Demonstrated Safety Profile (DRd)

Primary Safety Analysis

Frontline DARZALEX^® + Rd provides a demonstrated safety profile¹*

Discontinuation rates due to any adverse event: 7% with DRd vs 16% with Rd²

Infusion-related reactions (IRRs) with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4¹
IRRs of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion¹
Most IRRs occurred during the first infusion¹

DRd=DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d); IRR=infusion-related reaction; Rd=lenalidomide (R) + dexamethasone (d)

^*Median duration of study treatment was 25.3 months (range: 0.1–40.44 months) in the DRd group and 21.3 months (range: 0.03–40.64 months) in the Rd group.¹

^†Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in DARZALEX^® + Rd arm, were headache, urinary tract infection, hyperglycemia, hypocalcemia, vomiting, chills, paresthesia, and hypertension.¹

Most frequent adverse reactions reported in ≥10% of patients and with at least 5% greater frequency in DARZALEX^® + Rd arm^1†

Discontinuation rates due to any adverse event: 7% with DRd vs 16% with Rd²

Infusion-related reactions (IRRs) with DRd occurred in 41% of patients; 2% were Grade 3 and <1% were Grade 4¹
IRRs of any grade or severity may require management by interruption, modification, and/or discontinuation of the infusion¹
Most IRRs occurred during the first infusion¹

Most frequent hematologic laboratory abnormalities¹

Most frequent hematologic laboratory abnormalities, graph

Most frequent hematologic laboratory abnormalities for DRd and Rd, graph

DRd=DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d); Rd=lenalidomide (R) + dexamethasone (d)

^*Median duration of study treatment was 25.3 months (range: 0.1–40.44 months) in the DRd group and 21.3 months (range: 0.03–40.64 months) in the Rd group.¹

^†Adverse reactions that occurred with a frequency of ≥10% and <20%, and with at least a 5% greater frequency in DARZALEX^® +Rd arm, were headache, urinary tract infection, hyperglycemia, hypocalcemia, vomiting, chills, paresthesia, and hypertension.¹

DRd=DARZALEX FASPRO/DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d).

First dose of the every-2-week dosing schedule is given at Week 9. First dose of the every-4-week dosing schedule is given at Week 25.^1,2

*See the Dosage and Administration section of the full Prescribing Information for more detail. When DARZALEX FASPRO^® or DARZALEX^® is administered as part of a combination therapy, see the Prescribing Information for dosage recommendations for the other drugs.

^†Cycle=28 days.

^‡The option of splitting the first dose for DARZALEX^® is not applicable to DARZALEX FASPRO^®.^1,2

You are now viewing a follow-up analysis of the MAIA study. This information is not included in the current Prescribing Information and has not been evaluated by the FDA. TEAEs are reported as observed. The follow-up analysis was not adjusted for multiplicity and conclusions should not be drawn.

Follow-Up Safety Analysis

DARZALEX^® + Rd offers your patients a frontline treatment that’s supported by 64.5 months of safety evaluation³*^†

Cumulative rates of discontinuation due to TEAEs were 15% for DRd vs 24% for Rd³

Cumulative Grade 3/4 infection rates were 43% for DRd vs 30% for Rd^3†
Hematologic adverse events included in the follow-up analyses are investigator-reported TEAEs and not investigator-reported treatment-emergent laboratory abnormalities
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX^® infusion. If ocular symptoms occur, interrupt DARZALEX^® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX^®¹

AE=adverse event; DRd=DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d); FDA=U.S. Food and Drug Administration; Rd=lenalidomide (R) + dexamethasone (d); TEAEs=treatment-emergent adverse events.

