{"product_id":"daratumumab-plus-lenalidomide-after-transplant-better-outcomes-for-multiple-myeloma-patients-across-all-risk-groups","title":"Daratumumab Plus Lenalidomide After Transplant: Better Outcomes for Multiple Myeloma Patients Across All Risk Groups","description":"\u003cp\u003eNew research shows that adding daratumumab to standard lenalidomide maintenance therapy after a stem cell transplant significantly improves outcomes for patients with newly diagnosed multiple myeloma—including those with high-risk genetic features. In the phase 3 AURIGA study, patients receiving daratumumab plus lenalidomide (D-R) were more than four times as likely to achieve minimal residual disease (MRD) negativity—meaning no detectable cancer cells—compared to those receiving lenalidomide alone, and they had a 47% lower risk of disease progression or death. These benefits held across all age groups, racial groups, and risk categories, including patients with the most aggressive, genetically high-risk forms of the disease.\u003c\/p\u003e\n\n\u003ch1\u003eDaratumumab Plus Lenalidomide After Transplant: Better Outcomes for Multiple Myeloma Patients Across All Risk Groups\u003c\/h1\u003e\n\n\u003ch2\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\"\u003eWhy This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#understanding\"\u003eUnderstanding Multiple Myeloma and the Treatment Landscape\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#study-design\"\u003eThe AURIGA Study: Design and Participants\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#how-conducted\"\u003eHow the Study Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Findings: MRD-Negative Conversion Rates\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#high-risk\"\u003eFindings in High-Risk Genetic Subgroups\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#pfs\"\u003eProgression-Free Survival Results\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety Profile in Older and Black Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of This Analysis\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations for Patients\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 the AURIGA trial, adding daratumumab to lenalidomide maintenance after stem cell transplant increased MRD-negative conversion at 12 months to 50.5% versus 18.8% with lenalidomide alone.\u003c\/li\u003e\n\u003cli\u003eThe same trial found a 47% lower risk of disease progression or death with daratumumab plus lenalidomide compared with lenalidomide alone.\u003c\/li\u003e\n\u003cli\u003eBenefits were seen across age groups, racial groups, and cytogenetic risk categories, including patients with high-risk genetic features.\u003c\/li\u003e\n\u003cli\u003eAmong patients meeting modified IMS 2024 high-risk criteria, 41.2% receiving daratumumab plus lenalidomide achieved MRD negativity versus 0% receiving lenalidomide alone.\u003c\/li\u003e\n\u003cli\u003eLow blood cell counts and some infections were more common with daratumumab plus lenalidomide; three deaths due to treatment side effects occurred, all in older patients.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eWhy This Research Matters\u003c\/h2\u003e\n\n\u003cp\u003eMultiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. Despite major advances in treatment over the past two decades, certain patients continue to face poor outcomes—particularly those with high-risk genetic abnormalities (HRCAs) in their cancer cells.\u003c\/p\u003e\n\n\u003cp\u003eThe standard approach for transplant-eligible patients involves induction therapy (chemotherapy to shrink the cancer), followed by high-dose chemotherapy and an autologous stem cell transplant (ASCT)—a procedure where the patient's own stem cells are collected, the bone marrow is destroyed with high-dose chemotherapy, and the stem cells are returned to rebuild the bone marrow. After recovery from transplant, patients typically receive maintenance therapy to keep the cancer from coming back. Lenalidomide (R) has been the standard maintenance treatment.\u003c\/p\u003e\n\n\u003cp\u003eThis study investigates whether adding daratumumab—a targeted antibody therapy—to lenalidomide maintenance could improve outcomes, particularly for patients who are at high risk of relapse.