MAIA trial demonstrated the efficacy and safety of frontline DARZALEX® + Rd in newly diagnosed, transplant-ineligible multiple myeloma1
Featuring clinical results at 28 months and ~5 years
Primary endpoint was progression-free survival (PFS).2‡
Key secondary endpoints included: percentage of patients with complete response (CR) rate, very good partial response (VGPR) rate, minimal residual disease (MRD)-negativity rate (next-generation sequencing [NGS]; 10-5), overall response rate (ORR), overall survival (OS), duration of response, and safety.2
Baseline demographics and disease characteristics were similar between the 2 treatment groups.1
- ~50% of patients were 75 years old or older2
- The trial also included patients with various Eastern Cooperative Oncology Group (ECOG) performance status, cytogenetic profiles, and International Staging System (ISS) disease stages2
- DRd nearly doubled the number of patients who achieved complete response (CR) or better vs Rd alone
- Median duration of response has not yet been reached with DRd vs 34.7 months (95% CI: 30.8, not estimable) for Rd alone
- Median time to response was 1.05 months with DRd (range: 0.2-12.1 months) and with Rd alone (range: 0.3-15.3 months)
Superior minimal residual disease (MRD) rates vs Rd alone after 28 months of follow-up.1
- 24% of patients were MRD negative with DRd (95% CI: 19.9, 28.9)1
- 7% of patients were MRD negative with Rd (95% CI: 4.9, 10.5)1
- 1.7x more patients receiving DRd achieved complete response (CR) or better vs Rd alone
- Median duration of response was not reached with DRd vs 43.9 months (95% CI: 37.7, 52.9) for Rd alone
Most frequent adverse reactions reported in ≥20% of patients and with at least a 5% greater frequency in the DARZALEX® + Rd arm1*†
Treatment-emergent laboratory abnormalities1
- Discontinuation rates due to any adverse event: 7% with DRd vs 16% with Rd
- Infusion-related reactions (IRRs) with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4
- For 37% of patients, infusion-related reactions (IRRs; any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
- Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
- Incidence of infusion modification due to reactions was 36%
- DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
- Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
- Type and screen patients before starting DARZALEX®
- Inform blood banks when a patient is on DARZALEX®
- Identify any DARZALEX®-treated bloodsamples
- Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Brochure on daratumumab and serological testing
Identification card to give to patients taking daratumumab
Additional TEAEs (any grade ≥20% and/or Grade 3/4 ≥10%) reported in the DARZALEX® + Rd arm were thrombocytopenia, arthralgia, nasopharyngitis, decreased appetite, upper respiratory tract infection, pyrexia, headache, pain in extremity, dizziness, and vomiting.3
Treatment-emergent adverse events are reported as observed. These analyses have not been adjusted for multiple comparisons and no conclusions should be drawn.
