TWICE-WEEKLY IXAZOMIB PLUS LENALIDOMIDE-DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: LONG-TERM FOLLOW-UP DATA FOR PATIENTS WHO DID NOT UNDERGO STEM CELL TRANSPLANTATION (SCT)
Author(s): ,
Paul Richardson
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Craig Hofmeister
Affiliations:
Ohio State University,Columbus,United States
,
Cara Rosenbaum
Affiliations:
University of Chicago Medicine,Chicago,United States
,
Myo Htut
Affiliations:
Hematology and Stem Cell Transplant, City of Hope National Medical Center,Duarte,United States
,
David Vesole
Affiliations:
John Theurer Cancer Center, Hackensack University Medical Center,Hackensack,United States
,
Jesus Berdeja
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Michaela Liedtke
Affiliations:
Stanford Comprehensive Cancer Center,Stanford,United States
,
Ajai Chari
Affiliations:
Mount Sinai School of Medicine Ruttenberg Treatment Center,New York,United States
,
Stephen Smith
Affiliations:
Fred Hutchinson Cancer Research Center, University of Washington,Seattle,United States
,
Daniel Lebovic
Affiliations:
University of Michigan Cancer Center,Ann Arbor,United States
,
Noopur Raje
Affiliations:
Massachusetts General Hospital,Boston,United States
,
Eileen Liao
Affiliations:
Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Xiaoquan Zhang
Affiliations:
Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
,
Deborah Berg
Affiliations:
Millennium Pharmaceuticals Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited,Cambridge,United States
Rachid Baz
Affiliations:
H. Lee Moffitt Cancer Center & Research Institute,Tampa,United States
EHA Learning Center. Richardson P. Jun 25, 2017; 182067
Dr. Paul Richardson
Dr. Paul Richardson

Access to EHA Members only content is an EHA membership benefit. Click here to join EHA or renew your membership here.


Abstract
Discussion Forum (0)
Rate & Comment (0)

Abstract: S780

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30

Location: Hall D

Background
Addition of a proteasome inhibitor to a doublet backbone therapy has been shown to improve efficacy in newly diagnosed multiple myeloma (NDMM) patients (San Miguel et al, N Engl J Med 2008, Durie et al, Lancet 2017). Data from two phase 1/2 studies indicate that the combination of ixazomib plus lenalidomide-dexamethasone (IRd) is feasible and active in patients with NDMM, with weekly and twice-weekly ixazomib dosing having been investigated (Kumar et al, Lancet Oncol 2014; Richardson et al, Blood 2013).

Aims
This phase 1/2 study (NCT01383928) evaluated twice-weekly ixazomib plus Rd as induction therapy, followed by maintenance therapy with single-agent ixazomib. We report long-term efficacy and safety data in patients who did not withdraw from the study in order to receive SCT. 

Methods
Patients with NDMM (SCT-eligible or SCT-ineligible) received twice-weekly oral ixazomib (3.0 or 3.7 mg on days 1, 4, 8, and 11) plus lenalidomide (25 mg on days 1–14) and dexamethasone (20 mg [10 mg in cycles 9–16] on days 1, 2, 4, 5, 8, 9, 11, and 12) for up to sixteen 21-day cycles, followed by maintenance therapy with single-agent twice-weekly ixazomib. Patients received therapy until disease progression or toxicity. Those who proceeded to SCT did not receive further ixazomib therapy. Response/progression was assessed per IMWG criteria after cycles 1, 2, 3, 4, and then every 2 cycles during induction and maintenance.

Results
Of the 64 enrolled patients, 40 continued on study treatment without early withdrawal for SCT; long-term follow-up of these 40 patients is reported here. The median age of patients was 66 years (range 34–82), and 45%/38%/18% of patients had ISS disease stage I/II/III. At a median follow-up of 47.0 months, the overall response rate (ORR; ≥partial response [PR]) in the response-evaluable population was 95%, the complete plus very good partial response (CR+VGPR) rate was 68%, and the CR rate was 32%. Median time to first response was approximately 1 cycle (0.72 months). Median time to a best response of ≥CR was 4.2 months. Patients received a median (range) of 14 (1–75) treatment cycles. Median progression-free survival (PFS) for patients not proceeding to SCT was 24.9 months. Median overall survival (OS) was not estimable; the 2-year Kaplan-Meier estimate for OS was 92%. A total of 78% of patients had grade ≥3 treatment-related adverse events (AEs); the most common treatment-related grade ≥3 AEs and serious AEs are shown in the Table. 

After completing induction therapy with IRd, 18 patients went on to receive maintenance with single-agent ixazomib on a twice-weekly dosing schedule. Patients who went on to maintenance received a median (range) of 31.5 (17–75) treatment cycles. Among the patients who received maintenance treatment, the ORR (≥PR) was 94%, the CR+VGPR rate was 89%, and the CR rate was 44%. Two (11%) patients improved their responses during maintenance (1 VGPR to stringent CR, and 1 VGPR to near-CR). Five (28%) patients who received maintenance therapy had an onset of a grade ≥3 treatment-related AE in cycle 17 or beyond. Rash (aggregate term) was infrequent with single-agent ixazomib during maintenance (1 patient, 6%).

Conclusion
In patients with NDMM, twice-weekly ixazomib plus Rd resulted in exceptional response rates in patients who did not receive a SCT and who received maintenance therapy. The responses were deep and durable, with long PFS and a high 2-year OS estimate. The majority of AEs had an onset during induction, and the incidence of AEs during maintenance was infrequent. 

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

Keyword(s): Survival, Proteasome inhibitor, Oral, Myeloma

Code of conduct/disclaimer available in General Terms & Conditions
Anonymous User Privacy Preferences

Strictly Necessary Cookies (Always Active)

MULTILEARNING platforms and tools hereinafter referred as “MLG SOFTWARE” are provided to you as pure educational platforms/services requiring cookies to operate. In the case of the MLG SOFTWARE, cookies are essential for the Platform to function properly for the provision of education. If these cookies are disabled, a large subset of the functionality provided by the Platform will either be unavailable or cease to work as expected. The MLG SOFTWARE do not capture non-essential activities such as menu items and listings you click on or pages viewed.


Performance Cookies

Performance cookies are used to analyse how visitors use a website in order to provide a better user experience.



Google Analytics is used for user behavior tracking/reporting. Google Analytics works in parallel and independently from MLG’s features. Google Analytics relies on cookies and these cookies can be used by Google to track users across different platforms/services.


Save Settings