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(daratumumab and hyaluronidase-fihj)

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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)
Medical Information

DARZALEX FASPRO - ANDROMEDA Study

Last Updated: 08/13/2026

SUMMARY

  • ANDROMEDA is a phase 3 study evaluating the efficacy and safety of DARZALEX FASPRO for subcutaneous (SC) use in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd) compared to bortezomib, cyclophosphamide, and dexamethasone (VCd) alone in newly diagnosed patients with systemic immunoglobulin light-chain (AL) amyloidosis.1
    • Kastritis et al (2021)1 reported primary results of the study with a median follow-up of 11.4 months. The primary endpoint of hematologic complete response (CR) was achieved in 53.3% of the D-VCd arm vs 18.1% of the VCd arm, respectively (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). The most common all-grade treatment-emergent adverse events (TEAEs) occurring in >25% of patients in the D-VCd arm were diarrhea, peripheral edema, constipation, peripheral sensory neuropathy, fatigue, nausea, and upper respiratory tract infection.
    • Comenzo et al (2021)2 presented updated efficacy and safety results of the ANDROMEDA study, with a median follow-up of 25.8 months. Hematologic CR rate was achieved by 60% of patients in the D-VCd arm vs 19% in the VCd arm (odds ratio [OR], 6; 95% CI, 3.8-9.6; P<0.0001). No new safety concerns were reported, except for 1 additional grade 3/4 TEAE (fatigue: D-VCd, 5%; VCd, 3%). The most common any grade TEAEs occurring in >20% of patients in the D-VCd arm were peripheral edema, diarrhea, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, upper respiratory tract infection, anemia, and dyspnea.
    • Kastritis et al (2026)3 published final analysis of major organ deterioration (MOD) progression-free survival (PFS) and overall survival (OS) from the phase 3 ANDROMEDA study with a median follow-up of 61.4 months. The updated hematologic CR rate was 59.5% for D-VCd vs 19.2% for VCd (OR, 6.03; 95% CI, 3.80-9.58; P<0.0001). There was an improvement for D-VCd vs VCd in MOD-PFS (hazard ratio [HR], 0.44; 95% CI, 0.31-0.63; P<0.0001) and OS (HR, 0.62; 95% CI, 0.42-0.90; P=0.0121). Safety data for D-VCd were consistent with the primary analysis.  
    • Other relevant literature has been identified in addition to the data summarized above.4-13

CLINICAL DATA

Phase 3 Study of DARZALEX FASPRO in Newly Diagnosed Systemic AL Amyloidosis

ANDROMEDA (AMY3001; NCT03201965) is a phase 3, randomized, prospective, active-controlled, multicenter study evaluating the efficacy and safety of D-VCd compared to VCd alone in newly diagnosed patients with systemic AL amyloidosis.1

Study Design/Methods

ANDROMEDA Study Design1

Abbreviations: AEs, adverse events; AL, immunoglobin light chain; BMI, body mass index; CR, complete response; Dara, daratumumab; DM, diabetes mellitus; eGFR, estimated glomerular filtration rate; IV, intravenous; MOD-PFS, major organ deterioration progression-free survival; MM, multiple myeloma; OS, overall survival; PFS, progression-free survival; PO, orally; rHuPH20, recombinant human hyaluronidase enzyme PH20; SC, subcutaneous; QW, every week; Q2W, every 2 weeks; Q4W, every 4 weeks; VCd, bortezomib, cyclophosphamide, dexamethasone.
aEach cycle was 28 days each.
bDivided into 20 mg as premedication and 20 mg on the day after Dara dosing for patients in the VCd plus daratumumab SC arm.
cBMI <18.5 kg/m2.
dComposite of endpoints occurring from randomization to whichever occurs first: death, clinical manifestation of cardiac or renal failure, or hematologic progressive disease.

Primary Efficacy and Safety Analysis of the ANDROMEDA Study

Kastritis et al (2021)1 reported primary results of the ANDROMEDA study with a median follow-up of 11.4 months (range, 0.03-21.3).

Results

Baseline Characteristics
  • Baseline patient demographics and disease characteristics were balanced between both arms from the primary results in the intention-to treat population (ITT).1
    • Across arms, the median age was 64 years (range, 34-87), the median baseline difference between involved and uninvolved free light-chain (dFLC) levels was 187 mg/L (range, 1-9983), and 76.8% of patients had cardiac stage II or higher.
  • Overall, 65.5% (n=254) of patients had ≥2 organs involved; 71.4% had cardiac involvement, 59% had kidney involvement.1
Treatment Exposure and Patient Disposition

