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DARZALEX® (daratumumab)

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DARZALEX + DARZALEX FASPRO - Retreatment

Last Updated: 06/11/2025

SUMMARY

  • Janssen cannot recommend any practices, procedures or practice guidelines that deviate from the product labeling or are not approved by the regulatory agencies.
  • Talbot et al (2025)1 conducted a non-interventional, prospective dynamic cohort study to assess the real-life management of multiple myeloma (MM) exploring the efficacy of anti-CD38-based retreatment, the EMMY Study.
  • Souren et al (2025)2 conducted a single-center, retrospective study comparing efficacy and safety of patients receiving DARZALEX as first-line treatment and as retreatment.
  • Tan et al (2024)3 presented the results from a retrospective study that evaluated clinical outcomes of DARZALEX-based retreatment in patients with relapsed/refractory multiple myeloma (RRMM).
  • Abdallah et al (2023)4 conducted a single-center, retrospective, chart review to evaluate the efficacy and safety of retreatment with DARZALEX-based therapy in patients with RRMM who were refractory to DARZALEX, and compared the response data after retreatment with the response data after the first DARZALEX-based line of therapy.
  • Szabo et al (2022)5,6 conducted a retrospective real-world study that evaluated the life expectancy and clinical outcomes in patients who discontinued their first DARZALEXcontaining index regimen (IR).
  • Other relevant literature has been identified in addition to the data summarized above.7-10

PRODUCT LABELING

CLINICAL DATA

EMMY Study – Retreatment with Anti-CD38-Based Combinations in Real-Life

Talbot et al (2025)1 conducted a non-interventional, prospective dynamic cohort study to assess the real-life management of MM in France exploring the efficacy of anti-CD38-based retreatment, the EMMY Study.  

Study Design/Methods

  • Study conducted in 73 centers in France with patients treated from January 1, 2018 to December 31, 2022.
  • Included any patient initiating treatment for MM over a 3-month period from October 2017 to December 2022.
  • Patients who initiated a second line of treatment with an anti-CD38-based combination after exposure to daratumumab or isatuximab were identified and analyzed.
  • Overall population was analyzed for progression-free survival (PFS) and overall survival (OS) by line of treatment, combination with anti-CD38 (immunomodulatory, proteasome inhibitor [PI], others), consecutive or non-consecutive anti-CD38 lines, and anti-CD38 refractory status.

Results

Patient Characteristics
  • The EMMY study included 286 patients who received 2 lines of treatment with an anti-CD38-based combination for MM or RRMM with baseline characteristics summarized in Table: Baseline Characteristics.

Baseline Characteristics1 
Characteristics
N=286
Age at retreatment with anti-CD38, years
   Median
69.9
   <65, n (%)
99 (34.6)
   65-69, n (%)
44 (15.4)
   70-74, n (%)
57 (19.9)
   75-79, n (%)
61 (21.3)
   80-84, n (%)
18 (6.3)
   ≥85, n (%)
7 (2.4)
Sex, n (%)
   Male
154 (53.8)
ECOG Score, n (%)
   0-1
175 (75.8)
   2-3
56 (24.2)
ISS at diagnosis, n (%)
   I
31 (19.4)
   II
50 (31.3)
   III
78 (48.8)
High-risk cytogenetics, n (%)
   Yes
49 (36.3)
   No
86 (63.7)
Retreatment with anti-CD38, n (%)
   Daratumumab-Daratumumaba
145 (51)
   Daratumumab-Isatuximabb
120 (42)
   Isatuximab-Daratumumabc
19 (7)
Consecutive lines of anti-CD38, n (%)
133 (46.5)
Median duration between consecutive lines, months
0.8 (Q1-Q3, 0.1-6.4)
Non-consecutive lines of anti-CD38, n (%)
   1 middle line
81 (28.3)
   ≥2 lines
72 (25.2)
Median duration between non-consecutive lines, months
15.7 (Q1-Q3, 9.1-24.9)
Abbreviations: ECOG, Eastern Cooperative Oncology Group; ISS, International Staging System; Max, maximum; Min, minimum; Q, quartile.
aDratumumab administered after Daratumumab.
bDaratumumab administered after Isatuximab.
cIsatuximab administered after Daratumumab.

