J&J Medical Connect
DARZALEX®

(daratumumab)

This information is intended for US healthcare professionals to access current scientific information about J&J Innovative Medicine products. It is prepared by Medical Information and is not intended for promotional purposes, nor to provide medical advice.

DARZALEX® (daratumumab)

Medical Information

+ Save link

DARZALEX + DARZALEX FASPRO - Use of Montelukast as a Pre-/Post-Medication

Last Updated: 08/09/2024

Overview

DARZALEX for IV use + DARZALEX FASPRO for SC use are not approved by the regulatory agencies for use of montelukast as a pre- or post-infusion medication. Janssen does not recommend the use of DARZALEX or DARZALEX FASPRO in a manner that is inconsistent with the approved labeling.

EAP Study1

  • A multicenter, open-label protocol provided early access to DARZALEX for patients with RRMM (N=348). Administration of pre-infusion dosing of montelukast was allowed at the investigator's discretion.
    • Sixty patients received montelukast as premedication during therapy. Of those, 50 received montelukast 10 mg prior to the first infusion. Patients who received montelukast vs those who did not had a median first infusion duration of 6.7 vs 7.6 hours.
    • IRRs for the first infusion occurred in 38% of patients receiving montelukast vs 59% in those who did not receive montelukast. Respiratory and gastrointestinal symptoms were lower in patients receiving montelukast while chills were observed at a similar rate in both groups.

Retrospective Studies2-4

  • A retrospective study was conducted that evaluated the use of montelukast as a premedication on the incidence of IRRs with DARZALEX infusions (N=73).
    • The incidence of IRRs was lower in patients receiving montelukast (44.4%) compared to those who did not receive montelukast (65.2%); P=0.044. Gastrointestinal symptoms, including abdominal pain, nausea, vomiting, and diarrhea were observed at a similar rate in both groups.
  • Another retrospective study evaluated the use of montelukast as a premedication on the incidence of IRRs with the first infusion of DARZALEX (N=141).
    • The incidence of IRRs for the first infusion was lower in patients who received montelukast (27%) compared with those who did not receive montelukast (45%). Dyspnea occurred in 16% of patients receiving montelukast vs 48% of patients who did not receive montelukast; P=0.0274. Pulmonary, gastrointestinal, and systemic symptoms were observed at a similar rate in both groups.
  • A real-world retrospective study evaluated the safety of DARZALEX FASPRO in patients with newly diagnosed MM and patients with RRMM, irrespective of eligibility for ASCT, as well as in patients with AL amyloidosis (also including patients with severe renal failure and advanced disease) (N=189).
    • All patients received premedication with dexamethasone, chlorphenamine, and acetaminophen. Of them, 161 received montelukast as premedication for IRR prophylaxis.
    • IRR events with the first administration of DARZALEX FASPRO were low (4%), mainly grade 1-2 (3.5%), with only 1 severe IRR grade 3-4 (0.5%). In patients who received montelukast in addition to standard premedication, the incidence of IRRs remained low (3.8% vs 7.6%; OR, 0.43; P=0.4). Grade 1-2 hematological toxicities were observed in 16% of patients, including thrombocytopenia (4%), neutropenia (5%), and lymphopenia (6%).

Clinical Trials5-14

  • Data from the DARZALEX clinical studies (POLLUX, CASTOR, CASSIOPEIA, ALCYONE, MAIA) + DARZALEX FASPRO clinical studies (COLUMBA, PLEIADES, ANDROMEDA) show that montelukast was administered either as a pre- or post-infusion medication and/or given concomitantly; however, no data are available on the efficacy or safety of the combination.

Additional Relevant Literature15-21

  • Other relevant literature describing the use of montelukast as a pre/post-medication have been referenced in the REFERENCES tab in addition to the data summarized within this iPDF.

Note: ASCT, autologous stem cell transplant; EAP, early access treatment protocol; IRR, infusion-related reaction; IV, intravenous; MM, multiple myeloma; OR, odds ratio; RRMM, relapsed or refractory multiple myeloma; SC, subcutaneous.

  • This was a multicenter, open-label study providing early access to DARZALEX treatment designed to collect safety data including IRRs.1
  • Patients were on a 28-day cycle and treated weekly for 8 weeks with DARZALEX 16 mg/kg IV; then every other week for 16 weeks; and then monthly until progression of their disease, diminished clinical benefit, unacceptable toxicity, or end of study.1
  • Pre-infusion medications included: acetaminophen (650-1000 mg), diphenhydramine (25-50 mg), and methylprednisolone (100 mg for infusions 1 and 2, then 60 mg for remaining infusions). Pre-infusion medication was administered approximately 1 hour before dosing.1
    • Administration of pre-infusion dosing of montelukast 10 mg was allowed at the investigator's discretion. This summary is focused on the outcome of patients who received montelukast pre-infusion vs those who did not.
  • Post-infusion medications for 2 days following infusion included: methylprednisolone (20 mg) for all patients and diphenhydramine (25-50 mg), inhaled corticosteroids, and bronchodilators for patients with COPD and asthma.1

Select Inclusion Criteria1:

  • Age ≥ 18 years
  • ECOG performance score 0-2
  • Disease progression within 60 days after prior treatment
  • Double refractory to a PI and immunomodulatory drug or received ≥3 prior therapies that included a PI and immunomodulatory drug

Select Exclusion Criteria1:

  • COPD with FEV1 <50%
  • Uncontrolled asthma or moderate/severe asthma within the past 2 years
  • Cardiac disease, arrhythmia, or clinically significant abnormal ECG
  • Hypersensitivity to monoclonal antibodies
  • Prior exposure to any anti-CD38 monoclonal antibody
  • CrCl ≤20 mL/min/1.73 m2

Assessment1:

