Discussants: Matt Kalaycio, MD¹; Sagar Lonial, MD²

From Cleveland Clinic, Cleveland, OH¹; Emory University, Atlanta, GA²

Address for correspondence: Matt Kalaycio, MD, Cleveland Clinic Main Campus, Mail Code R32, 9500 Euclid Avenue, Cleveland, OH 44195

E-mail: kalaycm@ccf.org

Biographical sketch:

Dr. Kalaycio has been published in numerous scientific publications including Bone Marrow Transplantation, Journal of Clinical Oncology, and Leukemia. He also is the editor of a book on leukemia and co-editor of a book on clinical malignant hematology. His research interests focus on testing new treatments for leukemia.

Dr. Kalaycio received his degree from West Virginia University School of Medicine in Morgantown. He completed his residency in internal medicine at Mercy Hospital of Pittsburgh and fellowships in hematology and medical oncology and bone marrow transplantation at Cleveland Clinic.

Dr. Lonial is involved in numerous professional organizations including the American Society of Clinical Oncology, American Society of Hematology, and the American Society for Blood and Marrow Transplantation. He serves as Vice Chair of the Myeloma Committee in the Eastern Cooperative Oncology Group and as Chair of the Steering Committee for the Multiple Myeloma Research Consortium. Additionally, he is on the board of directors for the International Myeloma Society, and on the scientific Advisory Board for the International Myeloma Foundation.

New Treatments

Dr. Kalaycio: I would like to spend the remainder of our conversation on some of the exciting new treatments that are coming down the pike for myeloma, both approved and soon to be approved. There were some interesting data presented both at American Society of Hematology (ASH) and at ASCO regarding relapsed refractory myeloma. I think with the varied choices that we have to treat relapsed refractory myeloma, it's unclear what's best.

I don't think anybody knows what's best at this point. Maybe that's going to become clearer, or maybe not, depending on how you look at it. The approach to those patients who have started with 3-drug combinations, got their autotransplant, are on maintenance, and have then progressed is becoming—in my mind—more difficult as we get more options. We don't have a standard approach to these patients at this point, outside of the context of a clinical trial. I'm wondering if you guys have come up with one.

Dr. Lonial: Well, there's no standard algorithm. I think that's because some of it depends in large part on the tempo of relapse. What was the patient's response to their initial therapy? What was their toxicity with initial therapy? For instance, if a patient were to get RVD induction, a single transplant, and then progress on lenalidomide maintenance, my first thought at that point would probably be to use a bortezomib based combination.

I would not give up on bortezomib unless they had a lot of toxicity with their initial bortezomib based approach, in which case I might think about using a carfilzomib based approach—class switching, progressing on an IMiD, switch to a PI in that situation. Then the question is going to be, double it or triple it? That, to me, really represents the big question in early relapse. I talked to you about how I think about classifying patients in the newly diagnosed setting, in terms of three categories.

I think that there are a couple of categories for patients in the early relapse setting as well. Early, to me, means one to three prior lines of therapy. Once you get beyond three prior lines of therapy, you're now in the late or refractory relapse category. I think the real question that's evolving in the myeloma world right now for an early relapse is, is three drugs better than two? I think we've asked this question in the newly diagnosed myeloma setting, and I think we've almost universally answered that three drugs is better than two across the board for newly diagnosed patients. You can pick your partners however you want. In general, I think triplets are better than doublets. In the early relapse setting, it has not been so clear. We now have data from, say the Carfilzomib, Lenalidomide, and Dexamethasone versus Lenalidomide and Dexamethasone for the Treatment of Patients with Relapsed Multiple Myeloma (ASPIRE) trial, which looked at carfilzomib with lenalidomide and dexamethasone (len/dex) versus len/dex.¹