- Cumulative Grade 3/4 infection rates were 41% for DRd vs 29% for Rd3
- Cumulative rates of discontinuation due to TEAEs were 13% for DRd vs 22% for Rd3
- Hematologic adverse events included in the follow-up analyses are investigator-reported TEAEs and not investigator-reported treatment-emergent laboratory abnormalities
- DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions
- For 37% of patients, infusion-related reactions (IRRs; any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
- Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
- Incidence of infusion modification due to reactions was 36%
- DARZALEX® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
- Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®
- Type and screen patients before starting DARZALEX®
- Inform blood banks when a patient is on DARZALEX®
- Identify any DARZALEX®-treated blood samples
- Ask patients to tell other healthcare professionals that they've taken DARZALEX®
Brochure on daratumumab and serological testing
Identification card to give to patients taking daratumumab
- To explore the impact of treatment duration on long-term clinical outcomes, a post hoc analysis was conducted based on DRd treatment duration (<18 vs ≥18 months), excluding patients who discontinued therapy due to disease progression during the first 18 months4,7
- This post hoc subset analysis was based on patients who were treated for at least 18 months and excluded patients who discontinued therapy due to disease progression during the first 18 months4,7
- For the DRd arm, it included 283 patients who were treated for at least 18 months, out of 368 patients of the primary intent-to-treat (ITT) analysis of the MAIA trial. For the Rd arm, it included 204 patients who were treated for at least 18 months, out of 369 patients of the primary ITT analysis of the MAIA trial1,4,7
- Response data presented are cumulative deepest response rates achieved by 6, 9, and 18 months for patients who continued all study treatment for at least 18 months
~50% of patients achieved a ≥CR by 18 months of DRd treatment compared with ~9% by 6 months of treatment4,7
~30% of patients achieved a ≥CR by 18 months of Rd treatment compared with ~4% by 6 months of treatment4,7
- Median duration of response was not reached with DRd vs 34.7 months (95% CI: 30.8-not estimable) for Rd alone1†
- Patients achieved longer duration of response with continuous DRd (a triplet regimen) vs continuous Rd (a doublet regimen)3,4
- Most frequently reported treatment-emergent adverse events (TEAEs) that met the threshold of cumulative any grade TEAE >30% or Grade 3/4 TEAE >10% are presented4
- Combined TEAE rates are the sum of the percentages of the most frequently reported TEAEs, at each cycle period
- Percentages represent number of patients with >1 TEAE by treatment cycle divided by total number of patients treated within the treatment window
- Only TEAEs with onset date falling within the cycle intervals were calculated. Each patient was calculated once per preferred term for each cycle interval. The same patient could be calculated in multiple cycle intervals and for multiple preferred terms. TEAEs may not have resolved by the next cycle
- Decrease in adverse event (AE) rates over time from treatment initiation was observed for most AEs in both treatment arms. Cataract tended to increase over time in both treatment arms (see rates below)4
- 13% of intent-to-treat (ITT) patients discontinued treatment due to a TEAE with DRd (n=364) vs 22% with Rd alone (n=365)3
