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CE

Pharmacist Perspectives on Multiple Myeloma Management

  • Authors: Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC; Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA; Jared E. Matya, PharmD, BCOP
  • CE Released: 5/25/2023
  • Valid for credit through: 5/25/2024
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  • Credits Available

    Pharmacists - 0.50 Knowledge-based ACPE (0.050 CEUs)

    You Are Eligible For

    • Letter of Completion

Target Audience and Goal Statement

This activity is intended for oncology pharmacists.

The goal of this activity is for learners to be better able to evaluate multiple myeloma (MM) therapies, mitigate drug-drug interactions and treatment side effects, and counsel patients as part of the interprofessional care team.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Pharmacologic management of MM 
  • Have greater competence related to
    • Managing adverse events associated with MM therapies
  • Demonstrate greater confidence in their ability to
    • Educate patients with MM about their treatment


Disclosures

Medscape, LLC requires every individual in a position to control educational content to disclose all financial relationships with ineligible companies that have occurred within the past 24 months. Ineligible companies are organizations whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

All relevant financial relationships for anyone with the ability to control the content of this educational activity are listed below and have been mitigated. Others involved in the planning of this activity have no relevant financial relationships.


Faculty

  • Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC

    Assistant Professor of Pharmacy
    Mayo Clinic College of Medicine
    Director of Pharmacy
    Minnesota Oncology
    St. Paul, Minnesota

    Disclosures

    Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC, has the following relevant financial relationships:
    Speaker or member of speakers bureau for: GlaxoSmithKline; Janssen; Sanofi

  • Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA

    Clinical Pharmacy Manager
    Division of Hematologic Malignancies and Cellular Therapies
    Oncology Pharmacy Residency Program Director
    The University of Kansas Cancer Center
    Westwood, Kansas

    Disclosures

    Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, has the following relevant financial relationships:
    Consultant or advisor for: AstraZeneca; Bristol Myers Squibb Company; Genentech; Incyte Corporation; Kite Pharma, Inc.; Omeros Corporation; Sanofi
    Speaker or member of speakers bureau for: Omeros Corporation

  • Jared E. Matya, PharmD, BCOP

    Adjunct Clinical Assistant Professor
    Clinical Pharmacist Practitioner
    Transplant and Cellular Therapy
    University of Nebraska Medical Center
    Omaha, Nebraska

    Disclosures

    Jared E. Matya, PharmD, BCOP, has the following relevant financial relationships:
    Consultant or advisor for: AstraZeneca; Genmab

Editor

  • Megan Whitney, DMD

    Medical Education Director, Medscape, LLC

    Disclosures

    Megan Whitney, DMD, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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    For Pharmacists

  • Medscape designates this continuing education activity for 0.50 contact hour(s) (0.050 CEUs) (Universal Activity Number: JA0007105-0000-23-183-H01-P).

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CE

Pharmacist Perspectives on Multiple Myeloma Management

Authors: Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC; Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA; Jared E. Matya, PharmD, BCOPFaculty and Disclosures

CE Released: 5/25/2023

Valid for credit through: 5/25/2024

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Activity Transcript

Kirollos S. Hanna, PharmD, BCPS, BCOP, FACCC: Hello and welcome to today's program where we will be discussing pharmacist perspectives on the management of multiple myeloma. My name is Kirollos Hanna. I'm an assistant professor of pharmacy at the Mayo Clinic College of Medicine. I'm also the director of pharmacy at Minnesota Oncology in St. Paul, Minnesota. Joining me today are our expert panelists, Dr Zahra Mahmoudjafari. She's a clinical pharmacy manager in the Division of Hematology Malignancies and Cellular Therapies at the University of Kansas Cancer Center, and Dr Jared Matya, adjunct clinical assistant professor and clinical pharmacy practitioner at the University of Nebraska Medical Center. Welcome, Zahra and Jared. I'm really excited to spend the next 30 minutes with you both.

Due to the sake of time, I'll just kick us right off and give us a brief introduction of multiple myeloma and then Jared and Zahra will also walk us through some treatment approaches for patients with both treatment-naive disease as well as those in the relapse setting and scattered throughout the presentation, we'll be having some expert panel discussions. As many of you know, multiple myeloma is an incurable disease. When we look at the incidence as of 2023, it's estimated that roughly 36,000 people will be diagnosed with multiple myeloma with about 12 and a half to 13,000 people suffering from or succumbing to the disease.

