APL meeting, Rome, Italy. Sept Salvage Therapy with Chemotherapy- or Arsenic Trioxide-based Regimens for Acute Promyelocytic Leukemia in First Relapse. P. Montesinos, J. Esteve, E. Vellenga, C. Rivas, S. Brunet, M. Arnan, J. D. González, P. Sánchez, J. Díaz-mediavilla, A. Verdeguer, L. Escoda, E. Amutio, V. Rubio, I. Pérez, R. Guàrdia, J. Bueno, B. Lowenberg, and M.A. Sanz. On behalf of the PETHEMA, HOVON and GATLA Groups

Background Arsenic trioxide (ATO) is currently regarded as the best treatment option in relapsed acute promyelocytic leukemia (APL). The efficacy and safety of salvage therapy using ATO-based approaches compared with chemotherapy-based regimens is not well established.

Objectives We analyze the clinical outcome of 110 APL patients in first relapse who received salvage therapy with chemotherapy- or ATO-based regimens.

Patients and Methods From June 1997 to May 2009, 110 of 1,225 patients included in three subsequent PETHEMA trials (LPA96, LPA99 & LPA2005) relapsed after front-line therapy. Salvage therapy: 67 patients (61%) CT-based regimens. 43 patients (49%) ATO-based regimens.

Salvage therapy: CT-based regimens Induction with ATRA plus mitoxantrone plus cytarabine (n=46), plus etoposide (n=7), or other anthracycline-based regimens (n=14). Consolidation with one cycle of chemotherapy followed by SCT. Patients not eligible for SCT received one additional consolidation cycle with or without maintenance therapy.

Salvage therapy: ATO-based regimens Induction with ATO (0.15 mg/kg) ± ATRA (45mg/sqm) until CR. Consolidation with one cycle of ATO (5d x 5w) plus ATRA (15d), followed by SCT. Patients not eligible for SCT received maintenance therapy with ATO plus ATRA with or without gemtuzumab ozogamicin or other agents.

Patient characteristics (1) Characteristic Total (n=110) CT- based (n=67) ATO- based (n=43) P Age, median (range)40 (2-81)37 (2-73)42 (10-81)NS Gender, % Male63 NS FAB, % M3V33 (30)19 (28)14 (33)NS BCR3 isoform, %58 (54)23 (53)23 (55)NS Secondary APL, %6 (5)3 (4)3 (7)NS

ATO-Based group (n=43) CT-Based group (n=67) Relapse-risk group at APL diagnosis

ATO-Based group (n=43) CT-Based group (n=67) Type of relapse

Patient characteristics (2) Characteristic Total (n=110) CT- based (n=67) ATO- based (n=43)P Early relapse (<18 months), N (%) 54 (49)40 (60)14 (33)0.01 Follow-up in months, median (range) 38 (2-134) 62 (6-134) 18 (2-53) <0.01

Results: Induction therapy ATO-Based group (n=43) CT-Based group (n=67) P = 0.49

Results: Molecular Remission ATO-Based group (n=38) CT-Based group (n=56) P = 0.13

ATO-Based group (n=38) CT-Based group (n=56) Post-remission therapy *4 mobilization failures, 7 early relapses before planned SCT *No mobilization failures, 6 early relapses before planned SCT

Results in the overall series according to salvage therapy OS RFS 63% 44% P = 0.05 ATO-based (n=43) CT-based (n=67) DFS 34% 33% P = 0.51 ATO-based CT-based 37% 34% P = 0.61 ATO-based (n=38) CT-based (n=56)

OS after Auto-SCT according to salvage therapy 87% 60% P = 0.03 ATO-based (n=19) CT-based (n=20)

OS after Allo-SCT according to salvage therapy 100% 56% P = 0.15 ATO-based (n=4) CT-based (n=14)

OS in patients not receiving SCT according to salvage therapy 38% 26% P = 0.98 ATO-based (n=15) CT-based (n=22)

Concluding remarks High rates of second CR with either ATO (88%) or chemotherapy regimens (84%). The 2-year DFS and RFS were similar with both approaches. An apparent benefit in terms of OS was observed in the ATO-based group (P=0.05), especially in patients undergoing SCT. A longer follow-up is required in the ATO-based group to confirm these results.

Participating Institutions H.U. La Fe, Valencia H. Central, Asturias H.J. Canalejo, Coruña H. General, Jerez H. Clinic, Barcelona H.C. S. Carlos, Madrid H. Clínico, Valencia H. Cruces, Baracaldo H. 12 Octubre, Madrid H.C.U. Salamanca H. Son Dureta, Mallorca H.U. P. del Mar, Cádiz H. Insular, Las Palmas C.H. Xeral-Calde, Lugo H. General, Alicante H.S.P.Alcántara, Cáceres H. Carlos Haya, Málaga H.C.U. Santiago H. Reina Sofia, Córdoba H. Dr. Peset, Valencia H. San Pau, Barcelona H. Joan XXIII, Tarragona H.U. V. D'Hebron, Barcelona C.H. León H. Navarra, Pamplona H.C. Valladolid H. G. Albacete H. M. Valdecilla, Santander H.U. V. D'Hebron (Inf), Barna H. La Princesa, Madrid H.U. G. Trias i Pujol, Barna H. Dr. Negrin, Las Palmas H. M-Infantil, Las Palmas H. Basurto, Bilbao H. R. Hortega, Valladolid H.C.U. Zaragoza H.G.E. Ciudad de Jaén H.U. V. Victoria, Málaga H.General, Castellón H.U. V. Arrixaca, Murcia H. Montecelo, Pontevedra F. Jiménez Díaz, Madrid C.H. de Segovia H. Meixoeiro, Vigo H. Severo Ochoa, Leganés H.G. Murcia H. San Jorge, Huesca H. Ramón y Cajal, Madrid

Participating Institutions Fundaleu, Buenos Aires H. Rossi, La Plata H. General San Martín, La Plata H. General San Martín, Paraná I. Trasplante de Médula Ósea, La Plata H. Clemente Álvarez, Rosario GATLA (Argentina ) I. P. de Hematología, Paraná H. de Clínicas, Buenos Aires H.U. del Aire, Madrid H. del Mar, Barcelona H. Dr. Trueta, Gerona H. Niño Jesús, Madrid H.G. Valencia F. Hospital, Brno (Czec Rep.) H.U. Arrixaca (Inf), Murcia H. Xeral-Cies, Vigo H. Txagorritxu, Vitoria H. General (Inf), Alicante H. Río Carrión, Palencia H. C. Haya (Inf), Málaga H. P. Asturias, A. Henares H. Mutua, Terrasa H. N.S. Sonsoles, Ávila H. Sta María Rosell, Cartagena H. San Rafael, Madrid H. Virgen de la Cinta, Tortosa H. C. Haya (Inf), Málaga H. Virgen del Rocío, Sevilla H. Maciel, Montevideo (Uruguay) HOVON (The Netherlands ) H. La Paz (Inf), Madrid H.C. San Carlos (Inf), Madrid I.C.O., Hospitalet de Llobregat H.U. La Fe (Inf), Valencia SHOP (Spain )