Combination Therapy With DARZALEX® (daratumumab) Provides Clinical Benefit In Relapsed Myeloma Interview with:

Dr. Ajai Chari, MD Associate Professor of Medicine Multiple Myeloma Program and Associate Director of Clinical Research Mount Sinai Hospital, New York

Dr. Ajai Chari

Dr. Ajai Chari, MD
Associate Professor of Medicine
Multiple Myeloma Program and
Associate Director of Clinical Research
Mount Sinai Hospital, New York What is the background for this study? Would you briefly explain multiple myeloma (How common is it, whom does it chiefly affect, etc.)?

Response: Multiple myeloma is a rare form of blood cancer that occurs when plasma cells grow uncontrollably in the bone marrow. It is estimated that approximately 30,280 people will be diagnosed and 12,590 will die from the disease in the United States in 2017. While some patients with multiple myeloma have no symptoms at all, symptoms can include bone fracture or pain, low red blood counts, fatigue, calcium elevation, kidney problems or infections. Despite tremendous progress, most patients with multiple myeloma continually relapse or become resistant to available therapies, such as proteasome inhibitors (PIs) and immunomodulatory agents. Therefore, these patients continue to need new options.

The MMY1001 (EQUULEUS) study is a Phase 1b, open-label study assessing daratumumab in combination with multiple backbone regimens for multiple myeloma. In one arm of the study, supporting the recent approval of DARZALEX (daratumumab), the treatment was assessed in combination with pomalidomide and dexamethasone in patients with multiple myeloma who had received a prior PI and an immunomodulatory agent. Data from the study showed that the addition of daratumumab resulted in an overall response rate (ORR) of 59.2 percent (95 percent CI: 49.1 percent, 68.8 percent), with very good partial response (VGPR) achieved in 28.2 percent of patients. Complete response (CR) was achieved in 5.8 percent of patients and stringent CR (sCR) was achieved in 7.8 percent of patients. How does DARZALEX differ from other treatments for myeloma? What are the main advantages and safety profile of this new treatment regimen?

Response: DARZALEX is the first CD38-directed antibody approved anywhere in the world. DARZALEX works by targeting and attaching itself to CD38, a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage, and directly killing them, and/or allowing the immune system to destroy them.

Clinical trial results show this new combination therapy using DARZALEX provides pronounced clinical benefit for patients who have relapsed on two of the most widely used treatments. Overall, the safety of this combination therapy was consistent with the known safety profiles of DARZALEX monotherapy and pomalidomide plus dexamethasone, respectively. What are the main takeaways of this milestone?

Response: This milestone marks the fourth approval for DARZALEX and broadens its use for patients across stages of relapse.

DARZALEX was first approved in November 2015 as a monotherapy for heavily pre-treated patients. It was more recently approved in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, earlier in the treatment paradigm for patients with multiple myeloma who have received at least one prior therapy. What recommendations do you have for future research as a result of this study?

Response: DARZALEX is being evaluated in a comprehensive clinical trial program that includes five Phase 3 studies across a range of treatment settings in multiple myeloma and other cancer types. This includes studies assessing its use as a mono- and combination therapy in various multiple myeloma settings, including for newly diagnosed, relapsed or refractory and smoldering multiple myeloma patients, as well as those who have received a stem cell transplant. Is there anything else you would like to add?

Response: Grant or Research Support: Amgen, Array Biopharma, Celgene, Millenium/Takeda, Novartis Pharmaceuticals, Janssen, Pharmacyclics

Consultant: Celgene, Millenium/Takeda, Novartis Pharmaceuticals, Janssen Thank you for your contribution to the community.


DARZALEX® (daratumumab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies

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