Dr Shain on the Evolving Role of Bispecific Antibodies in Multiple Myeloma Management

Kenneth Shain, MD, PhD, associate member, Malignant Hematology program, Department of Malignant Hematology; director, Myeloma Research Center, Moffitt Cancer Center; assistant professor, Department of Oncologic Sciences, the University of South Florida Morsani College of Medicine, discusses the evolving role of bispecific antibodies in the treatment of patients with multiple myeloma, particularly in the community setting.

During a workshop titled "Advancing Multiple Myeloma Care: From Frontline Strategies to Novel Therapies in Relapsed/Refractory Settings", Shain and colleagues focused on the advantages of bispecific antibodies as an accessible and effective therapy in the multiple myeloma treatment arsenal.

Bispecific antibodies offer a lower barrier to access, than CAR T-cell therapy, which can be more challenging to access in non-academic centers. This makes them a valuable next-line treatment option after CAR T-cell therapy or as an alternative treatment for patients who may not have access to CAR T-cell products, he explains.

Shain emphasizes that bispecific antibodies targeting BCMA and other emerging targets, such as GPRC5D, have demonstrated clinical effectiveness. These agents allow for flexible treatment sequencing, providing clinicians with the ability to tailor treatment based on patient response and durability following initial therapies, Shain states. Decisions regarding whether to switch targets or maintain the same target after CAR T-cell therapy are influenced by patient outcomes, he notes.

One key advantage of using bispecific antibodies in the community setting is their favorable safety profile, particularly with regards to cytokine release syndrome (CRS). Although CRS does occur with bispecific therapies, it is typically less severe compared than CRS events seen with CAR T-cell therapy, with most cases being grade 1/2, Shain explains.

Advances in prophylactic measures coupled with the shift from inpatient to outpatient administration of treatment have further reduced the incidence and severity of CRS, making bispecific antibodies safer and more feasible for use in the community setting.

Overall, bispecific antibodies provide community oncologists with a practical and effective therapeutic option with a manageable safety profile, Shain states. Shain concludes that these agents are becoming an increasingly integral part of the multiple myeloma treatment paradigm as their use expands beyond academic centers.


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Kenneth Shain, MD, PhD, discusses the evolving role of bispecific antibodies in the management of multiple myeloma.

 The IMW [International Myeloma Workshop] was a fantastic meeting put on by a great group of individuals. It was a great forum for us to learn and see what’s going on, both the stuff that we’ve participated in and what others have created and how we want to look at taking care of myeloma as a whole. One thing we need to think about that we didn’t discuss today is how we start taking care of patients a little differently using both therapies, as well as our ability to assess response and disease and care for our patients.

One thing I took away from the IMW was that there’s a lot of good things going on, but are there better ways in which we can treat patients? And who are the right patients to treat in certain ways? That means customizing or personalizing therapy a little. Can we use different biological end points to make those decisions? One that might be low hanging is a technical advancement or ability to make sure we can measure disease. That’s called minimal residual disease [MRD] testing and achieving minimal residual disease negativity. This means that if you have no measurable proteins in your blood, your imaging is negative. Within your bone marrow, we cannot find 1 in 100,000 or 1 in 1 million myeloma cells. If you’re MRD negative, we can’t find 1 in 100,000 and hopefully less than 1 in 1 million cells are myeloma. We call it an MRD-negative disease state.

That has become a significant goal of therapy for a lot of patients. We have a lot of questions. Should we drive everybody? Is that where they should go, or is it good for those who get there? Once you’re there, how long do you have to be there before we can stop therapy? Because in the context of myeloma, everything is continued therapy. One major thing I walk away from the INW with is that we’re all trying to address those questions differently. Is MRD the appropriate end point? Who gets there, and how long do we keep people there? It helps us make decisions about what we might need to add to therapy to get someone there.

More important, when can we stop or ease off therapy if someone has been there for long periods of time? Long periods of time are open ended. Where are the patients in terms of goals? How do we add things safely and smartly? Other questions that need to be answered: 4 drugs up front vs 3 drugs might get more people there. Maintenance therapy for a fixed duration with an MRD endpoint. These are all exciting questions.

These are goals we might want to think about achieving. All the drugs that we just talked about earlier, including immunotherapies, CELMoDs [cereblon E3 ligase modulators], and novel therapies, are all ways that maybe will help our patients get there, get there more often, and keep them there for longer periods of time. We have a lot of new tools, but 1 of the coolest new tools is our ability to try to get the disease that we can’t measure and use that to make decisions about how we manage our patients. That’s 1 thing I walk away from IMW with.