Treatment Exposure and Patient Disposition in Primary Analysis1
Parameter
D-VCd
VCd
Safety population (≥1 dose study treatment), n
193
188
Median duration of study treatment, months
9.6
5.3
Deaths, na
27
29
Intention-to-treat population, n
195
193
Discontinued treatment, n (%)
52 (26.9)
68 (36.2)
Subsequent therapyc
193
188
   Any, n (%)
19 (9.8)
79 (42)
   ASCT, n
13 (6.7)
20 (10.6)
   DARZALEX monotherapy or combo regimen, n
0
48
Abbreviations: ASCT, autologous stem cell transplant; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; VCd, bortezomib + cyclophosphamide + dexamethasone.
aOnepatient in the VCd arm died before receiving treatment.
bIncludesphysiciandecision and patient withdrawal.
cSubsequent non-cross resistant, antiplasma cell therapy.
  • The percentage of patients who completed the protocol-defined treatment completion of 6 cycles was 82.4% (n=159) in the D-VCd arm and 64.4% in the VCd arm (n=121).1
  • At the time of analysis, 141 of 195 patients (72.3%) continued with DARZALEX FASPRO monotherapy.1
  • A total of 56 deaths were reported (D-VCd, n=27; VCd, n=29); mostly due to amyloidosis-related cardiomyopathy.1
    • The incidence of deaths related to adverse events (AEs) was 11.9% (n=23) in the D-VCd arm and 7.4% (n=14) in the VCd arm.
    • Disease progression was reported as a cause of death in 1% of patients in the D-VCd arm and 4.8% in the VCd arm.
    • Other reasons for death were reported in 1% of patients in the D-VCd arm and 2.7% in the VCd arm.
Efficacy
  • At 6 months, 179 of the 195 patients in the D-VCd arm and 148 of 193 patients in the VCd arm had any type of hematologic response.1
  • The primary endpoint of hematologic CR was achieved in 53.3% of the D-VCd arm vs 18.1% of the VCd arm, respectively (relative risk ratio, 2.9; 95% CI, 2.1-4.1; P<0.001).1
  • The hematologic CR rate at 6 months was consistent with the overall hematologic CR rate: 49.7% in the D-VCd arm vs 14% in the VCd arm (OR, 6.1; 95% CI, 3.7-10; P<0.001).1
  • Median time to CR was 60 days vs 85 days in the D-VCd arm vs the VCd arm, respectively.1
  • At 6 months, cardiac progression was reported in 2.5% of patients in the D-VCd arm and 7.7% in the VCd arm and renal progression was reported in 4.3% of patients in the D-VCd arm and 11.5% in the VCd arm.1
  • Improvement in hematologic CR with D-VCd was consistent across subgroups. Overall response by subgroups was also reported and demonstrated benefit in the D-VCd arm.1
  • At 11.4 months, MOD-PFS was significantly better in the D-VCd arm compared to VCd alone (HR, 0.58; 95% CI, 0.36-0.93; P=0.02).1
  • Major organ deterioration event-free survival (MOD-EFS), hematologic progression, or subsequent treatment was better in the D-VCd arm compared to VCd alone (HR 0.39; 95% CI, 0.27-0.56).1
Safety

Most Common Adverse Events in the Safety Populationa,1
Most Common (>25%) Any Grade AEs
Most Common (≥5%) Grade 3/4 AEs
  • Diarrhea
  • Peripheral edema
  • Constipation
  • Peripheral sensory neuropathy
  • Fatigue
  • Nausea
  • Upper respiratory tract infection
  • Diarrhea
  • Peripheral edema
  • Lymphopenia
  • Hypokalemia
  • Neutropenia
  • Pneumonia
  • Syncope
  • Cardiac failureb
Abbreviation: AE, adverse event.aSafety population included patients who received at least 1 administration of treatment.
bIncludes overall and congestive heart failure.
  • Serious AEs occurred in 43% and 36.2% of the D-VCd and VCd arms, respectively, with the most common being pneumonia (D-VCd, 7.3%; VCd, 4.8%).1
  • Grade 3/4 infections were reported in 16.6% and 10.1% of the D-VCd and VCd arms, respectively.1
  • The rate of discontinuation due to AEs was 4.1 % in the D-VCd arm and 4.3% in the VCd arm.1
Systemic ARRs and ISRs
  • Grade 1/2 systemic ARRs related to DARZALEX FASPRO occurred in 14 (7.3%) patients with a median time to onset of 1.3 hours (range, 0.2-7.3). Most ARRs (86%) occurred at first administration.1
    • Systemic ARRs occurring in >1 patient in the D-VCd arm were chills (n=3), pyrexia (n=3), dizziness (n=2) and nausea (n=2).14
  • Local ISRs to any drug in the treatment regimen occurred in 28% and 23.9% of patients in the D-VCd and VCd arms, respectively.14
  • Local ISRs related to DARZALEX FASPRO occurred in 10.9% (n=21) patients in the D-VCd arm. All ISRs were reported as grade 1/2.14
  • DARZALEX FASPRO-related ISRs occurring in >1 patient were reported as injection-site erythema (n=10), injection-site pain (n=6), and infusion-site pain (n=2).14

Updated on Efficacy and Safety Analysis of the ANDROMEDA Study

Comenzo et al (2021)2 presented updated efficacy and safety results of the ANDROMEDA study at a median follow-up of 25.8 months.

