Daratumumab Combination Extends Survival to 7.5 Years in Older Patients With Newly Diagnosed Multiple Myeloma: Final Results of the MAIA Trial

Table of Contents

• Key Points
• Background: Why This Research Matters
• How the Study Was Conducted
• Key Findings: Survival Results
• Survival Results by Age Group
• Survival Across Other Patient Subgroups
• Minimal Residual Disease and Survival
• Time to Next Treatment and Later Therapies
• Safety and Causes of Death
• What These Results Mean for Patients
• Limitations of the Study
• Practical Points for Patients and Families
• Frequently Asked Questions
• Source Information

Key Points

• In 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.
• The 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.
• The 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.
• Median time to a next antimyeloma treatment was not reached with the three-drug combination versus 42.4 months with the two-drug regimen.
• No 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.

Background: Why This Research Matters

Multiple 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.

For 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.

Daratumumab 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.

Adding 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.

Earlier 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<0.001).

That 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<0.001). Minimal residual disease (MRD) negativity — meaning the cancer was undetectable at a very sensitive threshold of 10^–5 — occurred in 24.2% versus 7.3% (P<0.001).

After 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.

At 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^–5 threshold was seen in 18.8% of D-Rd patients versus 4.1% of Rd patients (P<0.0001). These deeper responses translated into PFS and OS benefits for transplant-ineligible patients with NDMM.

The 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.

How the Study Was Conducted

MAIA (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.

Patients 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.

The 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.

Patients 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).

All 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/m². Treatment continued until disease progression or unacceptable toxicity.

Patients 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.

The 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.

The 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.

Response 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).

Cytogenetic 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).

On 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.

The 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.

Time-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.

The 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.

Key Findings: Survival Results

A 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).

Most 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.

At 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%]).

The 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).

By 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).

In 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.

Estimated 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.

Survival Results by Age Group

Because 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.

In 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.

Survival results by age group were as follows:

• Younger than 70 years: 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).
• 70 to younger than 75 years: 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).
• 75 years or older: 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).
• 80 years or older: 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).

The 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.

Survival Across Other Patient Subgroups

The 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.

Results for selected subgroups, reported as median survival with D-Rd versus Rd and hazard ratio (95% CI), were:

• Male: 82.5 versus 60.6 months; hazard ratio 0.72 (0.55–0.94).
• Female: not estimable versus 67.8 months; hazard ratio 0.66 (0.49–0.89).
• Younger than 75 years: not estimable versus 79.6 months; hazard ratio 0.69 (0.52–0.92).
• 75 years or older: 72.3 versus 54.8 months; hazard ratio 0.67 (0.51–0.88).
• White race: 92.7 versus 65.5 months; hazard ratio 0.71 (0.57–0.87).
• Other race: 90.3 versus 49.1 months; hazard ratio 0.50 (0.25–0.99).
• North America: 92.7 versus 54.8 months; hazard ratio 0.57 (0.39–0.83).
• Other regions: 90.3 versus 66.8 months; hazard ratio 0.74 (0.58–0.93).
• Baseline creatinine clearance above 60 mL/min: 92.7 versus 69.9 months; hazard ratio 0.78 (0.60–1.01).
• Baseline creatinine clearance 60 mL/min or less: 90.3 versus 54.4 months; hazard ratio 0.57 (0.42–0.77).
• Normal baseline liver function: not estimable versus 63.8 months; hazard ratio 0.65 (0.53–0.80).
• Impaired baseline liver function: 63.5 versus 87.4 months; hazard ratio 1.31 (0.66–2.58).
• ISS stage I: not estimable versus not estimable; hazard ratio 0.79 (0.50–1.24).
• ISS stage II: 92.7 versus 61.7 months; hazard ratio 0.63 (0.46–0.85).
• ISS stage III: 65.2 versus 47.3 months; hazard ratio 0.68 (0.49–0.95).
• IgG type myeloma: 87.2 versus 69.3 months; hazard ratio 0.78 (0.60–1.00).
• Non-IgG type myeloma: 86.4 versus 53.7 months; hazard ratio 0.58 (0.37–0.89).
• High cytogenetic risk: 55.6 versus 42.5 months; hazard ratio 0.65 (0.40–1.06).
• Standard cytogenetic risk: not estimable versus 65.5 months; hazard ratio 0.66 (0.52–0.84).
• ECOG performance status 0: not estimable versus not estimable; hazard ratio 0.76 (0.52–1.12).
• ECOG performance status 1: 92.7 versus 58.3 months; hazard ratio 0.64 (0.48–0.84).
• ECOG performance status 2 or higher: 62.8 versus 39.0 months; hazard ratio 0.68 (0.44–1.04).