We’ve talked a lot about the therapeutics themselves. One thing that might get a little overshadowed with these new therapeutics and the excitement around the drugs we’ve talked about is how we think about using these things to manage the patients a little differently. We can make some decisions based on the depth of response and amounts of disease and other personalized components to myeloma.

Kenneth Shain, MD, PhD discusses multiple myeloma disease measurement, management, and personalization of treatment going forward.

Management of Patients with RRMM

Phase 3 data are driving new options in early relapse disease with monoclonal antibodies incorporated into triplet therapy. We talked a lot about the novel therapy melphalan flufenamide in late-relapse patients, the pluses and minuses of that, and the success that we hope can carry forward. We want to make sure we’re always thinking about other approved agents as well. Belantamab mafodotin is another agent that was recently approved for late-relapse therapy. BCMA [B-cell mutation antigen] targeting antibody-drug conjugate. Selinexor has been around for a while to treat those late-relapse patients as we learn that more combinations are available. Depending on how those data roll out, we can use selinexor in different combinations with bortezomib, selinexor, and dexamethasone, or soon-to-be other standard myeloma therapies in combination with selinexor. That’s an important thing for our patients. It’s a novel mechanism of action.

We need to take a step back and a step sideways. There’s a new group of agents or targeted ways of thinking about things in myeloma, like immunotherapies. When I say immunotherapies, I don’t mean the successful and incredibly important IMiDs [immunomodulatory imide drugs] and monoclonal antibodies. I mean these T-cell engaging direct or indirect T-cell engaging modalities. One is cellular, and 1 is noncellular. CAR [chimeric antigen receptor] T cells are an incredibly new and novel way of targeting myeloma cells and reducing disease burden in ways we’ve never seen before, even in late-late relapse patients. Response rate is between 73% and 95% in late-late relapse patients. Progression-free survival is from 7 to 20 months.

We now have approval with Abecma, or idecabtagene vicleucel, from BMS [Bristol Myers Squibb]. That’s an incredibly important new therapy. Hopefully, another new CAR T-cell product will be approved in the not-too-distant future, which will give more options for our patients and be more available to our patients in that setting. BCMA-targeting CAR T cells will be a very important part of our momentum moving forward. Lastly, we don’t want to forget about the direct bispecific T-cell engagers [BiTEs] out there. These are either pieces of antibodies or the antibodies themselves that are able to directly drag CD3-positive T cells to targets. Most of those are BCMA, but other new targets are being evaluated as well. These are all things that we know are being looked at in multiple clinical trials. There are some outstanding response rates and outstanding ways to think about things in patients with late-late relapse disease, where we’re seeing minimal residual disease, negative disease. We’re seeing great responses in places that we wouldn’t typically see it.

We need to harness our own immune system, whether it’s creating T cells that can be put into patients to target the myeloma and CAR T or utilizing the T cells in the marrow by using BiTEs or second and third generations of these. They might bring in more than 1 product or other cellular immune components that are important next steps for us. We have to be excited about the future from an immunotherapies perspective. We have a lot of new agents approved to help.

One group of agents I want to make sure we’re thinking about are CELMoDs [cereblon E3 ligase modulators], the next-generation immunomodulatory drugs. Iberdomide and a more recent 1, CC-92480, have been looked at in studies and are being looked at in combination studies that are effective even in late relapse. This is another group that will hopefully help us continue to change and evolve the landscape of treatment for myeloma patients. It’s an amazing and exciting time for how we can balance new immunotherapeutic-targeting agents, new generations of immunotherapy, and more traditional therapies that target myelobiology. There’s a lot more work to do to figure out how we use these them best and how we strategize around sequencing and personalizing therapy for our patients. Can we use patient attributes? Can we use disease attributes to help target better populations that may be more affected by 1 set of drugs vs another? If you hear enough of the drugs and the combinations of the new products we’ve talked about, you can get a feel for how exciting it is in terms of how we can help improve outcomes for all our patients. It’s an exciting time, and we keep pushing the limit as best we can and continue to push to that ultimate goal of taking care of our patients.

Dr Kenneth Shain, a multiple myeloma expert, discusses emerging therapies with newer mechanisms of action for patients with RRMM.