When we look at the incidence overall in terms of other cancers, it does account for about 14% of cancers and about 1.8% of new cancer diagnoses and roughly 2% for cancer-related deaths. The good thing about myeloma, it's very unlikely that you'll see a patient walking in through your doors who's younger with multiple myeloma. You look at the median age of diagnosis is right around 70 years of age. The actual number's about 69, and when you look at the trends over the past several years, the 5-year survival trends have continued to improve over time. We don't really know the etiology or have a full understanding of the etiology of multiple myeloma. There are some chromosomal and genetic abnormalities that may lead to the disease.

There could be some family history, certain chemical exposures that could also increase the risk of disease, but one area where we do know there is a significant increase in incidence is with our African-American population, which oftentimes also does serve as a significant disparity within this specific disease as well as clinical trial enrollment. One thing about myeloma is that we don't really have any established guidelines for preventing or screening, and thus why we continue to see myeloma continue and we don't really have a cure at the moment in time. When we look at myeloma, it's important for us to highlight that there are really 3 key stages of the disease, which I'll highlight on the next slide, but it's important for us to understand some key cytogenetic abnormalities that may bucket your patient in terms of risk factors.

Now, we do know that this disease is a malignancy of the plasma cell, which is a mature B-cell, and that's why oftentimes, these are protein producing cells, but when you look at the first stage of diseases, which we call MGUS or monoclonal gammopathy of unknown or undetermined significance, oftentimes those are patients that we just observe. When you look at the incidence of these patients with MGUS going to have active or full-blown symptomatic myeloma, it's roughly about 1% per year, 10% per 10 years, et cetera. So oftentimes, some patients with MGUS or even smoldering disease, we may never treat them. Now, there are some key cytogenetic abnormalities that we do have to call out, things like translocation 4;14, deletion 17p that may put your patient in a poor prognostic or a high-risk bucket.

These are just simply our approaches to treatment. As I mentioned, MGUS and smoldering are oftentimes observed stages of the disease, but when patients do become symptomatic, we do start to initiate treatment for our patients. It is recommended that they be monitored for active disease every 3 to 6 months within the guidelines. If you're familiar with myeloma and you've looked at the clinical trials for myeloma, these are the International Myeloma Working Group (IMWG) response criteria that you sometimes see that we try to achieve with some of our treatment options, things like stringent complete response. Oftentimes, the better the response, we'll see that deeper remission or that time to initiating a subsequent line treatment. Then Jared and Zahra will be walking us through triplet treatment approaches, quadruple drug-based regimens and what that means in terms of some of these responses.

It's also important for us to highlight that throughout the phases of multiple myeloma, we do tend to see a change in attrition of patients that oftentimes, throughout the phases, they either succumb to disease or are no longer eligible for certain therapeutic options, and thus why really initiating some of the best therapeutic options or even those quadruple approaches are starting to become more and more in favor to really try and optimize and expand upon the responses that we see. With that, I'll transition over to Jared, who will walk us through treatment approaches for newly diagnosed and early relapsed multiple myeloma. Jared, floor is yours.

Jared E. Matya, PharmD, BCOP​: All right. Thanks for the introduction, Kirollos, and we'll just get right into it. I think it's important to note, as Kirollos just mentioned, we lose a chunk of patients with each progressive line of therapy, and so this really makes optimization of our early line therapy critical. The National Comprehensive Cancer Network (NCCN) and other guideline writing bodies now suggest at least a triplet regimen for the vast majority of patients. It's also recommended to incorporate autologous stem cell transplant in those patients that are eligible in order to maximize the time before the next line of therapy is needed. Referral to a transplant center should be considered for most as even patients with comorbidities or with advanced age might be eligible for transplant.

An early referral is also important because it can have implications as far as induction therapy selection as many of the drugs we use upfront can inhibit stem cell collection and most transplant candidates are going to receive a combination of a proteasome inhibitor (PI), immunomodulatory drug (IMiD), and dexamethasone, whereas the non-transplant candidates might consider a daratumumab-containing regimen. Although triplet therapy is the standard of care, the selection of individual agents is really driven by a multitude of factors. Patient comorbidities and organ function can drive agent selection and dosing, distance and transportation issues might prompt the selection of maybe a weekly or even exclusively oral regimen.