The 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.

Most 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.

Minimal Residual Disease and Survival

No 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.

As previously reported, MRD-negativity rates at the 10^–5 sensitivity threshold were higher with D-Rd than with Rd: 118 of 368 patients (32%) versus 41 of 369 patients (11%); P<0.0001. Sustained MRD-negativity rates were 69 patients (19%) versus 15 patients (4%); P<0.0001.

When 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.

Time to Next Treatment and Later Therapies

Within 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.

Median 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<0.0001). A consistent trend was observed in a post hoc analysis that considered deaths from reasons other than disease progression as competing events.

Among 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.

Of 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.

Daratumumab-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.

By 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.

Notably, 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.

Safety and Causes of Death

In 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.

An 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.

Aside from disease progression and adverse events, primary causes of death occurring in at least 1% of patients in either treatment group were:

• Infections and infestations: 2% in the D-Rd group and 8% in the Rd group.
• General disorders and administration-site conditions (related to the patient's general health condition): 3% and 1%.
• Neoplasms (benign, malignant, or unspecified): 3% and 1%.
• Cardiac disorders: less than 1% and 2%.
• Nervous system disorders: 1% and 1%.
• Unknown cause: 4% and 7%.

Deaths 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.

What These Results Mean for Patients

In 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.

Median 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.

The 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.

The 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.

These 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.

Limitations of the Study

This long-term extension of MAIA had several important limitations that patients and families should understand.

First, 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.

Second, 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.

Third, 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.

Fourth, 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.

Finally, 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.

Practical Points for Patients and Families

These findings offer several practical takeaways for patients with newly diagnosed multiple myeloma who cannot undergo a stem cell transplant.

1. Ask about daratumumab-based first-line therapy. 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.
2. Understand that older age is not a barrier to benefit. 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.
3. Expect a longer time before the next treatment is needed. The median time to subsequent antimyeloma treatment was not reached with D-Rd, compared with 42.4 months with Rd.
4. Discuss the treatment schedule. 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.
5. Talk with your care team about side effects and monitoring. 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.
6. Ask about response testing, including MRD. Deeper responses, including MRD negativity, were more common with D-Rd. MRD negativity means the cancer is undetectable at a very sensitive threshold.

Patients 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.

Frequently Asked Questions

Who was the MAIA trial designed for?

It 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.

How much longer did people live on the three-drug combination?

In 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.

Does older age mean the combination will not help?

The 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.

What does a hazard ratio of 0.67 mean for me?

It 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.

How long before a different myeloma treatment was needed?

The 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.

What were the main safety findings in this long-term report?

No 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.

What should I ask my care team about treatment and monitoring?

Ask 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.

I 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?

A 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.

Source Information

Original article title: Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis.

Authors: 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.

Publication details: Leukemia (2026) 40:2530–2539. Published online 24 August 2026. DOI: https://doi.org/10.1038/s41375-026-03097-9

Clinical trial identifier: ClinicalTrials.gov NCT02252172

Funding: The study sponsor funded the study and, in collaboration with the authors, designed the trial and collected, analyzed, and interpreted the data.

This 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.