Emerging Therapies in RRMM

 Another thing to think about with melphalan flufenamide or new therapies is that with dosing strategy, it’s a very attractive schedule when it comes to how it’s delivered. Every 4 weeks is a very attractive schedule, but it still only needs required central access. Patients need central access to get melphalan flufenamide. That means it’s a little different from most of the therapies we give in myeloma. We like peripheral IV [intravenous]. We like subcutaneous things. Those are things we’re used to. Our patients aren’t all that used to my experience, used to needing central access. That step is a little different from what we’re used to, but it happens all the time in oncology and is part of what we’re going to do.

What’s been designed and looked at is the PORT study, comparing the safety of peripheral access melphalan flufenamide vs the current administration of central access. At the IMW [International Myeloma Workshop] in 2021, the data suggest that it probably is going to be well received in the peripheral blood. Those things are going to need further analysis and further verification, but it’s very exciting when you think about its use.

Can we then move from central access to an easier peripheral IV access for this therapy? There are more data that need to be examined and crunched a little, but it’s a step in a nice direction. Thankfully, we have the patients and people who have the experience throughout the course of myeloma and other drugs of changing its formulation to make it much more accessible, easier, and frequently much safer for patients—ie, subcutaneous Velcade vs IV and subcutaneous daratumumab vs IV. Those are all things that hopefully can help us walk the same line, instead of going from central- to peripheral-access melphalan flufenamide. These are all things that can make important steps in the right direction. The PORT study is an important way to move to the next goal.

Multiple myeloma expert Dr Kenneth Shain discusses the PORT study comparing central vs peripheral administration of melphalan flufenamide.

PORT Trial

 One thing we want to think about is targeting myeloma cells in a unique way, enriching for that target as a population of cells. We learn it’s approved and successful in late relapse patients. They created the OCEAN study, which is a randomized study looking at doublet vs doublet. It’s a nice randomization, the first 1 we’ve seen in a long time where it’s 2 drugs vs 2 drugs: melphalan flufenamide plus dexamethasone vs pomalidomide vs dexamethasone. This is in a relapsed patient population—2 to 4 prior lines of therapy in that window between the late-earlys and the early-late relapses. It’s a patient population mostly based on the study itself, based mostly in Europe and where doublet therapy remains the standard of care. What’s interesting about this study is that it’s head-to-head vs doublet: a well-established doublet in pomalidomide and dexamethasone vs melphalan flufenamide and dexamethasone. They showed that melphalan flufenamide had a superior progression-free survival [PFS]. The overall survivals weren’t all that dissimilar.

What was done in an intelligent way is that before randomization they were stratified by age, by prior lines of therapy, and other subgroup analyses that wanted to parse out where these things were going to be most beneficial and what subgroups were most beneficial. The data showed that in those patients who are over 75 years old, their stratification of age had a greater benefit for melphalan flufenamide over pomalidomide than vice versa. It was a very interesting observation. Maybe older patients are benefiting. They took in data looking at prior autologous stem cell transplant as well, so you could envision that older patients probably weren’t eligible or less likely to be eligible for transplant.

What they identified later on is the big differences and the big benefit from melphalan flufenamide and dexamethasone over pomalidomide, in terms of progression-free survival, was in patients who had not received prior autologous stem cell transplant. That means high-dose melphalan, a high dose of an alkylator, and stem cell transplantation. If you look at those patients, the benefit was marked and proven for those who did not receive prior stem cell transplant. We want to make sure we’re thinking about that as we develop new therapies and new therapeutics, whether alone or in combination: what subgroups are going to benefit these patients the most? That’s important for us to think about both in terms of progression-free survival and overall survival.

Those are the things I wanted to touch on with melphalan flufenamide. It’s a new drug to most of us, but it has a novel mechanism of action and can be specific for your myeloma cells. It’s a smarter therapy. Then we think about who can gain the most benefit from this. From phase 3 data looking at doublet therapy—melphalan flufenamide and dexamethasone vs pomalidomide-dexamethasone—there’s a subgroup of patients, which appears to be the right group: those who are older or did not have prior stem cell transplant.

Obviously, a number of questions remain open-ended. These are still hypothesis-generating statements, but is there a time frame between transplant and when it becomes more beneficial? Is it ever seeing an alkylator before? These are all things we need to continue to learn and grow with. But we’ve identified a therapy that was very successful, which led to its approval. From randomized data…there are subpopulations that may benefit 1 set of therapeutics better than another. These are exciting data for melphalan flufenamide and for our patients, but also thinking about how we want to target our own patients in different management strategies.