Previous Lines of Treatment
Characteristics
N=286
Previous lines of treatmenta, n (%)
   2
28 (9.8)
   3
43 (15)
   4
53 (18.5)
   5
56 (19.6)
   ≥6
106 (37)
Autologous stem cell transplant, n (%)
   Yes
164 (57.3)
   No
122 (42.7)
Refractory Status, n (%)
   Tri-refractory
151 (52.7)
   Quadri-refractory
119 (41.6)
   Penta-refractory
51 (17.8)
Exposure to PI, n (%)
   Yes
279 (97.6)
   No
7 (2.4)
PI, n (%)
   Bortezomib
276 (96.5)
   Carfilzomib
151 (52.8)
   Ixazomib
43 (15.0)
Refractory PI, n (%)
   Yes
210 (73.4)
   No
76 (26.6)
PI Refractory, n (%)
   1
105 (50.0)
   2
90 (42.9)
   3
13 (6.2)
Exposure to immunomodulatory drug, n (%)
   Yes
275 (96.2)
   No
11 (3.8)
Immunomodulatory drug, n (%)
   Thalidomide
120 (42.0)
   Lenalidomide
253 (88.5)
   Pomalidomide
167 (58.4)
Refractory to immunomodulatory drug, n (%)
   Yes
222 (77.6)
   No
62 (21.7)
Immunomodulatory drug refractory, n (%)
   1
115 (51.8)
   2
96 (43.2)
   3
11 (5.0)
Exposure to anti-CD38, n (%)
   Yes
286 (100.0)
Anti-CD38
   Daratumumab
267 (73.1)
   Isatuximab
19 (6.6)
Refractory to anti-CD38, n (%)
   Yes
209 (73.1)
   No
76 (26.6)
Exposure to alkylating agent, n (%)
   Yes
249 (87.1)
   No
37 (12.9)
Alkylating agent, n (%)
   Melphalan
207 (72.4)
   Cyclophosphamide
134 (46.9)
   Bendamustine
44 (15.4)
Abbreviations: PI, proteasome inhibitor.
aResults not provided.
Efficacy
  • A summary of outcomes related to PFS and OS is detailed in Table: PFS and OS Outcomes.
    • In patients refractory and non-refractory to anti-CD38, there were no significant differences in PFS or OS.
    • The choice of anti-CD38 in the treatment regimen showed no difference in PFS or OS.
    • There was no difference in PFS or OS with respect to treatment sequencing between anti-CD38 regimens.

PFS and OS Outcomes1 
Parameter
PFS, months
   Median PFS in all anti-CD38-retreated patients
5.1 (95% CI, 4.2-6.6)
   Median PFS in anti-CD38 non-refractory patients
9.5 (95% CI, 4.9-23.6)
   Median PFS in patients refractory to anti-CD38
4.6 (95% CI, 3.8-6.0)
   Median PFS in patients sensitive to anti-CD38 (n=29)
23.6 (95% CI, 11.6-NR)
   Median PFS in patients non-sensitive to anti-CD38 (n=248)
4.6 (95% CI, 3.8-6; P=0.0003)
OS, months
   Median OS in all patients (n=282)
17.3 (95% CI, 14-22.5)
   Median OS in patients with anti-CD38 in a consecutive line
22.3
   Median OS in patients with 1 non-consecutive line
16.2
   Median OS in patients with ≥2 middle lines
9.1
   Median OS in patients sensitive to anti-CD38 (n=29)
NR (P=0.0004)
   Median OS in patients non-sensitive to anti-CD38 (n=245)
14.8 (95% CI, 12.6-19.5)
Abbreviations: OS, overall survival; PFS, progression-free survival.

Retrospective Study in Patients Comparing DARZALEX-Based Regimens as First-Line Treatment and as Retreatment

Souren et al (2025)2 conducted a single-center, retrospective study comparing efficacy and safety of patients receiving DARZLEX as first-line treatment and as retreatment.

Study Design/Methods

  • The clinics medical information and documentation system was utilized to collect all disease specific data.
  • Treatment data was described as:
    • Total number of therapy lines received
    • Time between DARZALEX lines
    • Whether a different therapy was given in between DARZALEX lines
    • Number of DARZALEX cycles of the respective lines
    • Whether DARZALEX was administered in combination with other standard therapies or as monotherapy
  • Patients were divided into 3 subgroups:
    • D1 – First DARZALEX treatment
    • D2 – First DARZALEX retreatment
    • D3 – Second DARZALEX retreatment
  • Treatment duration and response were analyzed according to International Myeloma Working Group (IMWG) remission criteria.
  • Primary endpoint: PFS
  • Secondary endpoint: overall response rate (ORR), duration of response (DUR), adverse events (AEs)

Results

Patient Characteristics
  • At the Medical Center – University of Freiburg, 293 patients who met inclusion criteria (D1) were treated with DARZALEX from May 2016 through January 2023.
    • D2 – 22 patients received DARZALEX retreatment.
    • D3 – 7 patients received a second DARZALEX retreatment.
    • Of these, 13% (n=39) received ≥2 DARZALEX treatment lines.
    • Seventeen patients were excluded due to not fulfilling DARZALEX retreatment criteria defined as administration with another combination partner or after discontinuation of therapy.
  • Patient details pertaining to the total cohort of patients (D2 + D3) are described in Table: Baseline Characteristics of the Total Cohort (D2 + D3).