  • The NCI-CTCAE was used to assess safety for patients who received ≥1 DARZALEX dose and grade ≥3 TEAEs, SAEs, and AEs of special interest (bronchospasm, IRR, and laboratory abnormalities) were noted.
  • A total of 348 patients received ≥1 DARZALEX dose and were included in the analysis. Most patients were White (72%) and male (56%) with a baseline ECOG performance score of 0-1 (84%).1
  • The median (range) duration of treatment was 1.9 (0.03-6.01) months and the median number (range) of DARZALEX infusions received was 8 (1-17).1

Baseline Characteristics1

Patient Characteristic N=348
Age, median years (range) 65 (27-94)
Male, n (%) 193 (56)
Race, n (%)
White 251 (72)
Black or African American 59 (17)
Unknown or not reported 26 (8)
Asian 7 (2)
Othera 3 (1)
Multiple 2 (1)
Median weight, kg (range) 78 (43-189)
ECOG performance status, n (%)
0 90 (26)
1 201 (58)
2 57 (16)
Median duration of infusions, hoursb (range)
First infusion 7.4 (1.0-24.0)
Second infusion 4.4 (2.9-16.3)
All subsequent infusions 3.5 (0.8-26.1)

aDoes not include American Indian, Alaska Native, Native Hawaiian, or other Pacific Islander.
bDuration of infusion accounts for time of actual infusion, including any interruption.

  • Fifty-six percent of patients experienced an IRR.1
  • Overall, 60 patients received montelukast pretreatment and 288 patients did not. IRRs occurred at a greater frequency in patients who did not receive montelukast pretreatment. Likewise, 2% of the montelukast pre-treated cohort experienced grade 3/4 IRRs compared to 9% of the cohort that did not receive this pre-treatment; 4% and 11% of patients experienced gastrointestinal symptoms, respectively. Fourteen percent of patients in both groups experienced chills. Respiratory or thoracic symptoms were the most common IRRs.1
  • The median duration (range) of the first DARZALEX infusion was 6.7 (1.0-10.7) hours vs 7.6 (1.4-24.0) hours in montelukast pretreated vs no montelukast pretreated patients.1

Summary of Patients With Infusion Reactions1

Event, % All Patients
(n=348)		 Montelukast Pre-treated
(n=60)		 No Montelukast
(n=288)
Patients with an infusion reaction 56 33 61
Grade 3/4 8 2 9
First infusiona 56 38 59
Second infusion 2 4 2
All subsequent infusions 2 0 2
Patients with respiratory or thoracic symptoms 31 18 34
Cough 14 8 15
Dyspnea 9 5 9
Throat irritation 6 5 6
Nasal congestion 5 5 5
Wheezing 4 0 5
Bronchospasm 2 0 2

aFifty patients received montelukast prior to the first infusion, of whom 49 received montelukast >30 minutes before the first infusion.

  • A single-center, observational, retrospective chart review was conducted to evaluate the impact of administering montelukast as a premedication on the incidence of IRRs (graded per the NCI-CTCAE version 5) with DARZALEX infusions.2
  • Inclusion criteria: Age ≥18 years with documented MM and received DARZALEX in an outpatient setting2
  • Exclusion criteria: Received DARZALEX in an inpatient setting or DARZALEX FASPRO or had a history of prior DARZALEX infusions.2
  • Patients were divided in 2 groups: Patients who received montelukast 10 mg PO once 30-60 minutes prior to DARZALEX infusions (n=27) and patients who did not receive montelukast (n=46) prior to DARZALEX infusions.2
  • Pre-infusion medications included: Acetaminophen, diphenhydramine, cetirizine, and methylprednisone.2
  • Primary endpoint: Incidence of IRRs in montelukast and no montelukast groups.2
  • Secondary endpoints: IRR symptoms, rescue medication utilization, grade/severity of IRRs, and safety of 90-minute rapid-rate DARZALEX infusions.2
  • Of the 73 patients included in this study, 27 were in the montelukast group and 46 were in the no montelukast group.2
  • Baseline characteristics were similar between both groups.2
  • There were 22 (81.4%) vs 29 (63%) patients in the montelukast vs no montelukast group who received DARZALEX monotherapy.2
  • A total of 27 patients received 90-minute rapid-rate DARZALEX infusions.2

Summary of Patient Baseline Demographics2

Patient Characteristics Montelukast
(n=27) 		No Montelukast
(n=46)
Mean age, years (range) 65 (40-87) 67 (44-89)
Sex
Male, n (%) 20 (74.1) 26 (56.5)
Female, n (%) 7 (25.9) 20 (43.5)
Race, n (%)
Caucasian 24 (88.9) 45 (97.8)
African American 2 (7.4) 1 (2.2)
Other 1 (3.7) 0
Mean DARZALEX dose, mg (range) 1485 (800-2700) 1254 (800-2700)
Other premedications, n (%)
Acetaminophen 27 (100) 46 (100)
Diphenhydramine 25 (92.6) 46 (100)
Cetirizine 2 (7.4) 0
Methylprednisone 27 (100) 46 (100)
Concomitant therapy, n (%)
None 22 (81.4) 29 (63)
Bortezomib 0 4 (8.7)
Carfilzomib 0 3 (6.5)
Pomalidomide 1 (3.7) 0
Cyclophosphamide + bortezomib 1 (3.7) 2 (4.4)
Lenalidomide + carfilzomib 0 3 (6.5)
Dexamethasone + pomalidomide + venetoclax 0 1 (2.2)
Lenalidomide + dexamethasone 1 (3.7) 2 (4.4)
Pomalidomide + dexamethasone 0 1 (2.2)
Bortezomib + dexamethasone 0 1 (2.2)
Lenalidomide + methylprednisolone 1 (3.7) 0
Cyclophosphamide + bortezomib + dexamethasone 1 (3.7) 0
  • Overall, 57.5% (n=42) of patients experienced IRRs.2
  • Incidence of IRRs was higher in the no montelukast group (65.2%; n=30) compared with that in the montelukast group (44.4%; n=12); P=0.044.2
    • Majority of IRRs were grade 2, with 80% (n=24) vs 75% (n=9) of patients in the no montelukast vs montelukast group, respectively.2
  • The most common pulmonary symptom was throat irritation (no montelukast group, 36.7% [n=11]; montelukast group, 16.7% [n=2]).2
  • Gastrointestinal symptoms were similar across both groups.2
  • No grade ≥3 IRRs were reported.2
  • Diphenhydramine was the most common medication used for post-infusion management of IRRs with DARZALEX.2
  • No IRRs were reported for the 27 patients who received rapid-rate 90-minute DARZALEX infusions.2