\u003c\/p\u003e\n\n\u003ch2 id=\"understanding\"\u003eUnderstanding Multiple Myeloma and the Treatment Landscape\u003c\/h2\u003e\n\n\u003cp\u003eDaratumumab is a human IgGκ monoclonal antibody that targets a protein called CD38 found on myeloma cells. It works through direct effects on the tumor and by helping the immune system attack cancer cells. Because of its favorable benefits, daratumumab is already approved as a single agent for patients with relapsed\/refractory multiple myeloma and in combination with standard treatments for both newly diagnosed and relapsed patients. It is the first anti-CD38 antibody to show benefit in transplant-eligible, non-transplant, and transplant-ineligible patients with newly diagnosed multiple myeloma across multiple phases of therapy—including induction, consolidation, and maintenance.\u003c\/p\u003e\n\n\u003cp\u003eDespite rapid progress, certain patient and disease characteristics still predict poor outcomes, including ethnicity (with Black patients historically experiencing worse outcomes), age, and the presence of high-risk cytogenetic abnormalities. For decades, high-risk cytogenetics were defined by the presence of one or more of three specific chromosomal abnormalities:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003et(4;14) — a translocation between chromosomes 4 and 14\u003c\/li\u003e\n  \u003cli\u003et(14;16) — a translocation between chromosomes 14 and 16\u003c\/li\u003e\n  \u003cli\u003edel(17p) — a deletion of part of chromosome 17\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThis \"original\" definition was later revised to also include t(14;20) and gain\/amplification of chromosome 1q21 (gain\/amp[1q21]). And in 2024, the International Myeloma Society (IMS) presented an updated consensus definition of high-risk disease. Under the 2024 criteria, high-risk disease includes any of the following:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003edel(17p) present in at least 20% of cells\u003c\/li\u003e\n  \u003cli\u003eA TP53 mutation (a genetic change in a key tumor-suppressor gene)\u003c\/li\u003e\n  \u003cli\u003eBiallelic (both copies) deletion of 1p32\u003c\/li\u003e\n  \u003cli\u003eMonoallelic (one copy) deletion of 1p32 combined with gain\/amp(1q21)\u003c\/li\u003e\n  \u003cli\u003et(4;14), t(14;16), or t(14;20) combined with gain\/amp(1q21) and\/or monoallelic del(1p32)\u003c\/li\u003e\n  \u003cli\u003eA combination of high beta-2-microglobulin (ß2M; greater than 5.5 mg\/dL) with normal creatinine (less than 1.2 mg\/dL)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eBecause the IMS 2024 definition is so new, very few studies have reported outcomes for patients meeting these updated criteria. This analysis helps fill that gap.\u003c\/p\u003e\n\n\u003ch2 id=\"study-design\"\u003eThe AURIGA Study: Design and Participants\u003c\/h2\u003e\n\n\u003cp\u003eThe AURIGA study (ClinicalTrials.gov identifier NCT03901963) is a randomized, phase 3, open-label, active-controlled, multicenter clinical trial that was the first study designed to evaluate adding subcutaneous (under-the-skin) daratumumab to lenalidomide maintenance in transplant-eligible patients with newly diagnosed multiple myeloma.\u003c\/p\u003e\n\n\u003cp\u003eThe study enrolled patients from 52 sites across the United States and Canada. To be eligible, patients had to meet several important criteria:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eBe between 18 and 79 years old\u003c\/li\u003e\n  \u003cli\u003eHave newly diagnosed multiple myeloma with at least 4 prior cycles of induction therapy\u003c\/li\u003e\n  \u003cli\u003eHave received high-dose therapy and an autologous stem cell transplant within 12 months of starting induction\u003c\/li\u003e\n  \u003cli\u003eBe randomized within 6 months of their transplant\u003c\/li\u003e\n  \u003cli\u003eNever have received anti-CD38 antibody treatment\u003c\/li\u003e\n  \u003cli\u003eStill have detectable minimal residual disease (MRD positive) at a sensitivity threshold of 10⁻⁵ (meaning 1 cancer cell in 100,000 normal cells) as measured by next-generation sequencing\u003c\/li\u003e\n  \u003cli\u003eHave achieved at least a very good partial response (VGPR) or better after transplant\u003c\/li\u003e\n  \u003cli\u003eHave an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2, meaning they were fully active or ambulatory\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eA total of 200 patients were enrolled and randomized 1:1 to receive either daratumumab plus lenalidomide (D-R; n=99) or lenalidomide alone (R; n=101). Of note, 22% of the patients in the study were Black—a significant and important representation in a clinical trial for multiple myeloma.