PATIENT-REPORTED OUTCOMES FROM THE INNOVATE™ STUDY: RESULTS OF IBRUTINIB-RITUXIMAB IN WALDENSTRÖM MACROGLOBULINEMIA (WM)
Author(s): ,
Alessandra Tedeschi
Affiliations:
ASST Grande Ospedale Metropolitano Niguarda,Milano,Italy
,
Meletios A. Dimopoulos
Affiliations:
National and Kapodistrian University of Athens School of Medicine,Athens,Greece
,
Judith Trotman
Affiliations:
Concord Hospital, University of Sydney,Concord,Australia
,
Ramón García-Sanz
Affiliations:
Hospital Universitario de Salamanca,Salamanca,Spain
,
David Macdonald
Affiliations:
The Ottawa Hospital, University of Ottawa,Ottawa,Canada
,
Beatrice Mahe
Affiliations:
Centre Hospitalier Universitaire de Nantes,Nantes,France
,
Charles Herbaux
Affiliations:
Centre Hospitalier Régional Universitaire de Lille, Institute of Hematolog-Tranfusion,Lille,France
,
Leonard T. Heffner
Affiliations:
Winship Cancer Institute of Emory University,Atlanta,United States
,
Constantine S. Tam
Affiliations:
Peter MacCallum Cancer Centre & St. Vincent's Hospital and the University of Melbourne,Melbourne,Australia
,
Marzia Varettoni
Affiliations:
Division of Hematology, Fondazione IRCCS Policlinico San Matteo,Pavia,Italy
,
M. Lia Palomba
Affiliations:
Memorial Sloan Kettering Cancer Center,New York City,United States
,
Jeffrey V. Matous
Affiliations:
Colorado Blood Cancer Institute,Denver,United States
,
Chaim Shustik
Affiliations:
Royal Victoria Hospital at McGill University Health Centre,Montreal,Canada
,
Efstathios Kastritis
Affiliations:
National and Kapodistrian University of Athens School of Medicine,Athens,Greece
,
Steven P. Treon
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Jianling Li
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale,United States
,
Erik G. Poulsen
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale,United States
,
Bernhard Hauns
Affiliations:
Pharmacyclics LLC, an AbbVie Company,Sunnyvale,United States
,
Christian Buske
Affiliations:
Comprehensive Cancer Center Ulm, Institute of Experimental Cancer Research, Department of Internal Medicine III, University Hospital of Ulm,Ulm,Germany
Veronique Leblond
Affiliations:
Département d’ Hématologie Hôpital Pitié-Salpêtrière APHP, Sorbonne Université Paris,Paris,France
EHA Library. Tedeschi A. Jun 14, 2019; 266413; PF614
Alessandra Tedeschi
Alessandra Tedeschi
Contributions
Abstract

Abstract: PF614

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Anemia and fatigue can impair quality of life in patients (pts) with WM and are common reasons for the initiation of WM treatment. Ibrutinib, a first-in-class, once-daily inhibitor of BTK, is approved in the EU for the treatment of WM after ≥1 prior therapy or as first-line therapy in pts unsuitable for chemoimmunotherapy. In the US, ibrutinib is approved for the treatment of WM as single agent or in combination with rituximab. Single-agent ibrutinib has been shown to induce clinically meaningful improvements in pt-reported outcomes (PROs) in pts with rituximab-refractory WM (Trotman, EHA 2017). In the primary analysis of the phase 3 iNNOVATE study, ibrutinib-rituximab produced higher rates of sustained hemoglobin improvement and meaningful improvements in PROs when compared with placebo-rituximab (Dimopoulos NEJM 2018). Here, we report a more detailed analysis of PROs from iNNOVATE.

Aims
To evaluate data on PROs from the iNNOVATE study to assess pts’ perspectives of the therapeutic benefit of ibrutinib-rituximab.

Methods
Pts with symptomatic WM requiring therapy were randomized to daily 420 mg oral ibrutinib or placebo until progressive disease or unacceptable toxicity. Both arms also received rituximab (375 mg/m2/week IV at weeks 1–4 and 17–20). PRO measures evaluated in this analysis included FACIT-Fatigue (FACIT-F), FACT-An total score (TS) and anemia subscale score (AS), and EQ-5D-5L (© EuroQol Research Foundation. EQ-5D™ is a trade mark of the EuroQol Research Foundation) visual analog scale (VAS) and utility score (US).

Results
For the 150 randomized pts (75/arm), the most common reasons for initiating treatment were fatigue (61%), constitutional symptoms (32%), and anemia (32%). Baseline PRO scores were comparable in both arms. Overall (median follow-up, 26.5 months), more pts showed clinically meaningful improvement in FACIT-F, TS, and AS with ibrutinib-rituximab than placebo-rituximab (Table & Figure). The median time to PRO improvement was short (1-2 months) and comparable in both arms. A correlation analysis conducted at week 25 showed that changes in hemoglobin levels correlated with FACIT-F (Pearson coefficient r=0.28), TS (r=0.29), and AS (r=0.26) in the ibrutinib-rituximab arm; no meaningful correlations were observed on placebo-rituximab. Changes in IgM levels correlated with FACIT-F (r=-0.32), TS (r=-0.33), AS (r=-0.35), and EQ-VAS (r=-0.26) for ibrutinib-rituximab and with FACIT-F (r=0.29) and TS (r=0.35) for placebo-rituximab.

 

Table. Patients with clinically meaningful improvement in PROs

Patients, %

Ibrutinib-Rituximab (n=75)

Placebo-Rituximab (n=75)

P

FACIT-Fa

69

57

0.13

FACT-An TSb

73

59

0.06

FACT-An ASc

64

48

0.05

EQ-VASb

49

55

0.54

EQ-USd

43

36

0.37

aIncrease of ≥3 points; bIncrease of ≥7 points; cIncrease of ≥6 points; dIncrease of ≥0.08 points.

Conclusion
These results show that in pts with WM, clinical response and improvements in anemia with ibrutinib-rituximab are consistent with more pts showing clinically meaningful improvement in PROs compared with placebo-rituximab. Changes in IgM correlate with improvements in PROs in pts treated with ibrutinib-rituximab.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Ibrutinib, Quality of life, Waldenstrom's macroglobulinemia

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