{"product_id":"daratumumab-or-active-monitoring-for-high-risk-smoldering-multiple-myeloma","title":"Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma","description":"\u003cp\u003eThe AQUILA clinical trial tested whether early treatment with daratumumab (brand name: Darzalex), an antibody therapy already approved for active multiple myeloma, could prevent or delay progression to active disease in patients with high-risk smoldering multiple myeloma, a precursor condition for which no treatments are currently approved. The study followed 390 patients for a median of 65.2 months and found that those receiving subcutaneous (under-the-skin) daratumumab injections had a 51% lower risk of disease progression or death compared with those who were simply watched closely. Five years after starting the study, 63.1% of daratumumab-treated patients remained free of progression versus 40.8% of actively monitored patients, and overall survival was also better in the treatment group (93.0% vs. 86.9%). These findings suggest that early intervention with daratumumab may change the natural course of this high-risk precursor condition.\u003c\/p\u003e\n\n# Daratumumab: A New Early Treatment Option for High-Risk Smoldering Multiple Myeloma\n\n\u003ch2 id=\"table-of-contents\"\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eUnderstanding Smoldering Multiple Myeloma\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#why-this-matters\"\u003eWhy This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#study-design\"\u003eStudy Design: The AQUILA Trial\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#who-was-eligible\"\u003eWho Could Participate in the Trial?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#how-treatment-worked\"\u003eHow the Treatment Was Given\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#measuring-success\"\u003eHow Success Was Measured\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Findings: Delaying or Preventing Active Myeloma\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#survival-results\"\u003eSurvival Results: A Significant Improvement\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#response-rates\"\u003eResponse Rates: How Deep Was the Remission?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety: Side Effects and Risks\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#quality-of-life\"\u003eQuality of Life During Treatment\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eClinical Implications: What This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations for Patients and Caregivers\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn a 390-patient trial, subcutaneous daratumumab lowered the risk of progression or death by 51% versus active monitoring in high-risk smoldering myeloma.\u003c\/li\u003e\n\u003cli\u003eAt five years, 63.1% of daratumumab patients stayed progression-free versus 40.8% with monitoring; overall survival was 93.0% versus 86.9%.\u003c\/li\u003e\n\u003cli\u003eDaratumumab was given as under-the-skin injections for up to 36 months; treatment delayed the need for first-line myeloma therapy in most patients.\u003c\/li\u003e\n\u003cli\u003eSerious infections occurred in 16.1% of treated patients versus 4.6% of monitored patients; quality of life was maintained during treatment.\u003c\/li\u003e\n\u003cli\u003eThe trial was open-label and underrepresented Black patients, so discuss how findings apply to your individual situation with your oncologist.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eUnderstanding Smoldering Multiple Myeloma\u003c\/h2\u003e\n\u003cp\u003eMultiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow that normally helps fight infections. Before this cancer becomes \"active\" and causes symptoms, many patients go through a quiet, symptom-free phase called \u003cstrong\u003esmoldering multiple myeloma\u003c\/strong\u003e. Think of it as a warning sign — abnormal plasma cells are multiplying in the bone marrow, but they haven't yet caused the organ damage or classic symptoms that define active myeloma.\u003c\/p\u003e\n\u003cp\u003eThe current standard of care for smoldering multiple myeloma has been \"watch and wait\" — also called \u003cstrong\u003eactive monitoring\u003c\/strong\u003e. This means patients receive regular checkups and blood tests but no disease-specific treatment until the condition progresses to active multiple myeloma.\u003c\/p\u003e\n\u003cp\u003eHowever, not all smoldering myeloma is the same. Approximately one third of patients have what doctors call \u003cstrong\u003ehigh-risk\u003c\/strong\u003e smoldering multiple myeloma, meaning they have certain features that make progression to active disease much more likely. These patients face approximately a 50% risk of progression to active myeloma over time. The challenge has been that \u003cstrong\u003eno treatments have been approved\u003c\/strong\u003e for this precursor condition, leaving high-risk patients with no options beyond close observation.