Anne-Marie Jacob, a patient with multiple myeloma, discusses the treatment of multiple myeloma with bispecifics alongside a panel of experts.
At an Around the Practice® program hosted by CancerNetwork®, a patient with multiple myeloma, alongside a panel of health care providers, discussed her journey with the disease and her experiences with teclistamab (Tecvayli) and other agents. The discussion was led by Ajai Chari, MD, a professor of medicine and director of clinical research in the Multiple Myeloma Program at the Icahn School of Medicine at Mount Sinai in New York, New York.
The panelists were nurse practitioner Kiah Purcell, MSN, AGPCNP-BC; Annel Urena, BSN, RN, a clinical research nurse in the Multiple Myeloma Program; and Anne-Marie Jacob, a patient in remission who was diagnosed with multiple myeloma in 2012.
CHARI: What is your experience with myeloma?
JACOB: I started experiencing pains in my neck in 2012, so I decided to go to the emergency [department]. I explained exactly what was taking place and they requested several tests. I had blood drawn and imaging conducted. From the imaging, they found tumors on my spine [and] one on my neck, which was causing most of the pain.
They performed a bone marrow test and a bone density test. Then, I was told I had multiple myeloma. They explained the treatments they use. They also told me there was no cure, but that I needed radiation and chemotherapy. I asked how long the treatment would last. They said it could be ongoing. I asked questions [about] quality of life given the lack of a cure for myeloma. For some reason, I wasn’t scared. I’d prayed a lot, and I [felt I could] handle it.
They started radiation and chemotherapy. During that period, I couldn’t eat. All I could do was drink—liquids only. I lost a lot of weight, and I was very ill, but we kept going.
Even though it was rough, I managed to handle [this period] because of the people around me, who cared for me and were supporting me along the way. [However], it was very, very rough in the beginning. I experienced kidney failure at one point. [I’m grateful] it didn’t last very long because I’d just had 3 sets of chemotherapies.
CHARI: Do you recall how long you experienced neck pain?
JACOB: It was for a few months. I kept taking pain meds and it would go away, but I realized it wasn’t ever going away [permanently]. When I went to the hospital, they did [extensive] examination, and they put my neck in a brace. When they put my neck in that brace, the pain stopped.
CHARI: Most patients who develop myeloma are in their 60s and 70s.
JACOB: I got it at age 62.
CHARI: Our youngest patient was 18 and our oldest is 100. Anytime we give numbers, we have to keep in mind what’s typical and that there could be extremes.
You’re conveying something very important. Patients who are 60 or 70 years old will often have bone pain from arthritis. As such, when do you need to worry that the pain indicates something more serious? [We would say that] you should worry when it’s persistent, progressive, and not getting better.
JACOB: Everyone at first thought it was arthritis. I always said: What type of arthritis do I have that no pain meds can stop [the pain]? That’s when I decided to go to the hospital to find out what was wrong. I knew my body, I knew myself, and I knew something was wrong.
CHARI: How do patients typically present with myeloma in a clinical setting?
PURCELL: [They typically present] very fatigued, with severe pain, [and] sometimes shortness of breath. I’m usually treating patients with relapsed/refractory disease, but [they present with] fatigue and pain, and as the disease progresses, their pain worsens.
CHARI: The diagnostic criteria for myeloma include hypercalcemia, bone pain, constipation, [and] renal insufficiency. Sometimes people notice bubbles in their urine from the foam. Anemia, which [usually causes] fatigue without significant bleeding, tends to be gradual. Those are [some of] the symptoms.
We tend to see slightly more men than women [with this disease]. There are about 32,000 new cases [diagnosed in the United States each] year. We tend to see [this disease] more in African Americans than non–African Americans. That’s also true of the precursor condition known as monoclonal gammopathy of undetermined significance. Fortunately, the outcomes are improving in these disease spaces.
What resources do you employ to help patients with newly diagnosed or relapsed myeloma?
PURCELL: I rely on our social workers quite a lot. They’re great resources. Sometimes we refer [patients] to psychiatry if needed because [relapse can be] a huge burden. There’s a lot of anxiety that comes along with this, [with] not knowing when the disease will come back. We also always like to include nutrition as a resource.
