Patient-Centered Approach to Managing Bispecific Antibody Therapy

EP: 1.Patient Case: A 76-Year-Old Man with Pentarefractory Multiple Myeloma

EP: 2.Immunologic Therapies in Multiple Myeloma: Expert Insights

EP: 3.Impact of Teclistamab on the Management of Relapsed/Refractory Multiple Myeloma

EP: 4.Talquetamab and Elranatamab: Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma

EP: 5.Choosing Between CAR T and Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma

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EP: 6.Patient-Centered Approach to Managing Bispecific Antibody Therapy

EP: 7.Navigating Unmet Needs and Challenges in Multiple Myeloma Treatment

EP: 8.Future Landscape: Collaboration for Patients With Relapsed/Refractory Multiple Myeloma

Transcript:

David M. Dingli, MD, PhD: Personally, I think of the therapy of the relapsed/refractory patient with these agents to be a partnership between the center where I work with the community oncologists, where many of the patients are actually treated. The risks related to CRS [cytokine release syndrome] and neurotoxicity mainly occur early on. This is why there is the step-up dosing. We have shown that these agents can be given safely in the outpatient setting with careful monitoring. The patients have remote monitoring. They are seen regularly during this step-up dosing because they are educated, and they can be rapidly admitted and evaluated to our immune effector T-cell program if they develop toxicity so that it can be appropriately treated.

In our practice, we typically give these therapies in the outpatient setting. We do mandate that the patient needs to be close to the medical center in about 20 to 30 minutes of driving distance. We provide an inpatient service that is available 24 hours a day if the patient needs to be admitted so the patient will be admitted smoothly to the immune effector T-cell program without having to go to the emergency room. The transition from outpatient to inpatient if it necessary occurs very rapidly so that we can institute therapy for potential CRS and ICANS [immune effector cell-associated neurotoxicity syndrome] very quickly, and we’ve shown that if one does this, the therapy can be given safely and without necessarily admitting patients to the hospital.

Now we typically would observe the patient for between 7 and 9 days and then after the first full dose is given, which is on day 7, we’ll watch them for an additional couple of days, and if they’re doing well then, we work with the local oncologist to transition care...continue therapy. The data show that the risk of significant toxicity in the form of CRS and ICANS is very low if nonexistent at that point in time. Of course, we remain engaged with the care of the patient, and I would typically be seeing these patients every 3 months or so. We advise patients on the risks of infection, we talk about mitigating measures, which I’m sure we’ll be discussing later on in this conversation, and we make sure that we are available for the community oncologist if problems arise in the course of treatment of these patients closer to home.

The overarching principle is the education of the patients and the availability of a caregiver during the early step-up dosing because that’s where some of the more acute problems are going to arise. Patients have remote monitoring devices that will monitor their pulse, blood pressure, oxygen saturation, and temperature on a regular basis. They are provided with a contact number where they can be given prompt advice and encouraged to be admitted to the hospital if necessary. The patients are also being provided with a dose of dexamethasone. If they develop a fever, they can self-administer the dexamethasone and then immediately report to the treatment station where they are assessed.

If the patient has developed grade 1 or grade 2 CRS and the patient is treated, if they have not received steroids with the dose of dexamethasone, they also receive a dose of tocilizumab, and they are observed for several hours. Oftentimes in this scenario, that therapy will be enough to break the cycle of cytokine release syndrome.

Now, of course, the patient is at risk of infections because of their disease. We will obtain blood cultures. If the patient is neutropenic, we will start broad spectrum antibiotics. If the patient does not look stable, then they will be admitted for further observation. But if the patient is not neutropenic and stable, they can be managed in the outpatient setting as long as there is a reliable caregiver available.

If the patient develops neurotoxicity, the patient will be admitted to the hospital, we will obtain neuroimaging, we will engage our colleagues in neurology. Typically, again, we provide some steroids if the neurotoxicity occurs in the context of cytokine release syndrome, then often the patients will receive a dose of tocilizumab. Usually, with this therapeutic approach, both problems tend to resolve fairly promptly. The average duration of CRS and neurotoxicity will be 1 to 2 days at most.

Another important consideration for the patient who is on a bispecific antibody is infection prophylaxis because we know that patients on this type of drugs are at some risk of infections. Personally, I recommend the following approaches for all our patients. Number 1, they need to be current with vaccines. Typically, that means the influenza vaccine every year and season. I make sure that they are current with COVID-19 vaccines as well as pneumococcal vaccine. Recently I’ve been recommending that patients receive the RSV [respiratory syncytial virus] vaccine. Patients are also advised that if at any time they develop respiratory symptoms, they need to be seen promptly, at least tested for influenza, RSV, and COVID-19. If they’re positive, we can treat them pharmacologically promptly. We know that there are drugs that work for all of these viruses and that they can turn things around very rapidly. I also recommend that patients receive acyclovir or valacyclovir for HSV [herpes simplex virus] and VZV [varicella zoster virus] prophylaxis.

We typically provide PJP [Pneumocystis jirovecii pneumonia] prophylaxis in the form either of trimethoprim-sulfamethoxazole, if the patient knows that they’re allergic or … pentamidine or atovaquone sometimes. In many patients who are already hypergammaglobulinemic, especially if IgG levels are below 400, I would recommend consideration of [intravenous immunoglobulin] or subcutaneous immunoglobulin replacement therapy. Again, there are good data which show that the immunoglobulin replacement therapy goes a long way to minimize the risk of infections in these patients.

The patients do need to be monitored carefully. One is to have a very low threshold to investigate for infection if the patient develops a fever or if they develop, for example, unexplained cytopenia. In that situation, screening for [cytomegalovirus], as well as parvovirus B19 by [polymerase chain reaction], becomes important.

Transcript is AI-generated and edited for readability.