Reinduction Chemotherapy with Gemtuzumab Ozogamicin and Intermediate/High-Dose Cytarabine: A Single-Center Experience

Sohsuke Meshitsuka, Mitsuo Hori, Shoichi Mitsuhashi, Yasushi Okoshi, Hiroshi Kojima

Department of Clinical Oncology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan.
Department of Hematology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan.
Department of Hematology, Ibaraki Prefectural Central Hospital, Ibaraki, Japan; Ibaraki Clinical Education and Training Center, University of Tsukuba Hospital, Ibaraki, Japan.

DOI: 10.4236/ojbd.2014.41001                

Abstract

We performed a retrospective analysis of 9 patients with acute myeloid leukemia (AML) treated with gemtuzumab ozogamicin (GO) plus cytarabine as a salvage regimen (GO reinduction) for patients who did not achieve complete remission (CR) after the first cycle of induction chemotherapy or at first relapse. Cases of AML secondary to myelodysplastic syndrome or myeloproliferative disorder were included. CR was achieved in 6 of 9 patients, and 2 of 6 responders became long-term survivors. No non-responders survived longer than 6 months. Toxicity was mild, and the median duration of myelosuppression was less than 30 days. Stomatitis, nausea and sepsis occurred as non-hematological adverse events. Although our sample size was too small to permit definitive conclusions, GO reinduction should be considered for patients who relapse or do not achieve CR after the first cycle of induction chemotherapy. Some AML subtypes may respond more robustly than others, and further investigation is warranted.