Results

Treatment Exposure and Patient Disposition
  • Median duration of treatment for the D-VCd and VCd arms at clinical cutoff was 21.3 months and 5.3 months, respectively.2
  • At a median follow-up of 25.8 months, 149 patients (77.2%) within the D-VCd arm received DARZALEX FASPRO monotherapy following 6 cycles of D-VCd treatment; of these, 132 patients (88.6%) received 18 cycles and 17 patients (11.4%) were still receiving treatment.2
  • Treatment exposure and patient disposition from the additional follow-up are presented in Table: Treatment Exposure and Patient Disposition in Updated Analysis.2

Treatment Exposure and Patient Disposition in Updated Analysis2
Safety Population (≥1 dose of study treatment)
D-VCd
(n=193)
VCd
(n=188)
Median duration of study treatment (range), months
21.3 (0.03-25.8)
5.3 (0.03-7.3)
Median number of cycles / >3 cycles (range), %
24 (1-25) / 86
6 (1-6) / 80
DARZALEX FASPRO monotherapy maintenance (>6 cycles), %
77
-
DARZALEX FASPRO as subsequent therapy, %
3
34
Intention-to-treat population, n
193
188
   Discontinued treatment, %
36
36
      Death (on study treatment)
11
7
      Received ASCT
6
2
      Adverse event
6
4
      Subsequent therapy
3
12
      Othera
6
5
      Progressive disease
4
6
Abbreviations: ASCT, autologous stem cell transplant; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; VCd, bortezomib + cyclophosphamide + dexamethasone.
aIncludesphysiciandecision and patient withdrawal.
Efficacy
  • Hematologic CR rate was achieved by 60% of patients in the D-VCd arm vs 19% in the VCd arm (OR, 6; 95% CI, 3.8-9.6; P<0.0001).2
    • Rate of very good partial response (VGPR) or more was 79% in the D-VCd arm.
  • Improvement in hematologic CR rates with D-VCd vs VCd was consistent across subgroups. See Table: Subgroup Analysis of Hematologic CR Rates in Updated Analysis.2

Subgroup Analysis of Hematologic CR Rates in Updated Analysis2
Subgroup
D-VCd n/N (%)
VCd n/N (%)
OR (95% CI)
Overall
116/195 (59.5)
37/193 (19.2)
6 (3.8-9.6)
Age
   <65 years
68/108 (63)
20/97 (20.6)
6.6 (3.5-12.3)
   ≥65 years
48/87 (55.2)
17/96 (17.7)
5.7 (2.9-11.2)
Sex
   Male
65/108 (60.2)
17/117 (14.5)
8.9 (4.7-16.9)
   Female
51/87 (58.6)
20/76 (26.3)
4 (2-7.7)
Race
   White
89/151 (58.9)
28/143 (19.6)
5.9 (3.5-10.0)
   Asian
21/30 (70)
5/34 (14.7)
13.5 (4.0-46.3)
   Others
6/14 (42.9)
4/16 (25)
2.3 (0.5-10.6)
Baseline weight
   ≤65 kg
41/62 (66.1)
10/74 (13.5)
12.5 (5.4-29.2)
   65-85 kg
54/96 (55.3)
14/74 (18.9)
5.5 (2.7-11.2)
   >85 kg
21/37 (56.8)
13/45 (28.9)
3.2 (1.3-8.1)
Baseline cardiac stage
   I
24/47 (51.1)
13/43 (30.2)
2.4 (1-5.7)
   II
46/76 (61.8)
17/80 (21.3)
6 (3-12.2)
   IIIa
45/72 (62.5)
7/70 (10)
15 (6-37.5)
Cardiac involvement at baseline
   Yes
88/140 (62.9)
22/137 (16.1)
8.9 (5-15.7)
   No
28/55 (50.9)
15/56 (26.8)
2.8 (1.3-6.3)
Baseline renal stage
   I
21/39 (53.8)
6/36 (16.7)
5.8 (2-17.2)
   II
41/56 (73.2)
14/60 (23.3)
9 (3.9-20.8)
   III
11/19 (57.9)
5/18 (27.8)
3.6 (0.9-14.2)
Baseline ECOG PS score
   0
52/90 (57.8)
16/71 (22.5)
4.7 (2.3-9.4)
   1 or 2
64/105 (61)
21/122 (17.2)
7.5 (4.1-13.9)
FISH t(11;14)
   Present
31/51 (60.8)
7/55 (12.7)
10.6 (4-28.1)
Organ response rate at 6 months
   Cardiac response, %
42
22
2.4 (1.4-4.4), P=0.0029
   Renal response, %
54
27
3.7 (2.1-6.6), P<0.0001
Organ response rate at 18 months
   Cardiac response, %
53
24
3.3 (1.9-5.9), P<0.0001
   Renal response, %
58
26
4.4 (2.4-7.9), P<0.0001
Abbreviations: CI, confidence interval; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; OR, odds ratio; VCd, bortezomib + cyclophosphamide + dexamethasone.
aCardiac stage III includes both IIIA patients and patients who were IIIA at randomization and progressed to IIIB at cycle 1 day 1.
Safety
  • No new safety concerns were reported, except for 1 additional grade 3/4 TEAE (fatigue: D-VCd, 5%; VCd, 3%).2
  • Serious TEAEs occurred in 47% vs 36% of patients in the D-VCd arm vs VCd arm, respectively, with the most common being pneumonia (D-VCd, 7%; VCd, 5%).2
  • The rate of discontinuation due to TEAEs was 5% vs 4% in the D-VCd arm vs VCd arm, respectively.2
  • There were 34 vs 45 deaths reported in the D-VCd vs VCd arms, respectively. See Table: Deaths and Cause of Death in Each Treatment Arm.2

