Combination therapy demonstrated a sustained reduction in risk of progression/death of 29% and relative improvement of 50% in progression-free survival rate of ELd (21%) compared to Ld alone (14%)
The extended follow-up data is the longest of an Immuno-Oncology agent in relapsed/refractory multiple myeloma
The data showed a safety profile consistent with prior findings
PRINCETON, NJ, USA I June 24, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) presented four-year follow-up data from the Phase 3 ELOQUENT-2 study in which Empliciti (elotuzumab) plus lenalidomide/dexamethasone (ELd) continued to demonstrate efficacy in patients with relapsed/refractory multiple myeloma (RRMM), compared to patients treated with lenalidomide/dexamethasone (Ld) alone. The data also showed a safety profile consistent with prior findings. The results were presented in an oral session today during the 22nd Congress of the European Hematology Association in Madrid, Spain and offer the longest follow-up efficacy and safety data of an Immuno-Oncology agent.
ELd therapy maintained a reduction in the risk of disease progression or death of 29% (HR 0.71; 95% CI: 0.59 to 0.86). At four-years, ELd therapy continued to demonstrate a clinically meaningful and sustained relative improvement of 50% in progression-free survival (PFS) rate, 21% (95% CI: 16.6, 22.3), compared to Ld therapy, 14% (95% CI: 12.1,17.3). PFS benefits seen in patients receiving ELd therapy were consistent across certain patient subsets and sustained through two-year, three-year and four-year follow-up. Patients with high risk* (n=60 ELd, n=66 Ld) showed relative risk reduction of 36% (HR=0.64; 95% CI :0.43 to 0.97) and more than doubling of median PFS (15.2 ELd vs 7.4 Ld) with ELd in comparison to Ld.
Patients receiving ELd therapy demonstrated an overall response rate (ORR) of 79% (253/321 patients, 95% CI: 73.9 to 83.2), compared to 66% (214/325 patients, 95% CI: 60.4 to 71.0) among patients receiving Ld therapy alone. While OS was not pre-specified for the four-year follow-up, Empliciti in combination with Ld data also demonstrated a median overall survival (OS) benefit of 48 months (95% CI: 40.3 to 54.4) in favor of ELd versus a median OS of 40 months for Ld (95% CI: 33.3 to 45.4), a difference of 22% (HR 0.78; 95% CI: 0.63 to 0.96). Early separation of OS Kaplan Meier survival curves was maintained over time in favor of ELd versus Ld.
“These extended four-year follow-up data demonstrated that adding Empliciti to Ld yielded clinically relevant improvements and reductions in the risk of disease progression or death for patients with relapsed/refractory multiple myeloma, compared to Ld alone,” Meletios A. Dimopoulos, M.D., ELOQUENT-2 investigator and professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine. “This data at four-year follow-up is particularly notable as it suggests the ability of this Immuno-Oncology agent to build a sustainable immune response in some patients with advanced multiple myeloma.”
The rates of adverse events (AE) were similar between patients receiving ELd or Ld therapy and consistent with those reported at two- and three-year follow-up. The most common AEs (all grades) in ELd and Ld, respectively, were diarrhea (49%, 38%), fatigue (48%, 41%), anemia (43%, 38%), pyrexia (40%, 25%), constipation (36%, 28%), neutropenia (35%, 43%), cough (34%, 19%), back pain (31%, 29%), and muscle spasm (31%, 26%).
“The long-term efficacy data for Empliciti in patients with advanced multiple myeloma shows the combination of this Immuno-Oncology agent with standard lenalidomide/dexamethasone treatment can improve patient outcomes,” said Jonathan Leith, Ph.D., hematology development lead, Bristol-Myers Squibb. “These findings illustrate Bristol-Myers Squibb’s commitment to exploring how Immuno-Oncology agents might best help appropriate patients.”
About ELOQUENT-2
The ELOQUENT-2 trial randomized 646 patients with RRMM who had one to three prior therapies to receive either ELd (321 patients) or Ld (325 patients) in 28-day cycles until their disease progressed, the occurrence of unacceptable toxicity or they withdrew consent. In the ELd arm, patients were administered 10 mg/kg by IV of elotuzumab for weeks one and two of the 28-day cycle and then every other week, along with 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth. In the Ld arm, patients were given 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth.
The occurrence of treatment-related Grade 3–4 AEs in 5% or more of patients were generally comparable between the ELd and Ld groups: vascular diseases (10% vs. 8%; mostly venous-related), second primary malignancies (9% vs. 6%), and cardiac disorders (5% vs. 8%). ELd therapy did have a slightly higher incidence of infection compared to Ld (33% vs. 26%). ELd treatment also had higher overall rates than Ld of any grade infection (84% vs. 75%) and second primary malignancies (17% vs. 11%). However, exposure to ELd was longer than to Ld, with a median treatment cycle of 19 months (9 to 42) compared to 14 months (6 to 25), respectively. While disease progression and infection were major causes of deaths in both groups, fewer were reported with ELd (165) than with Ld (186) treatment.
On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received one to three prior therapies. On May 11, 2016, the European Commission approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Empliciti
Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.
Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.
