Yvonne Efebera, MD: Hi, I’m Dr Yvonne Efebera. I’m a professor at Ohio State University Comprehensive Cancer Center, focusing on multiple myeloma, amyloidosis, and transplant.
Thomas Martin, MD: Hi there, I’m Tom Martin. I’m at the University of California, San Francisco. I’m interim chief of hematology, director of transplant, and codirector of the myeloma program. We’re here today to discuss a lot of things about multiple myeloma.
Let’s start. We’re going to have an overview of myeloma, the complexity of the way patients present, and biology, and prognosis. Let me start. When patients present with myeloma these days, it’s quite heterogeneous. With the new biomarkers for the diagnosis of myeloma, we can have patients be asymptomatic when we’re initiating those therapies. Those are the patients who have light chain ratios of greater than 100 mg/L, have a bone marrow biopsy showing greater than 60% plasma cells, or have more than 1 bone lesion seen on MRI with a monoclonal protein. We know that within a year, they’re going to develop symptomatic myeloma, so we get started right away.
We go from asymptomatic patients—it’s actually easier to treat those patients because they tolerate everything better—to more typically presenting patients who have anemia, symptoms of fatigue, and shortness of breath. The anemia, or the elevated total protein, prompts a bone marrow biopsy and then the myeloma diagnosis. We pick therapies based on their clinical scenario. We go from asymptomatic, to typically presenting, to very aggressively presenting patients, patients who may come in with cord compression, hypercalcemia, renal failure, or have sepsis and are very sick due to infection. Those aggressively presenting patients warrant very quick induction therapy, a guided work-up that goes much faster, so that you can initiate therapy sometimes within 72 hours of them presenting.
And those patients, in general, have had a worse prognosis when they present very aggressively like that. At ASCO [the American Society of Clinical Oncology annual meeting] this year, there was a poster about patients who presented in renal insufficiency. With the novel drugs that we have right now, we can turn around the renal insufficiency quite quickly. In fact, their long-term prognosis is probably as good as those who don’t present with renal insufficiency. What do you think, Yvonne?
Yvonne Efebera, MD: Yes, I agree. In addition to these patients and their presentation, one of the most important things is looking at their risk assessment and what the prognostic factors are. What we have looked at the most is the cytogenetics, which tells us a lot about whether they are high risk or standard risk. High-risk patients are those with 17p deletion or TP53 deletion, translocation 4;14, 14;16, 14;20, LDH [lactate dehydrogenase] of greater than 2 times the institutional upper limit, and patients who have plasma cell leukemia. One area of contention is the gain of chromosome 1q. In some studies, those are listed as a high risk, and other studies don’t show that it may be a high risk.
Even in some clinical trials, like the BMT CTN Protocol 1401, which was completed a year ago, we excluded the gain of chromosome 1q as part of high risk. But in the allotransplant [allogeneic stem cell transplantation] trial, the BMT CTN Protocol 1302, we include those. It’s a gray area. Those high-risk features—the TP53 deletion, or 17p, translocation 4;14, 14;16, and 14;20, and hypodiploidy— and then the standard risk—trisomies or hyperdiploidy, and translocation 11;14—are the other mutations that we see. The treatment, what you give them initially, the maintenance that you give, and incorporating the transplant, will vary.
Transcript Edited for Clarity