Advancing Myeloma Care: Better Management, Broader Access, Earlier Treatment — Highlights From IMS 2026

At this year’s International Myeloma Society (IMS) Annual Meeting, new data highlighted several areas of active research that can optimize treatment choice, delivery and tolerability in myeloma. Key themes included: 

• Preventing and managing treatment toxicity: Long-term cancer surveillance, infection prevention, immunoglobulin monitoring, ocular assessments and risk-adapted neurologic monitoring remain essential to sustaining the benefits of myeloma therapy.  

• Moving highly active therapies earlier in relapse: Chimeric antigen receptor T-cell therapy, bispecific antibodies (bsAbs), and cereblon E3 ligase modulatory drug (CELMoD)-based combinations are being studied and used earlier to achieve deeper, longer-lasting responses.  

• Reducing hospital use through safe outpatient care: Structured outpatient and hybrid models may make chimeric antigen receptor (CAR) T-cell and bsAb therapy available to more patients and help expand access. 

• Using sustained minimal residual disease (MRD) negativity to personalize treatment: Serial MRD assessment may help identify patients who can reduce or discontinue their use of selected maintenance drugs, while also identifying those who may need continued treatment.  

• Planning treatment sequences around tumor targets: Responses after prior B-cell maturation antigen (BCMA)-directed therapy show that resistance is not always absolute.  

Read more below.

As Treatment Advances, So Does the Focus on Tolerability 

As myeloma treatments become more effective and patients remain on therapy longer, research is increasingly focused on preventing and managing side effects that can affect long-term health and quality of life. 

• Second primary malignancies: A retrospective analysis of 2,420 patients who underwent upfront autologous hematopoietic stem cell transplant found that 10% developed a second primary malignancy (SPM) during a median 74-month follow-up, with risk increasing over time. Older age, male sex and posttransplant lenalidomide maintenance were independently associated with higher SPM incidence, underscoring the importance of long-term cancer surveillance after transplant (abstract PA-434). 

• Infection prophylaxis: Two studies highlighted approaches to reducing infection risk in patients receiving intensive myeloma therapies. A national-registry analysis found that immunoglobulin replacement was associated with reductions in severe infections and hospitalizations among patients with hypogammaglobulinemia, supporting longitudinal immunoglobulin G (IgG) monitoring and consideration of intravenous/subcutaneous Ig in high-risk patients (abstract OA-30). In a small cohort of patients who had received ciltacabtagene autoleucel (cilta-cel) infusion, low, fixed-dose intravenous (IV)Ig prophylaxis was associated with predominantly mild, outpatient-managed infections, suggesting a potentially feasible prophylactic approach that warrants further study (abstract PA-429). 

• Neurotoxicity, CRS, and ocular toxicities: Investigators also evaluated strategies to prevent or mitigate specific treatment-related toxicities. A single prophylactic dose of cyclophosphamide did not prevent delayed neurotoxicity after cilta-cel in patients with high post-infusion absolute lymphocyte counts, a result that argues against routine use for this purpose (abstract OA-41). In preclinical studies, the oral p38 mitogen-activated protein kinase inhibitor POLB 001 reduced cytokine release syndrome (CRS)-associated cytokines without impairing tumor-cell killing mediated by BCMA-targeted bsAbs, although clinical efficacy and safety remain to be established (abstract PA-340). In the DREAMM-9 study, longer belantamab mafodotin dosing intervals were associated with less-severe patient-reported blurred vision while generally preserving vision-related functioning. Such results support exploration of dosing strategies that balance efficacy and ocular tolerability (abstract OA-20). 

Together, these presentations reinforce the importance of a proactive, risk-adapted approach to managing treatment-related complications, while recognizing that several proposed interventions remain investigational or require prospective validation. 

Resources for Patients: Do your patients have questions about treatments and their side effects? Direct them to this brochure. 

Successful Options in the Early Relapse Setting 

Several investigators examined the positioning of CELMoDs, T-cell engagers and antibody combinations to maximize response depth and duration without exhausting future treatment options. 

