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With plenty of data from the CheckMat-227 trial to go through, one expert breaks down the vital data that will directly impact the practice.

Implementing CheckMate-227 Data in the Practice

While high-risk multiple myeloma can be difficult to treat with aggressive therapies, treatment considerations with the help of diagnostic tools may prove helpful when determining when to de-escalate treatment for certain patients.

At a recent Community Case Forum hosted by Oncology Nursing News, Mark Davis, PA-C, a physician assistant from Texas Oncology, Southwest Forth Worth Cancer Center, and colleagues discussed disease burden and diagnostic tools, as well as risk stratification and treatment approaches in high-risk multiple myeloma.

“In terms of risk stratification, we use the International Staging System [ISS], which is more or less the old way of doing it…” Davis explained during the event, adding that providers use the revised ISS with lactate dehydrogenase (LDH) levels and high-risk cytogenetics of chromosomal abnormalities. “So somebody who has a double-hit myeloma, that means they have 2 chromosomal abnormalities, and that is going to put them at a higher risk classification.”

Factors associated with high-risk disease or the progressive relapse setting include those with newly diagnosed myeloma who have a revised ISS of III, extramedullary disease, circulating plasma cells, and cytogenic abnormalities. For patients with newly diagnosed multiple myeloma, cytogenic abnormalities associated with high risk for disease progression or relapse include Del(1p32), t(4;14), t(14;16), t(14;20), Del(17p) or monosomy 

 mutation, 1q21 gain or amplification, and MYC translocation.

“As an [advanced practice provider (APP)] we can really help clinicians not only identify high-risk patients based on cytogenetics but also those who have a short course of remission and identify them as high risk as well,” Davis said in an interview with Oncology Nursing News. “And so patients who have disease progression within 2 years of their induction therapy, [that] automatically puts them in a subgroup of high-risk disease. And we are trying to tailor therapies differently in those patient populations that have more aggressive disease.”

Factors that may impact treatment for patients include their personal preferences, physical activity, work productivity, comorbidities, quality of life, disease symptoms and control, treatment-related toxicities that could lead to discontinuation, treatment convenience (oral vs intravenous), and financial toxicity.

With high-risk myeloma, it is a disease that can be difficult to treat. To further complicate management, many patients are unable to receive intense treatment because of comorbidities.

At the Community Case Forum, Davis presented a case of a 76-year-old female with ISS stage II myeloma, who is not eligible for a transplant and also presents with early-stage Parkinson’s disease that is currently controlled with treatment. At diagnosis, she presented with severe lower back and neck pain, has experienced increasing fatigue and mobility challenges, and reported with an ECOG performance status of 1.

The case, Davis noted, highlights certain patients’ inability–for example, older, frail, or transplant-ineligible patients–to receive aggressive therapy, whether considered high risk or not, and, in turn, the need for treatment de-escalation.

The attendees were polled on what regimen should be prescribed for the frontline treatment of this patient, including:

bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd), which included CRd lite;

daratumumab (Darzalex) plus lenalidomide and dexamethasone (Dara-Rd);

ixazomib (Ninlaro) plus lenalidomide and dexamethasone (Ixa-Rd); or

a quadruplet regimen like Dara-VRd or Dara-VMP)

Results were evenly divided-50% of respondents said that they would consider VRd while the other half were in favor of Dara-Rd.

“Both of those responses are on par to what we would expect,” Davis said. “…Frail and elderly patients are technically considered high-risk patients because historically, they’re unable to go with more aggressive therapies that include transplants.”

He added that these patients will also often be offered, in the community setting, a doublet that has inferior results due to concerns of toxicity. “More recent data from the MAIA study [NCT02252172]

 showed similar tolerance in older patients who were treated with Dara-RD vs Rd. Hopefully, this data will encourage clinicians to move further away from doublets even in our frail patients.”

Similarly, he added, often patients who are elderly or frail would not be offered a quadruplet regimen either. “You're often going to have to de-escalate [treatment] in some form or fashion.”

To aid in predicting long-term remission, the use of minimal residual disease (MRD) is growing in the multiple myeloma landscape.

“There's now studies ongoing about de-escalating therapy based on MRD, but also just even outside of that, from a prognostic value, it's more accurate than our M spikes,” Davis explained. “…MRD is most valuable when patients are wanting to de-escalate, and this could be a leverage point.”

In the case study, the patient was treated with frontline Dara-Rd. Following 9 months of treatment, she presented with an ECOG performance score of 2, a complete remission that was followed by a partial response at month 1 and very good partial response at month 8, with stable chemistry labs. In addition, the patient experienced grade 3 neutropenia that lasted for 1 cycle of treatment and appeared refractory to a single dose of granulocyte colony-stimulating factor. Her imaging revealed no new findings.

At 12 months, the patient’s ECOG performance score was 1 and she is stable in CR, chemisty and hematology labs, and continuance of no new findings on her imaging. Of note, her Parkinson’s disease remained in control with daily functioning that was consistent with baseline findings.