Whenever we talk about any new therapy to us and utilization—we have direct evidence of melphalan flufenamide and dexamethasone vs pomalidomide and dexamethasone with doublet therapy—there are good things like improvement in maximum response rates, PFS, some populations benefiting more than others. We have to think about the potential emergent, adverse events that occur with the utilization of this therapy.

If you compare the arms—the reasons for discontinuation, the progression—all these things tend to be very similar. There’s not 1 significant set of toxicities driving discontinuation in 1 vs the other or more harm than 1 vs the other. But there are definitely some differences in terms of the toxicities that we have to think about when looking at melphalan flufenamide. Although we think of it as being a smarter therapeutic in terms of targeting myeloma cells vs nonmyeloma cells, because of this immune-peptidase as a requirement for metabolism to the act of therapy, we still see that is going to be some toxicity associated with marrow toxicity. There were significant increases in thrombocytopenia with melphalan flufenamide vs the pomalidomide and dexamethasone. With neutropenia, we think about marrow suppression. With infection, we think about marrow toxicities like anemia. All the lines you’re thinking about are the ones we most want to contribute and we’re thinking about along the lines of toxicities.

What else is along those lines? There’s not a lot that’s terribly different, but these are things we have to make sure we’re thinking about. This is a new drug with a more mild suppression. You’re going to require some more dose delays. It’s given differently. It’s going to be something that’s given on a 4-week basis vs an oral-monthly basis. These are all things you want to address up front with yourself and then with our patients so they know what they’re looking for. They know what to help us find out so we can better care for them.

When we think about myelomas, especially in this context, there are certain expectations in terms of the therapies that we use and in terms of the toxicity they have. When we’re talking about the treatment of relapsed and refractory patients and marrow suppression, these things aren’t unexpected when we talk about doublet or triplet agents in these patients. When you think about the adverse events we see with melphalan flufenamide, it may be higher than pomalidomide and dexamethasone. They aren’t things that were unexpected. These are things we all can handle and manage. They aren’t that dissimilar from those things that we knew. There was no new adverse event that we aren’t used to dealing with, that we aren’t used to supporting our patients through and making decisions about. In the end, although head-to-head, it was maybe more toxic from a myelosuppression perspective. It wasn’t outside our normal expectations of what might happen to individuals in that late-early relapsed setting.

Kenneth Shain, MD, PhD reviews phase 3 OCEAN study design and safety and efficacy data from patients with RRMM treated with melphalan flufenamide + dexamethasone doublet or pomalidomide + dexamethasone.

OCEAN Trial

 A newer therapy that’s been approved in the treatment of late relapse myeloma is a drug called melphalan flufenamide. It’s a new way of thinking about taking care of the disease. We’ve developed a lot of therapies that target myelobiology, in terms of proteasome inhibition, and we’ve done IMiDs, immunomodulatory imide drugs, in targeting that aspect of myelobiology. We have monoclonal antibodies, which target the myeloma cells specifically and then recruit other aspects of things. Melphalan flufenamide is a novel take on how we can target the myeloma smarter than we have in the past.

Melphalan flufenamide, an alkylating agent, is a more typical DNA-damaging agent that attacks cells by killing those that are dividing too quickly by alkylating and causing DNA damage. Melphalan flufenamide is a modified form of this in which the drug is smarter, so to speak, because it requires processing by these things called aminopeptidases, which are a higher expression in cancer cells and in myeloma cells. The drug is only metabolized and, therefore, active in the myeloma cells. The idea is that it’s a drug that will have more toxicity direct within the myeloma and less toxicity on a tumor microenvironment, as well as the person.

That’s the major way we think about it. It’s being cleaved and then activated, where then it takes on its alkylating activities within the context of the myeloma cell itself with greater specificity. That’s 1 important way we think about another way of making a superior therapy by targeting it better to the cancer cell itself and, in this case, a myeloma cell. Those are the things we want to think about when we talk about the new and novel ways in which melphalan flufenamide is an evolution of our therapy against myeloma cells.

Multiple myeloma expert Dr Kenneth Shain discusses mechanism of action of melphalan flufenamide and the advantage it might offer to fight cancer cells.

