x 10 days per cycle Not reported

Chemotherapy

28-day cycles

Regimen #4, IV x 10 days per cycle

Study Evidence Comparator Efficacy
Kantarjian et al. 2007 Randomized Phase II, <20 pts in this arm Decitabine IV x 5 days per cycle Seems to have inferior CR rate
Decitabine SC x 5 days per cycle Not reported

Chemotherapy

28-day cycles

Regimen #5, SC x 3 days per cycle

Study Evidence Comparator Efficacy
Garcia-Manero et al. 2013 Randomized Phase II Decitabine SC weekly Seems not superior

Chemotherapy

28-day +/- 3 day cycle for up to 12 months

Regimen #6, SC weekly

Study Evidence Comparator Efficacy
Garcia-Manero et al. 2013 Randomized Phase II Decitabine SC x 3 days per cycle Seems not superior

Chemotherapy

28-day +/- 3 day cycle for up to 12 months

References

  1. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, Klimek V, Slack J, de Castro C, Ravandi F, Helmer R 3rd, Shen L, Nimer SD, Leavitt R, Raza A, Saba H. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006 Apr 15;106(8):1794-803. link to original article contains protocol PubMed
  2. Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O'Brien S, Cortes J, Faderl S, Bueso-Ramos C, Ravandi F, Estrov Z, Ferrajoli A, Wierda W, Shan J, Davis J, Giles F, Saba HI, Issa JP. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood. 2007 Jan 1;109(1):52-7. Epub 2006 Aug 1. link to original article contains protocol PubMed
  3. Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Beeldens F, Muus P, Pflüger KH, Coens C, Hagemeijer A, Eckart Schaefer H, Ganser A, Aul C, de Witte T, Wijermans PW. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011 May 20;29(15):1987-96. Epub 2011 Apr 11. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Becker H, Suciu S, Rüter BH, Platzbecker U, Giagounidis A, Selleslag D, Labar B, Germing U, Salih HR, Muus P, Pflüger KH, Hagemeijer A, Schaefer HE, Fiaccadori V, Baron F, Ganser A, Aul C, de Witte T, Wijermans PW, Lübbert M. Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG). Ann Hematol. 2015 Dec;94(12):2003-13. Epub 2015 Sep 24. link to original article PubMed
  4. Garcia-Manero G, Jabbour E, Borthakur G, Faderl S, Estrov Z, Yang H, Maddipoti S, Godley LA, Gabrail N, Berdeja JG, Nadeem A, Kassalow L, Kantarjian H. Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes. J Clin Oncol. 2013 Jun 3. [Epub ahead of print] link to original article contains verified protocol PubMed
  5. Issa JP, Garcia-Manero G, Huang X, Cortes J, Ravandi F, Jabbour E, Borthakur G, Brandt M, Pierce S, Kantarjian HM. Results of phase 2 randomized study of low-dose decitabine with or without valproic acid in patients with myelodysplastic syndrome and acute myelogenous leukemia. Cancer. 2015 Feb 15;121(4):556-61. Epub 2014 Oct 21. link to original article contains verified protocol PubMed

Epoetin & Lenalidomide

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Regimen #1

Study Evidence Comparator Efficacy
Toma et al. 2015 Phase III Lenalidomide Seems to have superior erythroid response per IWG 2006 criteria

Chemotherapy

28-day cycles

Regimen #2

Study Evidence
Komrokji et al. 2012 Phase II

Chemotherapy

For 16 weeks; erythroid nonresponders or those with relapsed anemia then offered combined treatment:

Continue until treatment failure or limiting toxicity

References

  1. Komrokji RS, Lancet JE, Swern AS, Chen N, Paleveda J, Lush R, Saba HI, List AF. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood. 2012 Oct 25;120(17):3419-24. Epub 2012 Aug 30. link to original article contains protocol PubMed
  2. Toma A, Kosmider O, Chevret S, Delaunay J, Stamatoullas A, Rose C, Beyne-Rauzy O, Banos A, Guerci-Bresler A, Wickenhauser S, Caillot D, Laribi K, De Renzis B, Bordessoule D, Gardin C, Slama B, Sanhes L, Gruson B, Cony-Makhoul P, Chouffi B, Salanoubat C, Benramdane R, Legros L, Wattel E, Tertian G, Bouabdallah K, Guilhot F, Taksin AL, Cheze S, Maloum K, Nimuboma S, Soussain C, Isnard F, Gyan E, Petit R, Lejeune J, Sardnal V, Renneville A, Preudhomme C, Fontenay M, Fenaux P, Dreyfus F. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion. Leukemia. 2016 Apr;30(4):897-905. Epub 2015 Oct 26. link to original article contains protocol PubMed

Lenalidomide (Revlimid)

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Regimen #1

Study Evidence Comparator Efficacy
List et al. 2006 Phase II
Raza et al. 2008 Phase II
Santini et al. 2016 Phase III Placebo Superior RBC transfusion independence ≥ 8 weeks

Chemotherapy

28-day cycles

Regimen #2

Study Evidence Comparator Efficacy
Toma et al. 2015 Phase III Epoetin & Lenalidomide Seems to have inferior erythroid response per IWG 2006 criteria