Risk stratification is becoming increasingly incorporated into upfront decision making with the aim of increasing intensity in patients at the highest risk for relapse. As we discussed previously, a triplet regimen of a PI, IMiD, and dexamethasone is the standard of care for most patients. Bortezomib, lenalidomide and dexamethasone carries a category one recommendation for both transplant eligible and ineligible patients. A daratumumab-containing triplet can be considered for transplant ineligible patients and you'll also notice there's a melphalan containing regimen that carries a category one recommendation, but this regimen really isn't used all that frequently in the United States. There's a variety of regimens that are listed under useful in certain circumstances, and I'm not going to go into those in incredible depth, but just know that we have multiple agents available that really allowed for a tailored induction approach based on patient comorbidities, performance status, and also patient preference.

Dr Hanna: Jared, let me ask you this. In terms of these triplet vs quadruple-based regiments in terms of therapeutics, based on cytogenetics and so on and so forth, is there a standard? Do they look at certain buckets of patients where they go one route or another, or how are your providers approaching this patient population?

Dr Matya: That's a great question. I got some data I'll show on the next slide, but you'll notice that in that NCCN slide I just had that there was a quadruplet regimen of daratumumab, bortezomib, lenalidomide, and dex that was under other recommended regimens. We don't know exactly which patients will benefit the most, but there are 2 randomized controlled trials that have looked at the addition of daratumumab to normal induction triplets for transplant eligible patients. Both of these use bortezomib as the PI. The European CASSIOPEIA study used thalidomide for the IMiD, whereas the more US-based GRIFFIN used lenalidomide.

Both studies showed an increased response rate and also more deeper minimal residual disease (MRD)-negative responses. Looking at some of the longer-term follow-up data, it suggests there's also a progression-free survival (PFS) benefit here as well, and those MRD-negative statuses are being maintained for a long time. If you look at the data overall, the standard risk patients probably benefit a little bit more than the high-risk patients. However, it's worth noting that in those trials, there's only about 15% of the patients were high risk and it's sometimes hard to argue and say that we're going to give a higher risk patient less drug than a standard risk patient.

Dr Hanna: Sure. Zahra, how about you at Kansas? Are you guys doing anything different in the upfront setting?

Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA​: No. Pretty similar to what Jared's describing for sure. I think when we get into my slides as well, this space is rapidly evolving, but for this, we are pretty in sync as well.

Dr Hanna: Excellent. Excellent. Jared, I'll turn it back over to you to walk over through CASSIOPEIA and GRIFFIN and all of those with the CD38s.

Dr Matya: You bet. The other unanswered question, okay, so we don't know exactly who benefits the most, but then we also aren't quite sure when is the best time to incorporate these anti-CD30 antibodies. What's interesting is with the CASSIOPEIA trial, there were 2 randomization points. So they were randomized to receive daratumumab upfront in combination, but then there was also another randomization where they received it during the maintenance phase. What you can see is that these data would suggest that incorporation of dara upfront might provide the largest benefit, but of course, this is still an area of active research. The last thing I'll say about quadruple therapy is we do have an ongoing MASTER trial that's looking at daratumumab in addition to carfilzomib-based regimen, and the data look pretty promising for both risk groups in this patient population.

While we do have good initial data on quadruple therapy and it looks good, we do need more information before this probably becomes standard of care for all patients. Ongoing studies are going to hopefully confirm the efficacy of these regimens and also maybe shed some light on the optimal timing. We also need further data to really aid in patient selection for quad therapy. The data we have so far would suggest again that all risk groups are going to benefit based on efficacy alone, but we know that these drugs aren't completely benign, and so when we're adding these anti-CD38 antibodies, we see increased toxicity, specifically more cytopenias and the infection risk that comes along with that. Also, as I mentioned previously, these agents hinder stem cell collection, which is important because these are transplant eligible patients that are ultimately going to proceed to a consolidative transplant in the near future.