Melphalan flufenamide

 The treatment landscape in relapsed myeloma is a dynamic place. It’s changing significantly over time. We have a lot of new therapeutics and combinations approved and available for our patients, both in the early relapse setting as well as late relapse setting. We’re incorporating approved agents, new monoclonal antibodies targeting CD38, and isatuximab. We know we’re incorporating new formulations of drugs. We’ve been using another monoclonal antibody, daratumumab Faspro, which is under-the-skin or subcutaneous utilization of this monoclonal antibody. These are things that have been approved in phase 3 studies. We’re thinking more about late relapse disease with a number of exciting approvals, including melphalan flufenamide and belantamab mafodotin. These things are all helping us add therapies to our armamentarium. Obviously there will be a new frontier of cellular and noncellular direct immunotherapeutics like CAR [chimeric antigen receptor] T cells and BiTEs, which are bispecific T-cell engagers. Our landscape is changing as we go, and it’s important that we all continue to update and make sure we’re all on the same page about what’s available for our patients to best support their care and help them with algorithms to manage these patients as they walk through this chronic disease, moving from 1 therapy to the next.

In the early relapse setting, we have some strong phase 3 data that will help us drive new ways of taking care of patients. When you think about it, 2 of them revolve around isatuximab, a monoclonal antibody targeting CD38 as an IV [intravenous] formulation. ICARIA-MM has led to the approval of isatuximab in myeloma paired with pomalidomide and dexamethasone. The phase 3 study comparing isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone demonstrated superior progression-free survival and overall response rates.

These are exciting data, which allow us a second monoclonal antibody–targeting CD38 in the early relapse space. Isatuximab-based therapy is in IKEMA, which is a phase 3 study comparing isatuximab, Kyprolis [carfilzomib], and dexamethasone vs Kyprolis [carfilzomib] and dexamethasone. As suspected when we add an exciting and powerful monoclonal antibody targeting CD38 to these combinations, we have a triplet that is more effective with improved progression-free survival. All these things demonstrate the success and the importance of incorporating not just a monoclonal antibody, maybe during earlier lines of therapy in early relapse disease, but also the concept of 3 drugs is probably superior for most if not all patients than double therapy.

Another really important study is called the APOLLO study. This is another phase 3 study comparing subcutaneous formulation of daratumumab. We know that daratumab has been approved with pomalidomide and dexamethasone in the relapse setting, but this is focusing on that early phase of relapse. The study compared subcutaneous daratumumab—not IV—pomalidomide, and dexamethasone with pomalidomide and dexamethasone. It has been similar to what we would expect. There was a significant advantage within the context of adding a monoclonal antibody to the pomalidomide-dexamethasone backbone. In the subcutaneous formulation—meaning therapy is given in a faster and safer way to the same patient—there’s an improvement in overall response rates and a significant improvement in progression-free survival. Those are 3 highly successful treatment-altering phase 3 clinical trials to help dictate how we should be able to take care of our patients in the early relapse setting.

Adding to our stable therapies and finding the right patient for the right set of drugs is going to be critical for us. We learn more and more as we go along. That’s how I’d look at the 3 big, new phase 3 studies, which are important for us to think about how we use isatuximab as we continue to use Darzalex or daratumumab as an earlier line of therapy, a second monoclonal antibody to utilize in patients with strong, positive data from phase 3 randomized studies. We now know significant benefits of subcutaneous daratumumab in the phase 3 randomized study, in addition to pomalidomide-dexamethasone when it comes to Darzalex or daratumumab utilization.

Over the last decade, we’ve continued to identify new drugs with new targets or new mechanisms of action. In the world of myeloma and other cancers, as we get initial approvals late in disease state—with multiple relapses as monotherapy or doublet therapy with dexamethasone—and as we learn how to use these therapies, they become incorporated into early lines of therapy and in multidrug combinations. Triplet combinations are the most commonly utilized today. We realize that we need to treat patients earlier with the best drugs we have because we want to give them the best chance of long-term outcomes. Myeloma is a disease that’s heterogeneous, meaning that it’s different within patients. But even within the same patient, different clones that are growing. We need to target those by using as many mechanisms as we can. By using multiple targets and mechanisms of action, we’re able to do that in a given patient.