Baseline Characteristics of the Total Cohort (D2 + D3)2 
Characteristics
D2 + D3 (n=22)
Median age at ID, years, range
59 (40-82)
Gender, n (%)
   Male
14 (64)
   Female
8 (36)
Patients alive, n (%)
   Yes
20 (91)
   No
2 (9)
Type of MM, n (%)
   IgG
9 (41)
   IgA
6 (27)
   Light-chain only
7 (32)
   Kappa
11 (50)
   Lambda
11 (50)
ISS stage, n (%)
   I
6 (27)
   II
7 (32)
   III
9 (41)
R-ISS state, n (%)
   I
4 (18)
   II
10 (46)
   III
8 (36)
R-MCI, n (%)
   Fit (0-3)
7 (32)
   Intermediate (4-6)
13 (59)
   Frail (7-9)
2 (9)
Therapy Lines, n (%)
   2
2 (9)
   ≥3
20 (91; [3-7])
SCT, n (%)
   Yes
19 (86)
   No
3 (14)
   Autologous
19 (86)
   Allogenic
8 (36)
Abbreviations: ID, initial diagnosis; ISS, International Staging System; MM, multiple myeloma; R-ISS, revised International Staging System; R-MCI, Revised Myeloma Comorbidity Index; SCT, stem cell transplantation.
Efficacy

Therapy and Outcome Data for Respective DARZALEX Lines2 
First DARZALEX Treatment
(D1, n=22)
DARZALEX Retreatment
(D2, n=22)
Second DARZALEX Retreatment
(D3, n=7)
Median line of therapy (range)
2 (1-4)
4 (2-6)
5 (3-7)
Median number of DARZALEX-cycles (range)
9 (1-33)
11 (1-46)
8 (1-14)
Median duration (range) [weeks]
35 (4-126)
42 (2-146)
30 (3-53)
Combination, n (%)
19 (86)
20 (91)
7 (100)
Monotherapy, n (%)
3 (14)
2 (9)
0 (0)
DARZALEX-based therapy, n (%)
   DARZALEX
3 (14)
2 (9)
0 (0)
   DARZALEX/PIa
16 (72)
9 (41)
4 (57)
   DARZALEX/Immunomodulatory drug
3 (14)
5 (23)
1 (14)
   DARZALEX/Other
0 (0)
6 (27)
2 (29)
Median time interval between, (range) [weeks]
   D1 and D2 (n=22)
34 (1-131)
   D2 and D3 (n=7)
32 (1-109)
Therapy line in between yes/no (%)
   D1 and D2 (n=22)
9/13 (41/59)
   D2 and D3 (n=7)
2/5 (29/71)
Response, n (%)
   ORR
14 (64)
10 (46)
3 (43)
     sCR
0 (0)
1 (5)
1 (14)
     CR
0 (0)
0 (0)
0 (0)
     VGPR
6 (27)
3 (14)
0 (0)
     PR
7 (32)
6 (27)
2 (29)
     MR
1 (5)
0 (0)
0 (0)
     SD
8 (36)
10 (45)
4 (57)
     PD
0 (0)
2 (9)
0 (0)
PFS
   Median PFS, months
11.5
(95% CI:5.1-27)
12
(95% CI: 3.4 -NR)
NR
(95% CI: 2.8-NR)
   6-month PFS, %
77
(95% CI: 56.3-96.8)
72
(95% CI: 51.3-93.5)
83
(95% CI: 53.5-100)
   12-month PFS, %
42
(95% CI: 13.2-70.3)
45
(95% CI: 20.1-70.2)
NRb
   24-month PFS, %
28
(95% CI: 0-57.1)
45
(95% CI: 20.1-70.2)
-
Abbreviations: CI, confidence interval; CR, complete response; MR, minor response; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PI, proteasome inhibitor; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.aBortezomib was used in combination with DARZALEX across all lines in 64%, 27%, and 14% of patients in the D1, D2, and D3 groups, respectively. Bortezomib + dexamethasone (Vd) was added to DARZALEX in 45%, 18%, and 14% of patients in the D1, D2, and D3 groups, respectively.bD3 9-month PFS was 55.6% (95% CI: 6.9-100).
Safety
  • A summary of treatment emergent adverse events (TEAEs) that occurred during the different DARZALEX treatment lines is detailed within Table: Treatment Emergent Adverse Events.

Treatment Emergent Adverse Events2
Event, n (%)
First DARZALEX Treatment
(D1, n=20)a
DARZALEX Retreatment
(D2, n=21)a
Second DARZALEX Retreatment
(D3, n=7)
Hematologic
   Anemia
     Any Grade
17 (85)
20 (95)
7 (100)
     Grade 1
10 (50)
8 (38)
1 (14)
     Grade 2
2 (10)
7 (33)
2 (29)
     Grade 3
5 (25)
5 (24)
4 (57)
   Leukopenia
     Any Grade
13 (65)
14 (67)
5 (71)
     Grade 3/4
5 (25)
5 (24)
3 (43)
   Thrombocytopenia
     Any Grade
14 (70)
15 (71)
4 (57)
     Grade 3/4  
4 (20)
4 (19)
3 (43)
Nonhematologic Infection
7 (32)
4 (18)
2 (29)
aInsufficient data were available from some patients, this is why no hematological events could be determined here.

Retrospective Study in Patients With RRMM Retreated With DARZALEX-Based Regimens

Tan et al (2024)3 presented the results from a retrospective study that evaluated clinical outcomes of DARZALEX-based retreatment in patients with RRMM.

