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2096 Generation of a Large Observational Pan-European Data Platform for Treatment and Outcome Patterns in Patients with Waldenstrom's Macroglobulinemia

Health Services and Outcomes Research – Malignant Diseases
Program: Oral and Poster Abstracts
Session: 902. Health Services and Outcomes Research – Malignant Diseases: Poster I
Saturday, December 5, 2015, 5:30 PM-7:30 PM
Hall A, Level 2 (Orange County Convention Center)

Christian Buske1, Shalal Sadullah, FRCP, FRCPath2*, Efsthatios Kastritis, MD3*, Giulia Benevolo, MD4*, Ramon Garcia-Sanz, MD5*, Lukasz Bolkun, MD, PhD6*, Xavier Leleu, MD, PhD7, Wolfgang Willenbacher, MD8*, Roman Hajek, MD9, Ellen van der Spek, MD, PhD10*, Mei Cheng, PhD11*, Thorsten Graef, MD, PhD11 and Meletios A. Dimopoulos, MD3

1University of Ulm, Ulm, Germany
2James Pagent University Hospital, Norfolk, United Kingdom
3National and Kapodistrian University of Athens, Athens, Greece
4Division of Hematology, A.O.U. Citta della Salute e della Scienza di Torino, Torino, Italy
5Complejo Asistencial Universitario de Salamanca, Salamanca, Spain
6Medical University Hospital of Bialystok, Bialystok, Poland
7Maladies du Sang, Hôpital Claude Huriez, CHRU Lille, Lille, France
8Innsbruck Medical University, Innsbruck, Austria
9University Hospital of Ostrava, Ostrava, Czech Republic
10Rijnstate Hospital, Arnhem, Netherlands
11Pharmacyclics LLC, an AbbVie Company, Sunnyvale, CA

Introduction

Waldenström’s Macroglobulinemia (WM) is a rare indolent lymphoma with a low incidence of ~3 cases per million per year. There are few randomized trials and no well-established treatment standards in WM. Treatment landscapes for treatment-naïve and relapsed WM are heterogeneous and data on treatment choices and their outcome in patients (pts) outside clinical trials are lacking. The goal of this project was to generate data on epidemiologic/treatment patterns and efficacy outcomes for WM over a prolonged period of time (~10 yr) in a large pan-European effort.

Methods

In this observational chart review, physicians completed a retrospective electronic record for pts who fit the following inclusion criteria: confirmed WM, symptomatic disease at treatment initiation, front line treatment initiated between Jan 2000-Jan 2014, and availability of complete clinical/biologic evaluation at diagnosis/initial therapy. Study endpoints included initial/subsequent lines of treatment, progression-free survival (PFS), and overall survival (OS). The number of pt records per country was prespecified to balance the distribution between European countries.

Results

Of 454 pt records reviewed, cases were from France (n=92), United Kingdom (UK; n=72), Germany (n=66), Spain (n=60), Italy (n=56), Greece (n=25), Netherlands (n=25), Poland (n=21), Austria (n=19), and Czech Republic (n=16). Data were summarized across 5 lines of treatment for 454, 397, 160, 61, and 26 pts, respectively. Median age at initiation of front-line treatment was 65 yr (range, 29-89); 61% were male. The most common reasons for initiating treatment at diagnosis were constitutional symptoms (58%), cytopenias (72%; anemia [69%]), and IgM-related symptoms (57%). Choice of therapy varied with line of treatment; monotherapy fell from 31% in front-line to 20%/21% in 2nd/3rd-line (Table 1). Combination therapy with antibody increased from 40% in front-line to 64%/56% in 2nd/3rd-line. Across all lines, rituximab followed by cyclophosphamide, and to a lesser extent, chlorambucil, fludarabine, vincristine, and bendamustine, were the most common agents, excluding steroids, that were used as monotherapy or in any combination with use varying between countries (Table 1). Median PFS decreased with successive lines of treatment (29 vs 23 vs 16 mo), (Figure 1) and varied by country and choice of agents (Table 1). Median OS was 123 mo, but significantly lower in pts ≥75 yr (75 mo) or with high-risk IPSSWM risk score (91 mo) and similar for pts with low/intermediate risk groups. Considerable country-specific OS differences were noted. Other malignancies were reported in 12% after diagnosis of WM.

Conclusions

The retrospective chart review of WM pts treated in Europe shows that constitutional symptoms and anemia are the most common reasons for initiating therapy. Rituximab was the most commonly used agent across all lines of treatment. Outside clinical trials, monotherapy is widely used even at first relapse with notable differences between countries. This large observational dataset will be an important tool to improve understanding of treatment practice and survival of WM pts in Europe outside of clinical trials, as well as unmet medical needs in the community.     

