 For the broader audience, for colleagues who treat myeloma but unlike Dr Rossi and myself, don’t spend their whole life treating myeloma, I think we all have to be knowledgeable about these innovations. CAR [chimeric antigen receptor] T-cell therapy, for the foreseeable future, is going to remain in the setting of a cellular therapy program, but the bispecific antibody therapy is much more likely to arrive at any oncology office in the very near future. Very much like we had with monoclonal antibodies, there may be a bit of a learning curve to get over those first couple of weeks and the risk of CRS [cytokine release syndrome], but beyond that point, it’s likely to be embraced and utilized much like any other myeloma agent.



 As you were saying, the CRS seems to be contained to those early days, so it may be that we’ll have a hybrid system, where maybe centers that have more experience can get the first cycle through, as all of us become more comfortable and better at mitigating and understanding the toxicity. I do think and hope that our community partners will be welcoming and excited by this as well. Just as whenever you’re starting any new therapy, it’s important for the patients, the doctors, and the rest of their team to know what to expect. The experience we’ve had, especially with the taste alterations or the nails, can be very off-putting if you don’t know they’re coming. However, if their expectations are set and the supportive care is put in place, these can all be handled quite nicely and make it a much more tolerable and acceptable therapy earlier.



 Dr Rossi, I think we are clearly in the midst of an immunotherapy revolution in myeloma, and the next few years are going to be exciting for us and promising for our patients. We discussed quite a bit about bispecific antibodies today. We briefly mentioned the innovations coming with CAR T-cell therapy, with new products that may have a longer durability and hopefully yield longer-lasting responses. We should not forget the CELMoDs [cereblon E3 ligase modulators], which are oral agents like evolutions of the…agents that are showing great activity in patients with highly refractory disease and great combinability. We’re likely going to see a mixture of all of those in the next few years.

Thank you for this rich and very informative discussion. Before we conclude, I’d like to get some final thoughts from you, Dr Rossi, about the unmet needs and the future perspective in myeloma.



 Absolutely. I’m sure we will continue to push the boundaries. Every time we say these are the patients who need attention, the field steps up and develops new treatments. Regarding the whole concept of immune modulation, I think we’re in the early days. I’m thrilled to have approved therapies, but I recognize these are fairly rudimentary, and I think we have a lot of room to grow in the toxicity, the efficacy, the ease, and the cost. There’s always room for improvement, so we are in the early days of a really exciting new time in myeloma therapy.



 Thank you again, Dr Rossi, for this very insightful discussion. To our viewing audience, thank you for joining us. We hope you found this 

program to be useful and valuable to the management of your patients with multiple myeloma.

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Closing out their discussion on bispecifics in multiple myeloma, expert hematologist-oncologists share practical advice for community physicians alongside their hopes for the future. 

Relapsed/Refractory Multiple Myeloma: Future Directions in Care

 Dr Rossi, I’ll pick your brain on this issue. We discussed patients who are heavily pretreated, and we talked about the triple-class refractory setting, where most likely agents like teclistamab, talquetamab, and others will first become broadly available. I’d like to hear your thoughts. You are invested in myeloma in general, and in CAR [chimeric antigen receptor] T-cell therapy. How do you see bispecific therapy evolving and being used in the broader landscape of myeloma therapy in the future?



 I think it’s the interesting posit of modalities and targets, and not equating the two. Certainly, there’s a great deal of excitement with having approved products, CAR T cells targeting BCMA [B‑cell maturation antigen]. I look forward to there being the similar modality with new targets. That will posit its own question, but BCMA itself is an excellent target. There are so many different ways of targeting and using it, and we are participating in the studies that are trying to move, at least the CAR T targeting, up front, and using it after a short induction and seeing if we can do better. As you know, we’re excited about these amazing responses, but again, we’re looking at these very refractory, likely T-cell exhausted patients. I’m hopeful that as we move it forward and we have healthier, more robust T cells, these autologous programs will exceed our expectations, and we may go back to our original thought of being able to have a one and done treatment for at least a prolonged period. So many of the other treatments we use are a commitment to continuous therapy. I am cautiously optimistic. I’ll wait for the data, but I’m very hopeful that we’ll be able to move BCMA earlier, get longer first remissions that could be free of any maintenance or equivalent. That includes knowing and recognizing that myeloma is a very worthy opponent, it will still relapse, and then we’ll posit the question of what we do at that point.