Study Design/Methods

  • Patients with RRMM who had received DARZALEX-based retreatment at Memorial Sloan Kettering Cancer Center from January 1, 2015, to December 31, 2023, were included.
  • The last follow-up date for analysis was May 8, 2024.
  • Inclusion criteria: Patients with RRMM who had received ≥1 cycle of initial DARZALEX-based treatment and DARZALEX-based retreatment.
  • Exclusion criteria: Patients who had received initial DARZALEX-based treatment in the newly diagnosed multiple myeloma (NDMM) setting.
  • Responses were assessed according to the IMWG Response Criteria.
  • PFS and overall survival (OS) were evaluated via the Kaplan-Meier Method.
  • DARZALEX-based regimens used for treatment and retreatment have been summarized in Table: DARZALEX-Based Regimens Used for Treatment and Retreatment.

DARZALEX-Based Regimens Used for Treatment and Retreatment3
Agents, n (%)
Initial DARZALEX-Based Treatment
DARZALEX-Based Retreatment
DARZALEX monotherapy
51 (32)
7 (4)
DARZALEX + PI
27 (17)
43 (27)
   Bortezomib
21
21
   Carfilzomib
5
17
   Ixazomib
1
5
DARZALEX + IMiD
71 (45)
72 (46)
   Lenalidomide
26
15
   Pomalidomide
45
57
DARZALEX + IMiD + PI
3 (2)
10 (6)
DARZALEX + IMiD + cyclophosphamide
1 (0.6)
6 (4)
DARZALEX + othera
4 (3)
19 (12)
Abbreviations: IMiD, immunomodulatory agent; PI, proteasome inhibitor.
aOther includes cyclophosphamide, venetoclax, selinexor, and panobinostat.

Results

Patient Characteristics
  • A total of 157 patients with RRMM received DARZALEX-based retreatment, with a majority of patients receiving combination therapy for DARZALEX-based treatment and retreatment.
    • Of these, 32% of patients received DARZALEX monotherapy in treatment and 4% of patients in retreatment.
  • Of the 119 patients who were DARZALEX-refractory, 100 were DARZALEX-refractory at the start of DARZALEX-based retreatment.
  • The baseline patient characteristics in the DARZALEX retreatment cohort are summarized in Table: Key Baseline Patient Characteristics.

Key Baseline Patient Characteristics3
Characteristics
DARZALEX-Retreated Patients (N=157)
Age, median-years (IQR)
67 (60-74)
Sex, female/male, %
48/52
Race, n (%)
   White
111 (71)
   Black
27 (17)
   Asian
9 (6)
   Other/unknown
9 (6)
ISS disease stage, n/n (%)
   I
51/113 (45)
   II
44/113 (39)
   III
18/113 (16)
   Unknown
44
Cytogenetic risk
   Standard risk, n/N (%)
86/128 (67)
   High riska, n/N (%)
42/128 (33)
Prior lines of therapy at treatment (IQR)
2 (1-3)
Prior lines of therapy at retreatment (IQR)
4 (3-5)
Abbreviations: HRCA, high-risk cytogenetic abnormality; IQR, interquartile range; ISS, International Staging System.
aHRCAs are defined as one or more of the following: 1q+, del(1p), t(4;14), t(14;16), t(14;20),
del(17p)/monosomy 17.
Efficacy
  • At a median follow-up duration of 53.9 months (95% confidence interval [CI],
    48.3-60.1), the median PFS and OS in the DARZALEX retreatment cohort were 10.8 months (95% CI, 8.48-16.5) and 47.4 months (95% CI, 41.5-not reached [NR]), respectively.
  • Efficacy in the treatment vs retreatment cohort is summarized in Table: Efficacy in the DARZALEX Treated vs Retreated Cohort.

Efficacy in the DARZALEX Treated vs Retreatment Cohort3
Parameter, %
DARZALEX Treated
DARZALEX Retreated
ORR
52
70
   sCR/CR
3
6
   ≥VGPR
16
35
   VGPR
13
29
   PR
36
35
Abbreviations: CR, complete response; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.

Retrospective Chart Review in Patients with RRMM Retreated with DARZALEX

Abdallah et al (2023)4 conducted a single-center, retrospective, chart review to analyze the efficacy and safety of retreatment with DARZALEX in patients with RRMM who were refractory to DARZALEX, and compared the response data after retreatment with the response data after the first DARZALEX-based line of therapy.

Study Design/Methods

  • Key inclusion criteria: Patients with RRMM who were initially naïve to DARZALEX or any other anti-cluster of differentiation 38 (CD38) therapy and relapsed after receiving their first line of DARZALEX-based treatment.
  • DARZALEX-refractory patients were retreated with a DARZALEX based regimen.
  • Results are summarized as a comparison of the outcomes reported after the first line of DARZALEX treatment (designated as DARZALEX-naïve cohort) vs the current line of DARZALEX retreatment (designated as DARZALEX retreatment cohort).