\u003c\/p\u003e\n\n\u003cp\u003eThe treatment plan was as follows:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLenalidomide:\u003c\/strong\u003e All patients received 10 mg of lenalidomide daily on Days 1–28 of each 28-day cycle, with the possibility of increasing the dose to 15 mg after 3 cycles if tolerated and at the investigator's discretion.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDaratumumab (D-R group only):\u003c\/strong\u003e Patients received 1800 mg of daratumumab co-formulated with recombinant human hyaluronidase PH20 (2000 U\/mL, using ENHANZE® drug delivery technology) by subcutaneous injection—weekly during Cycles 1 and 2, every 2 weeks during Cycles 3 through 6, and every 4 weeks from Cycle 7 onward.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eTreatment continued for a planned maximum of 36 cycles (about 3 years) or until disease progression, unacceptable toxicity, or the patient chose to withdraw.\u003c\/p\u003e\n\n\u003ch2 id=\"how-conducted\"\u003eHow the Study Was Conducted\u003c\/h2\u003e\n\n\u003cp\u003ePatients were stratified at randomization by cytogenetic risk based on the investigator's assessment (standard risk\/unknown versus high risk), with high risk originally defined as having at least one of: del(17p), t(4;14), or t(14;16).\u003c\/p\u003e\n\n\u003cp\u003eThe primary endpoint—the main measure of success—was the MRD-negative conversion rate from baseline to 12 months of maintenance. This was defined as the proportion of patients who converted from having detectable MRD to achieving MRD-negative status (at a 10⁻⁵ sensitivity threshold) by 12 months after starting maintenance therapy, without having disease progression or starting subsequent anti-myeloma therapy.\u003c\/p\u003e\n\n\u003cp\u003eMRD was assessed by next-generation sequencing of bone marrow aspirate samples at a central laboratory using the clonoSEQ® assay (Adaptive Biotechnologies), with a minimum sensitivity threshold of 10⁻⁵. Bone marrow samples were collected at screening and after 12, 18, 24, and 36 months of maintenance treatment, within an accepted ±30-day window of the scheduled visit.\u003c\/p\u003e\n\n\u003cp\u003eResponse and disease progression were assessed using a validated computerized algorithm in accordance with the International Myeloma Working Group (IMWG) 2016 response criteria.\u003c\/p\u003e\n\n\u003cp\u003eThis post hoc (after-the-fact) subgroup analysis was conducted at the time of the primary analysis, which occurred after all randomized patients had either completed 12 months of maintenance, experienced disease progression, died, or discontinued study treatment. The analysis examined outcomes across several clinically relevant subgroups: race (Black or White), age (under 65 years or 65 years and older), ISS disease stage at diagnosis (I, II, or III), baseline response status (VGPR or complete response or better), and cytogenetic risk under the original, revised, and modified IMS 2024 criteria.\u003c\/p\u003e\n\n\u003cp\u003eSeveral important definitions were used for cytogenetic risk in this analysis:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOriginal criteria:\u003c\/strong\u003e Presence of del(17p), t(4;14), and\/or t(14;16)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRevised criteria:\u003c\/strong\u003e Presence of del(17p), t(4;14), t(14;16), t(14;20), and\/or gain\/amp(1q21)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModified IMS 2024 criteria:\u003c\/strong\u003e Presence of del(17p) in ≥20% of cells; del(1p32) co-occurring with gain\/amp(1q21); or t(4;14), t(14;16), and\/or t(14;20) co-occurring with gain\/amp(1q21) and\/or del(1p32)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn the AURIGA study, data were not collected on TP53 mutations, the difference between monoallelic versus biallelic del(1p32), or beta-2-microglobulin and creatinine levels at the time of diagnosis—so the IMS 2024 criteria were slightly modified based on data availability.