 I think those are great points and certainly are worth pursuing with myeloma. I think the points you made about the CAR T cells also apply to bispecifics, in a way. I hypothesize, at least, that the bispecifics might be even more dependent than CAR T on the innate status of T-cell health, because you’re not doing any manipulation on those T cells to make them engage and activate like you do with the CAR T cells. I would suspect the bispecifics would be even more impactful as you use them in earlier lines of therapy. We cannot forget that if we think of bispecifics and CAR T cells as being 2 breakthrough improvements in myeloma, the bispecifics have the characteristics of being much more scalable because you have an off-the-shelf product, where we don’t have that yet for CAR T, which is mostly an autologous product.

We’re starting to see a very rapid development of combinations with CD38 monoclonal antibodies, immunomodulatory agents, proteasome inhibitors, and any combination of the above. Those have a more conventional path of myeloma drug development, essentially combining and challenging the incumbent regimens, as we’ve seen in randomized trials, for example, the ongoing MajesTEC-3 trial. Very much like CAR T, it is just a matter of time before we pursue bispecific combinations in the newly diagnosed setting.

Luciano Costa, MD, and Adriana Rossi, MD, consider the possibility of earlier-line bispecific and CAR T-cell therapies in multiple myeloma. 

Moving Bispecific and CAR T-Cell Therapies to Earlier Lines of Therapy in MM

 I think, as in academia, whenever patients progress on a clinical trial, if they still have the performance status and can meet eligibility, we put them on further studies. We’ve certainly had a number of patients who’ve gone on to either other bispecifics or CAR [chimeric antigen receptor] T-cell therapies. What's been your experience on salvaging them once they relapse after the bispecific?



 I totally agree with you, Dr Rossi. I think at this point it would be naive of us to be too prescriptive of what the ideal sequence or ideal path is. Those things are going to be clarified only through larger data sets like your team did at Mount Sinai, and having those large observational cohorts where you describe how patients did after exiting one experimental agent and exploring other mechanisms of action. The important thing that makes me very comfortable pursuing whatever path is innovative and in front of us is that the benchmark for those patients is horrible. For patients with triple-class refractorymultiple myeloma, you give whatever combination of agents you have; the response rates are not greater than 20%, 30%. The survival is measured in a few months and the responses are very short-lasting. When you have agents with 70%, in the case of CAR T cells, 80%, 90% response rate, there’s certainly one or more steps above what is currently available. Just like you said, those patients, to the extent possible, go from trial to trial, as long as they, of course, maintain eligibility. There’s a lot of discussion about people willing to participate in clinical trials. What I find most reassuring is, oftentimes, we have difficulty explaining to a patient what to expect on the first trial. But once they overcome some of the misconceptions and once the patient participates, the second or third trial is almost never a problem. They see for themselves that it’s a win-win and, in this case, brings them options they wouldn’t have otherwise. We don’t follow any preset plan. We try to rotate the mechanism of action and look for the best option or the most promising option with a new mechanism of action available to the patient at that particular time.

In light of emerging bispecific and CAR T-cell therapies in multiple myeloma, experts consider how they might optimally sequence treatment.

Multiple Myeloma: Sequencing Novel Bispecific and CAR T-Cell Therapies

 Back to Dr Rossi to carry on our discussion.



 That is so interesting. At this very encouraging space, I think we find that patients who would have been considered to have no options now have not only responses but encouraging and positive outcomes. Could you tell us a little bit about how you chose this specific therapy at that time?



 That’s a great point, Dr Rossi. I think this patient would have been deemed terminal and not amenable to any available therapy more than two years ago. He’s now doing well thanks to the innovations that were brought through clinical trials. As I’m sure you have experienced yourself, we have those patients in front of us. We go by what is available, what trials we have, what mechanism of action we have not explored yet, and what this patient is likely to tolerate. At that point, we had the slots for the GPRC5D bispecific antibody. It had shown some good efficacy in preliminary results at earlier doses. We pursued because there was not a target that had been explored at that time. I chose this case on purpose because, historically, we have developed CD38 monoclonal targeting agents, BCMA [B‑cell maturation antigen] targeting agents, and GPRC5D targeting agents. It gives what I think is the wrong idea that we have to follow that particular path, but when you have a patient with triple-class refractory myeloma, any of those novel approaches are better than trying to recycle other older agents. That was his opportunity at the time. He could have very well gone on a CAR T-cell trial at the time, but it just so happened that he’s a lot better lined up for the antibody. I’m glad, because he did benefit from that for quite some time.



