What is consolidation therapy?

What is consolidation therapy? How long does it last? What are some consolidation strategies being used? So consolidation can be really grouped into two fashions and when we think about initial therapy for myeloma, I group it into three categories, induction, consolidation, and maintenance. Induction is where you get your initial therapy like VRD. Maintenance is usually just Revlimid or something like that. But consolidation can have two meanings. One is the transplant. So for some people, we consider consolidating them with high dose therapy and autologous stem cell transplant. That's classic consolidation. But there's also this term called post-transplant consolidation, where in between your transplant and your maintenance, you get three or four cycles of more aggressive therapy. So think about it like getting VRD, a transplant, four more cycles of VRD, and then Rev maintenance. This has been done a lot more in Europe than it has in the U.S. with studies like the EMNO2 and the Hovongi and MG. So far, post-transplant consolidation studies have only shown improvement in progression-free survival, but not overall survival. How do we use them in the clinic in the U.S.? I think if I give you induction and transplant and you still have kind of bulky disease, I may give you a little extra something to bring you down so that we go into maintenance in a lower setting than we would otherwise. But this is always on a patient-by-patient basis. So the term consolidation would be a type of treatment you would get after your initial therapy. We sometimes call the initial therapy induction therapy. And then we would follow it up with treatment to sort of eliminate as much of the minimal disease that's behind after the initial therapy. There's different strategies, and those strategies are dependent on the patient. So for some patients, you might consolidate them with an autologous stem cell transplant. This is a very heavy-duty therapy that requires multiple months of treatment at a specialized center, and that treatment does have more toxicities associated with it. But it's one of our most effective therapies for multiple myeloma. However, not all patients can tolerate such heavy-duty therapy, in which case we might recommend more mild treatment. In fact, it could just be continuation of the initial therapy, but just for more cycles. So maybe instead of giving four cycles of the initial treatment, you might give a total of 12 cycles, so for a period of a year, to try and get their disease into a longer remission. After consolidating the disease, you might then go on to maintenance therapy. Maintenance therapy would be a much gentler, milder therapy that we would give over an indefinite period of time until the disease comes back. So in conclusion, consolidation is sort of a therapy that we would give after the initial treatment to get the disease into a deeper remission. So consolidation comes in lots of flavors. So some people believe that an autologous stem cell transplant is insufficient to achieve a deep remission. And while we don't have the perfect answer at this time, we do believe that perhaps going on and receiving additional cycles of maybe the same treatment they had in the beginning as consolidation to deepen the remission might be more effective than going straight to maintenance therapy. So for example, if an initial treatment was Velcade, Revlimid, and Dexamethasone, and they received that for four cycles and then went on to autologous stem cell transplant, they might receive an additional four cycles of Velcade, Revlimid, Dexamethasone as consolidation to even deepen the remission further. That was studied in some recent trials and was found to achieve a deeper remission than patients who had just undergone an autologous transplant alone. So it depends on the patient and how much they can tolerate their performance status. We use a lot to assess whether or not they're able to go on and receive additional therapy. Consolidation can weaken the immune system further, for example, increase risks of infection and need for blood transfusions, for example, are more often in patients who receive consolidation. Consolidation is a probably loosely used word to basically describe usually any finite duration of therapy that is used after initial therapy for multiple myomas to potentially deepen the response or potentially improve the duration of response. And so probably the most common example of this is transplant. So basically a patient would receive usually four to six months of some form of induction frontline therapy with a three or four drug regimen in order to consolidate the response, hopefully deepen the response, and improve the duration response. Then high dose melphalan or chemotherapy would then be administered to the patient followed by autologous stem cell rescue as a consolidation therapy. There can be other forms of consolidation therapy or additional consolidation therapy approaches where even after transplant usually we go straight from transplant to mainstance therapy, typically lenalidomide mainstance therapy. But there can be situations where we consider additional consolidation with chemotherapy cycles with three or four drug chemotherapy cycles to fully deepen the response even after transplant. So there's certainly been strategies employed either using VRD or bortisomalendolidomidexmedicine for two cycles after transplant consolidation or even carfilzomalendolidomidexmedicine for additional cycles to hopefully deepen their response. And this particular approach probably be most relevant in high-risk multiple myeloma patients where a risk-adapted approach should be taken to hopefully deepen the response to hopefully get the patient's myeloma under better control before proceeding on with mainstance therapy to hopefully improve the duration of response. How are drugs dosed during the consolidation phase of treatment? It can vary as well. There's some consolidation approach that still use an attenuated combination of drugs and some approaches use the full dosages. So there could be some variations of how we use consolidation after transplant. But generally speaking, consolidation with this type of approach is for a fixed duration. So usually it's toward duration of period of time. So we wouldn't consider consolidation to be long-term mainstance therapy with three or four drug regimen, but usually it's for a fixed duration of period of time. Consolidation therapy is something we stole from our leukemia colleagues. So if you look back in the history of the treatment of leukemia, what we found is you could give a big dose of chemotherapy, kill all the leukemia people, go in remission, but they wouldn't stay in remission. So the only way to keep them in remission was by giving them repeated intensive chemo. So we stole that and said, okay, we don't need to do as much as that in terms of myeloma because we have the stem cell transplant, but we still think that giving some short bursts of intensive chemo can help. And that's what consolidation is. It's one of those philosophical questions of myeloma. When does consolidation end? When does maintenance begin? And we don't have a clear delineating factor, but generally we think of consolidation as the thing we do after the transplant. Once the patients recover from the toxicity of the transplant, maybe it's usually six, eight weeks, sometimes up to two or three months later, we'll give them a few cycles of consolidation. That's the other thing with consolidation. We think of it as not something that's going to last a year. It's two cycles, four cycles is generally consolidation. Usually consolidation, because it is still more intensive therapy, is three drug combinations. And right now in the United States, it tends to be Brevulamid, Velcade, Decadron, or the KRD. So the Kyproloid, Carfilzomid, Brevulamid, Dex are the most common consolidation regimens we use.