\u003c\/p\u003e\n\n\u003ch2 id=\"why-this-matters\"\u003eWhy This Research Matters\u003c\/h2\u003e\n\u003cp\u003eThere's an important question in myeloma care: Should we treat high-risk smoldering myeloma early, before it turns into active disease, or wait until symptoms develop? Waiting has costs — by the time active myeloma appears, patients may already have kidney damage, bone destruction, or anemia. Some research suggests that close monitoring alone may not prevent the organ damage that can occur when myeloma becomes active.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDaratumumab\u003c\/strong\u003e is a human monoclonal antibody that targets a protein called \u003cstrong\u003eCD38\u003c\/strong\u003e, which is found in large amounts on myeloma cells. It's already approved for treating active multiple myeloma, both as a single drug and in combination with other treatments. A phase 2 study called CENTAURUS showed that daratumumab had activity in patients with intermediate- or high-risk smoldering myeloma, which supported the design of this larger phase 3 trial.\u003c\/p\u003e\n\u003cp\u003eThis study, called \u003cstrong\u003eAQUILA\u003c\/strong\u003e, was designed to answer a straightforward question: Can giving subcutaneous (under-the-skin) daratumumab early — while patients still feel fine — delay or prevent progression to active multiple myeloma, compared with the traditional approach of active monitoring?\u003c\/p\u003e\n\n\u003ch2 id=\"study-design\"\u003eStudy Design: The AQUILA Trial\u003c\/h2\u003e\n\u003cp\u003eAQUILA was a \u003cstrong\u003ephase 3, open-label, multicenter, randomized trial\u003c\/strong\u003e. In plain language, this means it was a large, late-stage study designed to definitively test whether the treatment works. The trial was \"open-label,\" meaning both patients and doctors knew which group each patient was in. It was conducted at \u003cstrong\u003e124 sites across 23 countries\u003c\/strong\u003e, making it a truly global effort.\u003c\/p\u003e\n\u003cp\u003eBetween December 10, 2017, and May 27, 2019, a total of \u003cstrong\u003e390 patients\u003c\/strong\u003e were enrolled. They were randomly assigned in a 1:1 ratio — like flipping a coin — to one of two groups:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDaratumumab group:\u003c\/strong\u003e 194 patients received subcutaneous daratumumab injections\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eActive-monitoring group:\u003c\/strong\u003e 196 patients received no treatment, just careful observation\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eOne patient in the daratumumab group was assigned to treatment but never received it, leaving 193 patients who actually started treatment versus 196 who were monitored.\u003c\/p\u003e\n\u003cp\u003eThe trial was funded by Janssen Research and Development, the company that makes daratumumab. An independent ethics committee or institutional review board approved the trial at each site, and all patients gave written informed consent before joining.\u003c\/p\u003e\n\n\u003ch2 id=\"who-was-eligible\"\u003eWho Could Participate in the Trial?\u003c\/h2\u003e\n\u003cp\u003ePatients had to be 18 years or older and have a confirmed diagnosis of smoldering multiple myeloma (within the past 5 years) using standard \u003cstrong\u003eInternational Myeloma Working Group (IMWG)\u003c\/strong\u003e criteria. They also needed to have \"measurable disease\" and be generally healthy enough to participate, as measured by an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (on a scale where 0 means no symptoms and 5 means severe disability).\u003c\/p\u003e\n\u003cp\u003eMost importantly, all patients had to be considered \u003cstrong\u003ehigh risk\u003c\/strong\u003e for progression to active multiple myeloma. This was defined as having at least 10% clonal plasma cells in the bone marrow and at least one of the following risk factors:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eA serum M-protein level of at least 30 g per liter (M-protein is an abnormal antibody produced by myeloma cells)\u003c\/li\u003e\n  \u003cli\u003eIgA-type smoldering multiple myeloma (a specific subtype associated with higher risk)\u003c\/li\u003e\n  \u003cli\u003eImmunoparesis, meaning reduced levels of two uninvolved (normal) immunoglobulin types\u003c\/li\u003e\n  \u003cli\u003eA serum free light chain ratio (FLC ratio) of 8 to less than 100 — this measures the balance of two types of light chain proteins in the blood\u003c\/li\u003e\n  \u003cli\u003eMore than 50% but less than 60% clonal plasma cells in the bone marrow\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003ePatients could have multiple risk factors — in fact, \u003cstrong\u003e79.5% of the study population had at least three risk factors\u003c\/strong\u003e. Randomization was stratified (balanced) based on the number of risk factors (fewer than 3 vs. 3 or more) and other specific disease features.