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A PHASE 3 RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF ISATUXIMAB, POMALIDOMIDE, AND LOW-DOSE DEXAMETHASONE VS POMALIDOMIDE AND LOW-DOSE DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM)

S824

Attal, M.1; Richardson, P. G.2; Rajkumar, S. V.3; San-Miguel, J.4; Beksac, M.5; Spicka, I.6; Leleu, X.7; Schjesvold, F.8, 9; Moreau, P.10; Dimopoulos, M. A.11; Huang, J.S.-Y.12; Minarik, J.13; Cavo, M.14; Prince, H. M.15; Mace, S.16; Corzo, K. P.17; Campana, F.17; Le-Guennec, S.17; Dubin, F.17; Anderson, K. C.2

doi: 10.1097/01.HS9.0000561576.58696.ae
Simultaneous Sessions II: Immunotherapy in relapsed/refractory multiple myeloma
Free

1Institut Universitaire du Cancer Toulouse Oncopole, Toulouse, France

2Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

3Mayo Clinic, Rochester, MN, United States

4Clínica Universidad de Navarra, Navarra, Spain

5Ankara University, Ankara, Turkey

6Charles University in Prague, Prague, Czech Republic

7Hopital Claude Huriez, CHRU Lille, Lille, France

8Oslo Myeloma Center, Oslo University Hospital

9KG Jebsen Center for B cell malignancies, University of Oslo, Oslo, Norway

10CHU Nantes, Nantes, France

11National and Kapodistrian University of Athens, Athens, Greece

12National Taiwan University Hospital, Taiwan, Taiwan, Republic of China

13University Hospital Olomouc, Olomouc, Czech Republic

14Univeristy of Bologna, Bologna, Italy

15Epworth Healthcare and Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Australia

16Sanofi R & D, Vitry-Alfortville, France

17Sanofi-Genzyme Oncology, Cambridge, MA, United States

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Background:

Despite recent advances, multiple myeloma (MM) remains incurable, and new treatment options are needed to continue to improve patient outcomes. This is the first randomized, phase 3 trial of an anti-CD38 antibody in combination with pomalidomide (P) and dexamethasone (d) in RRMM.

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Aims:

The primary objective of this phase 3 trial (NCT02990338) was to demonstrate progression free survival (PFS) improvement of isatuximab (Isa), a novel anti-CD38 monoclonal antibody targeting a specific epitope, combined with Pd versus (vs) Pd in RRMM.

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Methods:

Patients (pts) with RRMM who received ≥2 prior lines, including lenalidomide (len) and a proteasome inhibitor (PI), refractory to last therapy were enrolled. IsaPd arm received Isa 10 mg/kg IV weekly for first 4 weeks (wks), then every 2 wks. Both arms received approved schedules of pom and dex (4 mg PO days 1-21; 40 mg [20 mg if >75 yrs] PO or IV weekly) every 28 days until progression or unacceptable toxicity.

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Results:

307 pts (154 IsaPd, 153 Pd) were randomized and analyzed (ITT). Patient characteristics were well balanced across arms. Median age: 67 (36-86) yrs; median prior lines of therapy: 3 (2-11); estimated GFR: <60 ml/min in 33.9% pts; 92.5% refractory to len, 75.9% to PI; and 19.5% pts had high-risk cytogenetics. At median follow-up of 11.6 months (mos), median PFS was 11.5 mos IsaPd vs 6.5 mos Pd; HR 0.596 (95% CI 0.44-0.81), P = 0.001. PFS benefit was consistent across all major subgroups. ORR (≥PR) was 60.4% IsaPd vs 35.3% Pd, P < 0.0001. VGPR rate or better was 31.8% IsaPd vs 8.5% Pd, and MRD negativity (NGS, 10−5) was seen in 5.2% IsaPd pts vs 0% Pd. At analysis date, overall survival (OS) was immature (99 events) but a trend to OS improvement in IsaPd (vs Pd) was observed (HR 0.687; 95% CI 0.461-1.023). Median treatment duration was 41 wks IsaPd vs 24 wks Pd; median Isa infusion (inf.) duration was 3.3 h at 1st inf. and 2.8 h at subsequent inf. Grade ≥3 AEs were observed in 86.8% IsaPd vs 70.5% Pd; 7.2% IsaPd and 12.8% Pd pts discontinued due to AEs; 7.9% IsaPd and 9.4% Pd pts died due to AEs. Inf. reactions were reported in 38.2% (2.6% grade 3-4) IsaPd. Grade ≥3 infections were seen in 42.8% IsaPd and 30.2% Pd, grade ≥3 neutropenia in 84.9% (febrile 11.8%) IsaPd and 70.1% (febrile 2.0%) Pd.

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Summary/Conclusion:

Isatuximab in combination with pomalidomide and dexamethasone significantly improved PFS and ORR vs pomalidomide and dexamethasone, with a manageable safety profile. Isatuximab in combination with pomalidomide and dexamethasone is an important new treatment option for the management of RRMM.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.