\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Findings: MRD-Negative Conversion Rates\u003c\/h2\u003e\n\n\u003cp\u003eThe primary analysis of AURIGA—reported earlier with a median follow-up of 32.3 months—found that D-R maintenance significantly improved the MRD-negative (10⁻⁵) conversion rate by 12 months compared with R alone: \u003cstrong\u003e50.5% versus 18.8%\u003c\/strong\u003e, respectively. This translates to an odds ratio of 4.51 (95% confidence interval [CI], 2.37–8.57; P\u0026lt;0.0001), meaning patients in the D-R group were more than four times as likely to achieve MRD negativity. In addition, D-R was associated with a 47% reduction in the risk of disease progression or death (hazard ratio [HR], 0.53; 95% CI, 0.29–0.97; P=0.0361).\u003c\/p\u003e\n\n\u003cp\u003eThis new subgroup analysis shows that the benefit of D-R was consistent across every subgroup examined. Here are the MRD-negative conversion rates by 12 months for key patient groups:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePatients under 65 years:\u003c\/strong\u003e D-R 49.2% (30\/61) versus R 19.7% (12\/61); odds ratio (OR) 3.95 (95% CI, 1.76–8.85)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePatients 65 years and older:\u003c\/strong\u003e D-R 52.6% (20\/38) versus R 17.5% (7\/40); OR 5.24 (95% CI, 1.86–14.74)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eWhite patients:\u003c\/strong\u003e D-R 46.3% (31\/67) versus R 20.6% (14\/68); OR 3.32 (95% CI, 1.55–7.10)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBlack patients:\u003c\/strong\u003e D-R 60.0% (12\/20) versus R 16.7% (4\/24); OR 7.50 (95% CI, 1.85–30.34)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eISS stage I:\u003c\/strong\u003e D-R 47.5% (19\/40) versus R 21.1% (8\/38); OR 3.39 (95% CI, 1.25–9.19)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eISS stage II:\u003c\/strong\u003e D-R 46.4% (13\/28) versus R 18.9% (7\/37); OR 3.71 (95% CI, 1.23–11.25)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eISS stage III:\u003c\/strong\u003e D-R 65.2% (15\/23) versus R 13.0% (3\/23); OR 12.50 (95% CI, 2.83–55.25)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eVGPR at study entry:\u003c\/strong\u003e D-R 38.0% (27\/71) versus R 15.5% (11\/71); OR 3.35 (95% CI, 1.50–7.46)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eComplete response (≥CR) at study entry:\u003c\/strong\u003e D-R 82.1% (23\/28) versus R 26.7% (8\/30); OR 12.65 (95% CI, 3.58–44.64)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThese numbers show that whether a patient was younger or older, White or Black, or had earlier- or later-stage disease, the addition of daratumumab consistently improved the chances of achieving deep remission.\u003c\/p\u003e\n\n\u003ch2 id=\"high-risk\"\u003eFindings in High-Risk Genetic Subgroups\u003c\/h2\u003e\n\n\u003cp\u003eOne of the most important aspects of this analysis is its focus on patients with high-risk cytogenetic abnormalities—the group that typically fares worst with standard treatment. The results were striking.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eBy original high-risk criteria\u003c\/strong\u003e (del[17p], t[4;14], and\/or t[14;16]):\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eD-R achieved MRD-negative conversion in 31.8% (7\/22) of patients versus only 6.7% (1\/15) with R alone (OR 6.53; 95% CI, 0.71–60.05)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003eBy revised high-risk criteria\u003c\/strong\u003e (adding t[14;20] and\/or gain\/amp[1q21]):\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eD-R achieved MRD-negative conversion in 43.8% (14\/32) versus 13.3% (4\/30) with R alone (OR 5.06; 95% CI, 1.43–17.88)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003e\u003cstrong\u003eBy modified IMS 2024 high-risk criteria:\u003c\/strong\u003e\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eD-R achieved MRD-negative conversion in 41.2% (7\/17) versus \u003cstrong\u003e0%\u003c\/strong\u003e (0\/8) with R alone\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAmong the modified IMS 2024 high-risk subgroups, no patient in the R group achieved MRD-negative conversion, while rates with D-R ranged from 20% to 75% depending on the specific abnormality:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003e≥20% del(17p):\u003c\/strong\u003e D-R 20.0% (2\/10) versus R 0% (0\/2)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003et(4;14)\/(14;16)\/(14;20) plus gain\/amp(1q21) and\/or del(1p32):\u003c\/strong\u003e D-R 40.0% (2\/5) versus R 0% (0\/6)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003edel(1p32) plus gain\/amp(1q21):\u003c\/strong\u003e D-R 75.0% (3\/4) versus R none in this subgroup\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eFor patients with cytogenetically ultra-high-risk disease—defined as having 2 or more revised HRCAs—the results were especially encouraging. \u003cstrong\u003eNo patient in the R group (0\/10) achieved MRD-negative conversion, whereas 54.5% (6\/11) of patients in the D-R group did.