Results

Patient Characteristics
  • Overall, 43 patients were included (single-agent DARZALEX treatment, n=12; DARZALEX-based combination treatment, n=31). The baseline patient and disease characteristics of patients in the DARZALEX retreatment cohort are summarized in Table: Key Baseline Patient and Disease Characteristics.
  • The median duration of follow-up after DARZALEX retreatment was 19.5 months
    (IQR, 10.3-25.93).
  • Patients had received a median of 2 lines of therapy (range, 1-8) before their first DARZALEX-based regimen and a median of 4 lines of therapy (range, 2-14) before the current DARZALEX-based retreatment.
  • The DARZALEX-based regimens received by both the cohorts are summarized in Table: Regimens Received During DARZALEX Treatment.
  • The treatment characteristics of the DARZALEX retreatment cohort are summarized in Table: Treatment Characteristics of Patients Retreated with DARZALEX-Based Regimen.

Key Baseline Patient and Disease Characteristics4
Characteristic
N=43
Median age (range), years
65 (41-83)
Sex, n
   Male
20
   Female
23
MM paraprotein type, n (%)
   IgG
29 (67)
   Non-IgG
4 (9)
   Light chain
10 (23)
R-ISS stage, n (%)
   III
20 (47)
   II
10 (23)
   I
10 (23)
   Unknown
3 (7)
Cytogenetic risk, n (%)
   High risk
18 (42)
   Standard risk
25 (58)
   Extramedullary disease
10 (23)
Median time to retreatment from initial myeloma diagnosis (range), months
47 (7-213)
Median time to retreatment from the end of the first DARZALEX-based line of therapy (range), months
1 (0.25-39)
Abbreviations: IgG, immunoglobulin G; MM, multiple myeloma; R-ISS, Revised International Staging System.

Regimens Received During DARZALEX Treatment4
Type of Treatment, n (%)
DARZALEX-Naïve (n=43)
DARZALEX Retreated (n=43)
D-Pd
15 (35)
19 (44)
D-Kd
2 (5)
17 (40)
D-Vd
9 (21)
6 (14)
D-Rd
1 (2)
1 (2)
DARZALEX/Nivolumaba
4 (9)
0
DARZALEX monotherapy
12 (28)
0
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; D-Pd, DARZALEX + pomalidomide + dexamethasone; D-Rd, DARZALEX + lenalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone.
aPatients from a clinical trial were enrolled.

Treatment Characteristics of Patients Retreated with DARZALEX-Based Regimen4
Characteristic, n (%)
All Patients Receiving Retreatment (n=43)
Patients Retreated with D-Pd (n=19)
Patients Retreated with D-Kd (n=17)
Patients Retreated with D-Vd (n=6)
PI exposure
43 (100)
19 (100)
17 (100)
6 (100)
PI refractory
40 (93)
19 (100)
15 (88)
6 (100)
Bortezomib exposure
42 (98)
18 (95)
17 (100)
6 (100)
Bortezomib refractory
36 (84)
15 (79)
15 (88)
5 (83)
Carfilzomib exposure
20 (47)
10 (53)
4 (24)
6 (100)
Carfilzomib refractory
20 (47)
10 (53)
4 (24)
6 (100)
IMiD exposure
41 (95)
18 (95)
17 (100)
5 (83)
IMiD refractory
36 (84)
16 (84)
15 (88)
5 (83)
Lenalidomide exposure
41 (95)
18 (95)
17 (100)
5 (83)
Lenalidomide refractory
34 (79)
15 (79)
14 (82)
5 (83)
Pomalidomide exposure
26 (60)
7 (37)
14 (83)
5 (83)
Pomalidomide refractory
23 (53)
5 (26)
13 (76)
5 (83)
DARZALEX exposure
43 (100)
19 (100)
17 (100)
6 (100)
DARZALEX refractory
43 (100)
19 (100)
17 (100)
6 (100)
Double refractory (IMiD+PI)
34 (79)
15 (79)
14 (82)
5 (83)
Triple Class refractory
33 (77)
14 (74)
14 (82)
5 (83)
Penta-refractory
9 (21)
3 (16)
3 (18)
3 (50)
Post-BCMA exposure
11 (26)
5 (26)
4 (24)
2 (33)
Number of patients who received ASCT before retreatment
32 (74)
14 (73)
14 (82)
4 (67)
Abbreviations: ASCT, autologous stem cell transplant; BCMA, B-cell maturation antigen; D-Kd, DARZALEX + carfilzomib + dexamethasone; D-Pd, DARZALEX + pomalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone; IMiD, immunomodulatory drugs; PI, proteasome inhibitor.
Efficacy
  • Efficacy outcomes in both the cohorts are summarized in Table: Efficacy Outcomes.
  • In the DARZALEX-naïve cohort:
    • The median time to first response was 27 days (range, 15-56).
    • The median duration of response was 12.4 months (95% CI, 5.8-24.8).
    • The median time to relapse or progressive disease (PD) was 6.77 months (95% CI, 4.57-12.97).
    • The ORR was 65% (n=13) in patients with Revised International Staging System (R-ISS) stage III and 65% (n=13) in patients with R-ISS stage I or II.
  • In the DARZALEX retreatment cohort:
    • The median time to first response was 28 days (range, 14-77).
    • Among patients who responded to retreatment, a response to the previous DARZALEX-based therapy was observed in 13 (62%) patients, including 5 (23%) patients previously achieving ≥VGPR and 8 (38%) patients previously achieving PR.
    • Eight (38%) patients who responded to retreatment (≥VGPR, 5% [n=1]; PR, 33% [n=7]) had not responded to the previous DARZALEX-based therapy.
    • Among patients who responded to retreatment, the most common regimen was DARZALEX in combination with pomalidomide and dexamethasone (D-Pd; 52% [n=11]), followed by D-Kd (43% [n=9]) and DARZALEX in combination with bortezomib and dexamethasone (D-Vd; 5% [n=1]).
    • The ORR was 55% (n=11) in patients with R-ISS stage III and 45% (n=9) in patients with R-ISS stage I or II.
    • The median PFS was 7.97 months (95% CI, 5.23-NR).
      • The median PFS was NR among patients with ≥PR and 5.2 months among patients with no response (hazard ratio [HR], 0.17; 95% CI, 0.05-0.58; P=0.0017).
    • The median OS was 32.6 months (95% CI, 19.5-NR).
      • The median OS was NR among patients with ≥PR and 32.6 months in patients with no response (HR, 0.63; 95% CI, 0.18-2.28; P=0.48).