Most Common IRRs2

Event, n (%) Montelukast
(n=27) 		No Montelukast
(n=46)
Pulmonary IRR symptoms
Throat irritation 2 (16.7) 11 (36.7)
Cough 0 9 (30)
Sinus congestion 1 (8.3) 6 (20)
Dyspnea 0 7 (23.3)
Other IRR symptoms
Gastrointestinal 3 (25) 9 (30)
Hives 1 (8.3) 2 (6.7)
Hypertension 4 (33.3) 4 (13.3)
Flushing 4 (33.3) 8 (26.7)
Pruritus 4 (33.3) 3 (10)
Rigors 2 (16.7) 1 (3.3)
Chills 1 (8.3) 1 (3.3)
Back pain 0 4 (13.3)
Rash 0 2 (6.7)
Chest pain 1 (8.3) 11 (36.7)
Metallic taste 0 1 (3.3)
Tongue swelling 0 1 (3.3)
Blurry vision 1 (8.3) 0
Hypotension 2 (16.7) 0
Fever 1 (8.3) 0
  • A single-center, retrospective chart review was conducted to assess the impact of administering montelukast as a premedication on the incidence of IRRs with the first infusion of DARZALEX.3
  • Inclusion criteria:
    • Age ≥18 years with documented MM, amyloidosis, or plasma cell leukemia3
    • Patients who had received ≥1 dose of DARZALEX3
  • Patients were divided in 2 groups: Patients who received montelukast 10 mg PO once 30-60 minutes prior to the first infusion of DARZALEX (n=94) and patients who did not receive montelukast (n=47) prior to the first infusion of DARZALEX.3
    • Some patients may have received montelukast 10 mg PO at home 12-24 hours prior to the first infusion.
  • Patients were treated with DARZALEX 16 mg/kg IV on day 1 or split-dose DARZALEX 8 mg/kg IV on days 1 and 2.3
    • Montelukast 10 mg PO was administered prior to split-dose DARZALEX infusion.
  • Pre-infusion medications: acetaminophen, diphenhydramine, and a corticosteroid.3
  • Primary endpoint: Incidence of IRRs with the first infusion of DARZALEX.3
  • Secondary endpoints: Incidence of IRR symptoms and rescue medications for IRR management.3
  • A total of 141 patients received DARZALEX infusion treatment.3

Summary of Patient Baseline Demographics3

Patient Characteristics Montelukast
(n=94) 		No Montelukast
(n=47)
Median Age, years (range) 70 (45-86) 71 (44-88)
Sex, male, n (%) 62 (66) 33 (70)
Median weight, kg (range) 77.5 (40.4-177.8) 87 (49.5-173)
Plasma cell disorder, n (%)
MM 86 (91) 46 (98)
Amyloidosis 7 (7) 1 (2)
Plasma cell leukemia 2 (2) 0
Comorbidities, n (%)
Asthma 4 (4) 0
COPD 9 (10) 3 (6)
CHF 6 (6) 4 (8)
Smoking history status, n (%)
Yes 45 (48) 21 (45)
No 49 (52) 26 (55)
Concomitant therapy, n (%)
Bortezomib 14 (15) 0
Carfilzomib 1 (1) 0
Ixazomib 1 (1) 0
Lenalidomide 13 (14) 5 (11)
Pomalidomide 35 (37) 23 (49)
None 32 (34) 19 (40)
Pre-infusion medications, n (%)
Acetaminophen 90 (100) 47 (100)
Diphenhydramine
25 mg 73 (78) 38 (81)
50 mg 21 (22) 9 (19)
Corticosteroid
Dexamethasone <20 mg 12 (13) 5 (11)
Dexamethasone 20 mg 67 (71) 32 (68)
Dexamethasone 40 mg 13 (14) 7 (15)
Methylprednisolone 2 (2) 3 (6)
Initial DARZALEX dose, n (%)
16 mg/kg on day 1 76 (81) 46 (98)
8 mg/kg on days 1 and 2 18 (19) 1 (2)
  • Overall, 33% (n=46) of patients experienced an IRR with the first infusion of DARZALEX.3
  • Incidence of IRRs in patients who received montelukast as a premedication was 27% (n=25) and in patients who did not receive montelukast was 45% (n=21); P=0.0371.3
  • Diphenhydramine was the most common medication used for post-infusion management of IRRs with DARZALEX (n=40; 87%).3
  • Patients who did not receive montelukast as a premedication and experienced IRRs received more corticosteroids (95% vs 52%; P=0.0022) and albuterol (57% vs 4%; P=0.0001) compared with those who received montelukast as rescue interventions for IRRs.3