\u003c\/p\u003e\n\u003cp\u003eThe median age of participants was \u003cstrong\u003e64 years\u003c\/strong\u003e (range 31 to 86), and patients had been living with the smoldering myeloma diagnosis for a median of 0.72 years before joining the trial. The median percentage of clonal plasma cells in the bone marrow was 20%. It's worth noting that \u003cstrong\u003eBlack patients were underrepresented\u003c\/strong\u003e, making up only 2.8% of the trial population, while Asian patients made up 7.9%.\u003c\/p\u003e\n\n\u003ch2 id=\"how-treatment-worked\"\u003eHow the Treatment Was Given\u003c\/h2\u003e\n\u003cp\u003ePatients in the daratumumab group received \u003cstrong\u003esubcutaneous (under-the-skin) daratumumab at a dose of 1800 mg\u003c\/strong\u003e, coformulated with an enzyme called recombinant human hyaluronidase PH20 to help the medication absorb properly. The treatment followed a specific schedule using 28-day cycles:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCycles 1 and 2:\u003c\/strong\u003e Daratumumab given weekly\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCycles 3 through 6:\u003c\/strong\u003e Daratumumab given every 2 weeks\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAfter cycle 6:\u003c\/strong\u003e Daratumumab given every 4 weeks\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eTreatment continued for \u003cstrong\u003e39 cycles, 36 months, or until confirmed disease progression\u003c\/strong\u003e — whichever came first. The median number of cycles patients actually received was 38, and the median treatment duration was 35.0 months (range 0 to 36.1). By the study cutoff date (May 1, 2024), \u003cstrong\u003e127 patients (65.5%) had completed the full course\u003c\/strong\u003e of 39 cycles or 36 months.\u003c\/p\u003e\n\u003cp\u003ePatients in the active-monitoring group received no disease-specific treatment. They were simply observed for 36 months or until disease progression, whichever came first. The median duration of active monitoring was 25.9 months (range 0.1 to 36.0).\u003c\/p\u003e\n\u003cp\u003eFor both groups, disease evaluations were done by a central laboratory \u003cstrong\u003eevery 12 weeks\u003c\/strong\u003e until progression was confirmed.\u003c\/p\u003e\n\n\u003ch2 id=\"measuring-success\"\u003eHow Success Was Measured\u003c\/h2\u003e\n\u003cp\u003eThe \u003cstrong\u003eprimary end point\u003c\/strong\u003e (main outcome) of the trial was \u003cstrong\u003eprogression-free survival\u003c\/strong\u003e — the length of time from randomization until either the disease progressed to active multiple myeloma or the patient died from any cause, whichever happened first.\u003c\/p\u003e\n\u003cp\u003eProgression to active myeloma was judged by an \u003cstrong\u003eindependent review committee\u003c\/strong\u003e using the standard IMWG \u003cstrong\u003eSLiM–CRAB diagnostic criteria\u003c\/strong\u003e. These criteria define active myeloma as the presence of:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSLiM:\u003c\/strong\u003e 60% or more clonal plasma cells in bone marrow, a serum free light chain ratio of 100 or more, or more than one MRI-detected bone lesion, \u003cem\u003eor\u003c\/em\u003e\n\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eCRAB:\u003c\/strong\u003e Elevated calcium levels, kidney dysfunction, anemia, or bone lesions\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eSecondary outcomes included overall response rate (partial response or better), complete response rate, time to disease progression, time to starting first-line treatment for active myeloma, and overall survival.\u003c\/p\u003e\n\u003cp\u003eThe trial was designed to have \u003cstrong\u003e85% power\u003c\/strong\u003e to detect a 37.5% lower risk of disease progression or death in the daratumumab group, meaning the study was large enough to reliably find a meaningful difference if one existed. The original plan called for 360 patients and 165 progression or death events.\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Findings: Delaying or Preventing Active Myeloma\u003c\/h2\u003e\n\u003cp\u003eAfter a median follow-up of \u003cstrong\u003e65.2 months\u003c\/strong\u003e (more than 5 years), the results were striking. Disease progression to active multiple myeloma or death occurred in:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e67 patients (34.5%)\u003c\/strong\u003e in the daratumumab group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e99 patients (50.5%)\u003c\/strong\u003e in the active-monitoring group\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThis translates to a \u003cstrong\u003e51% lower risk\u003c\/strong\u003e of progression or death with daratumumab (hazard ratio, 0.49; 95% confidence interval, 0.36 to 0.67; P\u0026lt;0.001). The p-value of less than 0.001 means there is less than a 0.1% chance these results happened by random luck — a highly statistically significant finding.