• EXCALIBER-RRMM: Iberdomide, an oral CELMoD, when administered with daratumumab and dexamethasone, improved depth of response at first relapse, with MRD-negative complete response (CR) achieved by 41.1% of patients versus 20.1% among those treated with daratumumab, bortezomib, and dexamethasone (DVd). These findings supported the approval of iberdomide in combination with daratumumab and dexamethasone for patients with relapsed/refractory multiple myeloma after at least 1 prior line of therapy. The oral administration of iberdomide may provide an opportunity to increase access to highly active therapy at first relapse while offering an alternative to continuously administered parenteral regimens. However, grade 3/4 neutropenia and infections were more common with iberdomide-daratumumab-dexamethasone, whereas peripheral neuropathy was more common with DVd, highlighting the importance of balancing efficacy, administration, and toxicity when selecting treatment (abstract LBA-12).  

• MajesTEC-3: Teclistamab plus daratumumab markedly reduced progression and improved overall survival versus daratumumab/dexamethasone plus pomalidomide or bortezomib in patients with one to three prior lines of therapy, without an apparent increase in nonrelapse mortality. The major driver was a profound reduction in disease progression: estimated 36-month cumulative progression incidence was 8.7% with teclistamab plus daratumumab versus 62.1% with the daratumumab-based triplet (abstract OA-49). 

• CAR T-cell therapy remains an option: Data from CARTITUDE-2 further support the role of cilta-cel in earlier-line relapsed/refractory multiple myeloma, with 50% of patients (10 of 20) remaining alive and progression free at five years after a single infusion without maintenance therapy; median progression-free survival (PFS) was 60.5 months. Long-term follow-up identified deaths from infections and breast cancer, as well as one case of acute myeloid leukemia; no new CAR T-cell–related neurotoxicity was reported. (abstract PA-288).  

These findings highlight the expanding range of highly effective treatment options available at first relapse, with emerging bsAb and CELMoD-based regimens offering additional approaches alongside CAR T-cell therapy. As treatment options continue to evolve, clinicians must weigh the relative benefits and practical considerations of each approach to select the most appropriate therapy for individual patients. 

Resource for Patients: Help your patients understand CELMoDs and what the new iberdomide approval means for treatment options with this MMRF blog post. 

Moving CAR T-Cell and bsAb Therapy Beyond the Hospital  

New studies suggest that highly structured outpatient care could reduce hospitalization associated with CAR T-cell and bsAb therapy and could expand access to these treatments. 

• Outpatient CAR T-cell therapy: In a 21-patient study of outpatient cilta-cel, remote monitoring, 24-hour clinical support, after-hours dexamethasone for grade 1 CRS and early tocilizumab allowed 86% of patients to avoid hospitalization within 30 days. None required overnight admission for CRS or immune effector cell-associated neurotoxicity syndrome (ICANS), although larger studies are needed to validate the approach (abstract PA-003). 

• Outpatient bsAb step-up dosing: This 463-patient real-world analysis examined outpatient, inpatient and hybrid step-up dosing of teclistamab and talquetamab across academic and community practices. Nearly all outpatients completed dosing, including community patients who received no preventive tocilizumab or dexamethasone. Although 29% of community outpatients required hospitalization within 14 days, their median stay was shorter than that of the inpatient group, highlighting how outpatient initiation can incorporate hospital care when needed (abstract PA-329). 

• Another multicenter study prophylactic tocilizumab during outpatient step-up dosing may reduce CRS, dose delays and hospitalization in selected patients and suggested. However, infections remained common, reinforcing the need for continued monitoring and supportive care (abstract PA-431). 

To summarize, outpatient delivery could help bring CAR T-cell and bsAb therapy closer to patients while reducing hospital burden. Safe implementation requires careful patient selection, caregiver support, close monitoring, prophylaxis—when possible—against treatment associated side effects, 24/7 clinical access, and clear pathways for rapid escalation. 

Resources for Patients: Help your patients understand the different immunotherapy treatment options available and what to expect from these approaches with this booklet. 