So we've talked a lot about our transplant eligible patients, but what about those patients that aren't eligible or don't desire to go to stem cell transplant? Triplet regimens either containing bortezomib or daratumumab in combination with lenalidomide and dex both have long-term efficacy and safety data in this patient population. Daratumumab, lenalidomide, dex is typically going to be continued indefinitely until disease progression and based on patient tolerance. For patients that are started on VRd, patients are usually either going to be maintained on lenalidomide monotherapy for a standard risk patient, whereas high risk patients are usually going to continue combination bortezomib, lenalidomide. Patient preference and tolerability can help you drive this decision. VRd carries a lower risk of cytopenias and infection, but carries a higher risk of neuropathy and does usually require more trips to the infusion center, whereas dara Rd might be a better choice for patients with existing neuropathy.

Standard triplet therapy might not be appropriate for all patients. Tolerability for frail patients can be improved by either decreasing the dose or the frequency of some of our standard regimens. A completely oral regimen using is ixazomib as the proteasome inhibitor is well tolerated and it might be an attractive option for patients that can't make frequent trips to an infusion center. We can also consider doublet therapy in really frail patients with standard risk disease. As we know, renal dysfunction is a common finding in patients with multiple myeloma. Historically, a cyclophosphamide-based regimen has been utilized in this patient population and this is still a great option and that actually can be an attractive option in patients with high disease burden for cytoreduction, but there are also dose adjustments based on renal dysfunction for lenalidomide as well.

This can be considered for most patients with the understanding that even with dose adjustments, these patients are still usually at higher risk for cytopenias and infections. Finally, of course, patients with existing peripheral neuropathy, we can go with a bortezomib-free approach, substituting carfilzomib or even forgoing a PI altogether and incorporating an anti-CD38 antibody. We'll touch briefly on our dosing strategies with our PIs. There are multiple dosing strategies for both. Carfilzomib is only available as an intravenous (IV) infusion, but can be either given once or twice weekly depending on the regimen selected. While cardiotoxicity is considered a class effect with the PIs, the incidence is highest with carfilzomib. Heart failure and hypertension are typically the most common presentation, but we can also see arrhythmias, effusions and even acute coronary syndrome. Most of this toxicity thankfully does tend to be reversible, but we do need to watch these patients closely.

Of course, as most of us know, bortezomib can be given either IV or sub-Q with subcutaneous administration being preferred due to a lower incidence of peripheral neuropathy. In worst case scenario, we can also utilize dose reductions and interruptions to help mitigate these adverse effects as well. I think this is an important slide for pharmacists. I'm not going to go into it in great detail, but it's a high-level summary of some of the complications and mitigation steps that we can employ for patients receiving therapy for myeloma. Again, I'm not going to go through all of them for the sake of time, but you can really see a large role for a clinical pharmacist as it relates to supportive care to ensure that patients are on the appropriate prophylaxis for infection and venous thromboembolism (VTE), ensuring appropriate pre-medications and of course suggesting dose adjustments based on toxicity and tolerability.

To close my section, we'll just touch very briefly on these early relapses before I turn it over to Zahra, but we know relapse is nearly universal in patients with multiple myeloma. Decisions for treatment after early line therapy are really going to be dictated based on how long they were in remission and also what agents have they been exposed to previously. In patients with a long disease-free interval, we could consider re-treatment with that upfront therapy, but again, we're going to usually lean on 3-drug regimens in this setting, and it's important to really look at what the patient's previous therapy was.

If a patient relapses soon after or while on treatment with bortezomib or lenalidomide, we're probably going to want to choose a drug from a different class or a different PI or IMiD for our next line therapy, and we're usually going to keep these on until disease progression. In addition to disease-related factors, it's also important to consider the patient perspective. How did they tolerate their prior lines of therapy? Did we have to alter their regimen for any reason? Can we select regimens that don't worsen existing adverse effects they're experiencing? Most importantly, what does the patient hope to get out of this next line of therapy? It's all those things intertwined together is how we make these therapy decisions.

Dr Hanna: So Zahra, Jared walked us through... He mentioned clinical pharmacists. We play so many different roles based on your health system. Sometimes it's an infusion pharmacist, sometimes it's someone integrated in the multiple myeloma team. How does that model look at the University of Kansas? I'd love to hear your perspective on that, and then Jared, if you have anything differing, maybe we can also cover that really quickly before getting to Zahra's section.