Deaths and Cause of Death in Each Treatment Arm2
Safety Population (≥1 dose of study treatment)
D-VCd
(n=193)
VCd
(n=188)
Total number of deaths, n (%)a
   11.4 months of follow-up
27 (14)
29 (15)
   20.3 months of follow-up
31 (16)
40 (21)
   25.8 months of follow-up
34 (17)
45 (24)
Death on therapy, n/N (%)
22/34 (64)
14/45 (31)
Primary cause of death, n (%)
   AEs
26 (14)
15 (8)
      Related to study treatment
6 (3)
2 (1)
      Unrelated to study treatment
20 (10)
13 (7)
   Disease progression
4 (2)
13 (7)
   Other
4 (2)
17 (9)
Abbreviations: AEs, adverse events; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; VCd, bortezomib + cyclophosphamide + dexamethasone.
aOne patient in the VCd arm died before receiving treatment.

Most Common Any Grade (≥20%) and Grade 3/4 (≥5%) TEAEs2
Patients, %
D-VCd
(n=193)
VCd
(n=188)
≥1 Any grade TEAEs
98
98
   Peripheral edema
37
36
   Diarrhea
36
30
   Constipation
36
29
   Fatigue
29
28
   Peripheral sensory neuropathy
34
20
   Nausea
29
28
   Insomnia
25
25
   Upper respiratory tract infection
26
11
   Anemia
25
23
   Dyspnea
25
17
≥1 Grade 3/4 TEAEs
62
57
   Lymphopenia
13
10
   Pneumonia
8
4
   Fatigue
5
3
   Syncope
6
6
   Diarrhea
6
4
   Cardiac failure
6
3
   Neutropenia
5
3
   Peripheral edema
3
6
   Hypokalemia
2
5
Abbreviations: TEAEs, treatment-emergent adverse events.

Final Analysis of MOD-PFS and OS From the ANDROMEDA Study

Kastritis et al (2026)3 published results of the final analysis of MOD-PFS and OS from the ANDROMEDA study with a median follow-up of 61.4 months (range, 0.0-71.2).