Incidence of IRRs With First DARZALEX Administration3

Event, n (%) Montelukast
(n=94) 		No Montelukast
(n=47)
P-value
IRRs 25 (27) 21 (45) 0.0371
IRR symptoms
Pulmonary 15 (60) 17 (81) 0.1988
Gastrointestinal 7 (28) 2 (10) 0.1506
Systemic 15 (60) 12 (57) 1.0
Pulmonary IRR symptoms
Cough 7 (28) 8 (38) 0.5376
Dyspnea 4 (16) 10 (48) 0.0274
Throat irritation 7 (28) 7 (33) 0.7553
Sinus congestion 4 (16) 6 (29) 0.4748
Systemic IRR symptoms
Chills 5 (20) 4 (19) 1.0
Rigors 4 (16) 1 (5) 0.3566
Back pain 1 (4) 2 (10) 0.585
Hives 2 (8) 1 (5) 1.0
Chest pain/tightness 8 (32) 5 (24) 0.7437
Hypertension 1 (4) 3 (14) 0.318
  • A multicenter, retrospective, real-world study was conducted to evaluate the safety of DARZALEX FASPRO in patients with newly diagnosed MM and patients with RRMM, regardless of their eligibility for ASCT.4
  • Inclusion criteria4:
    • Age ≥18 years with diagnosis of MM or AL amyloidosis (including patients with severe renal failure and advanced disease) per international guidelines
    • Patients who had received ≥1 dose of DARZALEX FASPRO outside clinical trials in absence of previous exposure to the IV formulation
  • DARZALEX FASPRO dosage: Patients were administered DARZALEX FASPRO at a fixed dose of 1800 mg as either a single agent or in combination with standard chemotherapy until progression of disease or unacceptable toxicity.4
  • Premedication:All patients were given premedication with a bolus dose of dexamethasone 20 mg, chlorphenamine 10 mg, and oral acetaminophen 1000 mg. For IRR prophylaxis, 161 (85%) of patients were premedicated with montelukast.4
  • Post medication: Dexamethasone 20 mg was given on the day after the first administration, or as otherwise indicated.4
  • Primary endpoint: Safety of DARZALEX FASPRO, particularly the incidence and severity of IRRs.4
  • Of the total 189 patients, 180 were diagnosed with MM and 9 with AL amyloidosis.4

Key Baseline Characteristics4

Patient Characteristics Total Cohort
(N=189)		 GFR <40
mL/min (n=33)		 P-value
Median Age, years (range) 67 (36-85) 70 (45-85) 0.2
Sex, male/female, n (%) 97 (51)/92 (49) 18 (55)/15 (45) 0.7
Diagnosis, n (%)
MM 189 (95) 33 (100) 0.7
Light chain amyloidosis 9 (5) - -
R-ISS stage, n (%)
I 40 (21) 1 (3) 0.01
II 64 (34) 8 (24) -
III 55 (29) 21 (64) -
Montelukast premedication, n (%) 161 (85) 32 (97) 0.03
First-line therapy, n (%) 123 (65) 21 (64) 0.72
1 prior therapy, n (%) 44 (23) 8 (24) -
≥2 prior therapies, n (%) 22 (12) 4 (12) -
GFR ≥40 mL/min, yes/no, n (%) 156 (83)/33 (17) 33 (100) -
Extramedullary disease, n (%) 28 (15) 4 (12) 0.6
High genetic risk, n (%) 26 (14) 6 (18) 0.48

NOTE: Hyphens indicate blank cells implying values not determined or data not available.

  • Overall, 4% (n=8) of patients experienced an IRR (grade 1-2, 3.5% [n=7]; severe, 0.5% [n=1]) during the first infusion of DARZALEX FASPRO.4
  • Median time for IRR onset was 2.5 hours (range, 1-7 hours). Patients who experienced grade 3-4 IRRs recovered completely after high-dose steroids and antihistamines.4
  • Incidence of IRRs in patients who received montelukast in addition to standard premedication were generally lower (3.8% vs 7.6%; OR, 0.43; P=0.4).4
  • IRRs were not reported in patients with severe renal dysfunction; however, hematological and nonhematological toxicities were observed, particularly in patients treated with DARZALEX FASPRO in combination with chemotherapy.4

Incidence of IRRs During First DARZALEX FASPRO Administration4

Event, n (%) Total (N=189) DARZALEX FASPRO in Combination (n=171) DARZALEX FASPRO Single Agent (n=18) GFR <40 mL/min (n=33)
IRR rate 8 (4) 8 (5) - 0
IRR rates on total 8 (0.4) - - 0
Grade 1-2 7 (3.5) 7 (4) - -
Grade 3-4 1 (0.5) 1 (0.6) - -
Pneumonia
Grade 1-2 4 (2) 4 (2) - 1 (3)
Grade 3-4 4 (2) 4 (2) - 1 (3)
Thrombocytopenia
Grade 1-2 8 (4) 7 (4) 1 (5) 4 (12)
Grade 3-4 - - - -
Neutropenia
Grade 1-2 10 (5) 10 (5) - 4 (12)
Grade 3-4 - - - -
Lymphopenia
Grade 1-2 12 (6) 12 (6) - 5 (15)
Grade 3-4 - - - -
Diarrhea
Grade 1-2 4 (2) 4 (2) - 2 (6)
Grade 3-4 - - - -
CMV reactivation
Grade 1-2 1 (0.5) 1 (0.6) - 1 (3)
Grade 3-4 - - - -
  • The effects of several patient, disease, and treatment-related characteristics on IRR incidence were examined using univariate logistic regression analysis.4
  • Significant correlation with extramedullary disease (OR, 6.37; 95% CI, 1.49-27.2; P=0.01) and high-risk cytogenetic disease (OR, 6.87; 95% CI, 1.60-29.4; P=0.009) was observed.4

