{"product_id":"daratumumab-combination-extends-survival-to-7-5-years-in-older-patients-with-newly-diagnosed-multiple-myeloma-final-results-of-the-maia-trial","title":"Daratumumab Combination Extends Survival to 7.5 Years in Older Patients With Newly Diagnosed Multiple Myeloma: Final Results of the MAIA Trial","description":"\u003cp\u003eIn the final analysis of the MAIA trial, 737 patients with newly diagnosed multiple myeloma were followed for a median of 89.3 months (about 7.5 years). These patients were not eligible for stem cell transplant. The combination of daratumumab, lenalidomide, and dexamethasone (D-Rd) extended median overall survival to 90.3 months (7.5 years). Median overall survival was 64.1 months (5.3 years) for lenalidomide and dexamethasone alone (Rd). This represents a 33% relative reduction in the risk of death (hazard ratio 0.67; 95% confidence interval 0.55–0.82), and an estimated 53.1% of patients on D-Rd were alive at 7 years versus 39.3% on Rd. Patients on D-Rd also went much longer before needing a next line of myeloma therapy (median not reached versus 42.4 months), and no new safety concerns related to death were found; adverse events were not collected in this analysis.\u003c\/p\u003e\n\n\u003ch1\u003eDaratumumab Combination Extends Survival to 7.5 Years in Older Patients With Newly Diagnosed Multiple Myeloma: Final Results of the MAIA Trial\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\"\u003eBackground: Why This Research Matters\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#study-methods\"\u003eHow the Study Was Conducted\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#key-findings\"\u003eKey Findings: Survival Results\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#age-subgroups\"\u003eSurvival Results by Age Group\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#subgroups\"\u003eSurvival Across Other Patient Subgroups\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#mrd\"\u003eMinimal Residual Disease and Survival\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#subsequent-therapy\"\u003eTime to Next Treatment and Later Therapies\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#safety\"\u003eSafety and Causes of Death\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#clinical-implications\"\u003eWhat These Results Mean for Patients\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations of the Study\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#recommendations\"\u003ePractical Points for Patients and Families\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 737 transplant-ineligible patients with newly diagnosed multiple myeloma, median overall survival was 90.3 months with daratumumab plus lenalidomide and dexamethasone versus 64.1 months with lenalidomide and dexamethasone alone.\u003c\/li\u003e\n\u003cli\u003eThe three-drug combination reduced the risk of death by about one-third during follow-up (hazard ratio 0.67), and an estimated 53.1% versus 39.3% of patients were alive at 7 years.\u003c\/li\u003e\n\u003cli\u003eThe survival benefit appeared generally consistent across age groups, including patients aged 80 or older, though these age analyses were exploratory and some subgroups were small.\u003c\/li\u003e\n\u003cli\u003eMedian time to a next antimyeloma treatment was not reached with the three-drug combination versus 42.4 months with the two-drug regimen.\u003c\/li\u003e\n\u003cli\u003eNo new safety concerns emerged; during the long-term extension only death-related safety data were collected, so the longer-term side-effect profile is not fully described.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eBackground: Why This Research Matters\u003c\/h2\u003e\n\u003cp\u003eMultiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow. Many patients are diagnosed when they are older or when they have other health conditions. For these patients, high-dose chemotherapy followed by an autologous stem cell transplant is often not a safe option. An autologous stem cell transplant is a procedure that uses the patient's own stem cells to restore the bone marrow.\u003c\/p\u003e\n\n\u003cp\u003eFor patients who cannot have a transplant, the standard first treatment has been a combination of two drugs. The two drugs are lenalidomide, an oral drug that alters how cancer cells grow and helps the immune system, and dexamethasone, a steroid that helps kill myeloma cells. This two-drug regimen is called Rd.\u003c\/p\u003e\n\n\u003cp\u003eDaratumumab is a human monoclonal antibody of the IgGκ type. A monoclonal antibody is a laboratory-made immune protein that targets one specific marker. Daratumumab targets CD38, a protein found on the surface of myeloma cells. It fights myeloma in two ways: it attacks the cancer cells directly, and it stimulates the patient's immune system to attack the cancer cells.\u003c\/p\u003e\n\n\u003cp\u003eAdding daratumumab to first-line (frontline) combination therapy has consistently shown clinical benefit in patients with newly diagnosed multiple myeloma (NDMM). The MAIA study was designed to test whether adding daratumumab to Rd would help patients who could not receive a transplant.