U.S. FDA-APPROVED INDICATION FOR EMPLICITI ™
EMPLICITI™ (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
SOURCE: Bristol-Myers Squibb
Post Views: 57
Combination therapy demonstrated a sustained reduction in risk of progression/death of 29% and relative improvement of 50% in progression-free survival rate of ELd (21%) compared to Ld alone (14%)
The extended follow-up data is the longest of an Immuno-Oncology agent in relapsed/refractory multiple myeloma
The data showed a safety profile consistent with prior findings
PRINCETON, NJ, USA I June 24, 2017 I Bristol-Myers Squibb Company (NYSE:BMY) presented four-year follow-up data from the Phase 3 ELOQUENT-2 study in which Empliciti (elotuzumab) plus lenalidomide/dexamethasone (ELd) continued to demonstrate efficacy in patients with relapsed/refractory multiple myeloma (RRMM), compared to patients treated with lenalidomide/dexamethasone (Ld) alone. The data also showed a safety profile consistent with prior findings. The results were presented in an oral session today during the 22nd Congress of the European Hematology Association in Madrid, Spain and offer the longest follow-up efficacy and safety data of an Immuno-Oncology agent.
ELd therapy maintained a reduction in the risk of disease progression or death of 29% (HR 0.71; 95% CI: 0.59 to 0.86). At four-years, ELd therapy continued to demonstrate a clinically meaningful and sustained relative improvement of 50% in progression-free survival (PFS) rate, 21% (95% CI: 16.6, 22.3), compared to Ld therapy, 14% (95% CI: 12.1,17.3). PFS benefits seen in patients receiving ELd therapy were consistent across certain patient subsets and sustained through two-year, three-year and four-year follow-up. Patients with high risk* (n=60 ELd, n=66 Ld) showed relative risk reduction of 36% (HR=0.64; 95% CI :0.43 to 0.97) and more than doubling of median PFS (15.2 ELd vs 7.4 Ld) with ELd in comparison to Ld.
Patients receiving ELd therapy demonstrated an overall response rate (ORR) of 79% (253/321 patients, 95% CI: 73.9 to 83.2), compared to 66% (214/325 patients, 95% CI: 60.4 to 71.0) among patients receiving Ld therapy alone. While OS was not pre-specified for the four-year follow-up, Empliciti in combination with Ld data also demonstrated a median overall survival (OS) benefit of 48 months (95% CI: 40.3 to 54.4) in favor of ELd versus a median OS of 40 months for Ld (95% CI: 33.3 to 45.4), a difference of 22% (HR 0.78; 95% CI: 0.63 to 0.96). Early separation of OS Kaplan Meier survival curves was maintained over time in favor of ELd versus Ld.
“These extended four-year follow-up data demonstrated that adding Empliciti to Ld yielded clinically relevant improvements and reductions in the risk of disease progression or death for patients with relapsed/refractory multiple myeloma, compared to Ld alone,” Meletios A. Dimopoulos, M.D., ELOQUENT-2 investigator and professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine. “This data at four-year follow-up is particularly notable as it suggests the ability of this Immuno-Oncology agent to build a sustainable immune response in some patients with advanced multiple myeloma.”
The rates of adverse events (AE) were similar between patients receiving ELd or Ld therapy and consistent with those reported at two- and three-year follow-up. The most common AEs (all grades) in ELd and Ld, respectively, were diarrhea (49%, 38%), fatigue (48%, 41%), anemia (43%, 38%), pyrexia (40%, 25%), constipation (36%, 28%), neutropenia (35%, 43%), cough (34%, 19%), back pain (31%, 29%), and muscle spasm (31%, 26%).
“The long-term efficacy data for Empliciti in patients with advanced multiple myeloma shows the combination of this Immuno-Oncology agent with standard lenalidomide/dexamethasone treatment can improve patient outcomes,” said Jonathan Leith, Ph.D., hematology development lead, Bristol-Myers Squibb. “These findings illustrate Bristol-Myers Squibb’s commitment to exploring how Immuno-Oncology agents might best help appropriate patients.”
About ELOQUENT-2
The ELOQUENT-2 trial randomized 646 patients with RRMM who had one to three prior therapies to receive either ELd (321 patients) or Ld (325 patients) in 28-day cycles until their disease progressed, the occurrence of unacceptable toxicity or they withdrew consent. In the ELd arm, patients were administered 10 mg/kg by IV of elotuzumab for weeks one and two of the 28-day cycle and then every other week, along with 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth. In the Ld arm, patients were given 25 mg of lenalidomide by mouth for days 1-21 of the cycle and the weekly equivalent of 40 mg of dexamethasone by mouth.
The occurrence of treatment-related Grade 3–4 AEs in 5% or more of patients were generally comparable between the ELd and Ld groups: vascular diseases (10% vs. 8%; mostly venous-related), second primary malignancies (9% vs. 6%), and cardiac disorders (5% vs. 8%). ELd therapy did have a slightly higher incidence of infection compared to Ld (33% vs. 26%). ELd treatment also had higher overall rates than Ld of any grade infection (84% vs. 75%) and second primary malignancies (17% vs. 11%). However, exposure to ELd was longer than to Ld, with a median treatment cycle of 19 months (9 to 42) compared to 14 months (6 to 25), respectively. While disease progression and infection were major causes of deaths in both groups, fewer were reported with ELd (165) than with Ld (186) treatment.
On November 30, 2015, the U.S. Food and Drug Administration (FDA) approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received one to three prior therapies. On May 11, 2016, the European Commission approved Empliciti in combination with lenalidomide and dexamethasone in patients with multiple myeloma who have received at least one prior therapy.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ individual tumor biology can be used as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.
About Empliciti
Empliciti is an immunostimulatory antibody that specifically targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 also is expressed on Natural Killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage.
Empliciti has a dual mechanism-of-action. It directly activates the immune system through Natural Killer cells via the SLAMF7 pathway. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via antibody-dependent cellular toxicity.
Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for commercial activities.
U.S. FDA-APPROVED INDICATION FOR EMPLICITI ™
EMPLICITI™ (elotuzumab) is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received one to three prior therapies.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.
SOURCE: Bristol-Myers Squibb
Post Views: 57