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eProgression-free survival at 5 years\u003c\/strong\u003e was:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e63.1%\u003c\/strong\u003e with daratumumab\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e40.8%\u003c\/strong\u003e with active monitoring\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eIn other words, nearly two-thirds of treated patients remained progression-free at 5 years, compared with about four in ten untreated patients. The benefit was consistent across all prespecified patient subgroups, meaning the treatment helped a broad range of patients regardless of age, disease type, or number of risk factors.\u003c\/p\u003e\n\u003cp\u003eBeyond the formal definition of progression, daratumumab also delayed the \u003cstrong\u003etime to disease progression\u003c\/strong\u003e substantially. The median time to progression (using either IMWG biochemical or SLiM-CRAB criteria) was:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e44.1 months\u003c\/strong\u003e in the daratumumab group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e17.8 months\u003c\/strong\u003e in the active-monitoring group\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThat's a hazard ratio of 0.51 (95% CI, 0.40 to 0.66) — daratumumab more than doubled the time patients lived without their disease advancing.\u003c\/p\u003e\n\u003cp\u003eTreatment with daratumumab also dramatically reduced the need for more intensive treatment later. By the study cutoff, first-line treatment for active multiple myeloma had been initiated in:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e64 patients (33.2%)\u003c\/strong\u003e in the daratumumab group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e105 patients (53.6%)\u003c\/strong\u003e in the active-monitoring group\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe hazard ratio was 0.46 (95% CI, 0.33 to 0.62), and at 5 years, the estimated chance of needing first-line treatment was \u003cstrong\u003e29.7% versus 55.9%\u003c\/strong\u003e — meaning untreated patients were nearly twice as likely to need systemic therapy within 5 years.\u003c\/p\u003e\n\n\u003ch2 id=\"survival-results\"\u003eSurvival Results: A Significant Improvement\u003c\/h2\u003e\n\u003cp\u003ePerhaps the most meaningful finding for patients is the difference in overall survival. By the study cutoff, \u003cstrong\u003e41 patients had died\u003c\/strong\u003e in total:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e15 patients (7.7%)\u003c\/strong\u003e in the daratumumab group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e26 patients (13.3%)\u003c\/strong\u003e in the active-monitoring group\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThis represents a \u003cstrong\u003e48% lower risk\u003c\/strong\u003e of death with daratumumab (hazard ratio, 0.52; 95% confidence interval, 0.27 to 0.98). At 5 years, \u003cstrong\u003eoverall survival was 93.0% with daratumumab and 86.9% with active monitoring\u003c\/strong\u003e. This means that out of 100 patients, about 93 in the treatment group were alive at 5 years compared with about 87 in the monitoring group.\u003c\/p\u003e\n\u003cp\u003eThese survival benefits are particularly notable because many patients in the active-monitoring group eventually received treatment when their disease progressed — yet early intervention with daratumumab still provided a survival advantage.\u003c\/p\u003e\n\n\u003ch2 id=\"response-rates\"\u003eResponse Rates: How Deep Was the Remission?\u003c\/h2\u003e\n\u003cp\u003eEven though patients started with a symptom-free precursor condition, daratumumab was able to produce meaningful disease responses. The trial measured responses using standard IMWG criteria, assessed by a validated computer algorithm:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eA complete response (CR) or better\u003c\/strong\u003e — meaning no detectable disease — was achieved in \u003cstrong\u003e17 patients (8.8%)\u003c\/strong\u003e in the daratumumab group versus \u003cstrong\u003e0 patients\u003c\/strong\u003e in the active-monitoring group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eA very good partial response (VGPR) or better\u003c\/strong\u003e was achieved in \u003cstrong\u003e58 patients (29.9%)\u003c\/strong\u003e in the daratumumab group versus \u003cstrong\u003e2 patients (1.0%)\u003c\/strong\u003e in the monitoring group\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThese deep responses are clinically important because they suggest daratumumab can actually reduce the burden of abnormal plasma cells, not just hold them in check. The researchers noted that the clinical benefit of daratumumab appeared to be independent of whether a deep response was achieved — meaning even patients who didn't have a dramatic response still benefited from delayed progression.