\u003c\/strong\u003e\u003c\/p\u003e\n\n\u003cp\u003eSimilar trends were seen for overall MRD-negative conversion rates (at any time point during the study). Among ultra-high-risk patients, 63.6% (7\/11) in the D-R group achieved MRD negativity versus 0% (0\/10) in the R group. In the modified IMS 2024 high-risk subgroups, overall conversion rates ranged from 40% to 75% with D-R versus 0% with R.\u003c\/p\u003e\n\n\u003ch2 id=\"pfs\"\u003eProgression-Free Survival Results\u003c\/h2\u003e\n\n\u003cp\u003eProgression-free survival (PFS)—the length of time patients live without their disease worsening—is a critical measure for patients. At a median follow-up of 32.3 months, PFS favored D-R across all subgroups, including regardless of age, race, disease stage, or cytogenetic risk status.\u003c\/p\u003e\n\n\u003cp\u003eThe hazard ratios (where a value below 1.0 favors D-R) for key cytogenetic subgroups were:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStandard risk (original criteria):\u003c\/strong\u003e HR 0.59 (95% CI, 0.23–1.49)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHigh risk (original criteria):\u003c\/strong\u003e HR 0.60 (95% CI, 0.21–1.70); median PFS not reached in the D-R group versus 16.7 months in the R group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRevised standard risk (0 HRCAs):\u003c\/strong\u003e HR 0.69 (95% CI, 0.24–1.95)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRevised high risk (≥1 HRCA):\u003c\/strong\u003e HR 0.53 (95% CI, 0.21–1.31); median PFS not reached in either group\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModified IMS 2024 standard risk:\u003c\/strong\u003e HR 0.42 (95% CI, 0.16–1.07)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModified IMS 2024 high risk:\u003c\/strong\u003e HR 0.45 (95% CI, 0.13–1.53); median PFS of 32.8 months with D-R versus 16.7 months with R\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e0 HRCAs:\u003c\/strong\u003e HR 0.69 (95% CI, 0.24–1.95)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e1 HRCA:\u003c\/strong\u003e HR 0.36 (95% CI, 0.09–1.45)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003e≥2 HRCAs (ultra-high risk):\u003c\/strong\u003e HR 0.61 (95% CI, 0.17–2.25)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGain\/amp(1q21), regardless of other HRCAs:\u003c\/strong\u003e HR 0.46 (95% CI, 0.13–1.59)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eIn patients with isolated gain\/amp(1q21), the treatment effect could not be quantified because no PFS events (disease progression or death) occurred in the D-R group, compared with 4 events in the R group.\u003c\/p\u003e\n\n\u003cp\u003eThese results show a consistent trend toward improved progression-free survival with D-R maintenance, with some of the strongest effects seen in the highest-risk groups when using the most up-to-date definitions of high-risk disease.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety Profile in Older and Black Patients\u003c\/h2\u003e\n\n\u003cp\u003eBecause older patients (65 years and older) and Black patients have historically been underrepresented in clinical trials, the researchers specifically examined safety outcomes in these groups. The good news: no new safety concerns were identified.\u003c\/p\u003e\n\n\u003cp\u003eGrade 3\/4 cytopenia (low blood cell counts) was reported in both age groups, with a higher overall incidence in the D-R group compared with R:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eUnder 65 years: D-R 52.5% versus R 46.6%\u003c\/li\u003e\n  \u003cli\u003e65 years and older: D-R 56.8% versus R 47.5%\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eGrade 3\/4 infections showed a mixed picture by age:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eUnder 65 years: D-R 18.6% versus R 10.3%\u003c\/li\u003e\n  \u003cli\u003e65 years and older: D-R 18.9% versus R 17.5% (similar between groups)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eSerious treatment-emergent adverse events (TEAEs) were higher with D-R among younger patients (23.7% versus 12.1%), but similar among older patients (40.5% versus 37.5%).