 

Table 1. Use of Monotherapy or Combination Regimens and Median PFS in Front-, 2nd-, and 3rd-Line Settings Overall and by Country

Country

Number of Cases, n

Monotherapy, %

Combination Therapy With Antibody, %

Combination Therapy Without Antibody, %

Median PFS,

Months (95% CI)

Front
line

2nd
line

3rd
line

Front
line

2nd
line

3rd
line

Front
line

2nd
line

3rd
line

Front
line

2nd
line

3rd
line

Front
line

2nd
line

3rd
line

Overall

454

397

160

31

20

21

40

63

56

28

14

21

29.0
(25-31)

23.0
(20-26)

16.0
(10-18)

France

92

86

43

62

26

16

24

66

70

14

8

14

28.5
(22-32)

30.0
(20-37)

16.0
(9-32)

United Kingdom

72

64

19

18

22

21

19

55

42

63

23

37

31.5
(25-36)

20.0
(11-35)

13.0
(9-33)

Germany

66

52

18

9

8

22

61

81

50

30

8

11

36.5
(29-44)

24.0
(16-29)

8.0
(3-16)

Spain

60

58

21

43

28

38

38

59

52

18

12

5

18.0
(15-25)

16.0
(12-24)

11.0
(9-24)

Italy

56

47

20

20

17

15

57

68

70

23

6

15

30.5
(20-39)

30.0
(18-42)

17.0
(4-21)

Eastern European*

37

30

12

8

13

8

32

40

0

60

47

92

33.0
(26-38)

20.0
(16-26)

20.5
(4-38)

Smaller European**

71

60

27

35

22

26

56

67

63

7

12

11

23.0
(18-29)

16.0
(13-25)

16.0
(7-26)

*Includes Czech Republic and Poland

**Includes Austria, Greece, and Netherlands

Antibodies other than rituximab, <1%

 

 

Figure 1. Kaplan-Meier PFS Estimates by Line of Treatment

 

Disclosures: Buske: CELLTRION, Inc.: Consultancy , Honoraria . Sadullah: Roche: Honoraria , Speakers Bureau ; Novartis: Honoraria , Speakers Bureau ; Takeda: Consultancy , Honoraria , Speakers Bureau ; NAPP: Consultancy , Honoraria , Other: Travel, Accommodations, Expenses ; TEVA: Consultancy ; Boehringer: Other: Travel, Accommodations, Expenses . Kastritis: Janssen: Consultancy , Other: Travel, Accommodations, Expenses . Garcia-Sanz: Janssen: Honoraria , Other: Travel, Accommodations, Expenses ; Takeda: Honoraria , Other: Travel, Accommodations, Expenses ; Novartis: Research Funding . Leleu: Pierre Fabre: Honoraria ; BMS: Honoraria ; Novartis: Honoraria ; TEVA: Honoraria ; Amgen: Honoraria ; Takeda: Honoraria ; Celgene: Honoraria ; Janssen: Honoraria ; LeoPharma: Honoraria ; Chugai: Honoraria . Willenbacher: Celgene: Consultancy , Honoraria , Other: Travel, Accommodations, Expenses , Research Funding ; Roche: Consultancy , Other: Travel, Accommodations, Expenses , Research Funding ; Janssen: Consultancy , Other: Travel, Accommodations, Expenses , Research Funding ; Amgen: Consultancy , Other: Travel, Accommodations, Expenses , Research Funding ; Gilead: Consultancy , Other: Travel, Accommodations, Expenses , Speakers Bureau ; Novartis: Consultancy , Honoraria , Other: Travel, Accommodations, Expenses , Research Funding ; CTI: Consultancy , Other: Travel, Accommodations, Expenses . Hajek: Amgen: Honoraria ; Celgene: Consultancy ; Janssen: Consultancy . Cheng: Pharmacyclics LLC, an AbbVie Company: Employment . Graef: Pharmacyclics LLC, an AbbVie Company: Employment , Membership on an entity’s Board of Directors or advisory committees ; AbbVie: Equity Ownership . Dimopoulos: Janssen: Consultancy , Honoraria ; Celgene: Consultancy , Honoraria ; Onyx: Consultancy , Honoraria ; Amgen: Consultancy , Honoraria ; Novartis: Consultancy , Honoraria ; Genesis Pharma: Research Funding .

*signifies non-member of ASH