^*Median follow-up was 64.5 months.³

^†Safety analysis set. TEAEs are defined as any AE that occurs after the start of the first study treatment through 30 days after the last study treatment; or the day prior to start of subsequent antimyeloma therapy, whichever is earlier; or any AE that is considered related (very likely, probably, or possibly related) regardless of the start date of the event; or any AE that is present at baseline but worsens in toxicity grade or is subsequently considered drug related by the investigator.⁴

Most frequent TEAEs as observed (any grade reported in ≥30% of patients and/or Grade 3/4 reported in ≥20% of patients) in DARZALEX^® + Rd arm^3†

Cumulative rates of discontinuation due to TEAEs were 15% for DRd vs 24% for Rd³

Cumulative Grade 3/4 infection rates were 43% for DRd vs 30% for Rd^3†
Hematologic adverse events included in the follow-up analyses are investigator-reported TEAEs and not investigator-reported treatment-emergent laboratory abnormalities
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX^® infusion. If ocular symptoms occur, interrupt DARZALEX^® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX^®¹

AE=adverse event; DRd=DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d); FDA=U.S. Food and Drug Administration; Rd=lenalidomide (R) + dexamethasone (d); TEAEs=treatment-emergent adverse events.

^*Median follow-up was 64.5 months.³

DRd=DARZALEX FASPRO/DARZALEX^® (D) + lenalidomide (R) + dexamethasone (d).

First dose of the every-2-week dosing schedule is given at Week 9. First dose of the every-4-week dosing schedule is given at Week 25.^1,2

^†Cycle=28 days.

^‡The option of splitting the first dose for DARZALEX^® is not applicable to DARZALEX FASPRO^®.^1,2

Frequency of IRRs (any grade) across clinical trials (N=2,066)¹

37%

of patients had IRRs with the Week 1 infusion

of patients had IRRs with the Week 2 infusion

of patients had IRRs with the subsequent infusions

Less than 1% of patients had a Grade 3/4 IRR at Week 2 or subsequent infusions¹

IRR=infusion-related reaction.

Most IRRs occurred during the first infusion across clinical trials (N=2,066)¹

For 37% of patients, IRRs (any grade) occurred with the Week 1 (16 mg/kg) infusion; for 2% of patients, with the Week 2 infusion; and cumulatively, for 6% of patients with subsequent infusions
Median time to onset of an IRR was 1.5 hours (range: 0–73 hours)
Incidence of infusion modification due to reactions was 36%
DARZALEX^® can cause severe IRRs. Severe IRRs included bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX^® infusion. If ocular symptoms occur, interrupt DARZALEX^® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX^®

Management of IRRs¹

For IRRs of any grade/severity, immediately interrupt the DARZALEX^® infusion and manage symptoms. Management of IRRs may further require reduction in the rate of infusion or treatment discontinuation of DARZALEX^® as outlined in the following table.

IRR=infusion-related reaction.

IRR=infusion-related reaction.

Interference with serological testing¹

DARZALEX^® binds to CD38 found on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test) that may persist for up to 6 months after the last DARZALEX^® infusion.

Type and screen patients before starting DARZALEX^®

Identify any blood samples of patients treated with DARZALEX^®

Identify any blood samples of patients treated with
DARZALEX^®

Inform blood banks when a patient is on DARZALEX^®

Ask patients to tell other healthcare professionals that they’ve taken DARZALEX^®

Neutropenia and thrombocytopenia¹

DARZALEX^® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX^® until recovery of neutrophils or for recovery of platelets.

Interference with determination of complete response¹

Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.

Embryo-fetal toxicity¹

Based on the mechanism of action, DARZALEX^® can cause fetal harm when administered to a pregnant woman. DARZALEX^® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX^® and for 3 months after the last dose.

The combination of DARZALEX^® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.

Brochure on daratumumab and serological testing

Overview of what to know regarding serological testing interference and daratumumab.

Download Brochure

CD38=cluster of differentiation 38; IgG=immunoglobulin G.

Dosing (DARZALEX FASPRO^® + Rd and DARZALEX^® + Rd)

References:

DARZALEX^® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
Facon T, Kumar S, Plesner T, et al; the MAIA Trial Investigators. Daratumumab plus lenalidomide and dexamethasone for untreated myeloma. N Engl J Med. 2019;380(22):2104-2115.
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.) Annual Meeting & Exposition; December 10-13, 2022; New Orleans, LA.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.
Facon T, Kumar SK, Plesner T, et al. Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(11):1582-1596 [supplementary appendix].