 Absolutely. We had one of our fellows present at ASH [American Society of Hematology] our cohort of patients who’d had bispecifics and were then salvaged with further T-cell redirecting, be it CAR T or bispecific therapies. Not only is this relapse refractory space full of questions like how do we choose and how do we sequence and how do we combine our standard therapies, but now we are spoiled for choice in the T-cell redirecting where, again, we have different modalities and different targets and no real guidance or experience to say how to sequence them. It’s up to living through collecting this data and keeping an eye on them. I will mention that the GPRC5D targeting was evaluated in the MonumenTAL-1 trial. That was the equivalent early study where they used the step-up dosing. As you said, we’ve learned that this is how we primarily can mitigate the toxicity, and we evaluated two different schedules, one at 405 micrograms per kilo given weekly on a 21-day cycle and an alternative of 800 micrograms per kilo dose every other week on a 28-day cycle. The results were remarkably encouraging and the weekly schedule had an overall response rate of 70%; the biweekly, 67%; and a greater than CR [complete response] was 13% on the weekly and 19% on the every other week. With a little bit more follow-up at 10 months, about over half of the patients remained on therapy, so these are durable, deep responses. Again, CRS [cytokine release syndrome] is quite limited at grade one and two, with only one case of grade three that, interestingly, happened to be on the weekly schedule. There were a lot of new toxicities. Do you have any thoughts on how these unique toxicities to talquetamab might help or hinder us, and where to place it in our treatment paradigm?



 That’s very interesting. I think if you look across all bispecifics, the pattern of toxicity has been somewhat monotonous. You have the CRS with the initial doses or step-up dosing. You have the overall risk of infection, the hypogammaglobulinemia, and the transient cytopenias. Our dose seems to be more mechanism related, not necessarily unique to the target. I think with the GPRC5D, it is a little bit different. As a side note, when you do essentially tissue and tumor profiling, you find the GPRC5D, which is a transmitting brain receptor with unknown ligand and unknown function. It’s found in myeloma cells, plasma cells, and it’s found in some cells on the cutaneous tissue and some lymphocytes adjacent to our taste buds. That causes what is unique toxicity. You can have a skin rash and you can have some screen disformation, particularly in hands and feet. You can have nail dystrophy and dysesthesia. That is important to know because, to counsel patients, we try a lot of treatments. We use moisturizer and sometimes even steroid creams. We are careful to not break the nails and things like that, but those effects don’t have a major risk themselves other than being uncomfortable to patients. The important thing is, the experience tells us that those symptoms tend to improve or even disappear over time. I usually tell patients, “Hang in there; you are responding. This is going to get better.” Patients are willing to handle that for a few weeks or a few months in the interest of having their disease under control, which, of course, is something that they really value.

Comprehensive discussion on the MonumenTAL-1 trial of talquetamab, a GPRC5D- and CD3-targeted agent, in the setting of relapsed/refractory multiple myeloma.

MonumenTAL-1: Talquetamab in Relapsed or Refractory Multiple Myeloma 

 If it’s OK, I can proceed with bringing up the second case. This is a patient I have known for a number of years now. The patient is a 57-year-old Black veteran who presented 10 years prior to this decision point, with bone pain and bone lesions. At the time he was diagnosed with IgA [immunoglobulin A] myeloma, ISS [International Staging System] stage II, and had hyperdiploidy by FISH [fluorescence in situ hybridization]. I will not bother you with all his prior therapies, but before he met me, he had received 7 prior lines that include essentially all the 3 proteasome inhibitors: lenalidomide, pomalidomide, daratumumab. He had received 2 autologous transplants and had received a prior allogeneic transplant. His most recent line of therapy had been combination chemotherapy. It got to the point where his disease was active and none of the conventional agents were working, and he received what we call modified hyper-CVAD [cyclophosphamide, vincristine, doxorubicin, dexamethasone]. He had a very brief partial response that was followed shortly after with his progression.