Efficacy Outcomes4
Parameter, n (%)
DARZALEX-Naïve (n=43)
DARZALEX Retreated (n=43)
ORR
28 (65)
21 (49)
sCR
7 (16)
0
≥CR
11 (26)
3 (7)
CR
4 (9)
3 (7)
≥VGPR
16 (37)
6 (14)
VGPR
5 (12)
3 (7)
PR
12 (28)
15 (35)
SD
10 (23)
12 (28)
PD
5 (12)
10 (23)
Abbreviations: CR, complete response; ORR, overall response rate; PD, progressive disease; PR, partial response; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.
Safety
  • TEAEs reported in retreated patients are summarized in Table: Most Common TEAEs in DARZALEX Retreated Patients.
  • No treatment-related deaths were reported.
  • Treatment discontinuations occurred due to congestive heart failure, neutropenia, and thrombocytopenia.

Most Common TEAEs in DARZALEX Retreated Patients4
Event, n (%)
All Retreated Patients (n=43)
D-Pd/D-Rd
(n=20)
D-Kd
(n=17)
D-Vd
(n=6)
All Grades
Grade 3/4
All Grades
Grade 3/4
All Grades
Grade 3/4
All Grades
Grade 3/4
Hematologic
   Lymphopenia
36 (84)
24 (56)
16 (80)
11 (55)
15 (88)
10 (56)
5 (83)
3 (50)
   Anemia
30 (70)
10 (23)
13 (65)
5 (20)
12 (71)
4 (24)
5 (83)
1 (17)
   Leukopenia
28 (65)
11 (26)
15 (75)
8 (40)
9 (53)
2 (12)
4 (67)
1 (17)
   Neutropenia
27 (63)
16 (37)
15 (75)
15 (75)
9 (53)
1 (6)
3 (50)
0 (0)
   Thrombocyto-
   penia
25 (58)
9 (21)
8 (40)
3 (15)
12 (71)
4 (24)
5 (83)
2 (33)
Nonhematologic
   Elevated liver
   enzymes
8 (19)
0 (0)
5 (25)
0 (0)
3 (18)
0 (0)
0 (0)
0 (0)
   Hypertension
5 (12)
0 (0)
1 (5)
0 (0)
4 (24)
0 (0)
0 (0)
0 (0)
   Heart failure
3 (7)
1 (2)
0 (0)
0 (0)
2 (12)
1(6)
0 (0)
0 (0)
   GI symptoms
   (diarrhea,
   nausea,
   vomiting)
3 (7)
0 (0)
1 (5)
0 (0)
1 (6)
0 (0)
1 (17)
0 (0)
   Peripheral
   neuropathy
2 (5)
0 (0)
0 (0)
0 (0)
0 (0)
0 (0)
2 (33)
0 (0)
IRRs
7 (16)a
0 (0)
3 (15)
0 (0)
3 (18)
0 (0)
1 (17)
0 (0)
Abbreviations: D-Kd, DARZALEX + carfilzomib + dexamethasone; D-Pd, DARZALEX + pomalidomide + dexamethasone; D-Rd, DARZALEX + lenalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone; GI, gastrointestinal; IRR, infusion-related reaction; TEAE, treatment-emergent adverse event.
aAll IRRs were of grade 1.

Retrospective Real-World Study of Patients who Discontinued their DARZALEX-Containing IR

Szabo et al (2022)5 conducted a retrospective real-world study that evaluated the life expectancy and clinical outcomes in patients who discontinued their DARZALEX-containing IR.