URENA: Additionally, when patients are in the hospital setting, we [ensure that] we consult with them if they’re having any kind of infection that may require an inpatient or outpatient stay. We ensure that they know they have social resources, [including] support groups.
PURCELL: The social workers at Mount Sinai are excellent [when it comes to] arranging transportation and helping with finding funding through different foundations for co-pays and hospital stays. We’re lucky to have such a big team at Mount Sinai. We point [patients] toward [financial aid] because financial strain deeply affects patients’ quality of life.
CHARI: In a class [I once took], we felt that 50% of what you tell a patient with cancer in the first visit goes in one ear and out the other because of the emotional coping that comes from a new diagnosis. How would you counsel newly diagnosed patients to use the resources they have with the people in their lives?
JACOB: It’s important to [take advantage of] these resources. [Also], the people in your life need to understand what you’re going through [and] how you’re feeling. For instance, when I couldn’t eat, my brothers went crazy looking at me losing weight. I [told them it wasn’t] because I didn’t want to eat, but because [I couldn’t]. As a matter of fact, instead of them taking care of me, I had to take care of them—[I had] to make them feel better.
I had friends who were always there. They would call all the time, even from back in Trinidad, to find out how I was doing. Also, the concern that [my doctors] showed, and the questions they asked, were great. That’s very important. You need that.
CHARI: In the first visit, we as clinicians convey the symptoms of the myeloma, the staging and prognosis, and the treatment. Nowadays, our treatments often include multiple drugs to prevent adverse effects [AEs]. If you’re a patient walking into that first visit, you receive an onslaught of information.
Doctors are just a small part of the team. We [meet with patients], and then the nursing team follows up, saying, for example, “What they mean is this, this, and this.” [This way you understand] the written notes, and [you can rely on] your family members [for help].
CHARI: Historically, [myeloma] was [managed] with a 3-drug regimen: lenalidomide [Revlimid], bortezomib [Velcade], and dexamethasone, followed by lenalidomide [maintenance], which is what Anne-Marie received. She had some neuropathy [with this regimen]. She then had a transplant and lenalidomide maintenance. That was considered her first treatment, lasting from 2012 to 2015.
[Currently], there are excellent data supporting the addition of a frontline monoclonal antibody known as daratumumab [Darzalex]. We now tend to use this 4-drug regimen, [and we’re] still doing transplants if patients are eligible [followed by] maintenance therapy.
We [also] have the so-called immunomodulatory drugs: thalidomide, lenalidomide, and pomalidomide [Pomalyst]. We have the proteasome inhibitors: bortezomib, carfilzomib [Kyprolis], and ixazomib [Ninlaro]. We have the so-called immunologic agents, [including] the naked antibodies known as daratumumab and elotuzumab [Empliciti]. We have some new and exciting T cell–redirection therapies, and we have the XPO1 inhibitor known as selinexor [Xpovio].
So, in total, we have these 6 classes of drugs for myeloma. The flip side of lacking a cure [is that] every treatment works for a while and then stops working. As such, we generally try to use a drug until it either stops working or becomes intolerable. [Efficacy and safety] are equally important.
What was your quality-of-life experience with some of these agents?
JACOB: With some of those agents, I was very ill. I needed help to do everything—[even] to get up out of bed, to go to the bathroom. I [always] needed someone there to assist me. It was rough at that time.
I had to take one of the drugs twice a week. When I took it on a Thursday, by Saturday I’d be in an ambulance going to the emergency [department], either unconscious or partly unconscious. It used to be that bad.
CHARI: When we first met, you’d already received several of these agents. We gave you a 96-hour infusional chemotherapy and then put you on a daratumumab-based combination. You had progression. You did a clinical trial with selinexor and remained on that for about a year. You received a bispecific antibody; you had a transplant. Most recently you [began receiving] a combination of daratumumab and teclistamab.
Thanks to patients like you who started participating in these trials 4 years ago, this drug, [teclistamab], was approved recently. How do you decide whether to participate in clinical trials?
JACOB: At first, I thought maybe the myeloma would go away, even though they said there was no cure. I would feel good because I would see my numbers going down, [and] when they reached [zero], I asked what would happen if I came off the drug. [I was told] they would go back up again.
