Expert: Pharmacists Have Vital Role in Multiple Myeloma Treatment

Pharmacy Times interviewed Melody Chang, RPh, MBA, BCOP, vice president of pharmacy operations, American Oncology Network, about the crucial role that pharmacists play in the treatment and management of multiple myeloma. Chang highlights the importance of providing patients with clear and accessible information on treatment options, personalized education, optimizing regimens, and advocating for broader access to therapies. These strategies, according to Chang, may help address challenges patients may face when receiving treatment for multiple myeloma.

Pharmacy Times: What should pharmacists know about mechanisms of action, dosing considerations, and drug-drug interactions when treating multiple myeloma?

Melody Chang: Sure, pharmacists need to be well-versed in the 7 major categories using multiple myeloma treatment. The first one is the steroid, such as the high-dose dexamethasone (Decadron; Pfizer), [which] not only kills the multiple myeloma cells, but also reduces inflammation which can alleviate pain and pressure.

The second one is a proteasome inhibitor, like bortezomib (Velcade; Takeda and Janssen Biotech, Inc.), [which] works by inhibiting the proteasome, leading to an accumulation of proteins that induce cell death.

The third one is immunomodulatory drugs, such as lenalidomide (Revlimid; Bristol Myers Squibb), modulate the immune system and inhibit tumor growth. The fourth one is the monoclonal antibody, [which] targets specific protein, like CD38, or SLAMF7 on the myeloma cells inducing immune-mediated cell death. Examples are daratumumab (Darzalex; Janssen Biotech, Inc.) [and] isatuximab (Sarclisa; Sanofi) for the CD38 target, and elotuzumab (Empliciti; Bristol Myers Squibb and AbbVie) for the SLAMF7.

And other drugs with novel mechanisms, such as selinexor (Xpovio; Karyopharm Therapeutics)...it is an oral XPO1 inhibitor [which] helps restore the body's tumor suppressor pathways by preventing XPO1 from exporting tumor suppressor proteins out of the nucleus, therefore, retaining more anti-cancer materials within the nucleus. And these drugs that work particularly well if the patient experienced resistance to the monoclonal antibody target on CD38.

The sixth category [of] drugs is the chimeric antigen receptor (CAR) T-cell therapy. Currently, there are 2 CAR T-cell therapies for multiple myeloma, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), they both are BCMA-directed. This means that the patient's T-cells are collected and then modified in the lab to effectively target BCMA on the surface of myeloma cells, and then infused back into the patient's body as supercharged T-cells to attack myeloma cells. This treatment typically involves a single infusion.

The last one is the bispecific antibiotics, and like CAR-T therapy, which is custom made using each individual patient's T-cells, bispecific antibodies are off-the-shelf products. They are engineered to bind to 2 different antigens—typically 1 on the cancer cells, and the other 1 is on the T-cells—to recruit the immune system to attack the cancer. As off-the-shelf therapies, they are more readily available, do not require the 6 to 8 weeks lab production time needed for the CAR-T therapy. Because of that, they are considered more community-friendly options.

So currently, we have 3 FDA-approved bispecific antibodies for the treatment of multiple myeloma Two [are] BCMA-targeted therapies, [and the other is] GPRC5D-targeted. Unlike the CAR-T, which is a single infusion, bispecific requires 2 to 3 step-up doses following biweekly sub q or every 2 weeks until the disease progression.

Drug-drug interactions and dosing considerations are crucial components of multiple myeloma management, especially since many patients may be taking multiple medications for various conditions, therefore, pharmacist must regularly review each patient's medication profile for potential interactions. Before administering daratumumab, it is essential to perform a type and cross match for blood transfusions. This step is crucial because there are daratumumab and antibody that targets the CD38 protein presence multiple myeloma cells can also bind to the CD38 on the red blood cells, potentially leading to incorrect blood type testing results. Those same considerations must take into account patient-specific factors, such as renal function age, and the prior treatment history. Pharmacists should be well-versed in the necessary dosing adjustment for renal impairment and capable of recalculating doses as required to ensure safe and effective treatment.

Pharmacy Times: What resources or support services do you recommend pharmacists offer to patients to help them stay informed, engaged, and adhering with their treatment plans?

Chang: Pharmacists can provide patients with clear and accessible information about multiple myeloma and its treatment options. This may include this distributing pamphlets, sharing videos, and creating infographics that detail how treatments work, their potential [adverse events (AEs)], and the importance of sticking to their treatment regimens. Additionally, the pharmacist can offer tools to help patients effectively manage their medication schedules. These tools include pill organizers, mobile app reminders, and auto-refill services, ensuring that medications are taken correctly and on time, which is essential for the treatment success.

And then, regular check-ins with the patients are another key service pharmacists can provide. [These] discussions can focus on treatment progress, any AEs [they are] experienc[ing], and then other concerns the patients might have. Identifying and addressing issues early on can significantly enhance adherence to treatments and overall outcomes. Pharmacists serve as vital links between the patients and their health care teams. By facilitating communications, they help ensure that everyone involved is up to date on the patient's treatment plan, and then any necessary adjustments based on how the patient is responding or any AEs they are experiencing.

