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Frontline Management of Transplant Ineligible MM

CE

Frontline Management of Transplant-Ineligible Multiple Myeloma: Optimizing Therapy, Supportive Care, and Patient Outcomes

Pharmacists: 0.50 contact hour (0.05 CEUs)

Released: July 31, 2026

Expiration: January 30, 2027

James A. Davis
James A. Davis, PharmD, BCOP
Kelley L. Julian
Kelley L. Julian, PharmD, BCOP
CME/CE Information

Activity

Progress
1 2 3
Course Completed

Supportive Care in Frontline Therapy

Kelley L. Julian, PharmD, BCOP:
Shown here are different drugs that are currently used to treat patients in the newly diagnosed setting. I will talk about why antiviral prophylaxis, antibacterial prophylaxis, venous thromboembolism prevention, and bone-strengthening agents are critical for the role of pharmacists caring for patients with MM.  

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Improving Safety and Patient Satisfaction Through Subcutaneous Administration of Anti-CD38 mAbs

Kelley L. Julian, PharmD, BCOP:
First, I provide a brief overview of how pharmacists can improve safety and patient satisfaction.

Anti-CD38 monoclonal antibodies serve as the backbone of induction treatment in MM. When these agents were first introduced, they were available only in intravenous (IV) form. However, the development of subcutaneous (SC) formulations has significantly improved the treatment experience while maintaining efficacy. 

For example, an SC version of daratumumab is now available based on the results of the phase III COLUMBA trial. When we first started treating patients with daratumumab, they would be in the infusion room the entire day. Daratumumab requires a very slow titration because it is a large monoclonal antibody and can lead to infusion reactions. That means that administrators have to pause, premedicate, slow the rate, and titrate the drug. With the SC injection, the administration time is only 3-5 minutes.9   

Isatuximab is available on the market in IV formulation but is being studied in SC form in the phase III IRAKLIA trial and phase II IZALCO and ISASOCUT trials. Again, it is important to note that the administration time is low, at approximately 10 minutes, with an objective response rate that is similar to or better than what was seen with the IV formulation.

Moreover, the rate of infusion reactions with SC formulations is very low, nonexistent, or mostly low grade if they do occur.10-12 Not only do SC versions of these CD38 monoclonal antibodies improve safety, with a fraction of the reactions noted with IV versions, but they have demonstrated similar efficacy and improved patient, nurse, healthcare professional, and pharmacist satisfaction.  

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Infection Prophylaxis Measures

Kelley L. Julian, PharmD, BCOP:
It is important that patients being treated for MM, regardless of the treatment but especially with anti-CD38 antibodies and proteasome inhibitors, remain on herpes simplex virus and varicella zoster virus prophylaxis. Acyclovir is commonly recommended for this. Occasionally patients will be given valacyclovir. This medicine is recommended for the duration of treatment and for at least 3 months after the last dose. Otherwise, reactivation is possible because these drugs target lymphocytes in memory T-cells. 

For bacteria prophylaxis, levofloxacin is largely employed when patients are neutropenic. For fungal infections, we consider prophylaxis with an absolute neutrophil count <1000 cells/mm³. Pneumocystis jirovecii pneumonia prophylaxis varies by center, but we do this in patients who are receiving large doses of dexamethasone for long durations of time, and this is typically employed post transplant and in the relapsed setting.

For COVID-19 and influenza, often prophylaxis is recommended per seasonal recommendations, at patients’ request, or if they have known exposure or test positive for COVID-19. We do consider IV immunoglobulin on a monthly basis for patients who have hypogammaglobulinemia, as evidenced as an IgG <400 mg/dL. This is also often seen in the relapsed setting, but it is common for some patients in the upfront acute phase of treatment. 

It is also important to support patients who are neutropenic (absolute neutrophil count <1000 cells/mm³) with growth factor support per institutional guidance.13

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Bone-Modifying Therapy

Kelley L. Julian, PharmD, BCOP:
The 2 most commonly used bone-modifying agents are zoledronic acid and denosumab. As indicated here, there is a slight difference in cost. Most of my patients are receiving zoledronic acid. Occasionally, denosumab is recommended because it does not require a renal dose adjustment and is safe for patients with a creatinine clearance <30 mL/min, which can occur in patients who meet CRAB criteria. 

I have anecdotally treated patients who get severe hypocalcemia with denosumab, so it is critical to ensure that a robust repletion plan is in place and that the patient’s calcium can be closely monitored. Furthermore, I always get dental clearance prior to starting either of these agents to avoid any risks related to osteonecrosis of the jaw.13

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Thrombosis: Managing DVT and PE Risk

Kelley L. Julian, PharmD, BCOP:
Thrombosis is a major concern. Thus, deep vein thrombosis and pulmonary embolism risk must be managed in patients with MM. Their clot risk is the highest in the first 6 months of treatment, and IMPEDE and SAVED scores can help guide management.14 At my center, we start patients on immunomodulatory drugs and give them a prophylactic direct oral anticoagulant such as apixaban or rivaroxaban. Additional strategies are listed on this slide.

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Peripheral Neuropathy

Kelley L. Julian, PharmD, BCOP:
Regarding peripheral neuropathy, the main take-home point is that early reporting of these symptoms and intervention are critical. Peripheral neuropathy is often reversible. This is the dose-limiting toxicity of bortezomib, so we see high rates if we are not careful. It is the patients’ job to let us know if they are experiencing symptoms so we can dose adjust or prescribe medications like gabapentin to help.15

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Additional Considerations: We Treat People, Not Myeloma

Kelley L. Julian, PharmD, BCOP:
We treat people, not MM. Every day I talk to my patients about the financial toxicity associated with these drugs and provide them with resources to help with copays and so on. This is a very important part of the pharmacist’s role. Taking care of patients’ mental health and their physical and reproductive health and connecting with them early and often are also important because this is an incurable cancer. Pharmacists have a role in all of it.  

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Tenets of Frontline Therapy

Kelley L. Julian, PharmD, BCOP:
To conclude, we have transitioned to quadruplet therapy in all patients who are eligible for frontline treatment. However, careful attention should be paid to toxicities, and dose adjustment upfront is key to keep patients on treatment and remain on schedule, especially those who are ineligible for transplant. 

The optimal length of quadruplet therapy is still to be determined, and MRD is becoming an increasingly important factor, whether through a primary endpoint or possibly even a treatment factor for response-adapted approaches. It is very possible that quadruplets can lead to shorter times on therapy, and supportive care is, as always, a pillar to success and demands a holistic approach.

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