Each time [progression] happened, I would [find] another trial. My brothers would ask why I did it. I said, “I guess I might as well try it.” One of them told me about a friend who’d been on trial for 20-something years, and she’s still going. He said, “So go ahead and do it.” That helped give me courage to continue on these trials.
This [most recent] trial regimen was the best. I heard the word “remission” [for the first time] in almost 11 years of treatments. Also, with this treatment, I wasn’t very ill at all. Hearing the word “remission” was like music to my ears. I just kept thanking God, and I was grateful for the doctors and nurses, and all the people that work with me.
CHARI: How do you prepare patients for treatment?
PURCELL: Good patient education is the first thing that needs to happen. The patient needs to know what to expect and why they’ve been admitted. If they don’t understand that there’s a 70% rate of cytokine release syndrome [CRS], they’re not going to understand why we should admit them. You have to [carefully] educate them about the AEs, which if left untreated can be dangerous. [You also have to] explain to them how the drug works and what the administration process will be.
Teclistamab is given through a subcutaneous injection, so [the patient needs to know] what that looks like. We have them inpatient to monitor for CRS [and other toxicities]. We look at their labs and symptoms. We’ll give medication if needed.
[All in all], it’s a fairly complex visit. Patients don’t usually get all the information they need on their first visit because they’re focused on [other things], so reiterating [points about the potential] AEs, and explaining how admission goes, [is critical].
[Then], they’re admitted. They get the drug. They’ll receive small step-up doses. We start with a low dose and then slowly increase it to mitigate toxicity. [We need to] explain that they’re going to be in the hospital for a long time.
CHARI: What are the signs and symptoms you pay attention to when preparing for step-up doses?
URENA: When we’re stepping them up, or once I begin seeing them in the outpatient setting, they can have injection site reactions—[often] some type of rash on the abdomen area. We’re looking to ensure that there’s no CRS, so [we look for] low blood pressure, shortness of breath, fevers, or anything like that.
Once I see them in the outpatient setting, I just go over their AEs—any gastrointestinal symptoms [like] nausea, vomiting, or diarrhea. If they’re having any pain, I go over their labs and ensure that the nurses who administer the medication know the parameters [around when to] give the drug. I make myself into their resource, and I work collaboratively with the pharmacy to ensure that everything is going smoothly for the patient.
CHARI: Nurse practitioners do such a great job with [obtaining informed consent from patients] and with counseling in our practice. What are some of the supportive care agents clinicians use in this space?
PURCELL: It’s our practice to [get] consent for tocilizumab [Actemra], [in addition to consent for the study drugs, when handling] consent for these research trials, because we like to give tocilizumab in the event of CRS. It’s an [interleukin]-6 inhibitor. [Additionally], with CRS, people can also have neurotoxicity, so it’s good practice to [obtain] consent ahead of time because it’s difficult to [receive] consent from someone who isn’t neurologically intact.
We also sometimes give anakinra [Kineret], especially if they have neurotoxicity. We’re more likely to give anakinra than tocilizumab; [we also may give] dexamethasone, which we don’t have to [receive] consent for.
CHARI: What are some of the pre-meds we give for teclistamab prior to the first dose?
PURCELL: For teclistamab, we administer 16 mg of dexamethasone, as well as acetaminophen [Tylenol] and diphenhydramine [Benadryl]. It’s our practice to also give famotidine and montelukast [Singulair] just to prevent or lessen any infusion-related, allergic reactions, or CRS, during the 24 to 48 hours [after their first dose]. On trial, that was the requirement. The label also recommends premeds. Those [drugs] help mitigate the symptoms.
The nurses on the unit need to be educated on what to look out for. They can’t just administer a standing order of acetaminophen because it’s immediately available. They need to know that a fever might mean a patient is having this reaction called CRS, and that it might not be serious at first, but, if left untreated, it can progress quickly and become very serious.
CHARI: Sometimes patients are very reluctant to be admitted to a hospital. What would your advice be to such a patient?
