Examining Key Updates in First-Line Treatment Options for Multiple Myeloma

Panelists discuss how treatment strategies differ between transplant-eligible and transplant-ineligible multiple myeloma patients, with transplant eligibility determined by functional status rather than age alone, and how quadruple therapy regimens are increasingly used for transplant-eligible patients to achieve deep, durable responses.

Panelists discuss how autologous stem cell transplant remains essential in frontline multiple myeloma management despite improved quadruple therapy outcomes, emphasizing that current evidence still supports transplantation for eligible patients rather than deferring it.

Panelists discuss how quadruplet regimens show improved efficacy over triplet regimens without significantly increased safety concerns, with anti-CD38 antibodies being well tolerated and NCCN guidelines now recommending 4-drug regimens for transplant-eligible patients.

Panelists discuss how minimal residual disease (MRD) status can guide post-transplant treatment decisions, particularly for high-risk patients who don’t achieve MRD negativity and patients considering discontinuation of long-term maintenance therapy.

Panelists discuss how maintenance therapy should be tailored based on risk profiles, with standard-risk patients receiving single-agent lenalidomide while high-risk patients may benefit from combination maintenance strategies to achieve more durable responses.

Panelists discuss how autologous stem cell transplant (ASCT) deferral should be approached cautiously with concrete medical reasons, as transplant continues to provide superior progression-free survival and potentially curative outcomes for a subset of patients.

Panelists discuss how early relapse in standard-risk patients represents a failure of current risk assessment methods and may require advanced sequencing technologies to identify hidden high-risk features that traditional fluorescence in situ hybridization testing misses.

Panelists discuss how emerging therapies like CAR T cells and bispecific antibodies may transform frontline treatment by potentially replacing transplant or changing induction regimens, while considering the cost implications and need for sustainable care models.

Panelists discuss how the CEPHEUS trial demonstrated that quadruplet therapy (daratumumab, bortezomib, lenalidomide, and dexamethasone) significantly improved minimal residual disease negativity rates compared to triplet therapy in transplant-ineligible multiple myeloma patients, achieving approximately 60% vs 47% 10–5 responses while maintaining manageable safety profiles.

Panelists discuss how NCCN guidelines are expected to incorporate quadruplet-based regimens as reasonable treatment approaches for transplant-ineligible patients, while emphasizing the need for personalized treatment strategies that consider individual patient frailty and high-risk genetics rather than applying uniform approaches across all older patients.

Panelists discuss how to balance achieving deeper MRD-negative responses against increased toxicity risks in transplant-ineligible patients by personalizing therapy through dose modifications, weekly vs twice-weekly dosing schedules, and careful monitoring while maintaining treatment intensity similar to clinical trials.

Panelists discuss how newer immune-based therapies and bispecific antibodies may enable fixed-duration treatment approaches that could eliminate the need for stem cell transplant in older but fit patients, potentially allowing for treatment-free intervals after achieving deep responses.

Panelists discuss how quality of life (QOL) and treatment convenience should be balanced with maximal depth of response through personalized therapy approaches, emphasizing the importance of multidisciplinary care teams and the flexibility to adapt treatment regimens based on individual patient preferences and circumstances.

Panelists discuss how emerging evidence from first-line therapy trials continues to demonstrate the superiority of quadruplet over triplet regimens, with the CEPHEUS subgroup analysis confirming that even higher-risk and less-fit patients can benefit from 4-drug combinations while maintaining acceptable safety profiles.

Panelists discuss how the PERSEUS trial’s subgroup analysis reinforced that sustained minimal residual disease negativity predicts better long-term outcomes and demonstrated the potential for treatment de-escalation at the 2-year mark, while other trials like Advance showed dramatic increases in MRD negativity rates with quadruplet therapy.

Panelists discuss how recent updates from the phase 3 IsKia trial demonstrate that isatuximab combined with carfilzomib, lenalidomide, and dexamethasone improves minimal residual disease negativity rates by approximately 10% at both the 10–5 and 10–6 levels, particularly benefiting high-risk patients.

Panelists discuss how upcoming ASCO presentations will focus on long-term CAR T-cell therapy outcomes showing potential cure plateaus, minimal residual disease (MRD)–guided treatment escalation/de-escalation strategies, tri-specific antibodies, and the economic value of using MRD negativity to guide maintenance therapy discontinuation decisions.