Results

Baseline Demographics and Clinical Characteristics

Baseline Demographics and Clinical Characteristics15
Characteristic
D-VCd
(n=195)
VCd
(n=193)
Median age (range), years
62 (34-87)
64 (35-86)
   ≥65 years, n (%)
87 (44.6)
96 (49.7)
Male sex, n (%)
108 (55.4)
117 (60.6)
Race, n (%)a
   White
151 (77.4)
143 (74.1)
   Black or African American
6 (3.1)
7 (3.6)
   Asian
30 (15.4)
34 (17.6)
   American Indian or Alaska Native
1 (0.5)
2 (1.0)
   Native Hawaiian or Other Pacific Islander
0
1 (0.5)
   Multiple
0
1 (0.5)
   Not reported
7 (3.6)
5 (2.6)
ECOG performance status score, n (%)b
   0
90 (46.2)
71 (36.8)
   1
86 (44.1)
106 (54.9)
   2
19 (9.7)
16 (8.3)
AL isotype, n (%)c
   Lambda
158 (81.0)
149 (77.2)
   Kappa
37 (19.0)
44 (22.8)
Median time since amyloidosis diagnosis (range), days
48 (8-1611)
43 (5-1102)
Involved organs
   Median (range)
2 (1-5)
2 (1-6)
   Distribution, n (%)
      Heart
 140 (71.8)
137 (71.0)
      Kidney
115 (59.0)
114 (59.1)
      Liver
15 (7.7)
16 (8.3)
      Otherd
127 (65.1)
124 (64.2)
Cardiac stage, n (%)e
   I
47 (24.1)
43 (22.3)
   II
76 (39.0)
80 (41.5)
   IIIA
70 (35.9)
64 (33.2)
   IIIBf
2 (1.0)
6 (3.1)
Renal stage, n/N (%)g
   I
107/193 (55.4)
101/193 (52.3)
   II
67/193 (34.7)
74/193 (38.3)
   III
19/193 (9.8)
18/193 (9.3)
Abbreviations: AL, light-chain; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; ECOG, Eastern Cooperative Oncology Group; GFR, glomerular filtration rate; NT-proBNP, N-terminal pro-B-type natriuretic peptide; VCd, bortezomib + cyclophosphamide + dexamethasone.
aRace was reported by the patient.
bECOG performance status was scored on a scale from 0 to 5, with 0 indicating no symptoms and higher scores indicating increasing disability.
cData are based on immunofixation and AL measurement.
dOther included the gastrointestinal tract, lungs, the peripheral nervous system, the autonomic nervous system, and soft tissues.
eCardiac stage was classified in accordance with the European modification of the staging system of Mayo Clinic. Cardiac stage was based on 2 biomarker risk factors—NT-proBNP and high-sensitivity cardiac troponin T—that were assessed at a central laboratory.
fAll patients had a cardiac stage of I, II, or IIIA at screening; however, some converted to stage IIIB at cycle 1, day 1 (results determined by the central laboratory were made available only after cycle 1, day 1).
gRenal stage was based on the combination of estimated GFR and urinary protein excretion.
Treatment Exposure and Patient Disposition
  • At the cutoff of April 17, 2024, all patients completed study treatment and 124/193 patients in the D-VCd arm completed 2 years of DARZALEX FASPRO treatment.3
  • The median duration of treatment was 21.3 months (range, 0.03-26.7) in the D-VCd group and 5.3 months (range 0.03-7.3) in the VCd group.3
  • The most common reasons for discontinuation in the D-VCd arm were death (n=23), subsequent therapy (n=17), and adverse events (n=11).3
Efficacy
  • Hematologic CR was achieved by 116 patients (58.5%) in the D-VCd group vs 37 patients (19.2%) in the VCd group (OR, 6.03; 95% CI, 3.80-9.58; nominal P<0.0001).3
    • Of these, 131 patients achieved hematologic CR within 6 months (D-VCd, n=99; VCd, n=32).
    • Median time to hematologic CR 67.5 days (range, 8.0-879.0) in the D-VCd group and 85.0 days (range, 14.0-617.0) in the VCd group.
    • The median duration of hematologic CR was not reached in either group.
  • Efficacy data from the final analysis are presented in Table: Summary of Responses in the Final Analysis - ITT Population.3

Summary of Responses in the Final Analysis - ITT Population3
Parameter, n (%)
D-VCd
(n=195)
VCd
(n=193)
Overall hematologic responsea
179 (91.8)
148 (76.7)
   CR
116 (59.5)
37 (19.2)
   ≥VGPR
154 (79.0)
97 (50.3)
   VGPR
38 (19.5)
60 (31.1)
   PR
25 (12.8)
51 (26.4)
   No response
8 (4.1)
38 (19.7)
   Not evaluable
8 (4.1)
7 (3.6)
MOD-PFS
79 (40.5)
118 (61.1)
   Hematologic progression
41 (21.0)
63 (32.6)
   Major organ deterioration
3 (1.5)
11 (5.7)
   Death
35 (17.9)
44 (22.8)
Overall survival
46 (23.6)
66 (34.2)
Abbreviations: CR, complete response; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; MOD-PFS, major organ deterioration-progression-free survival; PR, partial response; VCd, bortezomib + cyclophosphamide + dexamethasone; VGPR, very good partial response.
aAssessed by Independent Review Committee.
  • When accounting for non-cross-resistant subsequent therapy and censoring, the hazard ratio for MOD-PFS was 0.44 (95% CI, 0.31-0.63; P<0.0001 [crossing prespecified boundary of 0.0495]).3
  • Subgroup analyses of MOD-PFS demonstrated similar results across clinically relevant subgroups as summarized in Table: MOD-PFS in Prespecified Subgroups.15