Univariate Logistic Regression Analysis of IRR Incidence4

Variable OR 95% CI P-value
Sex, female 0.62 0.14-2.67 0.52
Age, years 0.98 0.93-1.05 0.68
Heavy chain IgG 1.34 0.26-6.9 0.72
Light chain lambda 0.56 0.11-2.9 0.50
High-risk MM 6.87 1.60-29.4 0.009
β2-microglobulin levels 0.91 0.63-1.30 0.60
Albumin levels 1.11 0.34-3.60 0.83
LDH levels 0.99 0.99-1.01 0.78
GFR <40 mL/min - - 0.99
Anemia 0.83 0.55-3.6 0.74
Hypercalcemia 0.59 0.07-5.00 0.63
Osteolytic lesions 1.16 0.22-5.97 0.85
Extramedullary disease 6.37 1.49-27.2 0.01
Bone marrow plasma cells ≥60% 1.2 0.22-6.41 0.83
Montelukast premedication 0.5 0.09-2.62 0.41
Weight >65 kg 1.41 0.27-7.22 0.67
DARZALEX FASPRO not as first-line therapy 1.9 0.46-7.93 0.36
DARZALEX FASPRO as single agent - - 0.99
AL amyloidosis - - 0.99
  • Multivariate logistic regression analysis also showed significant association with high-risk cytogenetic disease (OR, 16.36; 95% CI, 2.44-109.73; P=0.005) and extramedullary disease (OR, 12.25; 95% CI, 1.95-76.72; P=0.007).4

Multivariate Logistic Regression Analysis of IRR Incidence4

Variable OR 95% CI P-value
High-risk MM 16.36 2.44-109.73 0.005
Extramedullary disease 12.25 1.95-76.72 0.007
Montelukast premedication 0.43 0.06-2.97 0.39
DARZALEX FASPRO not as first-line therapy 1.63 0.34-7.59 0.53
  • POLLUX (MMY3003; clinicaltrials.gov identifier: NCT02076009) was a phase 3, randomized, open-label, active-controlled, multicenter study that evaluated the safety and efficacy of D-Rd vs Rd in patients with RRMM (N=569).5 An updated result of this study, which evaluated the efficacy and safety of D-Rd vs Rd after a median follow-up of 79.7 months, has been reported.22
    • Use of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) as a pre-infusion medication was optional on C1D1 and was given approximately 1 hour prior to DARZALEX infusion. If necessary, PO pre-infusion medication was administered outside of the clinic 1 to 3 hours prior on the day DARZALEX infusion.10
    • Use of montelukast (or equivalent) as a post-infusion medication was considered for patients receiving DARZALEX who had higher risk of respiratory complications (eg, patients with mild asthma or patients who had FEV1 <80% during the study without any medical history).10
    • Concomitant medication use of montelukast was allowed. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • A total of 1 patient in the Rd arm received montelukast concomitantly.10
  • A total of 6 patients in the D-Rd arm received montelukast as a pre-dose medication.10

Montelukast as a Pre-dose Medication and Concomitant Medication10

Montelukast Use D-Rd Rd Total
Use as a pre-dose medication
Analysis set: ITT, n 283 - -
Number of patients, n (%) 6 (2.1) - -
Concomitant medication use
Analysis set: Safety, n 286 283 569
Number of patients, n (%) 0 1 (0.4) 1 (0.2)
  • CASTOR (MMY3004; clinicaltrials.gov identifier: NCT02136134) was a phase 3, open-label, randomized, multicenter, active-controlled study that evaluated the safety and efficacy of D-Vd compared with Vd alone in patients with RRMM (N=498).3 Updated efficacy and safety results with a median follow-up of 72.6 months have been reported.23
    • Use of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) as a pre-infusion medication was optional on C1D1 and was given approximately 1 hour prior to DARZALEX infusion. If necessary, PO pre-infusion medication was administered outside of the clinic 1-3 hours prior to the day of DARZALEX infusion.10
    • Use of montelukast (or equivalent) as a post-infusion medication was considered for patients receiving DARZALEX who had higher risk of respiratory complications (eg, patients with mild asthma or patients who had FEV1 <80% during the study without any medical history).10
    • Concomitant medication use of montelukast was allowed in the study. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • A total of 4 patients in the D-Vd arm received montelukast concurrently.10

Montelukast for Concomitant Medication Use10

Montelukast Use D-Vd Vd Total
Analysis set: ITT, n 251 247 498
Number of patients, n (%) 4 (1.6) 0 4 (0.8)
  • CASSIOPEIA (MMY3006; clinicaltrials.gov identifier: NCT02541383) is an ongoing, open-label, 2-arm, multicenter, phase 3 study, evaluating the safety and efficacy of D-VTd compared with VTd in patients with previously untreated MM who are eligible for high-dose chemotherapy and ASCT. Results from parts 1 and 2 (maintenance treatment) of the CASSIOPEIA study have been reported.5, 12
    • A pre-dose of montelukast 10 mg in the D-VTd arm during the induction and consolidation phases was given prior to C1D1 of DARZALEX infusion and was optional for all other doses.10
      • If the patient was in the D-VTd arm during part 1 of the study, a pre-dose of montelukast 10 mg was given prior to the first infusion and was optional for all other doses of DARZALEX during part 2 of the study.10
      • Montelukast was given up to 3 hours prior to DARZALEX administration.10
    • Post-dose of montelukast was not included in the clinical protocol.10
    • Concomitant medication use of montelukast was allowed in the study. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Results of montelukast administration are summarized in the following table10:

Montelukast as Pre-/Post-dose Medication and for Concomitant Medication Use10

Montelukast Use D-VTd VTd Total
Use as a pre-dose medicationa
Analysis set: Safety, n 536 - -
Number of patients, n (%) 499 (93.1) - -
Use as a post-dose medication
Analysis set: Safety, n 536 - -
Number of patients, n (%) 1 (0.2) - -
Concomitant medication use during the induction/ASCT/consolidation phase
Analysis set: ITT, n 543 542 1085
Number of patients, n (%) 12 (2.2) 2 (0.4) 14 (1.3)

aAccording to the protocol 10 mg of montelukast as pre-infusion medication is required prior to C1D1 of DARZALEX and is optional before all other doses.
  • ALCYONE (MMY3007; clinicaltrials.gov identifier: NCT02195479) is an international, ongoing, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the safety and efficacy of D-VMP compared with administration of VMP alone for the treatment of NDMM in patients who were ineligible for high-dose chemotherapy with ASCT (N=706).8 An updated result of this study, which evaluated the efficacy and safety of D-VMP vs VMP after a median follow-up of 78.8 months, has been reported.24
    • Use of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) as a pre-infusion medication was optional on C1D1 and was given approximately 1 hour prior to DARZALEX infusion. If necessary, PO pre-infusion medication was administered outside of the clinic 1 to 3 hours prior on the day DARZALEX infusion.10
    • Use of montelukast (or equivalent) as a post-infusion medication was considered for patients receiving DARZALEX who have higher risk of respiratory complications (eg, patients with mild asthma or patients who have FEV1 <80% during the study without any medical history).10
    • Concomitant medication use of montelukast was allowed in the study. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Overall, 7 patients (n=3 in the D-VMP arm and n=4 in the VMP arm) received montelukast concurrently.10
  • A total of 15 patients in the D-VMP arm received montelukast as a pre-dose medication.10

Montelukast as a Pre-dose Medication and for Concomitant Medication Use10

Montelukast Use D-VMP VMP Total
Use as a pre-dose medication
Analysis set: ITT, n 346 - -
Number of patients, n (%) 15 (4.3) - -
Concomitant medication use
Analysis set: Safety, n 350 356 706
Number of patients, n (%) 3 (0.9) 4 (1.1) 7 (1.0)
  • MAIA (MMY3008; clinicaltrials.gov identifier: NCT02252172) is an international, phase 3, randomized, open-label, active-controlled, multicenter study evaluating the safety and efficacy of D-Rd compared with Rd in patients with NDMM not eligible for high-dose chemotherapy and ASCT (N=737).13, 25 Updated safety and efficacy results with a median follow-up of 64.5 months have been reported.25
    • The pre-dose medication use of montelukast was at the discretion of the treating physician.10
    • Post-dose of montelukast was not included in the clinical protocol.10
    • Concomitant medication use of montelukast was allowed. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Overall, 15 patients (D-Rd, n=9; Rd, n=6) received montelukast concurrently.10
  • A total of 53 patients in the D-Rd arm received montelukast as a pre-dose medication.10

Montelukast as a Pre-dose Medication and for Concomitant Medication Use10

Montelukast Use D-Rd Rd Total
Use as a pre-dose medication
Analysis set: ITT, n 364 - -
Number of patients, n (%) 53 (14.6) - -
Concomitant medication use
Analysis set: Safety, n 368 369 737
Number of patients, n (%) 9 (2.4) 6 (1.6) 15 (2.0)
  • COLUMBA (MMY3012; clinicaltrials.gov identifier: NCT03277105) is an ongoing, phase 3, randomized, open-label, multicenter, noninferiority study evaluating the efficacy, PK, and IRRs of DARZALEX vs DARZALEX FASPRO in patients with RRMM.9 The primary and final analyses of the efficacy and safety results of the COLUMBA study after a median follow-up of 7.5 and 29.3 months, respectively, have been reported.9, 26
    • Pre-dose administration of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) is optional on C1D1. If necessary, all PO pre-dose medications may be administered outside of the clinic on the day of study drug administration, provided they are started within 1-3 hours before the study drug is administered.10
    • Post-dose of montelukast was not included in the clinical protocol.10
    • Concomitant medication use of montelukast was allowed. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Overall, 14 patients (n=8 in the DARZALEX arm and n=6 in the DARZALEX FASPRO arm) received montelukast concurrently.10
  • A total of 229 patients (n=115 in the DARZALEX arm and n=114 in the DARZALEX FASPRO arm) received montelukast as a pre-dose medication.10
  • A total of 9 patients (n=1 in the DARZALEX arm and n=8 in the DARZALEX FASPRO arm) received montelukast as a post-dose medication.10

Montelukast as a Pre-/Post-dose Medication and for Concomitant Medication Use10

Montelukast Use DARZALEX DARZALEX FASPRO Total
Use as a pre-dose medication
Analysis set: Safety, n 258 260 518
Number of patients, n (%) 115 (44.6) 114 (43.8) 229 (44.2)
Use as a post-dose medication
Analysis set: Safety, n 258 260 518
Number of patients, n (%) 1 (0.4) 8 (3.1) 9 (1.7)
Concomitant Medication Use
Analysis set: ITT, n 258 260 518
Number of patients, n (%) 8 (3.1) 6 (2.3) 14 (2.7)
  • PLEIADES (MMY2040; clinicaltrials.gov identifier: NCT03412565) is an ongoing, phase 2, nonrandomized, open-label, multicenter study evaluating the clinical benefit of DARZALEX FASPRO administered in combination with 4 standard-of-care treatment regimens in patients with MM (N=199). Updated efficacy and safety results of D-VRd (primary analysis), D-VMP, and D-Rd arm at a median follow-up of 3.9 months, 14.3 months, and 14.7 months, respectively, has been reported.11,27,28 Updated efficacy and safety results of D-Kd (primary analysis), D-Rd, and D-VMP arms at a median follow-up of 9.2 months, 25.7 months, and 25.2 months, respectively, has been reported.29 Final results of this study, which evaluated the efficacy and safety of D-Kd arm at a median follow-up of 12.4 months, has been reported.30
    • Pre-dose administration of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) is optional on C1D1 and can be administered up to 24 hours before the injection according to investigator discretion. If necessary, all PO pre-dose medications may be administered outside of the clinic on the day of study drug administration, provided they are started within 1-3 hours before the study drug is administered.10
    • Post-dose medication of montelukast (or equivalent) is considered for patients receiving DARZALEX FASPRO who have higher risk of respiratory complications (eg, patients with mild asthma or patients who have FEV1 <80% during the study without any medical history).10
    • Concomitant medication use of montelukast was allowed. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Overall, 14 patients (n=8 in the D-VRd arm, n=3 in the D-VMP arm, and n=3 in the D-Rd arm) received montelukast concurrently.10
  • A total of 128 patients (n=44 in the D-VRd arm, n=43 in the D-VMP arm, and n=41 in the D-Rd arm) received montelukast as a pre-dose medication.10
  • A total of 2 patients (n=2 in the D-VRd arm) received montelukast as a post-dose medication.10