Using MRD to Guide Treatment Decisions, Including When to Stop Treatment 

Emerging long-term data are strengthening the case for sustained MRD negativity used not only as a marker of deep response but as a potential tool for individualizing maintenance duration. In the mature CASSIOPEIA registry analysis (n=802), five-year sustained MRD negativity was associated with higher 96-month PFS, with sustained MRD negativity occurring more frequently with daratumumab maintenance than with observation (abstract OA-01). These findings reinforce sustained MRD negativity as a marker of durable disease control and provide a rationale for using MRD status to inform treatment decisions. 

• PERSEUS (MRD-guided discontinuation of daratumumab): Among patients receiving daratumumab plus lenalidomide maintenance after the combination of daratumumab, bortezomib, lenalidomide, and dexamethasone, 236 (73%) stopped daratumumab following at least two years of maintenance after achieving ≥CR and sustained MRD negativity for ≥12 months. At the time of analysis, 74% had remained off daratumumab, with a median of 44 months since discontinuation. Importantly, lenalidomide maintenance continued (abstract LBA-07). 

• GEM2014MAIN (MRD-guided discontinuation of all maintenance): Among 165 posttransplant patients who stopped maintenance after two years based on MRD-negative status, approximately half remained alive and progression free at the seven-year landmark. The findings provide longer-term evidence that MRD may help identify patients in whom maintenance can potentially be discontinued (abstract OA-17). 

These studies move MRD beyond consideration as only a snapshot of treatment response toward its use as a potential tool for treatment decision-making. CASSIOPEIA establishes the prognostic significance of sustained MRD negativity, while PERSEUS and GEM2014MAIN demonstrate how MRD status can be used to modify treatment: first by discontinuing daratumumab while continuing lenalidomide, then by discontinuing maintenance altogether. Prospective validation is still needed before MRD-guided treatment discontinuation becomes routine practice.

Resource for Patients: For patients looking to better understand MRD testing and what the results may mean for their treatment, the MMRF’s information sheet on minimal residual disease provides a clear overview.

Target Switching and Treatment Sequencing to Achieve the Deepest Responses 

New data suggest that prior exposure to antigen-directed therapy does not necessarily preclude benefit from subsequent targeted treatment and that biomarkers may help guide the decision of which target to pursue next. 

• BCMA after prior BCMA therapy: In a post hoc analysis of DREAMM-7 and DREAMM-8, 12 of 13 evaluable patients (92%) responded to a BCMA-directed, T-cell redirecting therapy after belantamab mafodotin, including all five whose disease had progressed on belantamab. However, only a few patients received the treatments consecutively, and the small sample limits conclusions about optimal sequencing (abstract PA-031). 

• Targeted immunotherapy after dual BCMA/G-protein coupled receptor (GPR) C5D exposure: In a 157-patient real-world cohort, patients receiving subsequent BCMA-, GPRC5D-, or Fc receptor homolog 5-directed therapy (FCRH5) had longer median PFS than those receiving conventional salvage (7.4 vs 3.9 months), suggesting targeted immunotherapy may retain activity even after exposure to multiple antigen targets (abstract OA-55). 

• Biomarkers may help select the next target: Low or absent GPRC5D expression was strongly associated with t(11;14) and primary resistance to GPRC5D-directed therapy. GPRC5D expression assessed by immunohistochemistry, together with fluorescence in situ hybridization, may therefore help identify patients unlikely to benefit from GPRC5D targeting and inform selection of alternative approaches (abstract PA-504). 

These findings support more deliberate sequencing of antigen-directed therapies, using prior treatment exposure and target expression to help select the next approach.

Resources for Patients: For a clear, patient-friendly guide to myeloma treatment options, The MMRF’s information booklet explains how different therapies work and what patients can expect from their treatment journey.  

Jointly provided by the MMRF and RedMedEd. 

This content is supported by sponsorships from Legend Biotech USA Inc. and Pfizer Inc., as well as by educational grants from GSK and Johnson & Johnson.