Study Design/Methods

  • Patients were classified into 4 cohorts based on the IR:
    • D-Vd
    • D-Rd
    • DARZALEX monotherapy (D-mono)
    • DARZALEX in combination with other regimens (D-other)
  • At the date of discontinuation of the IR (T0), patients were classified into 4 cohorts based on drug exposure:
    • Double class exposed (exposed to DARZALEX + 1 other class of drug)
    • Triple class exposed (exposed to DARZALEX + 2 other classes of drugs)
    • Quadruple class exposed (exposed to DARZALEX + 3 other classes of drugs)
    • Alkylator-bortezomib-carfilzomib-DARZALEX-lenalidomide-pomalidomide exposed

Results

Patient Characteristics
  • Overall, 474 patients who discontinued their DARZALEX-containing IR were included in the study. Key baseline characteristics of the included patients are summarized in Table: Key Baseline Patient Characteristics.
  • Median follow-up duration after T0 was 9.2 months (IQR, 1.817.6).

Key Baseline Patient Characteristics5,6
Characteristic
Discontinued IR
(N=474)
Median agea (range), years
66 (31-88)
ISSa, n (%)
   I
34 (21.0)
   II
59 (36.4)
   III
69 (42.6)
ECOG performance statusa, n (%)
   0
170 (39.5)
   1
176 (40.9)
   2
63 (14.7)
   >2
21 (4.9)
Risk status per fluorescence in situ hybridizationb, n (%)
   High risk
96 (26.0)
   Standard risk
273 (74.0)
Prior HDM-ASCT, n (%)
235 (49.6)
Number of lines of therapy before index regimen, median (range)
3 (0-15)
Index regimen, n (%)
   D-Rd
206 (43.5)
   D-mono
152 (32.1)
   D-Vd
63 (13.3)
   D-other
53 (11.2)
Response to index regimen, n (%)
   VGPR or better
146 (30.8)
   PR
135 (28.5)
   MR
34 (7.2)
   SD
70 (14.8)
   PD
57 (12.0)
   Unmeasurable/not available
32 (6.8)
ORR, n (%)
281 (59.3)
Duration of index regimen, median (range), months
5.3 (0.0-41.9)
Time from diagnosis to T0, median (range), years
4.1 (0.1-33.6)
Treatment exposure at T0, n (%)
   Double class exposed
12 (3)
   Triple class exposed
53 (11)
   Quadruple class exposed
350 (74)
   ABCDLP exposed
59 (12)
Abbreviations: ABCDLP, alkylator + bortezomib + carfilzomib + DARZALEX + lenalidomide + pomalidomide; Dmono, DARZALEX monotherapy; D-other, DARZALEX in combination with other regimens; D-Rd, DARZALEX + lenalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone; ECOG, Eastern Cooperative Oncology Group; HDMASCT, high-dose melphalan with autologous stem cell transplantation; IR, index regimen; ISS, International Staging System; MR, minimal response; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease; T0, time of discontinuation of the first DARZALEX-containing line of therapy; VGPR, very good partial response.
aAt the time of diagnosis of multiple myeloma.
bIf assessed more than once, the most recent result before the initiation of DARZALEX treatment is shown. Highrisk aberrations were defined by the presence of either t(4;14), t(14;16) or del17p, each detected with a cutoff of 10% according to national standards for cytogenetic evaluation.

Most Common Regimens Used at P16
Patient Cohort
Regimen, n [%]
Overall
D-Pd (57 [15])
According to IR
   D-Rd
Kd (20 [13])
   D-mono
D-Pd (41 [32])
   D-Vd
D-Rd (11 [22])
   D-other
Kd (7 [17])
According to drug class exposure at T0
   Double class exposed
D-Pd and DC (2 [25] each)
   Triple class exposed
D-Rd and D-Pd (7 [17] each)
   Quadruple class exposed
D-Pd (38 [14])
   ABCDLP exposed
D-Pd (10 [21])
Based on DARZALEX retreatment
   Yes
D-Pd (57 [30])
   No
Kd (36 [20])
Abbreviations: ABCDLP, alkylator + bortezomib + carfilzomib + DARZALEX + lenalidomide + pomalidomide; DC, DARZALEX + cyclophosphamide; D-mono, DARZALEX monotherapy; D-other, DARZALEX in combination with other regimens; D-Pd, DARZALEX + pomalidomide + dexamethasone; D-Rd, DARZALEX + lenalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone; IR, index regimen; Kd, carfilzomib + dexamethasone; T0, date of discontinuation of the IR.
  • The most common reasons for IR discontinuation were progressive disease (PD; 42%), toxicity (11%), and insufficient response (8%).
Efficacy
  • Median OS in the entire cohort was 12.2 months (95% CI, 9.914.7). Retreatment with DARZALEX was associated with longer OS (HR, 0.59; 95% CI, 0.41-0.87; P=0.006).
  • Survival data are summarized in Table: Median OS According to Patient Cohorts.