MOD-PFSa in Prespecified Subgroups7
Subgroup
D-VCd
VCd
D-VCd
VCd
HR (95% CI)
MOD-PFS (n/N)
Median MOD-PFS, Months
Sex
   Male
45/108
76/117
NE
22.14
0.46 (0.32-0.66)
   Female
34/87
42/76
NE
33.61
0.49 (0.31-0.78)
Age
   <65 years
38/108
52/97
NE
31.11
0.44 (0.29-0.67)
   ≥65 years
41/87
66/96
59.66
20.86
0.51 (0.34-0.75)
Baseline weight
   ≤65 kg
23/62
49/74
NE
20.40
0.35 (0.21-0.57)
   >65-85 kg
42/96
41/74
NE
23.66
0.58 (0.38-0.89)
   >85 kg
14/37
28/45
NE
38.21
0.47 (0.25-0.89)
Race
   White
64/151
87/143
NE
31.11
 0.50 (0.36-0.69)
   Asian
7/30
21/34
NE
16.33
0.25 (0.11-0.59)
   Other
8/14
10/16
53.59
24.05
0.83 (0.32-2.12)
Baseline cardiac stage
   I
18/47
22/43
NE
48.59
0.56 (0.30-1.04)
   II
27/76
50/80
NE
24.64
0.39 (0.24-0.62)
   IIIa/IIIb
34/72
46/70
59.66
20.86
0.51 (0.33-0.80)
Residence in a country that typically offers transplantation for patients with AL amyloidosis
   Yes
58/147
90/146
NE
26.74
0.45 (0.32-0.63)
   No
21/48
28/47
NE
31.11
0.53 (0.30-0.94)
Baseline creatinine clearance
   ≥60 mL/min
49/126
74/131
NE
28.42
0.46 (0.32-0.67)
   <60 mL/min
30/69
44/62
NE
29.90
0.47 (0.29-0.74)
Baseline cardiac involvement
   Yes
57/140
87/137
NE
21.88
0.44 (0.31-0.61)
   No
22/55
31/56
NE
42.41
0.55 (0.32-0.96)
Baseline renal stage
   I
13/39
22/36
NE
20.57
0.30 (0.15-0.60)
   II
20/56
35/60
NE
33.02
0.40 (0.23-0.70)
   III
7/19
13/18
59.33
45.50
0.49 (0.19-1.24)
Baseline alkaline phosphatase
   Abnormal
4/11
12/15
NE
17.74
0.20 (0.06-0.66)
   Normal
75/184
106/178
NE
30.23
0.50 (0.37-0.67)
Baseline ECOG PS score
   0
34/90
40/71
NE
43.96
0.47 (0.30-0.75)
   1 or 2
45/105
78/122
NE
20.83
0.49 (0.34-0.70)
Cytogenetic risk at study entry
   High risk
6/17
15/19
NE
16.39
0.24 (0.09-0.62)
   Standard risk
55/138
90/147
NE
28.42
0.46 (0.33-0.65)
FISH t(11;14)
   Abnormal
18/51
30/55
NE
34.10
0.41 (0.23-0.75)
   Normal
13/44
32/52
NE
20.27
0.33 (0.17-0.63)
Abbreviations: AL, light-chain; CI, confidence interval; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; HR, hazard ratio; MOD, major organ deterioration; NE, not estimated; PFS, progression-free survival; VCd, bortezomib + cyclophosphamide + dexamethasone.
aMOD-PFS is a composite endpoint defined as end-stage cardiac disease (requiring a cardiac transplant, left ventricular assist device, or intra-aortic balloon pump), end-stage renal disease (requiring hemodialysis or renal transplant), hematologic progression per consensus guidelines, or death.
  • The median OS was not reached in either group.3
    • There were 46 deaths (23.6%) in the D-VCd group vs 66 deaths (34.2%) in the VCd group (HR, 0.62; 95% CI, 0.42-0.90; P=0.0121 [crossing prespecified boundary of 0.0163]).
  • The estimated 5-year OS rates were 76.1% (95% CI, 69.3-81.6) for D-VCd vs 64.7% (95% CI, 57.1-71.2) for VCd.3
  • Subgroup analyses of OS demonstrated similar results across clinically relevant subgroups as summarized in Table: OS in Prespecified Subgroups.15

