Patient Profile 1: A 63-Year-Old Female with Relapsed Multiple Myeloma

Brea Lipe, MD: Hello and welcome to this OncLive® My Treatment Approach program titled, "Recent Advances in the Treatment of Multiple Myeloma at First Relapse." I am Brea Lipe, and I'm the associate professor at the department of medicine at the University of Rochester in New York, and the director of the multiple myeloma program. I am joined today by my colleague, Dr Peter Forsberg, and I would like to welcome him to introduce himself.

Peter Forsberg, MD: Hi, Dr Lipe. I'm Peter Forsberg, I'm associate professor at the University of Colorado and the director of our myeloma program. So happy to participate in the conversation today. So welcome and thanks for joining us. And today we're going to discuss recent updates in the treatment of relapse/refractory multiple myeloma, and its impact on clinical practice. So, we'll be doing that by presenting two hypothetical patient cases, and then discussing our treatment approach to illustrate how we incorporate recent data in our clinical practice. So, let's go ahead and get started. So as Dr. Lipe said, our- the name of our presentation today is my treatment approach, recent advances in the treatment of multiple myeloma and early relapse specifically. And this is a patient profile to start with. So, this is a patient who was diagnosis, a 63-year-old female. This was in January 2017 when she presented with anemia, hypercalcemia, and after being evaluated by her primary care physician was found to have acute onset severe rib pain. And then radiographs had evidence of non-displaced rib fractures, bilaterally. Workup showed an IgG kappa multiple myeloma, and subsequent bone marrow biopsy demonstrated 35% clonal plasma cells. And cytogenetics included FISH, which showed a gain of chromosome 1q. So, she underwent a PET CT, which confirmed lytic disease throughout the spine and multiple rib lesions, and was treated initially with RVD, or lenalidomide, revlimid, bortezomib, Velcade, and dexamethasone starting in February 2017. Completed five cycles, achieved a very good partial response and then proceeded with autologous stem cell transplant with melphalan 200 milligrams meter squared conditioning, and after recovery was started on lenalidomide maintenance. So unfortunately, at follow up, on four years follow up state reevaluation was found to have progressive disease and at that time was started on isatuximab, carfilzomib, dexamethasone as second line therapy in May of 2021. So as of last follow up, the patient continues on the isatuximab, carfilzomib and dexamethasone in a very good partial response and is tolerating therapy well without issue. So, I believe, I think that brings us into discussion. In terms of my initial impressions of this case, I think it's a pretty standard consideration. A patient in 2017 diagnosed with new myeloma in their early to mid-60s. Treated with RVD induction, has long been a standard of care initial combination. And then followed by an autologous stem cell transplant and lenalidomide maintenance. And we know that based on recent data that patients with this combination of induction followed by transplant, followed by maintenance can have really stable long-lasting remissions potentially. So, patient experiencing relapse several years in- following the initiation of their induction, is pretty common. So, I think this is a pretty common scenario for us to be dealing with. And I think that the main consideration that's sort of become more prominent in the last couple of years is, do we start still with RVD or would we think about using a four-drug combination in this patient for initial induction, incorporating a CD38 monoclonal antibody like daratumumab plus RVD. So, I think that's probably the biggest practice change that might inform how we treat this patient that'd be a little different than what we might have been doing in 2017. Certainly, something that's does not uniform necessarily across myeloma providers, but is appropriate consideration, I think. And I- but otherwise I think still considering stem cell transplant and often lenalidomide based maintenance remains our kind of primary standard of care. I guess, I'd ask you if you had any additional thoughts. And then, I know the question of defining relapse, how we identify a progressive event. Defining with biochemical versus clinical relapse and sort of characteristics and standard criteria that define those. Maybe sort of delineating how you define progressive disease for [myeloma] in your practice.

Brea Lipe, MD: So, I always think it's fun to kind of look back and we see these patients in our practice, and they were started on therapy in 2017 or whenever that might have been, and to think about how our practice has changed. And I would agree that quads are something that I use a lot more frequently now, pretty much uniformly for induction in patients who are able. The only other thing that I thought was different about this case, that I might have done something different about even back in 2017 was the gain of 1q and that portending some higher risk features. And I often even back then used a more combination maintenance approach for those patients with higher risk cytogenetics. But regardless the patient did really well after transplant with just lenalidomide maintenance, which is great. And so, I think that it does come to this interesting question of what biochemical versus clinical relapse is and how those are defined. And so, the goal in my practice is to always have biochemical relapses because by the time we have clinical relapses, that's really defined by those CRAB criteria or symptomatic myeloma. So, my goal is to avoid symptoms because those can be compounding over time and can increase the toxicities of our therapy. So, my goal is always to catch it before it gets to the point where the patients are beginning to have suffering and side effects. And what we know is that biochemical relapse, so that's defined by the International Myeloma Working Group, the relapse criteria, and it's a biochemical relapse when we don't have those classic myeloma symptoms. And that's pretty much the standard IMWG relapse criteria, which includes changes of 25% to the paraprotein, as long as it's at least a rise of 0.5 and changes to the involved versus uninvolved light chains of at least 10. And so, there are pretty standard criteria for that, that you can follow over time for patients who achieve a CR, which this patient might not have. But anytime you start to see the reemergence of a paraprotein that's also a biochemical relapse. And so, I think that it's important to keep close track of our patients. I like to follow my patients in their labs, even when they're several years out closely, just so that I know that when they're starting to have these biochemical relapses, so I can intervene before they get a clinical relapse. We know that on average patients with biochemical relapses will have symptomatic development of myeloma defining events within about five months. So, I think that just highlights the need to identify those biochemical relapses. When you intervene on that is- can be up for debate but constitutes a biochemical relapse it's relevant for treatment versus those patients who will just kind of slowly progress biochemically and might be- might not progress within five months symptomatically. So, I think it's just important to keep an idea on.