When I met the patient, he had progressive disease, and he had worsening hip pain, but he still had a good performance status. He had an ECOG score of 1, he had measurable paraprotein, and had great cardiac, renal, hepatic function. His bone marrow had 20% plasma cells. Similarly to Dr Rossi’s case, over the years, his myeloma had acquired a deletion of chromosome 17p, on top of the background of hyperdiploidy. I show his PET [positron emission tomography] scan because it’s quite interesting when you see what happened. He had several areas of extramedullary disease, had a big lesion in the liver that is shown there, had a lesion in the peritoneum that is not shown, and he had a lesion on the hip that was an extension yet adjacent to the bone, but clearly with a big element of soft tissue that was palpable on the physical exam. The patient was found to be eligible for a trial with a CD3/GPRC5D bispecific antibody. During therapy, he developed grade 1 CRS [cytokine release syndrome] during the step-up dosing, but there was no more CRS beyond the intended target dose. He did not have any infectious complication, but had transient grade 3 neutropenia that responded promptly with growth factor. After 2 cycles, he had a partial response. The assessment included a repeating PET scan. I have shown here those 2 areas that I showed initially, and you can see a very distinct difference in responses.

Essentially, the peritoneal lesion that I’m not showing here shrank. The liver lesion is about the same, slightly smaller. But the hip lesion, the lesion adjacent to the bone, had completely resolved, which I find quite interesting. We know for a fact that as myeloma evolves, you have different subclones, and it has been elegantly demonstrated that the disease biology can be quite different in one area versus another. This case exemplifies that very well. Somehow the disease that was on his pelvis was very responsive, but not the disease that was in the liver or in the peritoneum. The patient did well and continued therapy, but he then had disease progression during cycle 6. At that point, he had a complete resolution of all the toxicities from prior treatment. He still had a good performance status and good organ function. He was a very ambitious, trusting man who wanted to do what it takes to be well and to stick around for his family.

He agreed to participate in a phase 1 trial of an experimental anti-BCMA [B‑cell maturation antigen] CAR [chimeric antigen receptor] T-cell treatment. He successfully collected cells. We decided not to use bridging therapy. There was hardly anything that would be wise to use in somebody with such a refractory disease, but he tolerated lymphodepletion very well and tolerated infusion. He developed grade 1 CRS post-CAR T that was treated with tocilizumab. He did not have any neurological toxicity. He again had some grade 3 neutropenia and thrombocytopenia that was transient and did not require any intervention. At the end of the first month, the patient had a partial response. Toward the end of month 3, he had disappearance of the paraprotein. We couldn’t call him complete response [CR] yet because he still had abnormalities on a PET scan, but as you can see on the pain on the right, those abnormalities gradually became smaller and smaller and completely disappeared by month 9. Currently, the patient is in stringent CR 12 months after CAR T therapy, with an ECOG score of 0 and no ongoing toxicities.

Moving on to the second clinical scenario of multiple myeloma, Luciano Costa, MD, details his care of a heavily pretreated patient. 

Patient Scenario 2: A 57-Year-Old With Heavily Pretreated MM

 You chose, along with the patient, to enroll in the MajesTEC-1 trial. Can you tell us a little about the design of that study, the population included, and the major findings?



 This was a phase 1/2 study of teclistamab. They had their dose escalation followed by expansion. It caught us in this time of moving therapies from intravenous to subcutaneous. The dose escalation identified that the optimal phase 2 dose would be 1500 μg/kg subcutaneously, dosed weekly. In the dose expansion, they worked their way up from 80 to 3000 μg/kg. Encouragingly in these very heavily pre-exposed patients, they saw that at the phase 2 dose, the overall response rate was up to 65% and the CR [complete response] or greater was at 40%, which in such a relapsed setting is an encouraging place to be. Of note in the other dose levels, the overall response rate was still 60% with 35% CR or better, so these are very encouraging deep responses in this patient population. At the last time of presentation, the limitation is that follow-up is quite short, but patients tend to be, at least as far as we’ve seen them and being able to follow them, maintaining durable responses.



 Thank you, Dr Rossi. That’s an excellent summary. You gave us the experience and data that are unique to the MajesTEC-1 trial, but I would say a lot of those things are generalizable, and we have been seeing the observation across other BCMA [B‑cell maturation antigen]-directed T-cell engagers. Of course, the signature toxicity tends to be CRS [cytokine release syndrome], but because most of it is subcutaneous routing and with the use of step-up dosing, you don’t give the intended dose right on the first administration. You work toward the dose within the first week of therapy. The CRS has been overall mostly grade 1 or grade 2. Grade 3 CRS has been extremely rare, not only for teclistamab but also for other bispecifics. The important thing as we think about expanding the use of those agents, bringing them to earlier lines of therapy, and essentially getting those agents approved and put to broader use, is that the CRS is a phenomenon of the first week of therapy.

