Triplet vs Quad Therapies: Personalized Anti-CD38 Regimens to Maximize Efficacy and Tolerability

EP: 1.Shifting Standards of Care: Insights from CEPHEUS on Anti-CD38 Therapy

EP: 2.From Subgroups to Sustained Response: IMROZ Efficacy in Frailty and MRD Outcomes Across Trials

Now Viewing

EP: 3.Triplet vs Quad Therapies: Personalized Anti-CD38 Regimens to Maximize Efficacy and Tolerability

EP: 4.The Patient Voice: Practical Factors Influencing Anti-CD38 Therapy Value

EP: 5.Bridging the Gap: Ways to Overcome Barriers of Access to Anti-CD38 Therapies

When deciding between triplet and quadruplet regimens for transplant-ineligible multiple myeloma, treatment decisions should account for patient fitness, disease risk factors, and the treatment’s toxicity profile. Importantly, adding an anti-CD38 monoclonal antibody generally does not increase toxicity substantially, but concerns such as infection risk—especially in the context of respiratory viruses such as COVID-19—must be considered. For many patients, particularly those over 80 years or with significant frailty, the standard combination of a CD38 antibody with lenalidomide and dexamethasone (a triplet) may already offer excellent outcomes, including a progression-free survival (PFS) of around 5 years. In contrast, more aggressive approaches, such as quadruplets, may be reserved for patients with high-risk features such as advanced stage, unfavorable cytogenetics, or poor early response.

Ongoing studies, such as the BENEFIT trial, aim to evaluate whether adding a proteasome inhibitor like bortezomib to an anti-CD38-based triplet improves outcomes. However, with long-term follow-up still pending, the decision to intensify treatment must balance potential benefits against risks like peripheral neuropathy, especially in older or frail individuals. Real-world flexibility allows clinicians to start with triplet therapy and escalate later if needed, based on tolerability and response. There is increasing recognition that the intensity and frequency of drug dosing may have more impact on tolerability than the sheer number of drugs used.

When selecting between available anti-CD38 therapies, differences are noted in administration, scheduling, and health care system considerations. While both drugs appear comparable in efficacy and safety, one offers subcutaneous dosing with shorter administration time and monthly maintenance, whereas the other is IV with more frequent dosing. Patient convenience, nurse time, pharmacy workload, and overall health care system logistics often influence this choice. New delivery methods, such as on-body injector formulations, may further shift preferences in practice depending on how they impact workflow and reimbursement structures.