Nurses Compare Tactics in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

Case Summary

• 76-year-old female
• Diagnosis: Stage II ISS (International Staging System) disease
• ECOG Performance Status: 1
• Coexisting Condition: Early-stage Parkinson's disease, well-controlled with treatment
• Main Symptoms: Severe lower back and neck pain
• The hematologist-oncologist determines that the patient is not a suitable candidate for a transplant.

The patient expresses the following:

• Lifestyle Preferences: Enjoys spending time outside but limited by increasing fatigue and mobility challenges.
• Patient's Goal: To live longer, improve energy, and enhance mobility to spend quality time with grandkids.

Typical Treatment Approaches

For patients with newly diagnosed multiple myeloma, frontline treatment usually involves either a triplet or quadruplet therapy regimen, Beth Faiman, Phd, CNP, of the Cleveland Clinic, said. The 3 different triplet regimens often considered are D-Rd (daratumumab [Darzalex], lenalidomide [lenalidomide], and dexamethasone); VRd (bortezomib [Velcade], lenalidomide, and dexamethasone); and VRd-lite.

Faiman asked her colleagues what standard treatment looks like for a patient like this: someone with a good functional status and who wants to be active but has some parkinsonian symptoms.

Many colleagues responded that D-Rd would be the standard approach. Daniel Verina, DNP, of Mount Sinai Medical Center, for example, answered succinctly that this would be their first choice. However, Kaylee Timlin, MSN, of the University of Colorado, said they might try VRd or daratumumab plus VRd. Some participants remarked that in just a few years, the standard approach for a treatment like this has moved from a frontline doublet therapy to a triplet combination.

“I feel like 3 years ago, we would have said maybe give her some Rd [lenalidomide/dexamethasone] or Vd [bortezomib/dexamethasone] and see how she does, but that is not where we are at right now these days,” Faiman remarked, noting that certain trials like the phase 3 MAIA trial (NCT02252172) and SWOG S0777 trials (NCT00644228) have confirmed the potential benefit of upfront triplet regimens for patients with newly diagnosed disease.

In the MAIA trial, a 5-year analysis of progression-free survival (PFS) and overall survival (OS) showed that frontline treatment DRd significantly reduce the risk of death vs Rd alone. The median PFS was 61.9 months vs 34.4 months with Rd (HR, 0.55; 95% CI, 0.45-0.67). Moreover, at 60 months, 66% of patients in the daratumumab arm were still alive vs 53% with Rd alone (HR, 0.48; 95% CI, 0.53-0.86; P = .0013).¹

Moreover, 1.7 times more patients who received DRd achieved a complete response (CR) or better with the addition of daratumumab vs Rd alone; the median duration of response was not reached with DRd vs 43.9 months (95% CI, 37.7-52.9) for Rd alone.

In the SWOG S0777 trial, a 5-year follow-up showed that more patients with previously untreated transplant-ineligible multiple myeloma were alive following treatment with VRd (69%) vs Rd (56%) at 5 years of follow-up.²

Ultimately, the patient in this case-based presentation received treatment with DRd.

“Frontline treatment with DRd was initiated [with this patient] because the MAIA study was pretty well done, and we know 3 drugs are better than 2 drugs,” Faiman explained.

The Presence of High-Risk Features

Of note, the presence of high-risk features can alter or change a provider’s treatment approach, on which the panel agreed. Faiman explained that DRd is a good regimen in this setting, as is VRd; however, she pointed out that a clinical trial may also be appropriate. Timlin, responded that she would want her patient to be receiving a proteasome inhibitor regardless of whichever treatment was selected.

When the patient is frail, as in this case, there may be times that 2 drugs may be better than 3. In fact, Rob Newman, NP, of Mount Sinai,spoke up and noted that because of the Parkinson’s and mobility issues, they might prefer a doublet for their patient instead of a triplet. And Kiah Purcell, NP, of Mount Sinai, shared that for their super-frail patients, they like to start with daratumumab monotherapy.

“You [could] start with daratumumab monotherapy for those super-frail patients,” she said. “See how they do, and if they respond, we’ll continue with it alone. And if not, then we will add something.”

Lisa Hwa, DNP, of the Mayo Clinic, added that sometimes with those really frail patients, her team will even start with a lower dose and see how their patient does, if they can get a response.

Aligning Treatment Goals With Disease Risk and Frailty Levels

“So how do therapy goals and treatment challenges differ based on a patient's disease risk and level of frailty?” Faiman asked her colleagues. “Would you still consider transplant for her?”

Faiman went on to remind the panel that the oncologist had voted no on the transplant, based on the availability of systemic therapy alternatives, but that because the patients is 76 and mobile, with a decent performance status and organ status, the argument could be made for transplant.

Dennis Reducci, NP, of the University of Miami, shared that at their institution, the team would most likely consider a transplant in this situation.

Purcell shared that she thinks it would be worth having the patient come in for a consult.

“Come in, and have the team say no,” she said.

Faiman concluded by noting that the nurse practitioner or advanced practice provider play a big role determining the patient’s individual goals and guiding them through their shared decision-making.

“It is not [always] recognized as our scope of practice by some physician partners,” she said, “but we play a strong role in giving patients options, too.”

References

1. Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596. doi:10.1016/S1470-2045(21)00466-6
2. Durie BGM, Hoering A, Sexton R, et al. Longer term follow-up of the randomized phase III trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (Pts) with previously untreated multiple myeloma without an intent for immediate autologous stem cell transplant (ASCT). Blood Cancer J. 2020;10(5):53. Published 2020 May 11. doi:10.1038/s41408-020-0311-8