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety: Side Effects and Risks\u003c\/h2\u003e\n\u003cp\u003eAs with any medication, daratumumab comes with potential side effects. The study tracked these carefully, comparing the treatment group to the active-monitoring group. Here's what they found:\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eGrade 3 or 4 adverse events\u003c\/strong\u003e (serious or life-threatening side effects) occurred in \u003cstrong\u003e40.4% of patients in the daratumumab group\u003c\/strong\u003e versus \u003cstrong\u003e30.1% in the active-monitoring group\u003c\/strong\u003e. The most common serious side effect in both groups was \u003cstrong\u003ehypertension (high blood pressure)\u003c\/strong\u003e, occurring in 5.7% of treatment patients versus 4.6% of monitored patients.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerious adverse events\u003c\/strong\u003e (events requiring hospitalization or otherwise medically significant) occurred in \u003cstrong\u003e29.0%\u003c\/strong\u003e of daratumumab patients versus \u003cstrong\u003e19.4%\u003c\/strong\u003e of monitored patients. The most common serious adverse event was \u003cstrong\u003epneumonia\u003c\/strong\u003e, seen in 3.6% of daratumumab patients versus 0.5% of monitored patients.\u003c\/p\u003e\n\u003cp\u003eKey safety points to be aware of:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eInfections:\u003c\/strong\u003e Grade 3 or 4 infections occurred in 16.1% of daratumumab patients versus 4.6% of monitored patients. This is expected, since daratumumab affects the immune system's ability to fight certain infections. COVID-19 events occurred in 8.8% of daratumumab patients versus 5.1% of monitored patients.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTreatment discontinuation:\u003c\/strong\u003e Adverse events led to stopping treatment in \u003cstrong\u003e5.7%\u003c\/strong\u003e of daratumumab patients (11 patients). This is a relatively low rate, suggesting the treatment was generally tolerable.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eInfusion\/injection reactions:\u003c\/strong\u003e Systemic (whole-body) reactions related to the injection occurred in \u003cstrong\u003e16.6%\u003c\/strong\u003e of patients, with only 1.0% experiencing grade 3 or 4 reactions. Local reactions at the injection site occurred in \u003cstrong\u003e27.5%\u003c\/strong\u003e of patients, with none being grade 3 or 4.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDeaths related to adverse events:\u003c\/strong\u003e Adverse events leading to death occurred in only 2 patients (1.0%) in the daratumumab group — both from COVID-19 or COVID-19 pneumonia — and in 4 patients (2.0%) in the monitoring group, from pulmonary edema, cardiac arrest, pulmonary embolism, and cardiac failure.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSecond primary cancers:\u003c\/strong\u003e These were observed in 18 patients (9.3%) in the daratumumab group and 20 patients (10.2%) in the monitoring group — essentially no difference, which is reassuring.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe researchers concluded that \u003cstrong\u003eno new safety concerns were identified\u003c\/strong\u003e with subcutaneous daratumumab in this patient population, and side effects were consistent with the drug's known safety profile from its use in active multiple myeloma.\u003c\/p\u003e\n\n\u003ch2 id=\"quality-of-life\"\u003eQuality of Life During Treatment\u003c\/h2\u003e\n\u003cp\u003eA treatment only makes sense if it doesn't harm the quality of life it's designed to preserve. The study measured patient-reported outcomes using three validated questionnaires:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe EORTC Quality of Life Questionnaire–Core 30 (a general cancer quality-of-life measure)\u003c\/li\u003e\n  \u003cli\u003eThe EORTC Quality of Life Questionnaire–Multiple Myeloma Module (a myeloma-specific measure)\u003c\/li\u003e\n  \u003cli\u003eThe EuroQol 5-Dimension 5-Level questionnaire (a general health-status measure)\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eResults showed that \u003cstrong\u003equality-of-life scores at baseline were maintained over the trial duration in both groups\u003c\/strong\u003e, and scores did not differ substantially between the daratumumab and active-monitoring groups. This is good news — it means patients receiving daratumumab didn't experience a meaningful decline in their daily quality of life despite the side effects of treatment.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eClinical Implications: What This Means for Patients\u003c\/h2\u003e\n\u003cp\u003eThese results could change the standard of care for high-risk smoldering multiple myeloma. Here's what the findings mean for patients:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eA treatment option now exists where none existed before.\u003c\/strong\u003e For decades, the only approach for smoldering myeloma was to watch and wait. This study shows that a well-tolerated, under-the-skin injection can significantly delay or even prevent progression to active disease.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eEarly treatment may prevent organ damage.\u003c\/strong\u003e The researchers noted that daratumumab \"may delay or even prevent end-organ damage and progression to active multiple myeloma.