Median OS According to Patient Cohorts5
Patient Cohort
Median OS (95% CI), months
P value
According to IR
   D-Rd
11.4 (8.9-16.1)
0.0003
   D-mono
13.3 (10.4-20.7)
   D-Vd
17.8 (12.7-NR)
   D-other
5.8 (1.5-9.2)
According to drug class exposure at T0
   Double class exposed
15.3 (8.9-NR)
0.002
   Triple class exposed
22.5 (11.3-NR)
   Quadruple class exposed
12.6 (10.0-15.8)
   ABCDLP exposed
8.3 (4.1-10.6)
According to DARZALEX retreatment
   Patients with DARZALEX retreatment
23.6 (17.5-NR)
<0.0001
   Patients without DARZALEX retreatment
11.3 (9.5-15.1)
Abbreviations: ABCDLP, alkylator + bortezomib + carfilzomib + DARZALEX + lenalidomide + pomalidomide; CI, confidence interval; D-mono, DARZALEX monotherapy; D-other, DARZALEX in combination with other regimens; D-Rd, DARZALEX + lenalidomide + dexamethasone; D-Vd, DARZALEX + bortezomib + dexamethasone; IR, index regimen; NR, not reached; OS, overall survival; T0, date of discontinuation of the IR.
  • ORR in patients who received retreatment with DARZALEX and in those who did not was 48% and 41%, respectively. Response to retreatment following discontinuation of IR is summarized in Table: Response After the First Retreatment.

Response After the First Retreatment6
Parameter, n (%)
Patients With DARZALEX Retreatment
(n=192)
Patients Without DARZALEX Retreatment
(n=183)
≥VGPR
40 (20.8)
25 (13.7)
PR
52 (27.1)
49 (26.8)
MR
10 (5.2)
15 (8.2)
SD
48 (25.0)
40 (21.9)
PD
29 (15.1)
38 (20.8)
Unknown
13 (6.8)
16 (8.7)
Abbreviations: MR, minimal response; PD, progressive disease; PR, partial response; SD, stable disease; VGPR, very good partial response.
  • PD on DARZALEX-containing IR was reported in 46% patients retreated with DARZALEX vs 80% patients treated without DARZALEX.
  • The most frequently used regimen in patients retreated with DARZALEX were D-Pd (n=57 [30%]), D-Rd (n=44 [23%]), and D-Vd (n=22 [12%]).
  • The most frequently used regimen in patients retreated without DARZALEX were carfilzomib-dexamethasone (n=36 [20%]), pomalidomide-dexamethasone (n=22 [12%]), and carfilzomib-pomalidomide-dexamethasone (n=16 [7%]).
  • Of the patients who received a subsequent line of therapy after T0, 192 (51%) were retreated with a DARZALEX-containing regimen in P1.
  • Median time to next treatment was 4.6 months both in patients with and without DARZALEX retreatment.

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 11 June 2025.

 

References

Show
1 Talbot A, Hulin C, Perrot A, et al. Retreatment with Anti-CD38-Based Combinations in Multiple Myeloma in Real-Life: Results from the Emmy Cohort Study. Clinical Lymphoma, Myeloma and Leukemia. 2025.  
2 Souren L, Ihorst G, Greil C, et al. Response to daratumumab-retreatment in patients with multiple myeloma. Ann Hematol. 2025;104(2):1059-1067.  
3 Tan C, Rueda C, Shekarkhand T, et al. Clinical outcomes of retreatment with daratumumab-based regimens in anti-CD38 refractory multiple myeloma. Poster presented at: The American Society of Clinical Oncology [ASCO] Annual Meeting; May 31-June 4, 2024; Chicago, IL.  
4 Abdallah A, Mahmoudjafari Z, Ahmed N, et al. Clinical efficacy of retreatment of daratumumab‐based therapy (D2) in daratumumab‐refractory multiple myeloma. Eur J Haematol. 2023;110(6):626-632.  
5 Szabo AG, Thorsen J, Iversen KF, et al. The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab‐containing line of therapy. Am J Hematol. 2022;97(3):E117-E120.  
6 Szabo A, Thorsen J, Iversen K, et al. Supplement to: The clinical course and life expectancy of patients with multiple myeloma who discontinue their first daratumumab-containing line of therapy. Am J Hematol. 2022;97(3):E117-E120.  
7 Ciardiello A, Korde N, Hultcrantz M, et al. Clinical efficacy of daratumumab (DARA)-based second line therapy after DARA-containing and DARA-free induction therapies in multiple myeloma: A single center experience. Abstract presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022; Chicago, IL.;40(16_suppl).  
8 Atrash S, Thompson-Leduc P, Tai M, et al. Treatment patterns and effectiveness of patients with multiple myeloma initiating Daratumumab across different lines of therapy: a real-world chart review study. BMC Cancer. 2021;21(1):1207.  
9 Nooka A, Joseph N, Kaufman J, et al. Clinical efficacy of daratumumab, pomalidomide, and dexamethasone in patients with relapsed or refractory myeloma: utility of re-treatment with daratumumab among refractory patients. J Traditional Complementary Medicine. 2019;125:2991-3000.  
10 Kim E, Harrington C, Yee A, et al. Practical considerations and role of daratumumab retreatment for relapsed refractory multiple myeloma. Poster presented at: 17th Annual International Myeloma Workshop; September 12-15, 2019; Boston, MA.  
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