\u003c\/p\u003e\n\n\u003cp\u003eThe frequency of TEAEs leading to treatment discontinuation was higher with D-R in both age groups: 11.9% versus 6.9% in patients under 65, and 18.9% versus 10.0% in patients 65 and older.\u003c\/p\u003e\n\n\u003cp\u003eDeaths due to treatment-emergent adverse events were low overall—only 3 deaths—all occurring among the older patients.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThis analysis provides strong evidence that adding daratumumab to lenalidomide maintenance after stem cell transplant benefits patients regardless of age, race, or cytogenetic risk status. The consistency of the findings across every subgroup examined is notable.\u003c\/p\u003e\n\n\u003cp\u003eFor Black patients, the results are particularly meaningful. Black patients in the D-R group achieved a 60.0% MRD-negative conversion rate—the highest of any age or race subgroup—compared to just 16.7% with lenalidomide alone (OR 7.50). This suggests that D-R maintenance may help address longstanding disparities in multiple myeloma outcomes.\u003c\/p\u003e\n\n\u003cp\u003eFor patients with high-risk cytogenetic abnormalities—especially those meeting the newest IMS 2024 criteria or with ultra-high-risk disease (2 or more abnormalities)—the results are transformative. In the modified IMS 2024 high-risk group, not a single patient receiving lenalidomide alone achieved MRD negativity, while 41.2% of those receiving D-R did. Even among patients with the most aggressive disease features, D-R maintenance produced measurable, meaningful benefits.\u003c\/p\u003e\n\n\u003cp\u003eThe fact that PFS trends favored D-R even in the highest-risk groups—with median PFS more than doubled in some analyses (32.8 months versus 16.7 months in the modified IMS 2024 high-risk group)—reinforces the clinical value of this combination approach.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of This Analysis\u003c\/h2\u003e\n\n\u003cp\u003eIt's important to understand what this study could and could not prove. Several limitations should be noted:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThis is a post hoc analysis.\u003c\/strong\u003e The subgroup analyses were performed after the main study results were known, which means they were exploratory in nature rather than pre-planned definitive tests.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSmall subgroup sizes.\u003c\/strong\u003e Many of the subgroups—particularly the high-risk cytogenetic groups—had small numbers of patients. For example, only 17 patients in the D-R group and 8 in the R group met the modified IMS 2024 high-risk criteria. Small sample sizes mean wider confidence intervals and less certainty about the exact size of the benefit.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eImbalances between treatment groups.\u003c\/strong\u003e There was an imbalance in the original high-risk cytogenetic criteria (D-R, n=22; R, n=15), primarily due to more D-R patients having del(17p). This was driven by investigators mixing cytogenetic assessments at the time of randomization with those based on data from screening or diagnosis. Notably, the modified IMS 2024 high-risk group also had an imbalance, with more high-risk patients in the D-R group (17 versus 8)—yet D-R still showed strong benefits.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eModified IMS 2024 criteria.\u003c\/strong\u003e Because data were not collected on TP53 mutations, beta-2-microglobulin and creatinine levels at diagnosis, or monoallelic versus biallelic del(1p32), the full IMS 2024 criteria could not be applied exactly as intended.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFollow-up duration.\u003c\/strong\u003e The median follow-up was 32.3 months, which is relatively short for evaluating long-term outcomes in multiple myeloma.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStatistical significance was not reached for PFS in subgroups.\u003c\/strong\u003e While the trends favored D-R consistently, the confidence intervals for PFS hazard ratios crossed 1.0 in the subgroups, meaning the PFS benefits were not statistically significant at the subgroup level—though the primary analysis did show significant benefit overall.