JACOB: They should accept the admission and they should go to the hospital for the first dosage of the medication. Not that you want to be in the hospital, but it’s a safer place to be. When you get the drug, you can’t be sure how you’ll react to it, how your body will react to it. At home, it takes longer to get the treatment that you need to assist you. In the hospital, everything is right there.
CHARI: Teclistamab has [around] a 70% response rate that is very deep and durable. You had what I always call the A-plus result. You’re minimal residual disease–negative, in stringent complete remission. We can’t detect myeloma anywhere in your body. Admission is an upfront hassle, but we always hope the long-term benefits [outweigh the costs].
Your main AE during this admission was low-grade CRS, and you had others as well. What was your experience with toxicities during your stay in the hospital?
JACOB: I got cytomegalovirus [CMV], which was taken care of quickly. I was in the hospital when it happened, so I was in the right place.
CHARI: The CRS was relatively low grade and managed with tocilizumab. You were able to get your doses and be discharged, correct?
JACOB: Yes, exactly.
CHARI: What should an outpatient team need to know about administering bispecifics?
PURCELL: They need [to perform] close follow-up for infections; monitoring for infection [continues] after discharge. Any fever or shortness of breath should be taken seriously. Anything indicative of an infection needs to be worked up.
At our facility, it’s our practice to monitor for CMV monthly because we’ve seen a lot of CMV reactivation in these patients. We’ve caught it in a few patients, and so we’ve been able to hold the drug and treat the CMV before it became serious. [We also perform] early testing for viral infections, as well as prophylactic measures such as intravenous immunoglobulin [IVIg], because teclistamab suppresses the immune system. [We do] anything we can to bolster the immune system and prevent infections. Spending less time in the hospital is extremely important [for these patients].
CHARI: Commercial teclistamab [comes with] a wallet card to be given to patients. In the United States, not everybody will be treated in an academic medical center, and they may not be coming to our hospital for problems. As such, the wallet card should warn providers, especially emergency [department] personnel, that this patient may have CRS [or other] unusual opportunistic infections.
How do you counsel people about COVID-19 prior to starting drugs like teclistamab?
URENA: We tell them to ensure that they take COVID-19–related precautions: masking, following CDC guidelines, and vaccinating. If they are COVID-19 positive, we ensure that they communicate with the team. [At that point], we collaborate with our pharmacy team to ensure that we can administer any type of medication, or any antibody therapy, to combat the infection.
[The patient needs to be] educated about swabbing and contacting their [care] team. Contracting COVID-19 is dangerous [for patients who are] so immunocompromised. They can end up in the hospital, and it can take a [serious] toll.
PURCELL: If a patient hasn’t already been on teclistamab, I would recommend getting a [COVID-19 vaccination] booster. Get whatever you need so you have a response before starting teclistamab. If the patient is already on teclistamab, they might not derive much benefit from the vaccine, so they might need additional boosters [later]. If you’re not on the therapy yet, I’d recommend getting vaccinated before you start.
CHARI: There are 3 COVID-19 components: prevention, detection, and treatment. All are important. Prevention [involves] vaccinating as much as possible [and] keeping up with the guidelines. For detection, I tell all my patients to have COVID-19 testing kits at home, a blood pressure machine, a thermometer, and a pulse oximeter, because the sooner you know, the better.
The home test can sometimes be [inaccurately] negative. If you have a fever, or any kind of respiratory symptoms, [it’s important to] call right away. [From the start of symptoms], we have 5 days to treat COVID-19 and very little time to treat the flu. It’s important for patients to come in [as soon as they are symptomatic] and get a full workup because the sooner we know which virus or bacterium it is, the sooner we can intervene.
Additionally, rates of hypogammaglobulinemia with teclistamab are very high, [although] this isn’t specific to this agent. All B-cell maturation antigen [BCMA]–targeting bispecific antibodies [tend to have these effects].
We’ve had patients with very unusual and serious infections while taking BCMA-targeting bispecific antibodies. How would you counsel patients regarding this?
PURCELL: Close communication with health care providers [is key]. I’m lucky enough to work in a practice in which we’re in very close communication [with each other], because it’s a research-oriented practice. When teclistamab rolls out to community health centers, resources [will be needed] to call patients back quickly and conduct close follow-up. What might seem like a little fever or chest pain might not be [so innocent]. [These infections] can progress [quickly]. We’ve seen CMV in multiple patients, some of whom end up in the hospital. We have a very low threshold before we bring in patients for a full workup.
