CureTalk In Conversation With Dr. Ravi Vij, Associate Professor of Medicine, Washington University School of Medicine
Dr. Ravi Vij, Associate Professor of Medicine, Washington University School of Medicine, St. Louis, MO, serves in the Section of Stem Cell Transplant and Leukemia, Division of Oncology. Dr. Vij’s research focus is the treatment of hematologic malignancies and hematopoietic stem cell transplantation. He is the principal investigator for the national Cancer and Leukemia Group-B (CALGB) trials in stem cell transplantation at Washington University. He also serves as the principal investigator on several national and institutional clinical trials looking at strategies for improving outcome of patients with multiple myeloma, acute myeloid leukemia, and myelodysplastic syndromes. To know more about Dr. Vij’s research, visit http://hematology.wustl.edu/faculty/vij/vijBio.html.
I had the privilege to talk to Dr. Vij about his research and recent developments in multiple myeloma treatment. In this conversation with CureTalk, Dr. Vij discusses efficacy of elotuzumab, FDA approval of carfilzomib, and antibody conjugate treatments for multiple myeloma
Hope you enjoy the interview!
Me: Elotuzumab stole the show for multiple myeloma at ASCO. Can you explain some basics about elotuzumab?
Dr. Vij: Elotuzumab is a humanized monoclonal antibody (IgG1) which is presently under phase III clinical investigation in both untreated and relapsed multiple myeloma. Elotuzumab has been under investigation for quite some time, and the encouraging results have brought it to fore. It is directed against cell surface glycoprotein CS1, which is expressed on tumor cells in multiple myeloma patients. Originally, elotuzumab showed lack of single agent activity; however, in combination with the routine, lenalidomide, and dexamethasone we have impressive results.
A phase 1 study of elotuzumab in combination with lenalidomide and low dose dexamethasone in relapsed/refractory multiple myeloma patients demonstrated very encouraging results with 82% response rate. The phase II trial showed that elotuzumab in combination with lenalidomide and low dose dexamethasone was generally well tolerated with a 92% overall response rate. The Phase III trial is ongoing.
Me: You talked at length about single agents like anti CD-38, siltuximab, and obatoclax, in the MMRF teleconference on ASCO updates. Which among these hold the most promise for multiple myeloma?
Dr. Vij: I would say that human CD 38 monoclonal antibody or daratumumab results are intriguing. It definitely appears to be a novel and promising agent for multiple myeloma. Hopefully, we will see even better results in combination trials with proteasome inhibitors and immunomodulatory drugs.
Obatoclax and siltuximab would need further investigations.
Me: Dr. Vij, you presented a study on carfilzomib as single agent in relapsed/refractory myeloma patients at the ASH 2011. What is your opinion on FDA approval of Carfilzomib?
Dr. Vij: Certainly, carfilzomib received a favorable vote from the recent ODAC panel and hopefully will be approved by the FDA in July 2012. Carfilzomib is a proteasome inhibitor and I think that it would be a very welcome addition to the armamentarium of multiple myeloma drugs. As a single agent, this next generation proteasome inhibitor offers a treatment option that is less neurotoxic and probably more efficacious thanVelcade.Carfilzomib when studied as single agent in relapsed/refractory patients not previously treated with Velcade produced responses up to 52%. Grade 1-2 dyspnea seems to occur in about a third of patients in clinical trials but is usually manageable. Carfilzomib is being compared head to head with Velcade in a trial called the ENDEAVOR trial and the response seems to be better than Velcade. Combination trials of Carfilzomib with Revlimid and low dose dexamethasone have shown limited toxicity, and rapid and impressive responses. The favorable side effect profile and lack of cumulative toxicity will likely permit it to be delivered and benefit patients for a longer period of time.
Me: Do you think a drug like TDM1 can be made for multiple myeloma too?
Dr. Vij: TDM-1 is conjugate antibody for breast cancer. Similar targeted therapy using a linker molecule to attach an antibody to a cytotoxic agent is an active area for drug development in multiple myeloma as well. Antibody drug conjugates like CD56 and CD138 have already shown activity in early clinical trials in myeloma.
Dr. Vij, it was a pleasure to talk to you. Thank you.