\u003c\/p\u003e\n\n\u003cp\u003eEarlier results from MAIA were already encouraging. At the first planned interim analysis, with a median follow-up of 28.0 months, D-Rd significantly improved progression-free survival (PFS) compared with Rd. PFS is the time a patient lives without the disease getting worse. The hazard ratio was 0.56 (95% confidence interval [CI], 0.43–0.73; P\u0026lt;0.001).\u003c\/p\u003e\n\n\u003cp\u003eThat first analysis also showed deeper responses with D-Rd. A complete response or better (≥CR, meaning no detectable signs of cancer) occurred in 47.6% of D-Rd patients versus 24.9% of Rd patients (P\u0026lt;0.001). Minimal residual disease (MRD) negativity — meaning the cancer was undetectable at a very sensitive threshold of 10\u003csup\u003e–5\u003c\/sup\u003e — occurred in 24.2% versus 7.3% (P\u0026lt;0.001).\u003c\/p\u003e\n\n\u003cp\u003eAfter a median follow-up of 56.2 months, D-Rd significantly improved overall survival (OS, the time from randomization until death from any cause) versus Rd. The hazard ratio was 0.68 (95% CI, 0.53–0.86; P=0.0013), and no new safety concerns appeared.\u003c\/p\u003e\n\n\u003cp\u003eAt a median follow-up of 64.5 months, the addition of daratumumab continued to produce deep and durable responses. Sustained MRD negativity lasting at least 12 months at the 10\u003csup\u003e–5\u003c\/sup\u003e threshold was seen in 18.8% of D-Rd patients versus 4.1% of Rd patients (P\u0026lt;0.0001). These deeper responses translated into PFS and OS benefits for transplant-ineligible patients with NDMM.\u003c\/p\u003e\n\n\u003cp\u003eThe current report presents the final, long-term survival analysis of MAIA. It includes overall survival results, a post hoc (after-the-fact) subgroup analysis of survival by age, and updated information on later myeloma treatments and deaths related to safety. The median follow-up for this analysis was approximately 7.5 years.\u003c\/p\u003e\n\n\u003ch2 id=\"study-methods\"\u003eHow the Study Was Conducted\u003c\/h2\u003e\n\u003cp\u003eMAIA (ClinicalTrials.gov identifier NCT02252172) was a randomized, open-label, active-controlled, parallel-group, multicenter, phase 3 study. \"Open-label\" means both patients and doctors knew which treatment was given. \"Phase 3\" means the study was large enough and designed to confirm effectiveness in a definitive way.\u003c\/p\u003e\n\n\u003cp\u003ePatients in the study were at least 18 years old. They had documented newly diagnosed multiple myeloma and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2. The ECOG score measures how well a patient can carry out daily activities; 0 means fully active and 2 means able to do self-care but unable to work. Patients were not candidates for high-dose chemotherapy and autologous stem cell transplant because of age (65 years or older). Other patients were not candidates because other health conditions would likely make that intensive treatment poorly tolerated.\u003c\/p\u003e\n\n\u003cp\u003eThe study protocol was approved by an independent ethics committee or institutional review board at each site. All patients provided written informed consent. The trial followed the principles of the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice guidelines.\u003c\/p\u003e\n\n\u003cp\u003ePatients were randomly assigned in a 1:1 ratio to receive D-Rd or Rd. Randomization was stratified (balanced) by three factors. The three factors were International Staging System (ISS) disease stage (I versus II versus III), geographic region (North America versus other), and age (younger than 75 years versus 75 years or older).\u003c\/p\u003e\n\n\u003cp\u003eAll patients received 28-day treatment cycles. Lenalidomide was given orally at 25 mg once daily on Days 1–21 of each cycle. A dose of 10 mg was recommended for patients with creatinine clearance of 30–50 mL\/min (a measure of kidney function). Dexamethasone was given orally at 40 mg on Days 1, 8, 15, and 22. A dose of 20 mg was recommended for patients older than 75 years or with a body mass index below 18.5 kg\/m\u003csup\u003e2\u003c\/sup\u003e. Treatment continued until disease progression or unacceptable toxicity.\u003c\/p\u003e\n\n\u003cp\u003ePatients in the D-Rd arm also received daratumumab at 16 mg\/kg intravenously. The schedule was once weekly during Cycles 1 and 2, once every 2 weeks during Cycles 3 through 6, and once every 4 weeks thereafter. At the investigator's discretion, patients with no known allergy or intolerance to sorbitol who were initially randomized to D-Rd could switch from intravenous to subcutaneous (under-the-skin) daratumumab. The switch could occur on Day 1 of any cycle. This option was added by protocol amendment to provide flexibility and prioritize patient safety during the COVID-19 pandemic.\u003c\/p\u003e\n\n\u003cp\u003eThe follow-up phase began after a patient stopped all study treatments. During the follow-up phase, patients were evaluated for subsequent antimyeloma therapy, PFS on the next line of therapy (as assessed by the investigator), second primary malignancies (new cancers), and survival. Patients remained in follow-up until death, loss to follow-up, withdrawal of consent, or study completion, whichever came first.