OS in Prespecified Subgroups15
Subgroups
D-VCd
VCd
D-VCd
VCd
HR (95% CI)
Death (n/N)
Median OS, Months
Sex
   Male
25/108
43/117
NE
NE
0.59 (0.36-0.96)
   Female
21/87
23/76
NE
NE
0.71 (0.39-1.28)
Age
   <65 years
16/108
18/97
NE
NE
0.74 (0.38-1.46)
   ≥65 years
30/87
48/96
NE
60.25
0.63 (0.40-0.99)
Baseline weight
   ≤65 kg
13/62
32/74
NE
NE
0.39 (0.21-0.75)
   >65-85 kg
26/96
20/74
NE
NE
0.96 (0.54-1.72)
   >85 kg
7/37
14/45
NE
NE
0.57 (0.23-1.41)
Race
   White
37/151
48/143
NE
NE
0.68 (0.44-1.04)
   Asian
4/30
14/34
NE
NE
0.25 (0.08-0.77)
   Other
5/14
4/16
NE
NE
1.71 (0.46-6.37)
Baseline cardiac stage
   I
3/47
7/43
NE
NE
0.34 (0.09-1.30)
   II
14/76
23/80
NE
NE
0.63 (0.32-1.22)
   IIIa/IIIb
29/72
36/70
NE
36.83
0.64 (0.39-1.05)
Residence in a country that typically offers transplantation for patients with AL amyloidosis
   Yes
36/147
53/146
NE
NE
0.61 (0.40-0.93)
   No
10/48
13/47
NE
NE
0.72 (0.31-1.64)
Baseline creatinine clearance
   ≥60 mL/min
26/126
34/131
NE
NE
0.72 (0.43-1.21)
   <60 mL/min
20/69
32/62
NE
49.61
0.50 (0.29-0.88)
Baseline cardiac involvement
   Yes
42/140
54/137
NE
NE
0.68 (0.45-1.02)
   No
4/55
12/56
NE
NE
0.31 (0.10-0.96)
Baseline renal stage
   I
7/39
10/36
NE
NE
0.49 (0.18-1.28)
   II
7/56
18/60
NE
NE
0.37 (0.16-0.90)
   III
5/19
8/18
NE
NE
0.66 (0.22-2.03)
Baseline alkaline phosphatase
   Abnormal
2/11
6/15
NE
49.61
0.34 (0.07-1.68)
   Normal
44/184
60/178
NE
NE
0.66 (0.44-0.97)
Baseline ECOG PS score
   0
10/90
18/71
NE
NE
0.39 (0.18-0.84)
   1 or 2
36/105
48/122
NE
NE
0.82 (0.53-1.26)
Cytogenetic risk at study entry
   High risk
3/17
9/19
NE
56.87
0.26 (0.07-0.96)
   Standard risk
31/138
51/147
NE
NE
0.59 (0.37-0.92)
FISH t(11;14)
   Abnormal
8/51
16/55
NE
NE
0.47 (0.20-1.11)
   Normal
7/44
20/52
NE
NE
0.34 (0.14-0.81)
Abbreviations: AL, light-chain; CI, confidence interval; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; HR, hazard ratio; NE, not estimated; OS, overall survival; VCd, bortezomib + cyclophosphamide + dexamethasone.
  • A total of 235 patients were evaluable for cardiac response (D-VCd, n=118; VCd, n=117) and 230 for renal response (D-VCd, n=117; VCd, n=113). Responses are summarized in Table: Cardiac and Renal Responses in Final Analysis.3
    • The median time to cardiac ≥VGPR was 14.9 months vs 16.4 months and the median time to cardiac CR was 16.3 months bs 20.9 months for D-VCd vs VCd, respectively.

Cardiac and Renal Responses in the Final Analysis3
Parameter
D-VCd
VCd
Cardiac response, n
118
117
   6 months, %
41.5
22.2
   12 months, %
56.8
28.2
   24 months, %
47.5
18.8
   36 months, %
39.0
12.8
   48 months, %
27.1
9.4
Cardiac CR, n (%)
48 (40.7)
16 (13.7)
Cardiac ≥VGPR, n (%)
76 (64.4)
37 (31.6)
Renal response, n
117
113
   6 months, %
53.8
27.4
   12 months, %
57.3
27.4
   24 months, %
51.3
22.1
   36 months, %
48.7
16.8
   48 months, %
40.2
15.0
Abbreviations: CR, complete response; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; VCd, bortezomib + cyclophosphamide + dexamethasone; VGPR, very good partial response.
Safety
  • Safety data for D-VCd were consistent with the primary analysis results.3
  • The most common grade 3/4 AEs were lymphopenia, pneumonia, diarrhea, cardiac failure, neutropenia, syncope, fatigue, hypokalemia, and peripheral edema as summarized in Table: Most Common Any-Grade and Grade 3/4 AEs.3

Most Common Any-Grade and Grade 3/4 AEsa,3
Event, n (%)
D-VCd (n=193)
VCd (n=188)
Any Gradeb
Grade 3/4b
Any Gradeb
Grade 3/4b
Peripheral edema
71 (36.8)
6 (3.1)
68 (36.2)
11 (5.9)
Diarrhea
70 (36.3)
11 (5.7)
57 (30.3)
7 (3.7)
Constipation
70 (36.3)
3 (1.6)
54 (28.7)
0
Peripheral sensory neuropathy
65 (33.7)
5 (2.6)
37 (19.7)
4 (2.1)
Fatigue
55 (28.5)
10 (5.2)
53 (28.2)
6 (3.2)
Nausea
55 (28.5)
3 (1.6)
52 (27.7)
0
Upper respiratory tract infection
50 (25.9)
1 (0.5)
21 (11.2)
1 (0.5)
Anemia
49 (25.4)
8 (4.1)
44 (23.4)
9 (4.8)
Insomnia
49 (25.4)
0
47 (25)
2 (1.1)
Dyspnea
49 (25.4)
5 (2.6)
32 (17)
6 (3.2)
Lymphopenia
37 (19.2)
25 (13)
28 (14.9)
19 (10.1)
Hypokalemia
26 (13.5)
4 (2.1)
28 (14.9)
10 (5.3)
Pneumonia
24 (12.4)
16 (8.3)
12 (6.4)
8 (4.3)
Neutropenia
21 (10.9)
10 (5.2)
12 (6.4)
5 (2.7)
Cardiac failure
18 (9.3)
12 (6.2)
10 (5.3)
5 (2.7)
Syncope
16 (8.3)
12 (6.2)
12 (6.4)
12 (6.4)
Abbreviations: AE, adverse event; D-VCd, DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone; VCd, bortezomib + cyclophosphamide + dexamethasone.
aThe safety population included patients who received at least 1 dose of the study treatment.
bAEs of any grade that were reported in >25% of patients in either treatment arm and grade 3/4 AEs that were reported in ≥5% of patients in either treatment arm are listed.
  • Serious AEs occurred in 47.2% of patients in the D-VCd arm vs 36.2% in the VCd arm.3
    • The most common serious AEs were pneumonia (D-VCd, 7.3%; VCd, 4.8%) and cardiac failure (D-VCd, 7.3%; VCd, 4.3%).
  • Study treatment was discontinued due to AEs in 5.2% vs 4.3% of patients in the D-VCd and VCd groups, respectively.3
  • Deaths due to AEs within 30 days of the last study treatment occurred in 22 patients (11.4%) in the D-VCd arm and 14 patients (7.4%) in the VCd arm. Most deaths were determined to be unrelated to study treatment.3
  • Systemic ARRs with DARZALEX FASPRO occurred in 14 patients (7.3%); all were grade 1/2 and 86% occurred during the first injection.3