And then, connecting patients with support groups and other community resources is another role pharmacists can play. Being part of the community provides emotional support and the valuable insights from others facing similar health challenges [can] enhanc[e] the patient's ability to manage their condition.

Lastly, pharmacists can assist patients in navigating the complex landscape of health care financing. This includes provide information about insurance coverage, copay assistance programs, and the patient aid programs offered by pharmaceutical companies or nonprofit organizations, helping to ease the financial burdens of treatment.

Pharmacy Times: What comorbidities do patients often face, and how do pharmacists address these when treating patients?

Chang: Patients with multiple myeloma most often face several health challenges, including bone disease, renal impairment, infection risks, and anemia. Pharmacists play a crucial role in managing these comorbidities by providing information on managing bone health, emphasizing the importance of calcium and vitamin D, and regularly reviewing patients and medications to identify potential drug-drug interactions and contraindications, [is] especially important for those with renal impairment. And also, advising vaccination and preventative measures to reduce the risk of infections, and monitoring blood count and the renal function, enabling them to alert the health care providers to significant changes promptly. Through these actions, the pharmacist contributes significantly to the comprehensive care of multiple myeloma patients.

Pharmacy Times: When it comes to managing AEs that are associated with multiple myeloma treatments, what are some challenges that pharmacists face and how can they effectively address them?

Chang: Managing AEs from multiple myeloma therapies presents several challenges, including neuropathy [gastrointestinal] issues, and bone marrow suppression. So informing patients about potential AEs and their [severity] are important. Collaborate closely with the health care team to monitor patients and adjust doses as necessary, and recommend supportive care options such as supplements for neuropathy, or antiemetics for nausea.

Especially for the neuropathy, studies have shown that administering or bortezomib subcutaneously—rather than intravenously—can significantly reduce the incidence and severity of peripheral neuropathy without compromising efficacy. So the subcutaneous route offers a lower peak plasma concentration, which may contribute to reduce the neurotoxicity. For patients who develop neuropathy, those modifications of bortezomib may be necessary, [and] reducing the dose or frequency, or even pausing treatment can allow that recovery from neuropathy. And if neuropathy becomes a problem—despite this adjustment—consider switching to another proteasome inhibitor with a lower risk of neuropathy, such as carfilzomib (Kyprolis; Onyx Pharmaceuticals, Inc.). [This drug] is typically used with caution in patients with cardiac issues, but [it] has a lower rate of peripheral neuropathy. Beyond the drug adjustments, supportive measures, such as physical therapy, occupational therapy, and pain management, possible use of a medication like gabapentin (Neurontin; Pfizer) can be beneficial as well.

Pharmacy Times: Can you discuss how real-world evidence is used to evaluate the efficacy and safety of treatments used in clinical practice?

Chang: The real-world evidence is increasingly valuable in assessing the efficacy and safety of treatments in clinical practice, particularly for complex diseases like multiple myeloma. [Data are] derived from various data resources outside of traditional randomized control trials, including electronic health records, insurance claims database, patient registries, and the direct patient input, [that can be found in] mobile apps and other technologies. Real-world evidence offers several benefits, and they provide insights into the long-term safety and efficacy of therapy, and guiding the treatment adjustment and regulatory decisions as well. [Data] also supports more tailored treatment approach[es] by identifying which subgroups of a patient benefit more from certain therapies.

So, in summary, real evidence plays a crucial role in the health care ecosystem by bridging the gap between clinical research and everyday clinical practice.

Pharmacy Times: Are there any recent or upcoming clinical trials that you’re excited about or you think will be significant in multiple myeloma care?

Chang: I'm particularly excited about the recent upcoming developments in the field of multiple myeloma care, especially regarding the advances in CAR-T therapy and the bispecific antibodies, and these treatments offer new hope for patients who have exhausted other options. In addition, and we know another CD38...isatuximab, it is currently been explored for subcutaneous administration and the use in frontline therapy. And so, we have more options for the CD38 products.

Pharmacy Times: In your opinion, what are pressing challenges or unmet needs in treatment and how may pharmacists contribute to addressing these challenges, whether at an individual patient level or at a broader level?

Chang: Sure, the most pressing challenges in multiple myeloma treatment—in my opinion—include the drug resistance, managing complex treatment regimens, and addressing economic and access issues related to the high cost and acccess to the latest treatments, as well. So, pharmacists can play a significant role in addressing these challenges...[by firstly], advocat[ing] for broader access to the therapies and provid[ing] personalized education to help patients navigate their treatment options. [Secondly], work[ing] closely with other health care professionals to optimize treatment regimens and their support system. [Lastly,]—and it's very important—is to encourage patients to participate in clinical trials where appropriate. So, [these] contributions are vital in advancing the care and the treatment options available to patients with multiple myeloma.