\u003c\/p\u003e\n\n\u003cp\u003eThe primary endpoint was PFS, which has been reported previously. Secondary endpoints included the rate of complete response or better and the rate of very good partial response or better (≥VGPR). Secondary endpoints also included the MRD-negativity rate, the overall response rate, overall survival, and time to subsequent antimyeloma treatment. Durability of MRD negativity was a prespecified exploratory endpoint.\u003c\/p\u003e\n\n\u003cp\u003eResponse and disease progression were assessed using a validated computer algorithm based on International Myeloma Working Group criteria. MRD assessments were performed by a central laboratory. These assessments occurred at baseline and at the time of suspected complete response or stringent complete response. These assessments also occurred at 12, 18, 24, 30, 36, 48, and 60 months after Cycle 1 Day 1 (plus or minus 1 month) for patients with a near complete response or better. MRD was evaluated by next-generation sequencing using the clonoSEQ assay (version 2.0; Adaptive Biotechnologies, Seattle, WA, USA).\u003c\/p\u003e\n\n\u003cp\u003eCytogenetic risk was assessed locally by fluorescence in situ hybridization or karyotype testing. High cytogenetic risk was defined as the presence of at least one of the following abnormalities: del(17p), t(14;16), or t(4;14).\u003c\/p\u003e\n\n\u003cp\u003eOn July 20, 2021, a protocol amendment led to a long-term extension of MAIA, during which patients were followed for overall survival. During this extension, data collection in the clinical database was limited to subsequent antimyeloma therapies, survival follow-up, death-related information, end-of-treatment disposition, and end-of-study disposition. For this long-term analysis, adverse event data were not captured per protocol. The safety data captured were limited to death-related data.\u003c\/p\u003e\n\n\u003cp\u003eThe primary analysis was performed in the intention-to-treat (ITT) population, which included all patients who underwent randomization. The safety population included all patients who received at least one dose of study treatment. Statistical significance was reached at the second interim OS analysis. After that, long-term survival follow-up was extended to approximately 390 deaths, the point at which the median survival for the D-Rd group would likely be reached.\u003c\/p\u003e\n\n\u003cp\u003eTime-to-event endpoints, including overall survival and time to subsequent antimyeloma treatment, were compared between groups using a stratified log-rank test. The Kaplan-Meier method was used to estimate distributions. Hazard ratios and 95% confidence intervals were calculated using a stratified Cox regression model with treatment as the sole explanatory variable. For patient subgroups, nonstratified Cox regression models were used. All subgroup analyses reported here were exploratory in nature. SAS version 9.4 was used for all statistical analyses.\u003c\/p\u003e\n\n\u003cp\u003eThe study sponsor funded the study and, in collaboration with the authors, designed the trial and collected, analyzed, and interpreted the data. All authors had full access to all study data and were responsible for the decision to submit for publication.\u003c\/p\u003e\n\n\u003ch2 id=\"key-findings\"\u003eKey Findings: Survival Results\u003c\/h2\u003e\n\u003cp\u003eA total of 737 patients were randomized: 368 to D-Rd and 369 to Rd. Baseline characteristics were well balanced between the treatment groups. The median patient age was 73 years (range, 45–90; interquartile range, 70–78).\u003c\/p\u003e\n\n\u003cp\u003eMost patients randomized received at least one dose of study treatment: 364 of 368 (99%) in the D-Rd group and 365 of 369 (99%) in the Rd group. Based on the simplified frailty score criteria, 172 of 368 patients (47%) in the D-Rd group and 169 of 369 patients (46%) in the Rd group were classified as frail.\u003c\/p\u003e\n\n\u003cp\u003eAt the time of the clinical data cutoff for this final OS analysis (November 30, 2023), 285 of 364 patients (78%) in the D-Rd group and 345 of 365 patients (95%) in the Rd group had discontinued treatment. The most common reasons for stopping treatment were progressive disease (D-Rd, 119 of 364 [33%]; Rd, 141 of 365 [39%]) and adverse events (60 of 364 [16%] versus 94 of 365 [26%]).\u003c\/p\u003e\n\n\u003cp\u003eThe median follow-up in the ITT population overall was 89.3 months (range, 0.0–102.2; interquartile range, 85.3–93.0). In the D-Rd group, median follow-up was 89.6 months (range, 0.0–99.9; interquartile range, 85.2–93.4). In the Rd group, median follow-up was 88.9 months (range, 0.0–102.2; interquartile range, 85.5–92.3).\u003c\/p\u003e\n\n\u003cp\u003eBy the data cutoff, 175 patients (48%) in the D-Rd group and 218 patients (59%) in the Rd group had died. Median overall survival was 90.3 months (95% CI, 80.8–not estimable) with D-Rd versus 64.1 months (95% CI, 56.0–70.8) with Rd. The hazard ratio was 0.67 (95% CI, 0.55–0.82).