\" Since active myeloma can cause kidney failure, bone destruction, and severe anemia, preventing these complications is a major win.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSurvival is improved.\u003c\/strong\u003e A 48% reduction in risk of death, with 93% of treated patients alive at 5 years, is a compelling argument for early intervention in appropriately selected high-risk patients.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePatients may avoid or postpone intensive chemotherapy.\u003c\/strong\u003e Only one-third of daratumumab-treated patients needed first-line anti-myeloma therapy within the follow-up period, versus more than half of monitored patients. Avoiding or delaying chemotherapy is a significant quality-of-life benefit.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTreatment is time-limited.\u003c\/strong\u003e Patients did not receive daratumumab indefinitely — the protocol capped treatment at 36 months. The fact that the benefits persisted beyond the treatment period suggests a durable effect.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What This Study Couldn't Prove\u003c\/h2\u003e\n\u003cp\u003eWhile the AQUILA trial results are impressive, it's important to understand the study's limitations:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOpen-label design:\u003c\/strong\u003e Because patients and doctors knew who was receiving treatment, there's a theoretical risk of bias. However, the primary endpoint was assessed by an independent review committee, and sensitivity analyses using investigator assessments and computer algorithms showed high concordance, which strengthens confidence in the results.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLimited diversity:\u003c\/strong\u003e Black patients, who have higher rates of multiple myeloma and are diagnosed at younger ages, were underrepresented — only 2.8% of the trial population. This raises questions about how well the results apply to all racial and ethnic groups.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eProgression criteria evolution:\u003c\/strong\u003e The trial used risk criteria based on data available when the trial was designed. When the newer Mayo 2018 risk criteria were applied retrospectively, only \u003cstrong\u003e40.5%\u003c\/strong\u003e of patients were classified as high risk, suggesting the trial population included some patients who would not meet today's stricter definition of high-risk disease.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLong-term follow-up is still ongoing:\u003c\/strong\u003e While median follow-up exceeded 5 years, we need even longer follow-up to understand the full impact on long-term survival and to see whether the benefits persist or wane over time.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eComparative data are limited:\u003c\/strong\u003e The trial compared daratumumab to observation, not to other potential early treatments. We don't know from this study how daratumumab compares to other strategies that have been explored for high-risk smoldering myeloma.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations for Patients and Caregivers\u003c\/h2\u003e\n\u003cp\u003eIf you or a loved one has been diagnosed with high-risk smoldering multiple myeloma, here are some actionable considerations based on this research:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTalk to your oncologist about this study.\u003c\/strong\u003e Ask specifically whether you meet the criteria for high-risk smoldering myeloma and whether daratumumab might be an appropriate option for you. The treatment is already FDA-approved for active multiple myeloma, and this study provides strong evidence for its use in high-risk smoldering disease.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow your risk factors.\u003c\/strong\u003e Ask your doctor about your specific risk profile — your M-protein level, IgA status, free light chain ratio, bone marrow plasma cell percentage, and whether you have immunoparesis (reduced normal antibodies). This information determines whether you're considered high risk.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about subcutaneous versus intravenous daratumumab.\u003c\/strong\u003e This study used the subcutaneous (under-the-skin) formulation, which is given as an injection and is generally much faster and less burdensome than intravenous (IV) infusions, which can take hours.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eUnderstand the side effect profile.\u003c\/strong\u003e Be aware that daratumumab increases the risk of infections, particularly respiratory infections like pneumonia, and can cause injection-site reactions. Ask your doctor about preventive measures, such as vaccination, antiviral medications, or monitoring for infections.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss the monitoring plan.\u003c\/strong\u003e If you choose active monitoring, make sure you have a clear plan for regular follow-up — blood tests and bone marrow evaluations at defined intervals — so progression is caught as early as possible.