AEs for DRd across Cycles 1-304
Any TEAE ≥30% or Grade 3/4 ≥10%
Scroll to view data over time
DARZALEX® once-monthly administration start | |||||||||
---|---|---|---|---|---|---|---|---|---|
Any Grade TEAE | Cycles 1-2 (n=364) | Cycles 3-6 (n=348) | Cycles 7-10 (n=330) | Cycles 11-14 (n=312) | Cycles 15-18 (n=299) | Cycles 19-22 (n=285) | Cycles 23-26 (n=271) | Cycles 27-30 (n=259) | |
Hematologic | Neutropenia | 40.4% | 24.4% | 17.9% | 18.6% | 17.7% | 16.1% | 11.1% | 12.4% |
Anemia | 17.3% | 10.9% | 8.2% | 6.7% | 4.0% | 6.0% | 5.5% | 7.3% | |
Leukopenia | 14.0% | 5.7% | 4.2% | 3.8% | 3.0% | 3.5% | 4.1% | 2.3% | |
Lymphopenia | 13.7% | 4.6% | 3.6% | 4.8% | 5.7% | 4.2% | 4.4% | 3.5% | |
Nonhematologic | Constipation | 26.4% | 11.8% | 5.5% | 3.8% | 4.0% | 2.1% | 3.0% | 5.0% |
Nausea | 21.4% | 6.6% | 4.2% | 3.8% | 5.0% | 1.8% | 2.6% | 1.9% | |
Fatigue | 20.1% | 14.1% | 7.0% | 8.7% | 7.4% | 7.7% | 5.9% | 7.3% | |
Diarrhea | 15.9% | 15.5% | 15.8% | 16.0% | 18.4% | 17.5% | 14.0% | 10.0% | |
Dyspnea | 14.8% | 6.6% | 3.9% | 3.2% | 1.7% | 3.2% | 2.2% | 2.3% | |
Edema peripheral | 14.3% | 12.6% | 7.3% | 7.7% | 6.4% | 6.3% | 4.1% | 4.2% | |
Cough | 14.0% | 6.9% | 3.9% | 2.9% | 3.0% | 4.2% | 4.8% | 3.1% | |
Asthenia | 13.5% | 8.9% | 7.3% | 6.7% | 6.0% | 6.0% | 3.7% | 2.7% | |
Muscle spasms | 13.5% | 9.5% | 2.1% | 5.4% | 2.3% | 2.5% | 2.6% | 1.2% | |
Back pain | 9.9% | 6.3% | 6.4% | 5.1% | 4.0% | 6.7% | 3.7% | 5.4% | |
Insomnia | 9.9% | 7.2% | 5.2% | 7.4% | 3.0% | 4.2% | 3.0% | 3.1% | |
Weight decreased | 9.1% | 12.4% | 4.5% | 3.8% | 1.3% | 2.5% | 1.1% | 1.9% | |
Hypokalemia | 8.0% | 4.6% | 3.3% | 1.6% | 3.0% | 6.0% | 2.2% | 4.2% | |
Peripheral neuropathy | 6.3% | 4.0% | 5.2% | 5.4% | 5.4% | 7.0% | 2.6% | 3.1% | |
Bronchitis | 4.7% | 6.6% | 6.4% | 7.1% | 8.7% | 6.7% | 6.6% | 7.3% | |
Pneumonia | 4.7% | 6.6% | 3.9% | 4.2% | 4.7% | 5.3% | 3.3% | 2.3% | |
Cataract | 0.3% | 0.6% | 2.4% | 3.5% | 5.4% | 3.9% | 3.7% | 4.6% | |
Combined TEAE rates (sum of the percentages) | 292% | 186% | 128% | 130% | 120% | 123% | 94% | 95% |
Any Grade TEAE | Cycles 1-2 (n=365) | Cycles 3-6 (n=335) | Cycles 7-10 (n=297) | Cycles 11-14 (n=263) | Cycles 15-18 (n=237) | Cycles 19-22 (n=210) | Cycles 23-26 (n=187) | Cycles 27-30 (n=169) | |
---|---|---|---|---|---|---|---|---|---|
Hematologic | Neutropenia | 20.3% | 21.8% | 12.8% | 16.0% | 14.8% | 9.0% | 13.4% | 13.0% |
Anemia | 19.5% | 16.1% | 8.1% | 8.0% | 10.1% | 5.7% | 3.7% | 5.3% | |
Leukopenia | 4.4% | 2.4% | 1.3% | 3.0% | 3.0% | 2.4% | 2.7% | 4.1% | |
Lymphopenia | 7.1% | 5.7% | 2.0% | 3.4% | 1.7% | 1.9% | 0.5% | 3.0% | |
Nonhematologic | Constipation | 19.7% | 14.0% | 4.0% | 3.4% | 4.2% | 2.4% | 3.7% | 1.8% |
Nausea | 15.6% | 6.0% | 4.0% | 2.3% | 2.1% | 3.8% | 2.1% | 0.0% | |
Fatigue | 16.2% | 8.4% | 6.1% | 5.7% | 5.5% | 4.3% | 2.7% | 5.9% | |
Diarrhea | 15.6% | 15.2% | 12.5% | 12.5% | 15.6% | 14.8% | 9.1% | 12.4% | |
Dyspnea | 6.6% | 3.0% | 3.4% | 3.0% | 2.5% | 2.9% | 1.6% | 1.2% | |
Edema peripheral | 11.8% | 12.5% | 6.4% | 3.8% | 5.5% | 6.7% | 4.8% | 4.7% | |
Cough | 5.8% | 3.3% | 3.7% | 2.3% | 5.1% | 1.0% | 2.1% | 2.4% | |
Asthenia | 9.6% | 5.7% | 6.4% | 4.2% | 5.1% | 3.3% | 2.7% | 5.9% | |
Muscle spasms | 10.7% | 6.9% | 5.4% | 3.8% | 2.5% | 3.8% | 2.7% | 1.2% | |
Back pain | 6.8% | 8.1% | 5.7% | 6.5% | 4.6% | 7.1% | 5.9% | 3.6% | |
Insomnia | 12.6% | 9.3% | 6.7% | 5.7% | 5.1% | 2.9% | 2.1% | 4.1% | |
Weight decreased | 7.1% | 6.6% | 2.7% | 1.5% | 4.2% | 2.9% | 1.6% | 1.2% | |