Dr Mahmoudjafari: Yeah, absolutely. So really briefly, we're very fortunate to have clinical pharmacists in the treatment centers, not only from an infusion perspective, but also in clinic with our providers, nurse practitioners and clinical nurse coordinators. So they see patients with our provider, they are able to educate and monitor as well as help with treatment plans, so they're very involved in the management of our patients, not only in the early lines of therapy but in the relapse-refractory setting, and then should a patient need to transition to perhaps a chimeric antigen receptor (CAR) T-cell therapy, which I know I'll talk about here in a second, or transplant, we have another set of pharmacists who are highly involved there as well.

Dr Hanna: Excellent. Anything different on your end, Jared?

Dr Matya: I would say that really mirrors my practice. We have integrated pharmacists in the myeloma clinic. We cover a broad range of things. Of course, education is probably the cornerstone. We do a lot of work with our financial counselors to ensure that patients have access to therapy because we know these are all high-cost therapies. We do a lot of the monitoring and making dose adjustments and things in the long term. Very similar with Zahra's.

Dr Hanna: We have a very similar model as well. Zahra, floor is yours.

Dr Mahmoudjafari: Okay. All right. Well, I have a very brief amount of time. We're going to go through the novel approaches in the late relapse setting. If I were to give this presentation even a year ago, it would've been different. So I will try to do this justice, but we've had a lot occurring in the pipeline as it relates to multiple myeloma therapy and relapse after 4 or more therapies depending on how you count 4 or more therapies. So for more than 4 prior therapies in triple class exposed refractory patients, we have several options. Now, one of which no longer is available as an FDA-approved medication, that includes belantamab mafodotin, which is now only available on a compassionate use basis. The one class of therapies that I'll spend a little bit more time on is our CAR T-cell therapies, and then of course, our more recently approved bispecific antibody teclistamab. So just some brief information about belantamab mafodotin.

Again, it's only available current state for compassionate use. The reason why it was pulled off of the market is that it did have an initial accelerated approval on 32% overall response rate, but it was then withdrawn because of the confirmatory trial not meeting its primary endpoint. It also has some logistical hurdles. It had a Risk Evaluation and Mitigation Strategy (REMS) program and some significant toxicities as it relates to ocular toxicities. So this being removed from the market, it may come back depending on some changes in doses. We'll see, but at this point, only available via compassionate use. So there are 2 currently approved CAR T-cell therapies and you really can't spend a ton of time talking about CAR T-cell therapies without talking about the process in general. This is one slide, but this process in and of itself takes about 6 to 8 weeks, give or take, depending on how long it takes for the patient's cells to be collected via leukapheresis procedure, bridging chemo and lymphodepleting chemotherapy given as well as the CAR T-cell manufacturing time for the cells to finally be infused in the patient.

So all in all, this process takes quite a bit of time. Not only does the process take time for those CAR T-cells to be infused in our patients, but then there are also some short-term and long-term toxicities related to the CAR T-cell therapies that we're learning a lot more about. The first of which is cytokine release syndrome (CRS). This can occur within the first 7 to 10 days. Depending on the construct, this can occur even as early as 1 day post-CAR T-cell infusion. So the cardinal signal for CRS is a fever. It also includes degrees of hypoxia and hypertension. Primary management is supportive care primarily, but we do have an interleukin (IL)-6 antagonist called tocilizumab that we can use in the event of CRS. Not to be outdone by CRS, the other significant toxicity that occurs with CAR T-cell therapies is neurotoxicity. This is just a little bit different than other neurotoxicity seen with other therapies.

This one is graded by a neurotoxicity score looking at level of consciousness, what have you, and it's primarily managed with steroids, so there is a lot, and we could spend a whole hour just talking on acute toxicities with CAR T, but for now, there are toxicities related to it. Now we are all are also learning a lot about how to manage these patients long-term. So when you think about CAR T-cell therapies in commercial use, meaning FDA approval, really, they've only been on the market for 5 years. We're learning a lot more about the hematologic toxicities and the infectious complications. Some of the hematologic recovery periods can be prolonged. The patients are neutropenic for a longer period of time than we anticipate, and of course, then that lends itself to more infectious complications. So this is a great place for where pharmacists are involved in our clinics and not only the acute management, but also long-term management of these patients. Not to be outdone is a new class of bispecific antibodies. This is not the only medication in this class, but it's the only one currently approved and it includes teclistamab.