Chemotherapy

28-day cycles

References

  1. List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. link to original article PubMed
  2. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, Powell B, Greenberg P, Thomas D, Stone R, Reeder C, Wride K, Patin J, Schmidt M, Zeldis J, Knight R; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006 Oct 5;355(14):1456-65. link to original article contains protocol PubMed
  3. Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, Dreisbach L, Schiffer CA, Stone RM, Greenberg PL, Curtin PT, Klimek VM, Shammo JM, Thomas D, Knight RD, Schmidt M, Wride K, Zeldis JB, List AF. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008 Jan 1;111(1):86-93. Epub 2007 Sep 24. link to original article contains protocol PubMed
  4. Santini V, Almeida A, Giagounidis A, Gröpper S, Jonasova A, Vey N, Mufti GJ, Buckstein R, Mittelman M, Platzbecker U, Shpilberg O, Ram R, Del Cañizo C, Gattermann N, Ozawa K, Risueño A, MacBeth KJ, Zhong J, Séguy F, Hoenekopp A, Beach CL, Fenaux P. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. J Clin Oncol. 2016 Sep 1;34(25):2988-96. Epub 2016 Jun 27. link to original article contains verified protocol PubMed
  5. Toma A, Kosmider O, Chevret S, Delaunay J, Stamatoullas A, Rose C, Beyne-Rauzy O, Banos A, Guerci-Bresler A, Wickenhauser S, Caillot D, Laribi K, De Renzis B, Bordessoule D, Gardin C, Slama B, Sanhes L, Gruson B, Cony-Makhoul P, Chouffi B, Salanoubat C, Benramdane R, Legros L, Wattel E, Tertian G, Bouabdallah K, Guilhot F, Taksin AL, Cheze S, Maloum K, Nimuboma S, Soussain C, Isnard F, Gyan E, Petit R, Lejeune J, Sardnal V, Renneville A, Preudhomme C, Fontenay M, Fenaux P, Dreyfus F. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion. Leukemia. 2016 Apr;30(4):897-905. Epub 2015 Oct 26. link to original article contains protocol PubMed

Rabbit ATG (Thymoglobulin)

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Regimen

Study Evidence
Komrokji et al. 2014 Phase II

Immunotherapy

Supportive medications

  • Prednisone (Sterapred) 1 mg/kg/day PO, started 2 days before first rabbit ATG (Thymoglobulin) and continued at full dose during the 4 days, then tapered over the subsequent 14 days (tapering schedule not described)
  • Antibiotics per local practices

References

  1. Komrokji RS, Mailloux AW, Chen DT, Sekeres MA, Paquette R, Fulp WJ, Sugimori C, Paleveda-Pena J, Maciejewski JP, List AF, Epling-Burnette PK. A phase 2 multicenter rabbit anti-thymocyte globulin trial in patients with myelodysplastic syndromes identifying a novel model for response prediction. Haematologica. 2014 Jan 31. [Epub ahead of print] link to original article contains verified protocol PubMed

Temozolomide (Temodar)

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Regimen

Study Evidence
Brandwein et al. 2014 Phase II

Patient selection was based on MGMT expression by Western blot. See article for details.

Chemotherapy

  • Temozolomide (Temodar) 200 mg/m2/day PO on days 1 to 7; complete responders could receive 200 mg/m2/day PO on days 1 to 5

28-day cycle for up to 12 cycles

References

  1. Brandwein JM, Kassis J, Leber B, Hogge D, Howson-Jan K, Minden MD, Galarneau A, Pouliot JF. Phase II study of targeted therapy with temozolomide in acute myeloid leukaemia and high-risk myelodysplastic syndrome patients pre-screened for low O(6) -methylguanine DNA methyltransferase expression. Br J Haematol. 2014 Dec;167(5):664-70. Epub 2014 Aug 27. link to original article contains protocol PubMed

Relapsed/Refractory

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Garcia-Manero et al. 2016 (ONTIME) Phase III Rigosertib Seems not superior

No active antineoplastic therapy; considered the standard of care for MDS relapsed/refractory to hypomethylating agents.

References

  1. Garcia-Manero G, Fenaux P, Al-Kali A, Baer MR, Sekeres MA, Roboz GJ, Gaidano G, Scott BL, Greenberg P, Platzbecker U, Steensma DP, Kambhampati S, Kreuzer KA, Godley LA, Atallah E, Collins R Jr, Kantarjian H, Jabbour E, Wilhelm FE, Azarnia N, Silverman LR; ONTIME study investigators. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Mar 8. [Epub ahead of print] link to original article PubMed

Erlotinib (Tarceva)

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Regimen

Study Evidence
Komrokji et al. 2014 Phase II
Thepot et al. 2014 Phase I/II

This is the MTD in this dose-escalation trial.

Chemotherapy

References

  1. Komrokji RS, Padron E, Yu D, Fulp WJ, Rodriguez Y, Tinsley S, List AF, Lancet JE. Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes. Am J Hematol. 2014 Aug;89(8):809-12. Epub 2014 May 16. link to full article PubMed
  2. Thepot S, Boehrer S, Seegers V, Prebet T, Beyne-Rauzy O, Wattel E, Delaunay J, Raffoux E, Hunault M, Jourdan E, Chermat F, Sebert M, Kroemer G, Fenaux P, Adès L; Groupe Francophone des Myelodysplasies (GFM). A phase I/II trial of Erlotinib in higher risk myelodysplastic syndromes and acute myeloid leukemia after azacitidine failure. Leuk Res. 2014 Dec;38(12):1430-4. Epub 2014 Oct 7. link to original article PubMed

Response criteria

WHO International Working Group criteria (2000, modified in 2006)

  1. Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Löwenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4. link to original article PubMed
  2. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD, Pinto A, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Gore SD, Schiffer CA, Kantarjian H. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006 Jul 15;108(2):419-25. Epub 2006 Apr 11. link to original article PubMed

Prognosis