What we see in the MajesTEC-1 trial as well as in other bispecific trials is once you pass the first week, which we have watched the patients in the hospital for—but in the future, this probably won’t be the case— CRS becomes not an issue. It’s extremely rare, if not unheard of, to develop true cytokine release syndrome beyond that first week of therapy. I think that’s a very important thing because we didn’t know that, of course, when bispecifics started being developed. I would point out the subcutaneous route of our administration and the use of step-up dosing have been 2 highly successful strategies to mitigate the risk of CRS. Dr Rossi, other than the CRS, which is the first thing that comes to mind when you think those agents, what other toxicities do you think are important that people have to watch for or be aware of long term?



 As I think my case highlighted, the second most telling are infections. As we are manipulating the immune system, in the study, about half of the patients at the phase 2 dose did develop infections, and the only patient death on the study was due to pneumonia. Fevers and differentiating infections and CRS, and being able to manage both, would be our focus. The rest are mostly hematologic toxicities that we’ve become all too accustomed to handling and managing.



 I think that’s very important. Currently, those agents are given until progression. Since the CRS is a phenomenon the first week or so, long-term factors like cytopenias and the risk of infection become more important. I think we’re going to need more mature data to refine the strategies to mitigate those risks. I think many of us do, of course, universal prophylaxis for VZV [varicella-zoster virus] and HSV [herpes simplex virus] with acyclovir, not unlike with any other patient with myeloma. But also, we’ve become quite cognizant of the hypogammaglobulinemia, which is very common with any highly potent antimyeloma agent. We tend to be quite liberal in using IVIG [intravenous immunoglobulin therapy], particularly a secondary prophylaxis for bacterial infection. Just be aware and use proper dose emission or growth factor support to deal with the neutropenia and thrombocytopenia, which tend to be transient and very responsive to supportive measures. In the future, we might find out that at least in some circumstances, the patients may not need indefinite therapy. They may need some limited-duration therapy when you have agents as potent as teclistamab, for example.

Expert perspectives on the MajesTEC-1 trial, a study of BCMA- and CD3-targeted agent teclistamab in relapsed/refractory multiple myeloma.

MajesTEC-1: Teclistamab in Relapsed or Refractory Multiple Myeloma

 We have a plethora of phase 3 trials that give us guidance in terms of agents or combinations to choose. However, very few of those address the patients who have disease that is lenalidomide-refractory. When you have a patient who is not exposed to lenalidomide, or the disease has not progressed on lenalidomide, then you have lenalidomide-based options. For example, with daratumumab or carfilzomib, or even with bortezomib, or elotuzumab, or even ixazomib. When you have a bortezomib-naive trial, you have the options of carfilzomib and dexamethasone alone, or bortezomib combinations; for example, bortezomib in combination with daratumumab as shown in the CASTOR trial. We increasingly see more and more patients who have disease that is lenalidomide-refractory because the widespread use of lenalidomide is part of the initial therapy and continuous maintenance therapy. For those patients, we tend to have fewer choices.

Essentially, we have pomalidomide-based combinations like with pomalidomide-elotuzumab-dexamethasone or pomalidomide-daratumumab-dexamethasone, or carfilzomib-based combinations, like carfilzomib-dexamethasone or carfilzomib-daratumumab-dexamethasone, carfilzomib-isatuximab-dexamethasone as in the ICARIA trial. Or less well studied but often used is carfilzomib-cyclophosphamide-dexamethasone. Choosing between those agents can be quite complex. We always take into consideration the patient’s disease refractoriness, essentially avoiding, if at all possible, a class of agents for which the disease has shown to be refractory, but also taking into consideration the activity, the aggressiveness of the progression, and sometimes some disease features like the presence of high-risk abnormalities. Dr Rossi, in your case, the patient had somewhat of a good response to initial therapy, but then the disease quickly becomes what we call now triple-class refractory. The disease shows itself to not respond to at least 1 PI [proteasome inhibitor], 1 IMiD [immunomodulatory imide drug], and a CD38 monoclonal antibody. We know those are the real challenges. Tell us a little bit about your decision-making; how did you choose this particular therapy over any other available?



 Exactly to your point was where I started. She has already seen 2 PIs, 2 IMiDs, and the CD38. These are patients who are notoriously in a dire need of a novel therapy, and she had a very good performance status. I think as with the start of any therapy, you consider the disease itself. As you’ve mentioned, she was having progressive poor-risk features accumulating. You consider the rest of her very limited comorbidities; she had a very good performance status. Also taking into consideration her prior therapies, all of which she tolerated very well and had some response to. I know we all see these patients who, despite disease control over many years, never quite reach that CR [complete response], or what is now the grail of MRD [minimal residual disease] negativity. I’ve been very encouraged to date with the ability of these T-cell redirecting therapies to get these deep responses in patients who are penta-exposed and triple-class refractory for these studies. She also didn’t have anything that was BCMA [B‑cell maturation antigen] targeting, which I think is another great question now in our relapsed setting, as we have multiple modalities to target a single target. How do we put all of those together?

