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198 Allogeneic Stem Cell Transplantation for Relapsed / Refractory (R/R) Follicular Lymphoma (FL). a Joint Study Between the European Society for Blood and Marrow Transplantation (EBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR)Clinically Relevant Abstract

Clinical Allogeneic Transplantation: Results
Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results: Matched Related, Unrelated, and Alternative Donor Allograft Outcomes for Myeloid and Lymphoid Malignancies
Sunday, December 6, 2015: 8:45 AM
W304, Level 3 (Orange County Convention Center)

Anna Sureda, MD, PhD1*, Mei-Jie Zhang, PhD2,3*, Peter Dreger, MD4,5, Jeanette Carreras, MPH6*, Timothy S. Fenske, MD7, Herve Finel8*, Harry C. Schouten9, Silvia Montoto, MD10, Stephen Robinson11*, Sonali M. Smith, MD12, Ariane Boumendil, PhD13*, Mehdi Hamadani, MD14 and Marcelo C. Pasquini, MD15

1Hematology Department, Institut Català d'Oncologia - Hospital Duran i Reynals, Barcelona, Spain
2Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, WI
3CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI
4EBMT Lymphoma Working Party, Paris, France
5Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany
6Center for International Blood & Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
7Division of Hematology & Oncology, Medical College of Wisconsin, Milwaukee, WI
8Hopital Saint Antoine, EBMT Paris Study Office, Paris, France
9Department of Internal Medicine - Hematology, Maastricht University Medical Center, Maastricht, Netherlands
10St. Bartholomew`s and The Royal London NHS Trust, London, United Kingdom
11Bristol Oncology Centre, Bristol, United Kingdom
12University of Chicago, Chicago, IL
13EBMT Paris study office / CEREST-TC, Paris, France
14Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
15Medicine, Medical College of Wisconsin, Milwaukee, WI

Introduction. The definitive management of R/R FL remains controversial due to various treatment options, including chemoimmunotherapy, pathway inhibitors, and autologous stem cell transplantation (auto-SCT). These options can provide prolonged progression-free survival (PFS). Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the sole curative therapy for FL. Herein, we report the long term outcome of the largest sample of allo-SCT for FL ever studied as well as the identification of patient and disease related factors that were significantly associated with treatment failure. 

Patients. Eligible were adult patients with R/R FL having received a first allo-SCT between 2001 and 2011 from an HLA identical sibling donor (SIB) or a well-matched unrelated donor (MUD). Patients with transformed lymphoma were excluded from the analysis as well as planned second transplants, allotransplants from cord blood, mismatched donors, and transplants with ex vivo T cell depletion (TCD).

Results. 1567 patients met the eligibility criteria (EBMT, n = 1115; CIBMTR, n = 452). Demographics separated by data source demonstrate some differences in transplant practices between the two regions. The CIBMTR cohort had a higher proportion of MUD recipients [167 (37%) vs 252 (23%), p < 0.001], more cases with chemoresistant disease [113 (25%) vs 145 (13%), p < 0.001], less patients having received a prior auto-SCT [53  (12%) vs 403 (36%), p < 0.001], more use of myeloablative conditioning (MAC) (145 (32%) vs 220 (20%), p < 0.001) and less use of alemtuzumab in-vivo TCD [29 (6%) vs 201 (18%), p < 0.001] compared to the EBMT cohort. Median (range) follow up of survivors in months was 58 (3 – 130) and 54 (3 – 160) for CIBMTR and EBMT patients, respectively. Cumulative incidence of acute (grades II-IV) graft versus host disease (GVHD) was 20% (18-22) at 100 days and of chronic GVHD 45% (42-48) and 55% (52-58) at 1 and 3 years, respectively for the whole series; this risk was slightly but significantly reduced in the EBMT cohort. All major outcomes [non-relapse mortality (NRM), relapse/progression (R/P), overall survival (OS) and PFS] were comparable between the CIBMTR and EBMT samples (Table 1).

Outcomes

CIBMTR

EBMT

p-value

NRM

N

@ 1 y

@ 3 y

@ 5 y

450

21 (17-25)

27 (23-32)

31 (26-35)

1088

19 (16-21)

24 (21-27)

28 (25-31)

0.363

0.172

0.114

R/P

N

@ 1 y

@ 3 y

@ 5 y

450

13 (10-16)

16 (13-20)

17 (13-21)

1088

13 (11-15)

18 (15-20)

21 (18-23)

0.874

0.480

0.114

PFS

N

@ 1 y

@ 3 y

@ 5 y

450

66 (62-71)

56 (52-61)

52 (47-57)

1088

69 (66-72)

58 (55-61)

52 (48-55)

0.375

0.495

0.792

OS

N

@ 1 y

@3 y

@ 5 y

452

74 (70-78)

65 (60-69)

61 (56-65)

1104

75 (72-78)

67 (64-70)

62 (59-65)

0.589

0.455

0.695

Multivariate analysis indicated that NRM was significantly affected by age (HR 1.04, 1.02-1.05, p < 0.0001), chemoresistant disease (HR 1.61, 1.28-2.03, p < 0.0001), >= 5 lines of prior CT (vs 3-4) (HR 1.62, 1.20-2.19, p=0.0015) and Karnofsky performance score (KPS) < 80 (HR 2.05 (1.32-3.19, p=0.0014); R/P was significantly affected by grade 3 histology (HR 1.63, 1.16-2.26, p=0.0049) and chemoresistant disease (HR 1.46 (1.07-1.97), p=0.0156); PFS by grade 3 histology (HR 1.42, 1.15-1.76, p=0.0012), chemoresistant disease (HR 1.54, 1.28-1.86, p<0.0001), >= 5 lines of prior CT (vs 3-4) (HR 1.45, 1.13-1.85, p=0.0031), MAC (HR 1.36, 1.14-1.63, p=0.0008) and KPS < 80 (HR 1.78, 1.23-2.58, p =0.0022) and OS by age (HR 1.03, 1.02-1.04, p<0.0001), grade 3 histology (HR 1.44, 1.13-1.83, p=0.0031), chemoresistant disease (HR 1.59, 1.30-1.95, p<0.0001), >= 5 lines of prior CT (vs 3-4) (HR 1.63, 1.25-2.13, p=0.0003), MAC (HR 1.42, 1.16-1.73, p=0.0006) and KPS < 80 (HR 2.23, 1.52-3.25, p<0.0001). Of note, outcomes between SIB and MUD were similar (3y OS 68% and 62%, P=0.114). Moreover a significant impact of TCD and prior auto-SCT could not be detected.

Conclusions. This study represents an example of a fruitful cooperation between two important scientific transplant societies, the EBMT and CIBMTR. Despite significant differences in patient characteristics and transplant strategies between these 2 hitherto largest samples on allo-SCT for R/R FL, long-term disease control was similar and remarkably good with an R/P risk of about only 20% at 5 years. Chemoresistant disease, higher age, multiple pretreatment lines, poor KPS, and MAC all were predictors for an adverse outcome, whereas MUD, TCD, and prior auto-SCT had no impact on any survival endpoint.

Disclosures: Sureda: Takeda: Consultancy , Honoraria , Speakers Bureau . Fenske: Celgene: Honoraria ; Millennium/Takeda: Research Funding ; Pharmacyclics: Honoraria ; Seattle Genetics: Honoraria . Smith: Celgene: Consultancy ; Pharmacyclics: Consultancy .

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