Hypokalemia | 4.9% | 5.4% | 4.0% | 4.6% | 4.6% | 5.2% | 3.7% | 1.8% | |
Peripheral neuropathy | 3.8% | 3.6% | 3.7% | 4.9% | 3.8% | 4.3% | 0.5% | 4.1% | |
Bronchitis | 3.0% | 5.4% | 5.4% | 4.9% | 6.8% | 7.1% | 5.9% | 6.5% | |
Pneumonia | 3.3% | 4.5% | 3.7% | 2.7% | 2.1% | 1.0% | 1.6% | 3.6% | |
Cataract | 0.8% | 1.5% | 1.7% | 5.3% | 4.6% | 6.7% | 7.5% | 4.1% | |
Combined TEAE rates (sum of the percentages) | 205% | 165% | 110% | 108% | 114% | 99% | 81% | 90% |
DRd treatment in frail patient subgroup
The median age in frail subgroup was 77 years (range: 57-90 years), with 88% of patients having ECOG performance score ≥1. CCI was calculated based on retrospective review of each patient's medical history.8
Limitations: The retrospective assessment of frailty score was a limitation of this study. Retrospective CCI calculations were based on reported medical history, which may contain missing data and result in underestimating or overestimating the number of patients in each frailty subgroup. The ECOG PS score parameter used for frailty score calculations in the study is more subjective, with susceptibility to intra- and inter-observer bias, compared with the ADL and IADL scales used in the IMWG scoring system. While the frailty scale used in the study is based on parameters that are routinely assessed in clinical practice for clinical use, the use of comprehensive frailty assessments that more accurately reflect biological or functional frailty will remain important for the further optimization of treatment strategies for frail patients. Patients with an ECOG PS score ≥3 and patients with comorbidities that may interfere with the study procedures were excluded from MAIA; the inclusion and exclusion criteria for the study limits the generalizability of these results to more frail patients seen in clinical practice.8
Of the 2459 patients who received DARZALEX® at the recommended dose, 38% were 65 to 74 years of age, and 15% were 75 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. The incidence of serious adverse reactions was higher in older than in younger patients. Among patients with relapsed and refractory multiple myeloma (n=1213), the serious adverse reactions that occurred more frequently in patients 65 years and older were pneumonia and sepsis. Among patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (n=710), the serious adverse reaction that occurred more frequently in patients 75 years and older was pneumonia.
Of the 214 patients who received DARZALEX FASPRO® as combination therapy with pomalidomide and dexamethasone or DARZALEX FASPRO® as combination therapy with lenalidomide and low-dose dexamethasone for relapsed and refractory multiple myeloma, 43% were 65 to <75 years of age, and 18% were 75 years of age or older.
Adverse reactions occurring at a higher frequency (≥5% difference) in patients ≥65 years of age included fatigue, pyrexia, peripheral edema, urinary tract infection, diarrhea, constipation, vomiting, dyspnea, cough, and hyperglycemia. Serious adverse reactions occurring at a higher frequency (≥2% difference) in patients ≥65 years of age included neutropenia, thrombocytopenia, diarrhea, anemia, COVID-19, ischemic colitis, deep vein thrombosis, general physical health deterioration, pulmonary embolism, and urinary tract infection.
No clinically meaningful differences in the pharmacokinetics of daratumumab were observed in geriatric patients compared to younger adult patients.
DRd treatment in high-risk patient subgroup