\u003c\/p\u003e\n\n\u003cp\u003eIn plain terms, the hazard ratio of 0.67 means that patients on D-Rd had about a one-third lower risk of dying at any given point during follow-up. This risk was compared with patients on Rd. Median survival of 90.3 months equals about 7.5 years, and 64.1 months equals about 5.3 years.\u003c\/p\u003e\n\n\u003cp\u003eEstimated 7-year overall survival rates were 53.1% (95% CI, 47.8–58.2) in the D-Rd group and 39.3% (95% CI, 34.1–44.5) in the Rd group. This means that about 53 in 100 patients on D-Rd were alive at 7 years, compared with about 39 in 100 patients on Rd.\u003c\/p\u003e\n\n\u003ch2 id=\"age-subgroups\"\u003eSurvival Results by Age Group\u003c\/h2\u003e\n\u003cp\u003eBecause many patients with newly diagnosed myeloma are older, the researchers examined survival separately by age group. These analyses were exploratory, meaning they were designed to generate hypotheses rather than to provide definitive proof.\u003c\/p\u003e\n\n\u003cp\u003eIn the D-Rd and Rd groups, 78 of 368 patients (21%) and 77 of 369 patients (21%) were younger than 70 years. A total of 130 patients (35%) and 131 patients (36%) were aged 70 to younger than 75 years. A total of 160 patients (43%) and 161 patients (44%) were aged 75 years or older, including 66 patients (18%) and 71 patients (19%) aged 80 years or older.\u003c\/p\u003e\n\n\u003cp\u003eSurvival results by age group were as follows:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eYounger than 70 years:\u003c\/strong\u003e median not reached (95% CI, not estimable–not estimable) with D-Rd versus not reached (95% CI, 57.2–not estimable) with Rd; hazard ratio 0.66 (95% CI, 0.40–1.08).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e70 to younger than 75 years:\u003c\/strong\u003e median not reached (95% CI, 82.1–not estimable) with D-Rd versus 77.6 months (95% CI, 55.1–not estimable) with Rd; hazard ratio 0.70 (95% CI, 0.50–1.00).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e75 years or older:\u003c\/strong\u003e median 72.3 months (95% CI, 58.8–86.7) with D-Rd versus 54.8 months (95% CI, 47.3–63.1) with Rd; hazard ratio 0.67 (95% CI, 0.51–0.88).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e80 years or older:\u003c\/strong\u003e median 67.6 months (95% CI, 40.6–not estimable) with D-Rd versus 48.9 months (95% CI, 37.1–60.9) with Rd; hazard ratio 0.64 (95% CI, 0.42–0.97).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe survival benefit with D-Rd versus Rd was generally consistent across age groups. Even the oldest patients, those aged 80 years or older, appeared to benefit from the three-drug combination.\u003c\/p\u003e\n\n\u003ch2 id=\"subgroups\"\u003eSurvival Across Other Patient Subgroups\u003c\/h2\u003e\n\u003cp\u003eThe researchers also examined survival across other groups of patients defined by characteristics at study entry. The benefit of D-Rd over Rd was generally consistent across these subgroups.\u003c\/p\u003e\n\n\u003cp\u003eResults for selected subgroups, reported as median survival with D-Rd versus Rd and hazard ratio (95% CI), were:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eMale:\u003c\/strong\u003e 82.5 versus 60.6 months; hazard ratio 0.72 (0.55–0.94).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eFemale:\u003c\/strong\u003e not estimable versus 67.8 months; hazard ratio 0.66 (0.49–0.89).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eYounger than 75 years:\u003c\/strong\u003e not estimable versus 79.6 months; hazard ratio 0.69 (0.52–0.92).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e75 years or older:\u003c\/strong\u003e 72.3 versus 54.8 months; hazard ratio 0.67 (0.51–0.88).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWhite race:\u003c\/strong\u003e 92.7 versus 65.5 months; hazard ratio 0.71 (0.57–0.87).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOther race:\u003c\/strong\u003e 90.3 versus 49.1 months; hazard ratio 0.50 (0.25–0.99).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNorth America:\u003c\/strong\u003e 92.7 versus 54.8 months; hazard ratio 0.57 (0.39–0.83).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOther regions:\u003c\/strong\u003e 90.3 versus 66.8 months; hazard ratio 0.74 (0.58–0.93).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eBaseline creatinine clearance above 60 mL\/min:\u003c\/strong\u003e 92.7 versus 69.9 months; hazard ratio 0.78 (0.60–1.01).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eBaseline creatinine clearance 60 mL\/min or less:\u003c\/strong\u003e 90.3 versus 54.4 months; hazard ratio 0.57 (0.42–0.77).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNormal baseline liver function:\u003c\/strong\u003e not estimable versus 63.8 months; hazard ratio 0.65 (0.53–0.80).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eImpaired baseline liver function:\u003c\/strong\u003e 63.5 versus 87.4 months; hazard ratio 1.31 (0.66–2.58).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eISS stage I:\u003c\/strong\u003e not estimable versus not estimable; hazard ratio 0.79 (0.50–1.24).