So teclistamab's dosing schedule is just a little bit different than the CAR T-cells. It does not have the prolonged manufacturing period of about 6 to 8 weeks. It's actually quite readily available. It does have a step-up dosing with a recommended 48-hour inpatient monitoring time and a REMS or a risk evaluation mitigation strategy certified center. So the 0.06 milligrams per kilo on day 1, followed by 0.3 on day 4, and then finally by day 7. This also carries a risk of CRS and neurotoxicity. However, we do tend to give more steroids upfront as pre-medications in this patient class, in this drug class, and so we do see a lower incidence overall of CRS and neurotoxicity. We are learning, again, a lot more about the bispecific antibodies and not really letting the cat out of the bag, there are more to come.

There's a significant pipeline for multiple myeloma as it relates to bispecifics. Now again, with the bispecifics, there is very much the concern with the cumulative infection risk. Now we know, again, these patients are after 4 lines of therapy, they're heavily pretreated, they're pretty frail and fragile, and so we have to be really careful with how we help manage these patients. There is prophylaxis recommendations for herpes zoster, Pneumocystis jirovecii pneumonia (PJP) prophylaxis, ruling out hepatitis, making sure we have what I call a trifecta, so antifungal, antiviral, antibacterial when their absolute neutrophil count (ANC) is less than 500, and then of course, making sure that they receive their timely vaccinations. With that, I did that as quickly as I physically could so we can talk through some of these more practical issues.

Dr Hanna: Thank you, Zahra. So Jared, how about you in terms of your practice and everything and the economics and everything that Zahra walked us through? You're both in academic centers and I'm practicing in the community center. How are all these different things taken into consideration as you are implementing these cellular therapies specifically? Or even the REMS requirements. We saw belantamab come to market and you had to operationalize these ocular toxicities and seeing ophthalmology. Could you maybe walk us through that of what you guys are doing at your center?

Dr Matya: Yeah, a lot of what I'm doing at my center specifically with CAR T is we're trying to come up with guidelines for toxicity management. We're making sure the tocilizumab is available, which is part of the REMS requirement. I think an exciting area is you mentioned our friends in community practice. I think ultimately, a lot of these bispecifics are going to be able to be administered outside of the academic center, so we're partnering with some of our community practice pharmacists and providers on ways to mitigate toxicity and then manage it with agreements that will admit patients to the hospital or hopefully manage it in-house. That's, I would say, the next wave of things that we're doing at my institution as far as CAR T and bispecifics.

Dr Hanna: We in the community setting recently rolled out teclistamab to be given at one of our sites because there's just been so much interest. We do partner with the academics and the institutions around our metro area that do have hospitals because outside of Mayo Clinic, Mayo is the only place that I know of is doing outpatient, but they're outpatient unit is in the hospital as long as patients can stay within a certain radius of the organization and then when they're ready to be transitioned back or go to that community center, they can certainly come back to us. Zahra, maybe your experiences and you can walk us through the last few slides.

Dr Mahmoudjafari: Yeah. Absolutely. I would say the same. I think the future is for these medications, at least for the bispecifics, to be able to be administered safely in a community setting just in terms of access. I think that has been a limitation for our CAR T-cell therapies. Not only slot availability, manufacturing concerns, but just the fact that not all centers have had access to all of the CAR T-cell products either. So I think the way of the future is community and making sure we are able to do this safely in our community settings because we have a lot of novel targets in the pipeline. So these are just some examples of some CAR T-cell therapies and their prospective targets. They're really primarily in phase 1 or phase 2 trials at this point, but again, pretty refractory patients with median prior lines of therapy, but they are showing very impressive overall response rates.

So that is something that is really great, is despite some of these complexities that we have with treatment and monitoring, they're highly active in these very refractory patients. Not to be outdone in the CAR T-cell pipeline, the emerging bispecifics, and also novel targets. So again, we can spend hours just talking through this really exciting pipeline. They're all just a little bit different than the other, but really, the trick will be how do we increase access in our community settings and make sure our providers feel very comfortable with being able to administer these products and manage these side effects, both short term and long term. With that, I'll turn it over to you, Kirollos.

