MYC + diffuse large B-cell lymphoma is not salvaged by classical R-ICE or R-DHAP followed by BEAM plus autologous stem cell transplantation

Author:

Cuccuini Wendy12,Briere Josette234,Mounier Nicolas5,Voelker Hans-Ullrich6,Rosenwald Andreas6,Sundstrom Christer7,Cogliatti Sergio8,Hirchaud Edouard9,Ysebaert Loic10,Bron Dominique11,Soulier Jean12,Gaulard Philippe121314,Houlgatte Remi15,Gisselbrecht Christian16,Thieblemont Catherine241617

Affiliation:

1. Hematologie biologique, Hôpital Saint Louis, Assistance Publique–Hôpitaux de Paris (AP-HP), Paris, France;

2. Institut Universitaire d'hematologie, Hôpital Saint-Louis, Paris, France;

3. Anatomie Pathologie, Hôpital Saint Louis, AP-HP, Paris, France;

4. Institut Universitaire d'hématologie–Paris VII, Inserm U728, Paris, France;

5. Hemato-oncology, Centre Hospitalier Universitaire (CHU) de l'Archet, Nice, France;

6. Institute of Pathology, University of Wuerzburg (for Deutsche Studiengruppe Hochmaligne Non-Hodgkin-Lymphome [DSHNHL]), Wuerzburg, Germany;

7. Pathology, Uppsala University Hospital, Uppsala, Sweden;

8. Pathology, St Gallen Hospital (for Schweizerische Arbeitgeminschaft für Klinische Krebsforchnung [SAKK]), St Gallen, Switzerland;

9. Inserm U533, Institut du thorax, Faculté de Médecine, Université de Nantes, Nantes, France;

10. Service d'Hématologie, CHU Purpan, Toulouse, France;

11. Service Hématologie, Institut Jules Bordet, Bruxelles, Belgium;

12. Inserm U955, Créteil, France;

13. Université Paris Est, Créteil, France;

14. Department of Pathology, Hôpital Henri-Mondor, AP-HP, Créteil, France;

15. Inserm U954, CHU de Nancy, Nancy, France;

16. Groupe d'Etude des Lymphomes de l'Adulte (GELA), France; and

17. Hematology, Hôpital Saint Louis, AP-HP, Paris, France

Abstract

Abstract Approximately 5-10% of diffuse large B-cell lymphomas (DLBCL) harbor a 8q24/MYC rearrangement (MYC+). We determined the prognostic significance of MYC rearrangement in patients with relapsed/refractory DLBCL prospectively treated by R-ICE or R-DHAP followed by high-dose therapy and autologous stem cell transplantation. Twenty-eight (17%) of the 161 patients analyzed presented a MYC+ rearrangement, targeted as either simple hit (25%) or complex hits (n=75%) including MYC/BCL2, MYC/BCL6, and MYC/BCL2/BCL6. Results were statistically highly concordant in matched primary and relapsed biopsies (n = 45). Compared to the MYC− DLBCL patients, the MYC+ DLBCL patients presented with a more elevated lactico-deshydrogenase level (P = .0006) and a more advanced age adjusted international prognostic index (P = .0039). The 4-year PFS and OS were significantly lower in the MYC+ DLBCL patients than those in the MYC− DLBCL patients, with rates of 18% vs 42% (P = .0322), and of 29% vs 62% (P = .0113), respectively. Type of treatment, R-DHAP or R-ICE, had no impact on survivals, with 4-year PFS rates of 17% vs 19% and 4-year OS rates of 26% vs 31%. In conclusion, MYC rearrangement is an early event in DLBCL. MYC+ DLBCL patients have a significant inferior prognosis than MYC− DLBCL patients. Their outcome was not influenced by the proposed salvage therapy.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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