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Individualizing Treatment Strategies in MM
Individualizing Treatment Strategies in Multiple Myeloma: From Risk Assessment to Supportive Care

Released: July 10, 2026

James A. Davis
James A. Davis, PharmD, BCOP
Kelley L. Julian
Kelley L. Julian, PharmD, BCOP
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Key Takeaways
  • Risk-adapted, patient-centered care is essential across the myeloma continuum.
  • Anti-CD38–based regimens and MRD-driven treatment strategies are redefining standards of care.
  • Optimal outcomes require proactive toxicity management and supportive care.

James A. Davis, PharmD, BCOP:
The management of multiple myeloma (MM) has entered a period of meaningful clinical refinement. MM remains largely incurable for most patients, yet therapeutic advances have shifted the goals of care from short-term disease control toward deeper responses, longer remissions, improved drug tolerability, and increasingly individualized treatment selection. Anti-CD38 monoclonal antibodies now play a central role across the disease continuum, from high-risk smoldering multiple myeloma (SMM) to transplant-eligible and transplant-ineligible newly diagnosed disease. As oncology pharmacists, we must help translate increasingly complex data into safe, patient-centered, and practical treatment decisions.

Risk Stratification and Treatment Decision-making Across the Myeloma Continuum

James A. Davis, PharmD, BCOP:
One key starting point is distinguishing precursor plasma cell disorders from active myeloma. Monoclonal gammopathy of undetermined significance is generally observed rather than treated because of the asymptomatic nature and low risk of progression. SMM, however, occupies a more clinically challenging middle ground. Patients with this form of disease do not yet have myeloma-defining events, but some carry a substantially higher risk of experiencing progression to active myeloma. Modern risk stratification models, particularly the International Myeloma Working Group refined 2/20/20 model, have improved the ability to identify patients with SMM whose risk may justify early intervention. Serum M-protein, involved-to-uninvolved free light chain ratio, bone marrow plasma cell burden, and cytogenetic features all factor into this assessment.

The optimal management of high-risk SMM continues to be actively debated. Observation is still appropriate for many patients, especially those with low- or intermediate-risk disease. Yet for patients with clearly high-risk features, early treatment may delay progression to active myeloma. Daratumumab has emerged as an important option in this setting, supported by data showing delayed progression associated with this treatment compared with active monitoring. The clinical message is not that every patient with SMM should be treated, but rather that a careful discussion of treatment goals, potential toxicities, patient anxiety, logistics, and competing health priorities is warranted in high-risk patients. The goal of therapy in this setting is not indefinite disease suppression at all costs; it is to meaningfully delay progression while preserving quality of life.

Shared decision-making is especially important in smoldering disease. Some patients experience significant distress knowing that they have a premalignant or early malignant condition that may progress. Others may prioritize avoiding treatment until symptoms or myeloma-defining events appear. Anti-CD38 therapy may be appealing because it is generally better tolerated than many multiagent myeloma regimens, but it is not free of toxicities. Infection risk, treatment burden, monitoring requirements, and patient preference should all shape the treatment conversation.

Optimizing Frontline Therapy: Anti-CD38–Based Approaches, MRD, and Transplant Considerations

Kelley L. Julian, PharmD, BCOP:
In newly diagnosed multiple myeloma, the treatment paradigm has moved decisively toward deeper frontline responses. For transplant-eligible patients, quadruplet induction regimens incorporating an anti-CD38 monoclonal antibody with a proteasome inhibitor, an immunomodulatory agent, and dexamethasone have become standard of care. Improved depth of response and progression-free survival (PFS) seen with the combination of daratumumab plus bortezomib, lenalidomide, and dexamethasone vs the triplet regimen strongly support upfront quadruplet utilization. Isatuximab-based quadruplets have also demonstrated improved efficacy, including in higher-risk populations.

Minimal residual disease (MRD) has become a crucial marker in this evolving landscape. Complete response alone is no longer the most prognostic endpoint. MRD negativity reflects a deeper level of disease clearance and is prognostic for both PFS and overall survival (OS). As clinical trials increasingly incorporate MRD-guided treatment approaches, healthcare professionals are beginning to consider whether therapy can be intensified, continued, or de-escalated based on early response. This is particularly relevant in maintenance therapy, where doublet strategies such as anti-CD38 therapy plus lenalidomide may improve MRD conversion compared with lenalidomide alone in selected patients.

The role of autologous stem cell transplant is also becoming more nuanced. Transplant remains an important therapeutic tool and continues to provide meaningful PFS benefit for many patients. However, the absence of an OS advantage in some modern trial contexts has encouraged more individualized discussions. For patients who achieve deep responses with potent induction regimens, particularly those at standard risk, the timing and necessity of upfront transplant may become increasingly personalized. For individuals with high-risk disease, however, the need for durable disease control remains pressing, and intensive approaches continue to play an important role.