Shared insight on factors that help to determine optimal therapy for patients diagnosed with triple-class refractory multiple myeloma.

Triple-Class Refractory MM: Factors in Selecting Optimal Therapy   

 program titled, “Bispecifics in Multiple Myeloma: Translating Evidence to Clinical Practice.” I’m Luciano Costa, professor of hematology and oncology in the Department of Medicine at the University of Alabama at Birmingham. I am joined today by my colleague Dr Adriana Rossi. Dr Rossi, would you like to introduce yourself?



 Thank you so much. My name is Adriana Rossi. I’m an assistant professor at the Icahn School of Medicine in New York City, New York.



 Thanks, Dr Rossi. Welcome and thanks for joining us today. Today we’re going to discuss recent advances in the treatment of multiple myeloma, with a focus on bispecifics and the impact they will have in clinical practice. We present 2 real-world patient cases and discuss our treatment approach to illustrate how to incorporate recent data into our practice. Let’s get started with Dr Rossi presenting the first case.



 Thank you so much. This was a patient I have known since her original diagnosis. She was 66 in 2014 when she was found to have 30% plasmacytosis in the marrow and took the title of smoldering myeloma, which she held for about 3 years, at which time we started to notice progressive anemia followed by renal insufficiency. At that time, she was found to have 70% plasmacytosis in her marrow, now with a FISH [fluorescence in situ hybridization] notable for a gain of 1q. At that time, she enrolled in a frontline clinical trial of carfilzomib, lenalidomide, and dex [dexamethasone] and did well. Her end organ dysfunction resolved, and her best response was a VGPR [very good partial response], which she was able to maintain for about 2 years. At time of first relapse, she received dara [daratumumab] with a plan to get her to transplant, but unfortunately had no response. She was then treated with bendamustine, bortezomib, and dexamethasone, to which she had a partial response, and was then able to go to melphalan 200 [mg/m2] with a stem cell salvage. At that point, she still had detectable disease and was put on pomalidomide maintenance, which lasted for about a year, still with some disease.

In 2001, she progressed again, this time quite rapidly with an M spike of 4.8 [mg/dL]. Marrow at that time was back up to 60% plasmacytosis, and her FISH had a new deletion 17. Her PET [positron emission tomography] had numerous FDG [fluorodeoxyglucose]-avid lesions but no extramedullary disease was noted. She’s generally a fit lady. She has a history of hypertension and diabetes, both of which are very well controlled on her regimen, and there is no other end organ dysfunction. In our program, she is certainly a very good candidate for a clinical trial. At that time, the best fit in our program was a BCMA [B‑cell maturation antigen]-targeting bispecific antibody, which she received in the step-up doses of 60, 30, and 1500 mg. I have her response to show she did quite well in her first 4 cycles.

Of course, it never goes just so smoothly. First, she did tolerate her step-up dosing quite well, but on her first full dose, she did have grade 1 CRS [cytokine release syndrome]. By that, she had fevers and a headache. She received 1 dose of tocilizumab, at which time her symptoms completely resolved. When she came back, she tolerated her day 15 dosing. Interestingly, when she came in for her cycle 1 day 22, she was, again, noted to have fevers. At this time, it was due to an infection. She was noted to be adenovirus positive. She later had a COVID-19 infection. While she did have a number of fevers and we’re always monitoring for cytokine release syndrome, many times there is the overlap of infections in CRS, which I thought made this an interesting case.



 Thank you, Dr Rossi. That’s clearly a very interesting and illustrative case, not only in terms of therapies, but you also can almost see the natural history of myeloma, going from the smoldering to active myeloma, and accumulating additional chromosome abnormalities that we know are so impactful on the outcome of those patients. I think a case like this illustrates well how we often make decisions, particularly in the earlier lines of therapy.

Expert hematologist-oncologist Adriana Rossi, MD, shares a real-world patient scenario of triple-class refractory multiple myeloma managed with novel bispecific antibody therapy.

Adriana Rossi, MD, Weill Cornell Medical College

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