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eISS stage II:\u003c\/strong\u003e 92.7 versus 61.7 months; hazard ratio 0.63 (0.46–0.85).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eISS stage III:\u003c\/strong\u003e 65.2 versus 47.3 months; hazard ratio 0.68 (0.49–0.95).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIgG type myeloma:\u003c\/strong\u003e 87.2 versus 69.3 months; hazard ratio 0.78 (0.60–1.00).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eNon-IgG type myeloma:\u003c\/strong\u003e 86.4 versus 53.7 months; hazard ratio 0.58 (0.37–0.89).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eHigh cytogenetic risk:\u003c\/strong\u003e 55.6 versus 42.5 months; hazard ratio 0.65 (0.40–1.06).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStandard cytogenetic risk:\u003c\/strong\u003e not estimable versus 65.5 months; hazard ratio 0.66 (0.52–0.84).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eECOG performance status 0:\u003c\/strong\u003e not estimable versus not estimable; hazard ratio 0.76 (0.52–1.12).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eECOG performance status 1:\u003c\/strong\u003e 92.7 versus 58.3 months; hazard ratio 0.64 (0.48–0.84).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eECOG performance status 2 or higher:\u003c\/strong\u003e 62.8 versus 39.0 months; hazard ratio 0.68 (0.44–1.04).\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe researchers tested whether the treatment effect differed significantly between subgroups by examining the interaction term for each subgroup. The P-values for these interaction tests were as follows. Sex had P=0.73, age had P=0.92, race had P=0.35, region had P=0.30, baseline renal function had P=0.11, and baseline hepatic function had P=0.041. ISS disease stage had P=0.55 for stage I and P=0.74 for stage II. Type of multiple myeloma had P=0.24, and cytogenetic risk at study entry had P=0.97. ECOG performance status had P=0.64 for score 0 and P=0.82 for score 1.\u003c\/p\u003e\n\n\u003cp\u003eMost of these interaction tests did not show a statistically significant difference in treatment effect across subgroups. The one exception was baseline liver function (P=0.041). The number of patients with impaired liver function was small (31 in the D-Rd group and 29 in the Rd group), so this result should be interpreted with caution.\u003c\/p\u003e\n\n\u003ch2 id=\"mrd\"\u003eMinimal Residual Disease and Survival\u003c\/h2\u003e\n\u003cp\u003eNo further MRD data were collected after the previous analysis of MAIA at a median follow-up of 64.5 months. Therefore, the rates of MRD negativity and sustained MRD negativity for at least 12 months remained unchanged from that earlier analysis.\u003c\/p\u003e\n\n\u003cp\u003eAs previously reported, MRD-negativity rates at the 10\u003csup\u003e–5\u003c\/sup\u003e sensitivity threshold were higher with D-Rd than with Rd: 118 of 368 patients (32%) versus 41 of 369 patients (11%); P\u0026lt;0.0001. Sustained MRD-negativity rates were 69 patients (19%) versus 15 patients (4%); P\u0026lt;0.0001.\u003c\/p\u003e\n\n\u003cp\u003eWhen overall survival was assessed by MRD status, patients who achieved MRD negativity and sustained MRD negativity had longer overall survival than patients who did not. Importantly, D-Rd prolonged overall survival compared with Rd regardless of MRD status. This includes patients who did not achieve sustained MRD negativity.\u003c\/p\u003e\n\n\u003ch2 id=\"subsequent-therapy\"\u003eTime to Next Treatment and Later Therapies\u003c\/h2\u003e\n\u003cp\u003eWithin the ITT population, 146 of 368 patients (40%) in the D-Rd group had an event of starting subsequent antimyeloma therapy or dying from progressive disease without receiving subsequent therapy. In the Rd group, 211 of 369 patients (57%) had this event.\u003c\/p\u003e\n\n\u003cp\u003eMedian time to subsequent antimyeloma treatment was not reached (95% CI, 84.1–not estimable) in the D-Rd group versus 42.4 months (95% CI, 33.5–50.6) in the Rd group. The hazard ratio was 0.51 (95% CI, 0.41–0.63; P\u0026lt;0.0001). A consistent trend was observed in a post hoc analysis that considered deaths from reasons other than disease progression as competing events.\u003c\/p\u003e\n\n\u003cp\u003eAmong treated patients, 140 of 364 patients (38%) in the D-Rd group and 201 of 365 patients (55%) in the Rd group received at least one subsequent line of antimyeloma therapy while on study. Across subsequent therapy lines, the most common antineoplastic agents after D-Rd and Rd, respectively, were bortezomib (28% versus 42%), daratumumab (6% versus 29%), and carfilzomib (7% versus 12%) in treated patients. No patient in either group reported the use of BCMA-targeted or GPRC5D-targeted therapy. Two patients in the D-Rd group and two patients in the Rd group received investigational drugs in subsequent therapy lines.\u003c\/p\u003e\n\n\u003cp\u003eOf the 341 total patients who received subsequent antimyeloma therapy, proteasome inhibitor–based therapy was the most common first subsequent therapy class in both groups. This was used in 69 of 140 patients (49%) in the D-Rd group and 101 of 201 patients (50%) in the Rd group.