PRIMARY ANALYSIS OF THE RANDOMIZED PHASE II TRIAL OF BORTEZOMIB, LENALIDOMIDE, DEXAMTHASONE WITH/WITHOUT ELOTUZUMAB FOR NEWLY DIAGNOSED, HIGH RISK MULTIPLE MYELOMA (SWOG-1211)
Author(s): ,
Saad Usmani
Affiliations:
Hematologic Oncology & Blood Disorders,Levine Cancer Institute,Charlotte,United States
,
Sikander Ailawadhi
Affiliations:
Hematology Oncoogy,Mayo Clinic,Jacksonville,United States
,
Antje Hoering
Affiliations:
CRAB,Seattle,United States
,
Rachael Sexton
Affiliations:
CRAB,Seattle,United States
,
Brea Lipe
Affiliations:
University of Rochester,Rochester,United States
,
Jefrey Zonder
Affiliations:
Karmanos Cancer Institute,Detroit,United States
,
Madhav Dhodapkar
Affiliations:
Emory University,Atlanta,United States
,
Naalie Callander
Affiliations:
University of Wisconsin,Madison,United States
,
Todd Zimmerman
Affiliations:
Beigene,Chicago,United States
,
Peter Voorhees
Affiliations:
Hematologic Oncology & Blood Disorders,Levine Cancer Institute,Charlotte,United States
,
Brian Durie
Affiliations:
International Myeloma Foundation,Los Angeles,United States
,
S. Vincent Rajkumar
Affiliations:
Mayo Clinic,Rochester,United States
,
Paul Richardson
Affiliations:
Dana Farber Cancer Institute,Boston,United States
Robert Z. Orlowski
Affiliations:
MD Anderson Cancer Center,Houston,United States
EHA Library. Usmani S. 06/12/20; 295021; S201
Prof. Dr. Saad Usmani
Prof. Dr. Saad Usmani
Contributions
Abstract

Abstract: S201

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: New insights in the treatment of newly diagnosed multiple myeloma

Background
The introduction of immunomodulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT) has improved outcomes for patients with multiple myeloma (MM), but those with high risk MM (HRMM) have a poor long-term prognosis. 

Aims
S1211 is a randomized phase II trial (NCT01668719) comparing 8 cycles of lenalidomide, bortezomib and dexamethasone (RVd) induction followed by dose-attenuated RVd maintenance until disease progression with or without elotuzumab. 

Methods
Stem cell collection was allowed, but ASCT was deferred until progression. HRMM was defined by one of the following: gene expression profiling high-risk (GEPhi),  t(14;16), t(14;20), del(17p) or amplification 1q21, primary plasma cell leukemia (pPCL) and elevated serum LDH (> 2X ULN). Median progression-free survival (PFS) was the primary endpoint, using a one-sided stratified log-rank test at a one-sided significance level of 0.1. Secondary endpoints included overall response rate (ORR), adverse events (AE), serious adverse events (SAE) and OS. Response was assessed using the IMWG 2009 criteria.

Results
S1211 enrolled 103 evaluable patients, RVd n=54, RVd-Elo n=49. 75% had ISS II/III, 47% amp1q21, 38% del17p, 12% t(14;16), 9% GEPhi , 7% pPCL, 5% t(14;20) and 4% elevated serum LDH (18.5% > 1 feature). With median follow-up of 53 months (mos.), no difference in median PFS was observed [RVd-Elo=31 mos., RVd= 34 mos.,HR = 0.968 (80% CI=0.697-1.344), p=0.449].  No difference in OS was observed [RVd-Elo = 68 mos, RVd= not reached, HR = 1.279 (80% CI: 0.819, 2.000), p-value = 0.478].  72% pts had >Grade 3 AEs, no differences in the safety profile were observed except >Grade 3 infections (RVd 8%, RVd-Elo 16%), >Grade 3 sensory neuropathy (RVd 8%, RVd-Elo 13%).

Conclusion
In the first randomized HRMM study reported to date, the addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes.  However, the PFS and OS seen in both arms of the study exceeded the original statistical assumptions and support the role for PI/IMiD combination maintenance therapy for this patient population. The S1211 data will serve as an important benchmark for future HRMM clinical trials.

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

Keyword(s): High risk, Monoclonal antibody, Myeloma

Abstract: S201

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: New insights in the treatment of newly diagnosed multiple myeloma

Background
The introduction of immunomodulatory agents, proteasome inhibitors, and autologous stem cell transplantation (ASCT) has improved outcomes for patients with multiple myeloma (MM), but those with high risk MM (HRMM) have a poor long-term prognosis. 

Aims
S1211 is a randomized phase II trial (NCT01668719) comparing 8 cycles of lenalidomide, bortezomib and dexamethasone (RVd) induction followed by dose-attenuated RVd maintenance until disease progression with or without elotuzumab. 

Methods
Stem cell collection was allowed, but ASCT was deferred until progression. HRMM was defined by one of the following: gene expression profiling high-risk (GEPhi),  t(14;16), t(14;20), del(17p) or amplification 1q21, primary plasma cell leukemia (pPCL) and elevated serum LDH (> 2X ULN). Median progression-free survival (PFS) was the primary endpoint, using a one-sided stratified log-rank test at a one-sided significance level of 0.1. Secondary endpoints included overall response rate (ORR), adverse events (AE), serious adverse events (SAE) and OS. Response was assessed using the IMWG 2009 criteria.

Results
S1211 enrolled 103 evaluable patients, RVd n=54, RVd-Elo n=49. 75% had ISS II/III, 47% amp1q21, 38% del17p, 12% t(14;16), 9% GEPhi , 7% pPCL, 5% t(14;20) and 4% elevated serum LDH (18.5% > 1 feature). With median follow-up of 53 months (mos.), no difference in median PFS was observed [RVd-Elo=31 mos., RVd= 34 mos.,HR = 0.968 (80% CI=0.697-1.344), p=0.449].  No difference in OS was observed [RVd-Elo = 68 mos, RVd= not reached, HR = 1.279 (80% CI: 0.819, 2.000), p-value = 0.478].  72% pts had >Grade 3 AEs, no differences in the safety profile were observed except >Grade 3 infections (RVd 8%, RVd-Elo 16%), >Grade 3 sensory neuropathy (RVd 8%, RVd-Elo 13%).

Conclusion
In the first randomized HRMM study reported to date, the addition of elotuzumab to RVd induction and maintenance did not improve patient outcomes.  However, the PFS and OS seen in both arms of the study exceeded the original statistical assumptions and support the role for PI/IMiD combination maintenance therapy for this patient population. The S1211 data will serve as an important benchmark for future HRMM clinical trials.

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

Keyword(s): High risk, Monoclonal antibody, Myeloma

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