CHARI: Do we have any other recommendations for community practices using teclistamab and other bispecifics?
URENA: Patient education is critical. [Patients need to know] the signs and symptoms to look out for. Whoever’s taking care of them [needs to] look out for signs as well. [Care providers also need to] ensure that they’re monitoring for [signs of infection], taking care of standard precautions, [the] precautions related to COVID-19, and things of that nature.
As well as clarification of [potential] AEs, there should also be financial and emotional support [for patients]. Most of the time, these patients are going through a lot, and [these issues] aren’t covered much, especially in the community setting. In certain communities, there’s already a stigma around health care, [to the extent that] people don’t really trust health care [providers], so [it’s crucial to give] emotional support and compassionate care to these patients as well.
CHARI: Sometimes patients will have a lot of anxiety if we recommend skipping or delaying a dose over concerns about an infectious process. We had to do that with you, Anne-Marie. How do you process that? What was your reaction?
JACOB: Well, if they need to hold [back treatment], [it means] they have to take care of whatever [other problem] is occurring at that point. If there’s an infection that needs to be taken care of before resuming the medication, it’s important [not to ignore that].
JACOB: Right, [it’s risk-benefit] because you cannot be treated. You have the infection; you cannot be treated with the infection.
CHARI: How have you balanced a chronic disease with travel?
JACOB: I was only able to travel once in all the time [since I was diagnosed], but I do miss traveling.
CHARI: If a patient wants to travel, what do you tell them?
PURCELL: There are many factors at play. If their disease is well controlled, we can maybe spread out the dosing. [This is if] they’re not neutropenic, and therefore not at higher risk for infection, and they’re getting their IVIg. As long as they’re doing OK, there’s some wiggle room. I’ve had patients who go away for 26 days between their monthly doses. We also have patients who fly all over the place. They barely pop in for their treatment; they’re always traveling.
COVID-19 made it very difficult because [these patients are] in a group with a higher risk of serious AEs, and [higher risk of] serious illness, hospitalization, and even death [from COVID-19]. [Earlier in the pandemic], we strongly recommended that patients didn’t travel as much.
That [guidance] has relaxed now. If you’re doing well and your numbers look good, there [can be] good times to travel—but also times when it’s not the best choice.
CHARI: The key is communication. The right time can depend on other medical issues the patient may have, disease factors, and treatment. It’s also important to get travel insurance because you never know what’s going to happen, and you may need to cancel. [Regardless], we don’t treat patients to [reach] complete remission [just] for them to be stuck at home: We want them to be able to enjoy life.
There are some other exciting drugs under examination aside from T cell– redirecting therapies. [These are] known as cereblon E3 ligase modulators, which are oral medications like lenalidomide and pomalidomide. These are the next-generation compounds that appear to work even in patients for whom those older agents fail.
There’s also a product that binds to CD38—an antibody-drug conjugate that has attenuated interferon. These are needed because, for example, maybe you can’t just go from one T-cell redirection to another. If the T cells are exhausted, or a patient doesn’t have good T-cell function, we might want to try an agent with a different mechanism of action. Some of those demonstrate a lot of single-agent activity in the heavily treated population, which is nice to see.
CHARI: What should patients and health care providers in the community know about teclistamab?
PURCELL: [Teclistamab therapy] can seem overwhelming upfront, given the [necessity of hospital] admission, but there’s a chance for a long, durable remission and a high quality of life. Most of my patients on teclistamab feel very well. We have to watch out for infections, but they’re doing well.
If we’re giving the drug at a site lacking experience with CRS, with chimeric antigen receptor T-cell therapies or T-cell redirection, the staff needs to educate themselves. There is the Risk Evaluation and Mitigation Strategy program, but early detection is crucial. There’s a lot of infrastructure [necessary for this drug]. A lot of education needs to be done to bring this drug to a patient, but the benefits are immense.
URENA: In a community setting, trust is crucial, and it’s one of the biggest challenges. Monitoring is [also] crucial. If they have access, teclistamab will work well for the community and for the patient.