Literature Search

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 29 July 2026.

 

References

Show
1 Kastritis E, Palladini G, Minnema M, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58.  
2 Comenzo R, Palladini G, Kastritis E, et al. Subcutaneous daratumumab with bortezomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed light chain (AL) amyloidosis: 18-month landmark analysis of the phase 3 ANDROMEDA study. Oral Presentation presented at: The 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.  
3 Kastritis E, Palladini G, Minnema M, et al. Daratumumab-bortezomib-cyclophosphamide-dexamethasone in newly diagnosed amyloidosis: ANDROMEDA final survival analysis. [Published online May 12, 2026]. Blood. doi:10.1182/blood.2025032099.  
4 Comenzo R, Kastritis E, Maurer M, et al. Subcutaneous daratumumab + cyclophosphamide/bortezomib/dexamethasone in newly diagnosed AL amyloidosis: updated safety run-in results of ANDROMEDA. Oral Presentation presented at: The 17th International Symposium on Amyloidosis; September 14-18, 2020; Tarragona, Spain.  
5 Palladini G, Wechalekar A, Kastritis E, et al. Assessing clinical outcomes in patients with AL amyloidosis across different criteria for hematologic complete response: results from ANDROMEDA. Poster presented at: XVIII International Symposium on Amyloidosis; September 4-8, 2022; Heidelberg, Germany.  
6 Palladini G, Kastritis E, Maurer MS, et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood. 2020;136(1):71-80.  
7 Kastritis E, Palladini G, Minnema MC, et al. Subcutaneous daratumumab (DARA) + bortezomib, cyclophosphamide, and dexamethasone (VCd) in patients with newly diagnosed light chain (AL) amyloidosis: final analysis of the phase 3 ANDROMEDA study. Oral Presentation presented at: The 66th American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2024; San Diego, CA.  
8 Kumar S, Dispenzieri A, Bhutani D, et al. Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study. Amyloid. 2023;30(3):268-278.  
9 Suzuki K, Wechalekar AD, Kim K, et al. Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA. Ann Hematol. 2023;102(4):863-876.  
10 Comenzo R, Kastritis E, Minnema M, et al. Reduction in absolute involved free light chain and difference between involved and uninvolved free light chain is associated with prolonged major organ deterioration progression-free survival in patients with newly diagnosed AL amyloidosis receiving bortezomib, cyclophoshpamide, and dexamethasone with or without daratumumab: results from ANDROMEDA. Oral presentation presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual meeting.  
11 Wechalekar A, Palladini G, Merlini G, et al. Rapid and deep hematologic responses are associated with improved major organ deterioration progression-free survival in newly diagnosed AL amyloidosis: results from ANDROMEDA. Poster presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual meeting.  
12 Minnema M, Dispenzieri A, Merlini G, et al. Outcomes by cardiac stage in newly diagnosed AL amyloidosis: results from ANDROMEDA. Poster presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual meeting.  
13 Suzuki K, Kim K, Shimazaki C, et al. Subcutaneous daratumumab + bortezomib, cyclophosphamide, and dexamethasone in asian patients with newly diagnosed light-chain (AL) amyloidosis. Poster presented at: 22nd International Myeloma Society (IMS) Annual Meeting; September; September 17-20; Toronto, Canada.  
14 Kastritis E, Palladini G, Minnema M, et al. Supplement to: Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58.  
15 Kastritis E, Palladini G, Minnema M, et al. Supplement to: Daratumumab-bortezomib-cyclophosphamide-dexamethasone in newly diagnosed amyloidosis: ANDROMEDA final survival analysis. [Published online May 12, 2026]. Blood. doi:10.1182/blood.2025032099.  

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