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1514 Phase 2 Randomized Trial Comparing 6 Cycles of Standard RCHOP Chemotherapy Vs 6 Cycles of Brcap (bortezomib, rituximab, cyclophosphamide, adriamicine and prednisone) As First Line Treatment in Young Patients with Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL): Interim Analysis

Lymphoma: Chemotherapy, excluding Pre-Clinical Models
Program: Oral and Poster Abstracts
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Eva González-Barca, MD, PhD1*, Estrella Carrillo2*, Carlos Grande, MD3*, Alejandro Martín4*, Mónica Coronado5*, Santiago Montes-Moreno6*, Jaime Perez de Oteyza7*, Concepción Nicolas8*, Juan-Manuel Sancho9*, Luis Palomera, MD PhD10*, Javier Lopez Sr., MD, PhD11*, Armando Lopez-Guillermo12, Francisco Javier Peñalver13*, José Ángel Hernández, MD14*, Maria Jose Ramirez15*, Isidro Jarque16*, Joan Bargay, MD17*, Mª José Rodríguez18*, Miguel Canales19, Carmen Albo20*, Maite Encuentra21* and Dolores Caballero4*

1Department of Hematology / Institut Català d‘Oncologia, Hospital Duran i Reynals, Barcelona, Spain
2Department of Hematology / Instituto de Biomedicina de Sevilla (IBIS)/CSIC/Universidad de Sevilla, Hospital Universitario Virgen del Rocío, Sevilla, Spain
3Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain
4Department of Hematology / IBSAL, Hospital Universitario de Salamanca, Salamanca, Spain
5Department of Nuclear Medicine, Hospital Universitario La Paz, Madrid, Spain
6Department of Pathology / IFIMAV, Hospital Universitario Marqués de Valdecilla, Santander, Spain
7Department of Hematology, Hospital Universitario Sanchinarro, Madrid, Spain
8Department of Hematology, Hospital Central de Asturias, Asturias, Spain
9Servicio de Hematologia, Hospital Germans Trias i Pujol, Badalona, Spain
10Department of Hematology, Hospital Universitario Lozano Blesa, Zaragoza, Spain
11Department of Hematology, Hospital Ramon y Cajal, Madrid, Spain
12Hematology, Hospital Clinic, Barcelona, Spain
13Department of Hematology, Hospital Universitario Fundación Alcorcon, Madrid, Spain
14Department of Hematology, Hospital Universitario Infanta Leonor, Madrid, Spain
15Department of Hematology, Hospital de Jerez de la Frontera, Jerez de la Frontera. Cádiz, Spain
16Department of Hematology, Hospital Universitario La Fe, Valencia, Spain
17Department of Hematology. Hospital Son Llatzer, Palma de Mallorca, Spain
18Department of Hematology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
19Department of Hematology, Hospital Universitario La Paz, Madrid, Spain
20Department of Hematology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
21Department of Hematology / Institut Catalá d‘Oncologia, Hospital Duran i Reynals, L'Hospitalet de LLobregat, Spain

Background: survival of young patients with high IPI DLBCL treated with RCHOP chemotherapy needs to be improved. In this poor risk population the combination of RCHOP with new drugs is an attractive approach, along with performing an early evaluation with PET/CT after 2 to 4 cycles and change induction therapy if a complete response is not achieved. Bortezomib has been combined with RCHOP [1]. We present preliminary data of patients treated in a clinical trial comparing 6 cycles of RCHOP vs 6 cycles of BRCAP, a modified RCHOP regimen changing vincristine by bortezomib at a dose of 1.3 mg/m2 sc days 1, 8, and 15 of every 21 days cycle (NCT01848132).

Methods: patients younger than 70 yrs diagnosed of DLBCL with aIPI 2-3 or aIPI 1 with elevated beta2microglobulin were eligible. The main objective was to evaluate the proportion of patients who survives free of event at 2 years. Central pathology review was performed in all cases, and samples were classified as GC vs non-GC subtypes by IHC (Hans algorithm). PET/CTs were performed at diagnosis, after 2, 4 and 6 cycles (PET2, PET4 , and PET6), and were reviewed by at least 3 experts of a central panel at real time. Response was analyzed following the visual method with the Deauville scale, and for PET2 and PET4 the semiquantitative method was used. Patients with persistent disease after 4 cycles were considered a failure of therapy and were dropped out from the trial.

Results: data from the first 76 patients were analyzed. Diagnosis of DLBCL was confirmed in all except 3 pts, 36 pts were treated in the experimental arm and 37 in the control arm. Median age was 58.2 yo (range 23-70), 37 (50.7%) were males. Characteristics at diagnosis were: non-GC subtype 18/46 (39.1%), C-myc expression 35/43 (81.4%), bcl2 expression 43/49 (87.7%), double expression cmyc/bcl2 30/42 (71%), stage III-IV 64 (87.6%), ≥2 extranodal locations 27 (42.2%), ECOG 2-3 24 (33%), elevated LDH 43 (62.3%), elevated beta 2 microglobulin 47 (75.8%), aIPI 2: 42 (57.5%), aIPI 3: 21 (28.8%). Among 160 cycles of BRCAP chemotherapy, 5 (3.1%) on day 8, and 22 (13.7%) on day 15, were given without bortezomib due to a neutrophil count below 0.5 /L. The most common toxicities are shown in table 1 without significant differences between both arms. Twenty-one (32.8%) out of 64 patients had a positive PET2. Fifteen (26.8%) out of 56 patients who have finished the 4 cycles had a positive PET4 according to central review and were withdrawn of the trial.

Table 1: Episodes of treatment-related adverse events

Control arm:

RCHOP n=166

Experimental arm:

BRCAP n=160

Any grade

Grade 3-4

Any grade

Grade 3-4

Anemia

6

0

22

9 ( 5.6%)

Neutropenia

31

26 (15.6%)

47

37 (23.1%)

Thrombocytopenia

9

4 ( 2.4%)

16

5 ( 3.1%)

Febrile neutropenia

-

6 ( 3.6%)

-

10 ( 6.2%)

Fever

8

1 ( 0.6%)

8

0

Infection

4

1 ( 0.6%)

7

1 ( 0.6%)

Nausea/vomiting

12

0

19

0

Peripheral neuropathy

7

1 ( 0.6%)

7

1 ( 0.6%)

Diarrhea

4

0

8

0

Constipation

7

0

4

0

Hepatotoxicity

6

0

6

0

Conclusions: BRCAP regimen with bortezomib sc d1, 8, and 15 is feasible. Its main toxicity is hematological, and some patients cannot receive some doses of bortezomib due to neutropenia. Grade 3-4 non-hematological toxicity is rare, including peripheral neuropathy, and do not differ from RCHOP toxicity.

1.Ruan J et al, JCO 2011;29:690-7

Disclosures: Sancho: CELLTRION, Inc.: Research Funding . Lopez-Guillermo: Roche, Celgene, Mundipharma, Gilead, Novartis: Membership on an entity’s Board of Directors or advisory committees , Research Funding .

*signifies non-member of ASH