Dr Hanna: Thank you, Zahra. So just maybe 30 seconds each here. So best practices and clinical pearls. I think in myeloma, these cellular therapies and B-cell maturation antigen (BCMA) targeting and many other targets are really, really exciting. I think as we continue to see this space become more and more crowded, operational considerations around how we can administer these in the community setting, again, I'm putting on my community hat, partnering with local hospitals to ensure staff is trained and we have a response process in place in the event patients need urgent care is going to be very, very important, and keys to success. Zahra, I'll go back to you and then to Jared.

Dr Mahmoudjafari: Yeah, I would say for us, same, just like you mentioned. I think for me as an academic medical center, it's in my best interest to make sure that we understand the toxicities, we have an outlined algorithm for how to manage these toxicities, and then we spend some time making sure that our community partners feel comfortable managing toxicities as well. We've learned a lot with the CAR T-cell therapies in the last 5 years. Really, that same learning is occurring now with the bispecifics. More and more, we're becoming more comfortable with managing these patients outpatient. So for me, my big task is making sure that there is a treatment algorithm for toxicities that everyone can feel comfortable with, and then again, making sure operationally, we're ready to go.

Dr Hanna: Jared?

Dr Matya: Yeah. Similarly, I think... Obviously, Zahra's from Kansas. We both live in states with a large rural population where they can't all come to the major academic medical center in the eastern part of the state in my case, and so as our experience grows, we want to share that experience with our local community hospitals. I think the most important thing that we're doing right now is in the event that we do have high grade toxicity, especially with CAR Ts, my team sits down and we have a little M and M and what did we do right? What could we have done better? So that way, our management of those toxicities is ever-evolving, and then again, it's important to share those experiences because as Zahra said, these are only a 5-year-old therapy and I feel like we learned something with every patient that we infuse.

Dr Hanna: Excellent. Thank you both. So just to wrap us up and we'll have time probably for 1 question, clearly, pharmacy plays a significant role in the management of these patients as the therapeutic landscape becomes more and more complex and crowded as we have seen with myeloma over the past several years. We really want to make sure we're optimizing the treatment, especially early on into the patient's treatment journey, to really try and maximize that depth of response as well as balancing and optimizing the quality of life as well as cost reductions. It's clearly evident that patients and their caregivers play a key role, so education is very, very important along that treatment journey based on the complexities of these regimens. With that, I'll ask one question to my colleagues here. Again, Zahra, maybe I'll start off with you. In patients who are starting BCMA therapy, CAR T-cell, bispecifics, do you guys do anything to manage hypogammaglobulinemia that's secondary to these BCMA-targeted therapies?

Dr Mahmoudjafari: Yeah, absolutely. I think that intravenous immunoglobulin (IVIG) has a role in these patients no matter what. It's always very aggravated and something that we have to intentionally monitor for patients that receive CAR T-cell therapy specifically, and then more recently with the bispecific antibodies, we do check monthly IgG levels and do supplement IVIG at least monthly if a patient is less than 400. We also have to make sure that those are authorized from insurance perspective as well, so we are routinely supplementing with IVIG for these patients who are hypogammaglobulinemic.

Dr Hanna: Jared, are you guys doing the same?

Dr Matya: Exactly the same, yeah. Monthly monitoring and then thankfully... These people can have B-cell aplasia for quite some time, but we do have patients that we're able to stretch out to getting every 6 weeks IVIG, every 8 weeks, and then ultimately, those B-cells hopefully come back online and can start adding to the fight a little bit.

Dr Hanna: Just again, just stressing the role of pharmacy, and we had a question come in about how do we integrate pharmacists in the care for patients? I would say look at the literature. There are tons of literature that supports leveraging pharmacy and the value the pharmacists bring to the overall care team. With that, I will wrap us up here because we are at the top of the hour. Jared and Zahra, I can't thank you both enough for your expertise. This was a great discussion, although it was extremely fast, but I hope it was beneficial to our attendees. Please join us for future sessions. Thank you so much.

This transcript has not been copyedited.

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