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eParticipate in shared decision-making.\u003c\/strong\u003e The decision to treat early isn't right for everyone. Consider your age, overall health, personal preferences, and tolerance for the inconvenience and potential side effects of treatment versus the risk of progression to active disease.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eIf you're recently diagnosed, ask about clinical trials.\u003c\/strong\u003e While daratumumab is approved for active myeloma, the smoldering myeloma indication may be under regulatory review. Clinical trials may offer access to emerging treatments and contribute to advancing care for future patients.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is high-risk smoldering multiple myeloma?\u003c\/h3\u003e\n\u003cp\u003eSmoldering multiple myeloma is a symptom-free precursor condition with abnormal plasma cells in the bone marrow. High-risk means certain features make progression to active myeloma much more likely. In this trial, high-risk patients had at least 10% clonal plasma cells plus one or more risk factors, such as high M-protein or immunoparesis.\u003c\/p\u003e\n\u003ch3\u003eWhat is daratumumab and how does it work?\u003c\/h3\u003e\n\u003cp\u003eDaratumumab is a human monoclonal antibody that targets CD38, a protein found on myeloma cells. It is already approved for active multiple myeloma. In this trial, it was given as an under-the-skin injection to patients with high-risk smoldering myeloma to see if early treatment could delay or prevent progression.\u003c\/p\u003e\n\u003ch3\u003eWhat are the side effects of daratumumab?\u003c\/h3\u003e\n\u003cp\u003eIn the trial, serious infections occurred more often with daratumumab (16.1% had grade 3 or 4 infections) than with monitoring (4.6%). Injection-site reactions were common but not severe. High blood pressure was the most common serious side effect. Two treatment-related deaths occurred, both from COVID-19.\u003c\/p\u003e\n\u003ch3\u003eWho could participate in the AQUILA trial?\u003c\/h3\u003e\n\u003cp\u003ePatients had to be 18 or older with a confirmed diagnosis of high-risk smoldering multiple myeloma within the past five years. They needed measurable disease and good overall health, and had to meet specific risk criteria, such as having at least 10% clonal plasma cells plus additional risk factors.\u003c\/p\u003e\n\u003ch3\u003eWhat should I ask my doctor about early treatment?\u003c\/h3\u003e\n\u003cp\u003eAsk whether you are considered high-risk and meet criteria similar to the trial. Discuss the potential benefits of daratumumab, including delayed progression and improved survival, and its risks, such as infection. Ask about subcutaneous versus intravenous administration and what monitoring plan is right for you.\u003c\/p\u003e\n\u003ch3\u003eShould I get a second opinion before starting daratumumab for high-risk smoldering multiple myeloma?\u003c\/h3\u003e\n\u003cp\u003eIn a phase 3 trial of 390 patients with high-risk smoldering multiple myeloma, subcutaneous daratumumab reduced the risk of progression or death by 51% compared with active monitoring. At 5 years, 63.1% of treated patients were progression-free versus 40.8% monitored, and survival was 93.0% versus 86.9%. However, trial eligibility used older risk criteria, and only 40.5% would meet the newer Mayo 2018 high-risk definition. Side effects included more infections. A second opinion can help clarify your personal risk factors and whether early treatment is right for you. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e M.A. Dimopoulos, P.M. Voorhees, F. Schjesvold, Y.C. Cohen, V. Hungria, I. Sandhu, J. Lindsay, R.I. Baker, K. Suzuki, H. Kosugi, M.-D. Levin, M. Beksac, K. Stockerl-Goldstein, A. Oriol, G. Mikala, G. Garate, K. Theunissen, I. Spicka, A.K. Mylin, S. Bringhen, K. Uttervall, B. Pula, E. Medvedova, A.J. Cowan, P. Moreau, M.-V. Mateos, H. Goldschmidt, T. Ahmadi, L. Sha, A. Cortoos, E.G. Katz, E. Rousseau, L. Li, R.M. Dennis, R. Carson, and S.V. Rajkumar, for the AQUILA Investigators\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication details:\u003c\/strong\u003e The New England Journal of Medicine (NEJM), Volume 392, Issue 18, pages 1777-1788. Published online December 9, 2024, and updated May 8, 2025. DOI: 10.1056\/NEJMoa2409029\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e The trial was funded by Janssen Research and Development. ClinicalTrials.gov number NCT03301220.\u003c\/p\u003e\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace professional medical advice. Always consult your healthcare provider about your individual medical situation.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47494456279196,"sku":null,"price":0.0,"currency_code":"RUB","in_stock":true}],"url":"https:\/\/diagnosticdetectives.ru\/products\/daratumumab-or-active-monitoring-for-high-risk-smoldering-multiple-myeloma","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}