For transplant-ineligible patients, treatment selection must balance disease control with patient factors. Chronologic age alone is inadequate. Frailty, performance status, organ function, neuropathy risk, infection risk, social support, and treatment access should guide regimen choice. Many patients who are not candidates for transplant can still tolerate quadruplet therapy, but dose adjustment and proactive supportive care are essential. Trials evaluating daratumumab- or isatuximab-containing quadruplet approaches have shown improved MRD negativity and PFS compared with triplet approaches, reinforcing the value of anti-CD38 therapy, even in older or transplant-ineligible populations.

Personalizing Care Through Toxicity Management and Supportive Care

Kelley L. Julian, PharmD, BCOP:
Although dexamethasone remains embedded in frontline myeloma regimens, corticosteroid toxicity is common and clinically meaningful, especially in older adults. Insomnia, mood changes, hyperglycemia, muscle weakness, infection risk, gastrointestinal symptoms, and functional decline can undermine quality of life and adherence. For patients who respond well or develop steroid-related toxicity, early dexamethasone reduction or discontinuation is very reasonable. The clinical goal should be sustained disease control, not rigid preservation of steroid dosing if the patient is suffering avoidable harm.

Supportive care remains foundational to successful myeloma therapy. Antiviral prophylaxis is critical for patients receiving proteasome inhibitors and anti-CD38 monoclonal antibodies because of the risk of herpes simplex and varicella zoster reactivation. Antibacterial or antifungal prophylaxis may be appropriate during periods of neutropenia, and Pneumocystis jirovecii pneumonia prophylaxis may be considered in patients receiving prolonged or high-dose corticosteroids or in specific institutional contexts. Vaccination against seasonal respiratory viruses and appropriate management of COVID-19 risk remain important components of care.

Bone health is another important caveat to consider when selecting treatment. Zoledronic acid and denosumab reduce skeletal complications with contemporary treatment, but each requires thoughtful monitoring. Zoledronic acid requires renal dose adjustment, while denosumab can be useful in renal impairment but may cause significant hypocalcemia. Dental evaluation before initiation is essential to reduce the risk of osteonecrosis of the jaw. Calcium and vitamin D supplementation, renal monitoring, and ongoing assessment of skeletal symptoms should be built into routine practice.

Thrombosis prevention is essential, particularly for patients receiving immunomodulatory agents such as lenalidomide. Risk assessment tools validated in the newly diagnosed setting can help guide prophylaxis intensity, but clinical judgment remains important. Aspirin may be appropriate for lower-risk patients, whereas direct oral anticoagulants or other anticoagulation strategies may be preferred in patients with higher thrombotic risk. Bleeding risk, renal function, fall risk, drug interactions, and patient adherence must all be considered.

Peripheral neuropathy management requires early recognition and rapid intervention. Bortezomib remains highly effective, but neuropathy can become dose-limiting and may affect long-term function. Patients should be educated to report numbness, tingling, burning pain, gait changes, or difficulty with fine motor tasks early rather than waiting until symptoms are severe. Dose modification, schedule adjustment, route optimization, and supportive medications can help preserve both treatment efficacy and quality of life.

The route of anti-CD38 administration is another practical advancement. Subcutaneous daratumumab has reduced administration time and infusion-related burden compared with the original intravenous approach. Similar efforts with isatuximab, including subcutaneous and on-body injector strategies, aim to improve patient convenience, chair time, and clinic workflow. Even when administration becomes faster and more convenient, premedication and monitoring remain important, because administration-related reactions can still occur, albeit less frequently.

Delivering Patient-Centered Myeloma Care

James A. Davis, PharmD, BCOP:
Ultimately, modern myeloma care is no longer simply choosing the most active regimen. It is choosing the most appropriate regimen for a specific patient at a distinct point in the disease course. High-risk SMM requires careful risk assessment and shared decision-making. Newly diagnosed transplant-eligible disease increasingly favors anti-CD38–based quadruplet induction with MRD-informed treatment. Transplant-ineligible disease requires equal attention to efficacy and frailty-informed tolerability. Across all disease settings, pharmacists play a critical role in regimen optimization, toxicity prevention, adherence support, medication access, patient education, and longitudinal monitoring.

The continued integration of anti-CD38 monoclonal antibodies into induction treatment has raised the standard for depth of response in NDMM. The next step is ensuring that deeper responses translate into better quality of life for patients, which means fewer relapses, fewer complications, less treatment burden, and more individualized care. Achieving the best outcomes requires not only effective therapies but also healthcare professionals who recognize that the true focus is never myeloma alone; it is the individual living with it.

Your Thoughts
How do you approach treatment discussions with patients who have high-risk SMM, and what factors most influence your decision to recommend early intervention vs observation? Join the conversation by leaving a comment or answering the polling question.

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If approved, how often would you utilize a subcutaneous on-body injector vs IV formulation when using isatuximab for your patients with MM?

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