Montelukast as a Pre-/Post-dose Medication and for Concomitant Medication Use10

Montelukast Use D-VRd D-VMP D-Rd
Use as a pre-dose medication
Analysis set: All treated, n 67 67 65
Number of patients, n (%) 44 (65.7) 43 (64.2) 41 (63.1)
Use as a post-dose medication
Analysis set: All treated, n 67 67 65
Number of patients, n (%) 2 (3.0) 0 0
Concomitant medication use
Analysis set: All treated, n 67 67 65
Number of patients, n (%) 8 (11.9) 3 (4.5) 3 (4.6)
  • ANDROMEDA (AMY3001; clinicaltrials.gov identifier: NCT03201965) is an ongoing, prospective, active-controlled, multicenter, phase 3 study evaluating the efficacy and safety of D-VCd compared to VCd alone in newly diagnosed patients with systemic AL amyloidosis. Primary results of this study have been reported.14 Additionally, updated efficacy and safety results of this study after a median follow-up of 20.3 and 25.8 months have been published.31, 32
    • Pre-dose administration of a leukotriene inhibitor (montelukast 10 mg PO or equivalent) is optional on C1D1 and can be administered up to 24 hours before DARZALEX FASPRO infusion as per investigator discretion. If necessary, PO pre-infusion medications may be administered outside of the clinic on the day of DARZALEX FASPRO treatment, provided they are taken within 3 hours prior to the administration of DARZALEX FASPRO.10
    • Post-infusion dose of leukotriene inhibitor (montelukast or equivalent) should be considered for patients with a high risk of respiratory complications (eg, patients with mild asthma or patients with COPD who have FEV1 <80% at screening or developed FEV1 <80% during the study without any medical history).10
      • Post-infusion dose of leukotriene inhibitor was only required for patients with a high risk of respiratory complications.
    • Concomitant medication use of montelukast was allowed. The rate of use was recorded.10
    • The results presented in the subsequent tab is only limited to montelukast administration.
  • Results of montelukast administration are summarized in the following table10:

Montelukast as a Pre-/Post-dose Medication and for Concomitant Medication Use10

Montelukast Use D-VCd VCd D-Rd
Use as a pre-dose medication
Analysis set: Safety, n 193 - -
No of patients, n (%) 166 (86.0) - -
Use as a post-dose medication
Analysis set: Safety, n 193 - -
Number of patients, n (%) 1 (0.5) - -
Concomitant medication use
Analysis set: Safety, n 193 188 381
Number of patients, n (%) 7 (3.6) 3 (1.6) 10 (2.6)
AE Adverse event Ig Immunoglobulin
AL Amyloid light-chain IRR Infusion-related reaction
ASCT Autologous stem cell transplant ITT Intent-to-treat
C1D1 Cycle 1 day 1 IV Intravenous
CHF Congestive heart failure LDH Lactate dehydrogenase
CI Confidence interval MM Multiple myeloma
CMV Cytomegalovirus NCI-CTCAE National Cancer Institute Common Toxicity Criteria for Adverse Events
COPD Chronic obstructive pulmonary disease NDMM Newly diagnosed multiple myeloma
CrCl Creatinine clearance OS Overall survival
D-Kd DARZALEX FASPRO + carfilzomib + dexamethasone OR Odds ratio
D-Rd DARZALEX/DARZALEX FASPRO + lenalidomide + dexamethasone PK Pharmacokinetic
D-VCd DARZALEX FASPRO + bortezomib + cyclophosphamide + dexamethasone PI Proteasome inhibitor
D-Vd DARZALEX + bortezomib + dexamethasone Rd Lenalidomide + dexamethasone
D-VMP DARZALEX/DARZALEX FASPRO + bortezomib + melphalan + prednisone R-ISS Revised International Staging System
D-VRd DARZALEX FASPRO + bortezomib + lenalidomide + dexamethasone RRMM Relapsed or refractory multiple myeloma
D-VTd DARZALEX + bortezomib + thalidomide + dexamethasone SC Subcutaneous
EAP Early access treatment protocol TEAE Treatment
ECG Electrocardiogram VCd Bortezomib + cyclophosphamide + dexamethasone
ECOG Eastern Cooperative Oncology Group Vd Bortezomib + dexamethasone
FEV1 Forced expiratory volume in 1 second VMP Bortezomib + melphalan + prednisone
GFR Glomerular filtration rate VTd Bortezomib + thalidomide

A literature search of MEDLINE®, Embase®, BIOSIS Previews®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 01 July 2024.