\u003c\/p\u003e\n\n\u003cp\u003eDaratumumab-containing first subsequent therapy regimens were received by 15 patients (11%) in the D-Rd group and 49 patients (24%) in the Rd group. Best response to first subsequent antimyeloma therapy was assessed in patients who received that therapy and were evaluable (D-Rd, n=130; Rd, n=193), not only in those who received a daratumumab-containing regimen. Among these patients, a complete response or better was achieved in 6 patients (5%) in the D-Rd group and 8 patients (4%) in the Rd group. A very good partial response or better was achieved in 18 patients (14%) and 46 patients (24%), respectively.\u003c\/p\u003e\n\n\u003cp\u003eBy the end of data collection, 228 patients in the D-Rd group and 168 patients in the Rd group had not received subsequent antimyeloma therapy. All of these patients had discontinued the study. The most common reasons for discontinuation were death after study treatment and end of data collection. Death after study treatment occurred in 46 patients (20%) in the D-Rd group and 42 patients (25%) in the Rd group. End of data collection occurred in 137 patients (60%) and 68 patients (40%), respectively. Death while on study treatment was reported as the reason for discontinuation for 30 patients (13%) in the D-Rd group and 34 patients (20%) in the Rd group.\u003c\/p\u003e\n\n\u003cp\u003eNotably, 79 patients (35%) and 20 patients (12%) who had not received subsequent antimyeloma therapy were still receiving D-Rd and Rd as frontline therapy, respectively, at the end of data collection.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety and Causes of Death\u003c\/h2\u003e\n\u003cp\u003eIn the safety population, deaths were reported for 173 of 364 patients (48%) in the D-Rd group and 218 of 365 patients (60%) in the Rd group. The most frequent cause of death was disease progression: 76 patients (21%) in the D-Rd group and 88 patients (24%) in the Rd group.\u003c\/p\u003e\n\n\u003cp\u003eAn adverse event was the primary cause of death for 44 patients (12%) in the D-Rd group and 40 patients (11%) in the Rd group. Most of these adverse events were considered unrelated to study treatment.\u003c\/p\u003e\n\n\u003cp\u003eAside from disease progression and adverse events, primary causes of death occurring in at least 1% of patients in either treatment group were:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003eInfections and infestations: 2% in the D-Rd group and 8% in the Rd group.\u003c\/li\u003e\n\u003cli\u003eGeneral disorders and administration-site conditions (related to the patient's general health condition): 3% and 1%.\u003c\/li\u003e\n\u003cli\u003eNeoplasms (benign, malignant, or unspecified): 3% and 1%.\u003c\/li\u003e\n\u003cli\u003eCardiac disorders: less than 1% and 2%.\u003c\/li\u003e\n\u003cli\u003eNervous system disorders: 1% and 1%.\u003c\/li\u003e\n\u003cli\u003eUnknown cause: 4% and 7%.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eDeaths within 30 days of the last study treatment dose occurred in 31 patients (9%) in the D-Rd group and 35 patients (10%) in the Rd group. These deaths were most often due to adverse events: 29 patients (8%) in the D-Rd group and 32 patients (9%) in the Rd group.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-implications\"\u003eWhat These Results Mean for Patients\u003c\/h2\u003e\n\u003cp\u003eIn this final analysis of MAIA, median overall survival was reached for the first time in the D-Rd group after a median follow-up of approximately 7.5 years. D-Rd continued to show a clinical survival benefit versus Rd alone in transplant-ineligible patients with newly diagnosed multiple myeloma.\u003c\/p\u003e\n\n\u003cp\u003eMedian overall survival was 90.3 months (7.5 years) with D-Rd versus 64.1 months (5.3 years) with Rd. This sets a new benchmark for median overall survival in the transplant-ineligible population.\u003c\/p\u003e\n\n\u003cp\u003eThe survival benefit with D-Rd versus Rd was generally consistent across prespecified patient subgroups, including patients with high cytogenetic risk. When overall survival was assessed by age, survival trended in favor of D-Rd versus Rd across all age subgroups examined.\u003c\/p\u003e\n\n\u003cp\u003eThe D-Rd group also experienced a longer duration of therapeutic benefit compared with the Rd group. The median time to subsequent antimyeloma treatment was not reached with D-Rd versus 42.4 months with Rd. This means that patients on D-Rd went substantially longer before their disease required a next line of therapy.\u003c\/p\u003e\n\n\u003cp\u003eThese results further support the use of frontline D-Rd to maximize survival in patients with newly diagnosed multiple myeloma who are not eligible for transplant.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations of the Study\u003c\/h2\u003e\n\u003cp\u003eThis long-term extension of MAIA had several important limitations that patients and families should understand.