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations for Patients\u003c\/h2\u003e\n\n\u003cp\u003eBased on the findings of this study, patients with newly diagnosed multiple myeloma who are undergoing autologous stem cell transplant may want to discuss the following with their healthcare team:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about maintenance options after transplant.\u003c\/strong\u003e The addition of daratumumab to lenalidomide maintenance significantly increased MRD-negative conversion rates (50.5% versus 18.8%) and reduced the risk of progression or death by 47% compared to lenalidomide alone.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow your cytogenetic risk status.\u003c\/strong\u003e Understanding whether your myeloma has high-risk genetic features—including the newest IMS 2024 criteria such as del(17p) in ≥20% of cells, TP53 mutations, or combinations of abnormalities—can help guide treatment decisions. Ask your doctor whether your testing included evaluation of these markers.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDon't assume high-risk means hopeless.\u003c\/strong\u003e Even among patients with ultra-high-risk disease (2 or more high-risk abnormalities), 54.5% of those receiving D-R achieved MRD negativity, compared to 0% with lenalidomide alone.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConsider MRD testing.\u003c\/strong\u003e MRD status is a powerful indicator of how well treatment is working. Ask whether MRD testing via next-generation sequencing (such as clonoSEQ®) is available and recommended in your case.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRace and age should not limit treatment options.\u003c\/strong\u003e The benefits of D-R maintenance were observed across all age and racial groups, including older patients (65+) and Black patients, with no additional safety concerns identified in these populations.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss side effect management.\u003c\/strong\u003e While D-R was associated with higher rates of low blood cell counts and some infections, serious events were manageable and deaths due to treatment side effects were rare (3 total). Your care team can help monitor and manage these side effects.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSeek care at a center experienced in myeloma.\u003c\/strong\u003e This study was conducted at 52 academic and community sites across the US and Canada. Access to clinical trials and experienced multidisciplinary care can make a meaningful difference in outcomes.\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 minimal residual disease (MRD) negativity, and why does it matter?\u003c\/h3\u003e\n\u003cp\u003eMRD negativity means no cancer cells are detectable at a sensitivity of 1 in 100,000 cells, measured by next-generation sequencing. In the AURIGA trial, patients receiving daratumumab plus lenalidomide after transplant were more than four times as likely to achieve MRD negativity by 12 months compared with lenalidomide alone. MRD status is a powerful indicator of how well treatment is working.\u003c\/p\u003e\n\u003ch3\u003eWho was eligible for the AURIGA study?\u003c\/h3\u003e\n\u003cp\u003ePatients aged 18 to 79 with newly diagnosed multiple myeloma who had at least four prior cycles of induction therapy, received high-dose therapy and an autologous stem cell transplant within 12 months of starting induction, and were randomized within 6 months of transplant. They had to be MRD positive at a sensitivity of 10⁻⁵, have achieved at least a very good partial response after transplant, and have never received anti-CD38 antibody treatment.\u003c\/p\u003e\n\u003ch3\u003eWhat were the main results of adding daratumumab to lenalidomide maintenance?\u003c\/h3\u003e\n\u003cp\u003eIn the AURIGA trial, daratumumab plus lenalidomide (D-R) increased the MRD-negative conversion rate by 12 months to 50.5% versus 18.8% with lenalidomide alone. D-R also reduced the risk of disease progression or death by 47% compared with lenalidomide alone. These benefits were seen across age groups, racial groups, and cytogenetic risk categories, including high-risk disease.\u003c\/p\u003e\n\u003ch3\u003eDid the treatment work for patients with high-risk genetic features?