Another important reason why we need to incorporate therapies that are the best early on is because there’s way more attrition than we think about when it comes to treatment, meaning that as you walk from each subsequent line of therapy, we’re losing 30% to 50% of the patients for each therapy. That means that if we don’t use the best drugs we have early in the right accommodations, we may not be benefiting those patients because we’ll never get to use them later on. Overall, these things are all a culminating way for us to think about how we take care of patients. Right now, we think about newly diagnosed patients. Can we go from 3-drug therapy to 4-drug therapy? Can we give them all those drugs up front to make sure the maximum depth of response, which generally translates into longer-term outcomes? With novel therapies, monoclonal antibodies, and novel proteasome inhibitors, we’re able to drive disease down even in early relapse and, in the future, with CAR T and bispecifics, even in late relapse. These are all ways in which we should be affecting our patients.

Utilizing the best drugs in the right combination needs to start happening as early as possible so we can make sure our patients are seeing these drugs and getting maximal benefit from them. Identifying the right drugs and drug combinations is going to be critical. Thankfully, over the last several decades, we have a lot of new therapies available and new management strategies of multiple novel mechanisms of action. These are all things that we need to continue to incorporate into our therapy. We want to think about earlier therapy, getting these drugs in there as quickly as we can, with multiple mechanisms of action, and then try to balance those as we go across the landscape of treatment.

Kenneth Shain, MD, PhD provides an overview of recent advances in the treatment of relapsed and refractory multiple myeloma.

Relapsed/Refractory Multiple Myeloma Landscape

Kenneth H. Shain, MD, PhD, assistant member, Moffitt Cancer Center, discusses the evolving role of stem cell transplant in the treatment of patients with multiple myeloma.

If chimeric antigen receptor (CAR) T-cell therapy is taken out of the mix, stem cell transplant remains a critical part of the management of newly diagnosed patients, Shain says. The data continue to evolve in terms of overall survival benefit. However, progression-free survival and depth of response is where the inclusion of transplant has its greatest impact. The ideal sequence of treatment for this patient population is induction therapy, transplant, and then maintenance therapy, Shain says. Without transplant, the outcomes might not look the same.

This doesn’t necessarily mean that CAR T-cell therapy won’t eventually take the place of high-dose therapy or consolidation. Studies have been geared in this direction. Right now, CAR T cells are just a line of therapy, and it won’t have much of an effect of the role of transplant.

Dr. Shain Discusses the Role of Stem Cell Transplant in Myeloma

Kenneth H. Shain, MD, PhD, assistant member, Moffitt Cancer Center, discusses novel agents in multiple myeloma.

The triplet regimen of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (RVd) is widely accepted as the standard of care for the frontline treatment of patients with multiple myeloma, says Shain. Although, carfilzomib (Kyprolis) is also showing promise in triplets as well.

In June 2018, the FDA approved a supplemental new drug application adding overall survival data from the phase III ASPIRE trial to the label for carfilzomib for use in patients with relapsed or refractory multiple myeloma. In this trial, carfilzomib, lenalidomide, and dexamethasone reduced the risk of death by 21% compared with lenalidomide and dexamethasone alone for patients with relapsed multiple myeloma following prior treatment with 1 to 3 regimens. Shain says it is too early to tell if this will replace the standard of care, but the data is compelling.

In May, the FDA approved daratumumab (Darzalex) in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients with newly diagnosed multiple myeloma, but Shain says that the utility of this combination in the United States is still unknown.

Dr. Shain Discusses Novel Agents in Multiple Myeloma

Kenneth H. Shain, MD, PhD, assistant member, Moffitt Cancer Center, discusses the impact of subcutaneous therapy, such as bortezomib (Velcade) and daratumumab (Darzalex) for patients with multiple myeloma.

For certain drugs, subcutaneous use of therapy will be important for the field of myeloma, Shain explains. It has changed how physicians take care of patients in helping to mitigate some toxicities, as seen with subcutaneous treatment with bortezomib.

The implementation of this is something that’s going to take time, he says, as it is more of a delivery change versus a mitigation of toxicity change.

Dr. Shain on Subcutaneous Therapy for Patients With Multiple Myeloma

Kenneth H. Shain, MD, PhD, assistant member, Moffitt Cancer Center, discusses emerging agents in multiple myeloma.

Oprozomib, an oral agent, is an irreversible proteasome inhibitor that has shown good activity in highly refractory patients.

Additionally, there is marizomib, another proteasome inhibitor that is being looked at alone and in combinations. It still requires further study—but it is something exciting that is on the horizon, says Shain.

Kenneth H. Shain, MD, PhD

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