Frontline Multiple Myeloma Care: Clinical Operations and Nursing Strategy

In newly diagnosed multiple myeloma (NDMM), CD38-targeted monoclonal antibodies have established a new frontline standard of care. Guideline-supported frontline regimens now combine daratumumab (Darzalex) or isatuximab (Sarclisa) with lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone. Operationalizing these multi-drug quadruplets in outpatient settings requires rigorous coordination, toxicity assessment, and patient education.

Stephanie Sorrentino, BSN, OCN, Senior Director of Clinical Operations for New York Cancer and Blood Specialists, recently led an Oncology Nursing News case-based roundtable session focused on managing transplant-eligible and transplant-ineligible patients with NDMM. In an interview following the event, Sorrentino analyzed the primary clinical and logistical barriers, proposed nursing interventions, and outlined administrative protocols to optimize patient outcomes.

Operational Barriers to Frontline Quadruplets

While clinical trial data from the CEPHEUS (NCT03652064) and IMROZ (NCT02990338) studies support the efficacy of frontline quadruplets, community practices face real-world challenges in clinical adoption. Sorrentino identified key operational hurdles, starting with patient logistics:

"Accessibility is a major factor," Sorrentino explained. "Are patients able to get transportation to and from the facilities? What does their household look like? Do they have rides? Do they have assistance with maintaining their therapies? Does their health literacy meet what's needed to continue to follow through with the care at home and advise the team of specialists that care for them what is going on when they're outside of the office?"

Chair time and clinic capacity also represent significant administrative challenges.

"The other portion to that is time and availability," Sorrentino noted. "What is the chair length look like? How frequently are they coming in for visits? We now have the opportunity for [subcutaneous], which is a wonderful asset and really decreases infusion time. With your isatuximab, you might not see that ... right now it is a long infusion. Can somebody come and sit for that period of time?"

These workflow demands require clinical teams to assess patient-specific risk profiles:

"What do the hypersensitivity reactions look like?" Sorrentino asked. "Would the patient know to escalate something or would this be something we realistically need to monitor from a clinical standpoint because they don't have the capability to monitor for themselves?"

Coordinating Transitions of Care

For transplant-eligible patients, transition gaps between outpatient community clinics and specialized stem cell transplant centers pose safety risks. Clear, upfront coordination is essential to prevent patients from becoming lost in the healthcare system.

"The biggest thing here is establishing communication before starting," Sorrentino emphasized. "Ensure that both parts of the team—the transplant center and the oncology team—are on the same page. It's all signed off and now, how are we going to follow through?"

Sorrentino advocated for implementing nurse navigators as the central "communication middleman" to bridge this care gap. "They would contact each team," Sorrentino explained. "'Did they come for their harvesting? How did it go? Beautiful, it's completed. What is their next date of follow-up? When do they need to come see their oncologist?' It's a checks and balances throughout the time."

This continuous record-sharing prevents clinical errors during transition. "It's something as simple as, did we get the documents, did we see what happened at that visit?" Sorrentino noted. "We want to ensure the whole picture is brought over to each visit. This way we know what's going on. If there's something of concern, we're addressing it in real time, protecting the patient at all angles."

Optimizing Subcutaneous Administration Techniques

Clinical guidelines for subcutaneous daratumumab require injecting an 1,800-mg dose over 3 to 5 minutes. Because standard manual injections can lead to nurse hand fatigue and needle dislodgement, some clinics utilize winged infusion ("butterfly") sets. Supporting this adoption requires structured staff education and clear workflows:

"Showing the product is key," Sorrentino said. "How do we administer? What does the needle look like? Where are we placing it? Allow them to handle the wing set administration prior to being in front of a patient. You can use dummy systems or small jelly pads just to get comfortable with the hands-on portion."

To ensure patients receive the full therapeutic dose, clinics must address the priming volume of the tubing, which typically holds 0.6 mL of fluid:

"The other proponent is to ensure that the entirety of the dose is administered," Sorrentino explained. "This comes through systemwide workflows. If you are administering, how long is the infusion set that you're using? Ensure that normal saline solution is administered to ensure that that entirety of tubing is cleared so the patient gets the appropriate dose."

Looking to the future, investigational subcutaneous on-body injectors evaluated in trials like ISASOCUT (NCT05436665) are designed to deliver therapies via wearable devices. To operationalize these, Sorrentino advised listening to frontline staff feedback:

"Listen to the nurse's advice. Hear them out. Let them tell you what they think would work best," Sorrentino suggested. Clinical trials should begin with targeted patient pilots. "Start with a patient that we feel is an appropriate candidate—someone who has a good understanding of what is expected of them, knows what to escalate, and knows if this occurs, you have to come in versus how to troubleshoot if they don't need to come in... essentially a pilot with the appropriate patient population and go from there."