Keywords

Gemtuzumab Ozogamicin; AML; Reinduction; Salvage

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Fernandez, H.F., Sun, Z., Yao, X., Litzow, M.R., Luger, S.M., Paietta, E.M., Racevskis, J., Dewald, G.W., Ketterling, R.P., Bennett, J.M., Rowe, J.M., Lazarus, H.M. and Tallman, M.S. (2009) Anthracycline Dose Intensification in Acute Myeloid Leukemia. The New England journal of Medicine, 361, 1249-1259. http://dx.doi.org/10.1056/NEJMoa0904544
[2]	Mandelli, F., Vignetti, M., Suciu, S., Stasi, R., Petti, M.C., Meloni, G., Muus, P., Marmont, F., Marie, J.P., Labar, B., Thomas, X., Di Raimondo, F., Willemze, R., Liso, V., Ferrara, F., Baila, L., Fazi, P., Zittoun, R., Amadori, S. and de Witte, T. (2009) Daunorubicin versus Mitoxantrone versus Idarubicin as Induction and Consolidation Chemotherapy for Adults with Acute Myeloid Leukemia: The Eortc and Gimema Groups Study aml-10. Journal of Clinical Oncology, 27, 5397-5403.
[3]	Burnett, A.K., Hills, R.K., Milligan, D.W., Goldstone, A.H., Prentice, A.G., McMullin, M.F., Duncombe, A., Gibson, B. and Wheatley, K. (2010) Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the mrc aml12 Trial. Journal of clinical Oncology, 28, 586-595.
[4]	Buchner, T., Berdel, W.E., Haferlach, C., Haferlach, T., Schnittger, S., Muller-Tidow, C., Braess, J., Spiekermann, K., Kienast, J., Staib, P., Gruneisen, A., Kern, W., Reichle, A., Maschmeyer, G., Aul, C., Lengfelder, E., Sauerland, M.C., Heinecke, A., Wormann, B. and Hiddemann, W. (2009) Age-Related Risk Profile and Chemotherapy Dose Response in Acute Myeloid Leukemia: A Study by the German Acute Myeloid Leukemia Cooperative Group. Journal of clinical oncology, 27, 61-69.
[5]	Rowe, J.M., Kim, H.T., Cassileth, P.A., Lazarus, H.M., Litzow, M.R., Wiernik, P.H. and Tallman, M.S. (2010) Adult Patients with Acute Myeloid Leukemia who Achieve Complete Remission after 1 or 2 Cycles of Induction Have a Similar Prognosis: A Report on 1980 Patients Registered to 6 Studies Conducted by the Eastern Cooperative Oncology Group. Cancer, 116, 5012-5021. http://dx.doi.org/10.1002/cncr.25263
[6]	Sievers, E.L., Larson, R.A., Stadtmauer, E.A., Estey, E., Lowenberg, B., Dombret, H., Karanes, C., Theobald, M., Bennett, J.M., Sherman, M.L., Berger, M.S., Eten, C.B., Loken, M.R., van Dongen, J.J.M., Bernstein, I.D., Appelbaum, F.R. and Appelbaum, F.R. (2001) Efficacy and Safety of Gemtuzumab Ozogamicin in Patients with cd33-Positive Acute Myeloid Leukemia in First Relapse. Journal of Clinical Oncology, 19, 3244-3254.
[7]	Larson, R.A., Sievers, E.L., Stadtmauer, E.A., Lowenberg, B., Estey, E.H., Dombret, H., Theobald, M., Voliotis, D., Bennett, J.M., Richie, M., Leopold, L.H., Berger, M.S., Sherman, M.L., Loken, M.R., van Dongen, J.J.M., Bernstein, I.D., Appelbaum, F.R., Mylotarg Study Group (2005) Final Report of the Efficacy and Safety of Gemtuzumab Ozogamicin (Mylotarg) in Patients with cd33-Positive Acute Myeloid Leukemia in First Recurrence. Cancer, 104, 1442-1452. http://dx.doi.org/10.1002/cncr.21326
[8]	Chevallier, P., Delaunay, J., Turlure, P., Pigneux, A., Hunault, M., Garand, R., Guillaume, T., Avet-Loiseau, H., Dmytruk, N., Girault, S., Milpied, N., Ifrah, N., Mohty, M. and Harousseau, J.L. (2008) Long-Term Disease-Free Survival after Gemtuzumab, Intermediate-Dose Cytarabine, and Mitoxantrone in Patients with cd33(+) Primary Resistant or Relapsed Acute Myeloid Leukemia. Journal of Clinical Oncology, 26, 5192-5197.
[9]	Dastugue, N., Payen, C., Lafage-Pochitaloff, M., Bernard, P., Leroux, D., Huguet-Rigal, F., Stoppa, A.M., Marit, G., Molina, L., Michallet, M., et al. (1995) Prognostic Significance of Karyotype in de Novo Adult Acute Myeloid Leukemia. The Bgmt Group. Leukemia, 9, 1491-1498.
[10]	Giles, F.J., Kantarjian, H.M., Kornblau, S.M., Thomas, D.A., Garcia-Manero, G., Waddelow, T.A., David, C.L., Phan, A.T., Colburn, D.E., Rashid, A. and Estey, E.H. (2001) Mylotarg (Gemtuzumab Ozogamicin) Therapy Is Associated with Hepatic Venoocclusive Disease in Patients Who Have Not Received Stem Cell Transplantation. Cancer, 92, 406-413. http://dx.doi.org/10.1002/1097-0142(20010715)92:2<406::AID-CNCR1336>3.0.CO;2-U
[11]	Prebet, T., Etienne, A., Devillier, R., Romeo, E., Charbonnier, A., D’Incan, E., Esterni, B., Arnoulet, C., Blaise, D. and Vey, N. (2011) Improved Outcome of Patients with low- and Intermediate-Risk Cytogenetics Acute Myeloid Leukemia (aml) in First Relapse with Gemtuzumab and Cytarabine versus Cytarabine: Results of a Retrospective Comparative Study. Cancer, 117, 974-981. http://onlinelibrary.wiley.com/doi/10.1002/cncr.25554/abstract;jsessionid=CC12AA2454773B97BD79855 E4376FD6D.f01t04
[12]	Petersdorf, S., Kopecky, K., Stuart, R.K., Larson, R.A., Nevill, T.J., Stenke, L., Slovak, M.L., Tallman, M.S., Willman, C.L., Erba, H. and Appelbaum, F.R. (2009) Preliminary Results of Southwest Oncology Group Study s0106: An International Intergroup Phase 3 Randomized Trial Comparing the Addition of Gemtuzumab Ozogamicin to Standard Induction Therapy versus Standard Induction Therapy Followed by a Second Randomization to Post-Consolidation Gemtuzumab Ozogamicin versus No Additional Therapy for Previously Untreated Acute Myeloid Leukemia. ASH Annual Meeting Abstracts, 114, 790.
[13]	Ravandi, F., Estey, E.H., Appelbaum, F.R., Lo-Coco, F., Schiffer, C.A., Larson, R.A., Burnett, A.K. and Kantarjian, H.M. (2012) Gemtuzumab Ozogamicin: Time to Resurrect? Journal of Clinical Oncology, 30, 3921-3923.
[14]	Rowe, J.M. and Lowenberg, B. (2013) Gemtuzumab Ozogamicin in Acute Myeloid Leukemia: A Remarkable Saga about an Active Drug. Blood, 121, 4838-4841.
[15]	Burnett, A.K., Hills, R.K., Milligan, D., Kjeldsen, L., Kell, J., Russell, N.H., Yin, J.A., Hunter, A., Goldstone, A.H. and Wheatley, K. (2011) Identification of Patients with Acute Myeloblastic Leukemia Who Benefit from the Addition of Gemtuzumab Ozogamicin: Results of the mrc aml15 trial. Journal of Clinical Oncology, 29, 369-377.
[16]	Castaigne, S., Pautas, C., Terre, C., Raffoux, E., Bordessoule, D., Bastie, J.N., Legrand, O., Thomas, X., Turlure, P., Reman, O., de Revel, T., Gastaud, L., de Gunzburg, N., Contentin, N., Henry, E., Marolleau, J.P., Aljijakli, A., Rousselot, P., Fenaux, P., Preudhomme, C., Chevret, S., Dombret, H., Acute Leukemia French Association (2012) Effect of Gemtuzumab Ozogamicin on Survival of Adult Patients with De-Novo Acute Myeloid Leukaemia (alfa-0701): A Randomised, Open-Label, Phase 3 Study. Lancet, 379, 1508-1516. http://dx.doi.org/10.1016/S0140-6736(12)60485-1
[17]	Burnett, A.K., Russell, N.H., Hills, R.K., Kell, J., Freeman, S., Kjeldsen, L., Hunter, A.E., Yin, J., Craddock, C.F., Dufva, I.H., Wheatley, K. and Milligan, D. (2012) Addition of Gemtuzumab Ozogamicin to Induction Chemotherapy Improves Survival in Older Patients with Acute Myeloid Leukemia. Journal of Clinical Oncology, 30, 3924-3931.
[18]	Brunnberg, U., Mohr, M., Noppeney, R., Durk, H.A., Sauerland, M.C., Muller-Tidow, C., Krug, U., Koschmieder, S., Kessler, T., Mesters, R.M., Schulz, C., Kosch, M., Buchner, T., Ehninger, G., Duhrsen, U., Serve, H. and Berdel, W.E. (2012) Induction Therapy of aml with ara-c plus Daunorubicin versus ara-c plus Gemtuzumab Ozogamicin: A Randomized Phase ii Trial in Elderly Patients. Annals of Oncology, 23, 990-996.