\u003c\/p\u003e\n\n\u003cp\u003eFirst, data collection during the long-term extension was limited. The clinical database captured only subsequent antimyeloma therapies, survival follow-up, death-related information, and end-of-treatment and end-of-study disposition. Adverse events other than death-related data were not captured per protocol during this period. This means the long-term safety profile beyond death-related outcomes is not fully described in this report.\u003c\/p\u003e\n\n\u003cp\u003eSecond, no further MRD data were collected after the previous analysis at a median follow-up of 64.5 months. The MRD-negativity and sustained MRD-negativity rates reported here therefore reflect the earlier data cutoff and remained unchanged.\u003c\/p\u003e\n\n\u003cp\u003eThird, the subgroup analyses reported here, including the analyses by age and by MRD status, were exploratory in nature. Exploratory analyses are designed to generate hypotheses rather than to provide definitive conclusions. The number of patients in some subgroups was small, which limits how confidently those results can be applied to individual patients.\u003c\/p\u003e\n\n\u003cp\u003eFourth, the study was open-label, meaning patients and investigators knew which treatment was assigned. The authors note that this design might have led to a bias for early patient withdrawals in the Rd group.\u003c\/p\u003e\n\n\u003cp\u003eFinally, the trial enrolled patients who were not candidates for high-dose chemotherapy and autologous stem cell transplant because of age (65 years or older) or comorbidities. The results therefore apply specifically to this transplant-ineligible population and may not generalize to patients who are eligible for transplant or to other treatment settings.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003ePractical Points for Patients and Families\u003c\/h2\u003e\n\u003cp\u003eThese findings offer several practical takeaways for patients with newly diagnosed multiple myeloma who cannot undergo a stem cell transplant.\u003c\/p\u003e\n\n\u003col\u003e\n\u003cli\u003e\n\u003cstrong\u003eAsk about daratumumab-based first-line therapy.\u003c\/strong\u003e The three-drug combination of daratumumab, lenalidomide, and dexamethasone extended median survival to about 7.5 years in this trial, compared with about 5.3 years with lenalidomide and dexamethasone alone.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eUnderstand that older age is not a barrier to benefit.\u003c\/strong\u003e The survival benefit appeared consistent across age groups, including patients aged 80 years or older. In that oldest group, median survival was 67.6 months with D-Rd versus 48.9 months with Rd.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eExpect a longer time before the next treatment is needed.\u003c\/strong\u003e The median time to subsequent antimyeloma treatment was not reached with D-Rd, compared with 42.4 months with Rd.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDiscuss the treatment schedule.\u003c\/strong\u003e Daratumumab was given intravenously at 16 mg\/kg, weekly during Cycles 1 and 2, every 2 weeks during Cycles 3 through 6, and every 4 weeks thereafter. An option to switch to subcutaneous daratumumab was permitted under the amended protocol.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTalk with your care team about side effects and monitoring.\u003c\/strong\u003e In this long-term report, adverse events other than death-related data were not collected. Your care team will monitor you for side effects throughout treatment.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAsk about response testing, including MRD.\u003c\/strong\u003e Deeper responses, including MRD negativity, were more common with D-Rd. MRD negativity means the cancer is undetectable at a very sensitive threshold.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003ePatients should discuss these results with their hematologist to understand how they apply to their individual situation, including their age, overall health, kidney and liver function, and disease characteristics.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWho was the MAIA trial designed for?\u003c\/h3\u003e\n\u003cp\u003eIt enrolled 737 adults with newly diagnosed multiple myeloma who could not have high-dose chemotherapy and an autologous stem cell transplant, either because they were 65 or older or because other health conditions made that intensive treatment poorly tolerated. Median age was 73 years. Results apply to this transplant-ineligible group and may not generalize to patients who can have a transplant.\u003c\/p\u003e\n\u003ch3\u003eHow much longer did people live on the three-drug combination?\u003c\/h3\u003e\n\u003cp\u003eIn the final analysis, median overall survival was 90.3 months (about 7.5 years) with daratumumab plus lenalidomide and dexamethasone, compared with 64.1 months (about 5.3 years) with lenalidomide and dexamethasone alone. That is a 33% relative reduction in the risk of death during follow-up. About 53 in 100 patients on the three-drug regimen were alive at 7 years, versus about 39 in 100 on the two-drug regimen.\u003c\/p\u003e\n\u003ch3\u003eDoes older age mean the combination will not help?