  1. Chari A, Lonial S, Mark TM, et al. Results of an early access treatment protocol of daratumumab in United States patients with relapsed or refractory multiple myeloma. Cancer. 2018;124(22):4342-4349.
  2. Coffman K, Carstens C, Fajardo S. Daratumumab infusion reaction rates pre- and post-addition of montelukast to pre-medications. J Oncol Pharm Pract. 2023;29(2):333-337.
  3. Moore DC, Arnall JR, Thompson D, et al. Evaluation of montelukast for the prevention of infusion-related reactions with daratumumab. Clin Lymphoma Myeloma Leuk. 2020;20(10):e777-e781.
  4. De Novellis D, Fontana R, Palmieri S, et al. Safety of subcutaneous daratumumab in anti-CD38 monoclonal antibody-naïve patients with plasma cell disorders: a multicenter real-life experience. Target Oncol. 2023;18(6):885-892.
  5. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331.
  6. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766.
  7. Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394(10192):29-38.
  8. Mateos MV, Dimopoulos MA, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N Engl J Med. 2018;378(6):518-528.
  9. Mateos MV, Nahi H, Legiec W, et al. Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. Lancet Haematol. 2020;7(5):e370-e380.
  10. Data on File. Daratumumab + daratumumab and hyaluronidase - use of montelukast as a pre-/post medication US-SRSM-3617. 2020.
  11. Chari A, Goldschmidt H, San-Miguel J, et al. Subcutaneous (SC) daratumumab (DARA) in combination with standard multiple myeloma (MM) treatment regimens: an open-label, multicenter phase 2 study (PLEIADES). Oral presentation presented at: 17th International Myeloma Workshop (IMW); September 12-15, 2019; Boston, MA.
  12. Moreau P, Hulin C, Perrot A, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(10):1378-1390.
  13. Facon T, Kumar S, Plesner T, et al. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115.
  14. Kastritis E, Palladini G, Minnema MC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46-58.
  1. Roussel M, Merlini G, Chevret S, et al. A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis. Blood. 2020;135(18):1531-1540.
  2. Hamadeh IS, Reese ES, Arnall JR, et al. Safety and cost benefits of the rapid daratumumab infusion protocol. Clin Lymphoma Myeloma Leuk. 2020;20(8):526-532.e1.
  3. Chng WJ, Lin C, Li X, et al. Phase 2 study of daratumumab in combination with thalidomide and dexamethasone in Asian patients with relapsed/refractory myeloma (RRMM) - interim analysis of a trial by the Asian Myeloma Network (AMN). Blood. 2020;136(suppl 1):21.
  4. Lee R, Ng P, Ng W. A rapid daratumumab infusion protocol: safe and effective. J of Oncol Pharm Pract. 2020;26(Suppl 4):21.
  5. Kastritis E, Roussakis P, Kostopoulos IV. Short daratumumab consolidation in patients with al amyloidosis or LCDD improves complete responses rates and modifies bone marrow microenvironment. Oral presentation presented at: The 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.
  6. Shibayama H, Matsumoto M, Kosugi H, et al. Subcutaneous delivery of daratumumab in Japanese patients with relapsed/ refractory multiple myeloma. Int J Hematol. 2021;113(1):112-121.
  7. Maouche N, Allan J, Thompson L. Feasibility and safety of ninety-minute rapid rate daratumumab in myeloma: a prospective multicenter observational study. Poster presented at: British Oncology Pharmacy Association (BOPA) Symposium; October 9-11, 2021; Virtual.
  8. Dimopoulos MA, Oriol A, Nahi H, et al. Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): a randomized, open-label, phase III trial. [published online ahead of print January 4, 2023]. J Clin Oncol. doi: 10.1200/JCO.22.00940.
  9. Sonneveld P, Chanan-Khan A, Weisel K, et al. Overall survival with daratumumab, bortezomib, and dexamethasone in previously treated multiple myeloma (CASTOR): a randomized, open-label, phase III trial. [published online ahead of print November 22, 2022]. J Clin Oncol. doi: 10.1200/JCO.21.02734.
  10. Mateos MV, San-Miguel J, Cavo M, et al. Daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): updated analysis of the phase 3 ALCYONE study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.
  11. Kumar SK, Moreau P, Bahlis N, et al. Daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM): updated analysis of the phase 3 MAIA study. Poster presented at: 64th American Society of Hematology (ASH) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.
  12. Usmani SZ, Nahi H, Legiec W, et al. Final analysis of the phase III non-inferiority COLUMBA study of subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma. Haematologica. 2022;107(10):2408-2417.
  1. Chari A, Rodriguez-Otero P, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy (PLEIADES): an open-label phase II study. Br J Haematol. 2021;192(5):869-878.
  2. Chari A, Miguel JS, McCarthy H, et al. Subcutaneous daratumumab plus standard treatment regimens in patients with multiple myeloma across lines of therapy: PLEIADES study update. Poster presented at: 61st American Society of Hematology (ASH) Annual Meeting; December 7-10, 2019; Orlando, FL.
  3. Moreau P, Chari A, Haenel M, et al. Subcutaneous daratumumab (DARA SC) plus standard-of-care (SoC) regimens in multiple myeloma (MM) across lines of therapy in the phase 2 PLEIADES study: initial results of the DARA SC plus carfilzomib/dexamethasone (D-Kd) cohort, and updated results for the DARA SC plus bortezomib/melphalan/prednisone (D-VMP) and DARA SC plus lenalidomide/dexamethasone (D-Rd) cohorts. Poster presented at: 62nd American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2020; Virtual.
  4. Moreau P, Chari A, Oriol A, et al. Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS. [published online ahead of print March 07, 2023]. Blood Cancer J. doi:10.1038/s41408-023-00805-x.
  5. Kastritis E, Sanchorawala V, Palladini G. Subcutaneous daratumumab ± bortezomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed light chain amyloidosis: updated results from the phase 3 ANDROMEDA study. Oral presentation presented at: 57th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 4-8, 2021; Virtual.
  6. Comenzo RL, 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: 63rd American Society of Hematology (ASH) Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA/Virtual.