“MRD negativity at 12 months alone has also been associated with overall survival improvement. So again, it just highlights, for us, the relevance of deepening responses and maintaining somebody in a state of undetectable disease,” he said, highlighting that MRD negativity led to a median progression-free survival of 63 months, compared 27 months among patients with CR achievement, based on data from a pooled analysis of 3 Pethema/GemDavis clinical trials.

NCCN. Clinical Practice Guidelines in Oncology. Multiple myeloma, version 1.2025. Accessed December 12, 2024. 

https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf

Facon T, Kumar S, Plesner T, et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. 

. 2019;380:2104-2115. doi:10.1056/NEJMoa1817249.

Lahuerta JJ, Paiva B, Vidriales MB, et al. Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials. 

. 2017;35(25):2900-2910. doi:10.1200/JCO.2016.69.2517.

“Treatment effectiveness can have different meanings to patients,” a physician assistant said when discussing therapy for high-risk myeloma. 

High-Risk Myeloma Treatment Is Not One-Size-Fits-All

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Video content above is prompted by the following:

How do you help patients weigh the risks and benefits of different treatment options?

What tools or techniques do you use to ensure patients and caregivers fully understand their choices?

This program was made possible with support from Novartis Pharmaceuticals.

Panelists discuss how to help patients weigh the risks and benefits of different treatment options for paroxysmal nocturnal hemoglobinuria (PNH), outlining tools and techniques used to ensure that patients and caregivers fully understand their choices and make informed decisions.

Patient-Centered Approaches in EGFR-Mutated NSCLC

From your perspective, how have oral and subcutaneous therapies changed the quality of life for patients with 

What benefits have patients shared with you about their experiences with these newer administration routes?

-mutated NSCLC treatment, what developments are you most excited about?

Please highlight any trials, novel agents, or combinations you find promising.

How do you see the role of the multidisciplinary care team evolving as these therapies advance?

As patients take more charge of their care, how do you see the role of patient empowerment and self-management evolving?

What strategies have you found effective in supporting patients to take a more active role in their treatment journey?

How do you balance the benefits of home-based care with ensuring patients feel supported and connected to their health care team?

Panelists discuss how oral and subcutaneous therapies have improved the quality of life for patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), with Squires sharing patient benefits from newer administration routes, and Dr Scott highlighting promising developments in EGFR-mutated NSCLC treatments, while exploring the evolving role of patient empowerment, self-management, and the multidisciplinary care team in supporting patients through home-based care and active participation in their treatment journey.

Clinical Decision-Making and Sequencing Strategies in EGFR-Mutated NSCLC

How do the various EGFR-targeted therapies differ in terms of administration protocols and the strategies employed for effective patient management?

How do you tailor nursing interventions for patients on oral TKIs vs those receiving infusion or subcutaneous therapies, especially in managing adverse effects and ensuring adherence?

What strategies do you employ to facilitate open communication with patients about what to expect during their treatment and to address their concerns effectively?

How do you approach the sequencing of therapies across multiple lines of treatment in EGFR-mutated NSCLC? How do you approach shared decision-making and patient education when discussing treatment options for 

What factors influence your decision-making when moving from one line of therapy to the next?

How do resistance mechanisms impact your sequencing strategy, and what role does biopsy play in guiding these decisions?

Panelists discuss how EGFR-targeted therapies differ in administration protocols and management strategies, with Palmer sharing tailored nursing interventions for oral tyrosine kinase inhibitors (TKIs) vs infusion or subcutaneous therapies, and Dr Scott addressing approaches to sequencing treatments, shared decision-making, and the role of resistance mechanisms and biopsy in guiding therapy decisions for EGFR-mutated advanced non–small cell lung cancer (NSCLC).

Subcutaneous Amivantamab in Practice: Clinical Insights and AE Management

From a nursing perspective, how does the availability of subcutaneous amivantamab influence your approach to patient care and education?

Panelists discuss how the availability of subcutaneous amivantamab influences nursing approaches to patient care and education, with Squires sharing strategies for ensuring patients understand the new administration method and preparing them for treatment.

EGFR-Targeted Therapies in NSCLC: IV vs Subcutaneous Administration

How does amivantamab’s dual targeting of EGFR and MET potentially address resistance mechanisms and unmet needs in 

In your clinical experience, what makes a patient an ideal candidate for amivantamab?

Based on your experience with patients receiving IV amivantamab, can you describe the typical adverse event profile and your strategies for managing these adverse effects?

Panelists discuss how amivantamab’s dual targeting of EGFR and MET may address resistance mechanisms and unmet needs in EGFR-mutated advanced non–small cell lung cancer (NSCLC), with Dr Scott highlighting its potential clinical benefits, while Squires shares insights on managing the adverse event profile and strategies for managing adverse effects in patients receiving intravenous (IV) amivantamab.

Marina Garassino, MD

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