\u003c\/h3\u003e\n\u003cp\u003eThe survival benefit appeared generally consistent across age groups, including people aged 80 or older. In that oldest group, median survival was 67.6 months with the three-drug combination versus 48.9 months with the two-drug regimen. These age analyses were exploratory, meaning they were designed to generate hypotheses rather than provide definitive proof, and some subgroups were small.\u003c\/p\u003e\n\u003ch3\u003eWhat does a hazard ratio of 0.67 mean for me?\u003c\/h3\u003e\n\u003cp\u003eIt means patients on the three-drug combination had about a one-third lower risk of dying at any given point during follow-up compared with patients on lenalidomide and dexamethasone alone. It describes risk across the whole group studied, not a prediction for any one person. Patients should discuss what these results mean for their own situation with their hematologist.\u003c\/p\u003e\n\u003ch3\u003eHow long before a different myeloma treatment was needed?\u003c\/h3\u003e\n\u003cp\u003eThe median time to starting a subsequent antimyeloma treatment was not reached with the three-drug combination, compared with 42.4 months with lenalidomide and dexamethasone alone. In plain terms, patients on the three-drug regimen went substantially longer before their disease required a next line of therapy. This was measured across all randomized patients in the trial.\u003c\/p\u003e\n\u003ch3\u003eWhat were the main safety findings in this long-term report?\u003c\/h3\u003e\n\u003cp\u003eNo new safety concerns emerged. Disease progression was the most frequent cause of death, reported for 21% of patients on the three-drug combination and 24% on the two-drug regimen. An adverse event was the primary cause of death for 12% and 11% respectively, and most of those events were considered unrelated to study treatment. During the long-term extension, only death-related safety data were collected.\u003c\/p\u003e\n\u003ch3\u003eWhat should I ask my care team about treatment and monitoring?\u003c\/h3\u003e\n\u003cp\u003eAsk whether a daratumumab-based first-line combination is appropriate for you, and discuss the schedule: daratumumab was given intravenously at 16 mg\/kg, weekly in Cycles 1 and 2, every 2 weeks in Cycles 3 to 6, then every 4 weeks, with a permitted switch to under-the-skin dosing. Ask about side-effect monitoring and about response testing, including minimal residual disease.\u003c\/p\u003e\n\u003ch3\u003eI have newly diagnosed multiple myeloma and I'm not eligible for a stem cell transplant — when should I seek a second opinion on whether daratumumab should be added to my first-line treatment?\u003c\/h3\u003e\n\u003cp\u003eA second opinion is reasonable before starting first-line therapy, particularly to confirm that transplant is not an option for you and to review whether a daratumumab-based three-drug regimen fits your situation. In the MAIA trial, daratumumab plus lenalidomide and dexamethasone extended median overall survival to 90.3 months versus 64.1 months with lenalidomide and dexamethasone alone, with benefit generally consistent across age groups, including patients aged 80 years or older. A review can also weigh your kidney and liver function and disease characteristics. 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, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e Facon T, Kumar SK, Orlowski RZ, Bahlis N, Moreau P, Goldschmidt H, Basu S, Hulin C, Zweegman S, Weisel K, Perrot A, Jacquet C, Raje N, Manier S, Chari A, Hansson M, Mohty M, Delforge M, Plesner T, Cook G, Leleu X, Quach H, Venner CP, Tiab M, Macro M, Frenzel L, Wang G, Pei H, Bolyard K, Carson R, Borgsten F, Usmani SZ.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003ePublication details:\u003c\/strong\u003e Leukemia (2026) 40:2530–2539. Published online 24 August 2026. DOI: https:\/\/doi.org\/10.1038\/s41375-026-03097-9\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eClinical trial identifier:\u003c\/strong\u003e ClinicalTrials.gov NCT02252172\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e The study sponsor funded the study and, in collaboration with the authors, designed the trial and collected, analyzed, and interpreted the data.\u003c\/p\u003e\n\n\u003cp\u003e\u003cem\u003eThis patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and does not replace advice from a qualified healthcare professional. Patients should discuss treatment decisions with their own medical team.\u003c\/em\u003e\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":48245941338268,"sku":null,"price":0.0,"currency_code":"RUB","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0599\/5449\/5644\/files\/ddn-medical-article-daratumumab-combination-extends-survival-to-7-5-years-in-older-patients-with-newly-diagnosed-multiple-myeloma-final-resu-hero.png?v=1793773107","url":"https:\/\/diagnosticdetectives.ru\/products\/daratumumab-combination-extends-survival-to-7-5-years-in-older-patients-with-newly-diagnosed-multiple-myeloma-final-results-of-the-maia-trial","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}