\u003c\/h3\u003e\n\u003cp\u003eYes. In the AURIGA trial, among patients meeting modified IMS 2024 high-risk criteria, 41.2% receiving D-R achieved MRD-negative conversion versus 0% receiving lenalidomide alone. For those with ultra-high-risk disease (two or more high-risk abnormalities), 54.5% in the D-R group achieved MRD negativity compared with 0% in the lenalidomide-alone group. These findings come from small subgroups, so results should be interpreted with caution.\u003c\/p\u003e\n\u003ch3\u003eWhat side effects were reported with daratumumab plus lenalidomide?\u003c\/h3\u003e\n\u003cp\u003eIn the AURIGA trial, low blood cell counts (grade 3\/4 cytopenia) were more common with D-R than lenalidomide alone: 52.5% versus 46.6% in patients under 65, and 56.8% versus 47.5% in those 65 and older. Grade 3\/4 infections were also higher with D-R in younger patients (18.6% versus 10.3%) but similar in older patients (18.9% versus 17.5%). Three deaths due to treatment side effects occurred, all in older patients.\u003c\/p\u003e\n\u003ch3\u003eHow long does maintenance treatment last after a stem cell transplant?\u003c\/h3\u003e\n\u003cp\u003eIn the AURIGA trial, treatment continued for a planned maximum of 36 cycles (about 3 years) or until disease progression, unacceptable toxicity, or the patient chose to withdraw. Lenalidomide was given daily on days 1–28 of each 28-day cycle. Daratumumab was given subcutaneously weekly during cycles 1–2, every 2 weeks during cycles 3–6, and every 4 weeks from cycle 7 onward.\u003c\/p\u003e\n\u003ch3\u003eWhat should I ask my doctor about maintenance therapy after transplant?\u003c\/h3\u003e\n\u003cp\u003eAsk about maintenance options after transplant, including whether adding daratumumab to lenalidomide is appropriate for you. Ask about your cytogenetic risk status, including newer markers such as del(17p) in at least 20% of cells or TP53 mutations. Ask whether MRD testing via next-generation sequencing is available. Discuss side effect management, since D-R was linked to higher rates of low blood cell counts and some infections.\u003c\/p\u003e\n\u003ch3\u003eWhen should a patient with newly diagnosed multiple myeloma consider a second opinion about daratumumab plus lenalidomide maintenance after a stem cell transplant?\u003c\/h3\u003e\n\u003cp\u003eA second opinion can be useful before committing to maintenance therapy after transplant, especially when cytogenetic risk status is unclear. High-risk features include del(17p) in at least 20% of cells, TP53 mutations, and combinations of abnormalities under the 2024 criteria. Because many patients were not tested for all these markers, an independent review can clarify whether daratumumab plus lenalidomide is appropriate. MRD testing by next-generation sequencing also informs this decision. 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\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Foster L, Anderson LD, Chung A, Chaulagain CP, Pettijohn E, Cowan AJ, Costello C, Larson S, Sborov DW, Shain KH, Silbermann R, Voorhees P, Krevvata M, Pei H, Patel S, Khare V, Cortoos A, Carson R, Lin TS, Badros A.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e Blood Cancer Journal (2025) 15:154; published by Nature Publishing Group\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e https:\/\/doi.org\/10.1038\/s41408-025-01355-0\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinical trial registration:\u003c\/strong\u003e ClinicalTrials.gov Identifier NCT03901963\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\/support:\u003c\/strong\u003e The study involved authors affiliated with Johnson \u0026amp; Johnson (the manufacturer of daratumumab) and multiple academic medical centers. The corresponding author is affiliated with the University of Virginia Division of Hematology Oncology.\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research published in Blood Cancer Journal. It is intended for educational purposes and is not a substitute for professional medical advice. Patients should always consult their healthcare providers about their individual treatment plans.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47709987537052,"sku":null,"price":0.0,"currency_code":"USD","in_stock":true}],"url":"https:\/\/diagnosticdetectives.com\/ar\/products\/daratumumab-plus-lenalidomide-after-transplant-better-outcomes-for-multiple-myeloma-patients-across-all-risk-groups","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}