Sorrentino envisions wearable injectors improving treatment access. "We live in a world where everybody does not want to impact their day," Sorrentino noted. "To ensure that people can continue with their normal day-to-day lives—which is what we hope to do, right? To live a normal life, full life expectancy, and make it a manageable disease... it's a lot less time consuming. It's more accessible. If somebody lives nowhere near New York City, they can get the same treatment. It's going to help accessibility tremendously."

Differentiating and Documenting Peripheral Neuropathy

Bortezomib-induced peripheral neuropathy remains a major safety concern. Differentiating treatment-emergent symptoms from pre-existing diabetic neuropathy is critical:

"This is a difficult question, and I always think it comes down to when did the symptoms start," Sorrentino observed. "Did the patient come in and they didn't have controlled diabetes to begin with and they've already had baseline neuropathy? I don't really know if that patient would be a great candidate to start.”

To safely navigate these overlapping toxicities, real-time tracking is imperative. "Are we addressing the neuropathy and then it's going away with managing the diabetes, or is their diabetes well managed and they're having the neuropathy?" Sorrentino asked. "The timeframe of when the symptoms happen, how often they're happening, and real-time documentation is imperative to appropriately diagnose the neuropathy and see when or when not to remove the bortezomib."

Structuring Day One Patient Education

The initiation of continuous myeloma therapy is a highly intensive period for patients, often requiring weekly clinic visits. Managing this transition requires clear communication and patient trust:

"Day one is a delicate subject," Sorrentino said. "You don't want to throw everything at them at once. You want them to know the imperative information that they need to look at for right now. Then set a realistic expectation. 'Hey, as we evolve, as we see how you respond to this, we're going to see what can come next.' You're going to be coming in for many frequent visits for these first couple of months. This is to make sure you're tolerating, to keep track, keep an eye on your lab values, and we can move from there."

Nurses should prepare patients for the early treatment schedule while managing anxiety. "Provide some printed resources or some resources they can look up so that they're also getting educated material because the internet can be a very dangerous place if not used appropriately. You want to build a trust. You want them to know you're their team member. We are here to support you throughout this process."

At-home safety basics must be verified through structured recall:

"As you see the patients, go over it with them and get that read-back from them," Sorrentino advised. "Hey, this is what you should have at home. You want to have a thermometer at home, the phone number to call if x, y, and z occurs, and your care team's information. If this is a regimen where you might experience nausea, have the antiemetics before starting. This way, when you're not feeling well, it's on hand, and you know what to do."

Sorrentino also utilizes visual scheduling aids. "I print out a calendar, and each month we redo the calendar together, and they explain to me what they're doing," Sorrentino said. "The more that you can say it back, the more that you're going to remember it."

Honoring Patient Autonomy and Long-Term Quality of Life

As multiple myeloma transitions into a chronic disease, patients in deep, sustained complete response post-transplant may ask to stop maintenance therapy to improve their quality of life. Addressing these requests requires an honest clinical discussion and close follow-up:

"If a patient asks me, 'When can I come off?'... we'll say, at 2 years, let's repeat a marrow, see where we're at, see what percentage of plasma cells are there," Sorrentino explained. "Then we can have the conversation to come off treatment and just observe."

To prevent patients from being lost to follow-up, Sorrentino schedules regular check-ins. "Instead of being lost to follow-up, I need to see you 3 times a year, every 4 months or every 6 months, so we can check your blood count and see how you're doing," Sorrentino said. "I like to call them 'social visits' to see what you're doing."

Ultimately, Sorrentino emphasizes that oncology clinicians are guides, not commanders:

"Ultimately, we provide a service. We provide education," Sorrentino concluded. "But the patient is the driver of the car; I'm the passenger. I can guide you, but you make the final calls."

References

1. Usmani SZ, Vicari P, Pestourie K, et al; CEPHEUS Investigators. Daratumumab plus bortezomib, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma. Nat Med. 2025;31(4):1195-1202. doi:10.1038/s41591-024-03456-w. (NCT03652064)
2. Facon T, Dimopoulos MA, Yi Q, et al; IMROZ Investigators. Isatuximab, bortezomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma. N Engl J Med. 2024;391(17):1597-1609. doi:10.1056/NEJMoa2400712. (NCT02990338)
3. Sonneveld P, Dimopoulos MA, Boccadoro M, et al; PERSEUS Investigators. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313. doi:10.1056/NEJMoa2312054. (NCT04689230)
4. Mateos MV, Nahi H, Lauking W, et al; COLUMBA Investigators. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Lancet Haematol. 2020;7(5):e370-e380. doi:10.1016/S2352-3026(20)30070-3. (NCT03277105)
5. Bobin A, Al-Obeidi A, Rhyner L, et al. Isatuximab on-body injector versus intravenous administration in transplant-ineligible newly diagnosed multiple myeloma. Blood. 2025;146(Supplement 1):7566. doi:10.1182/blood-2025-146-S1-7566. (NCT05436665)