Darzalex Faspro (Page 7 of 8)

14.3 Light Chain Amyloidosis

In Combination with Bortezomib, Cyclophosphamide and Dexamethasone

The efficacy of DARZALEX FASPRO with VCd was evaluated in ANDROMEDA (NCT03201965), an open-label, randomized, active-controlled trial. Eligible patients were required to have newly diagnosed light chain (AL) amyloidosis with at least one affected organ, measurable hematologic disease, Cardiac Stage I-IIIA (based on European Modification of Mayo 2004 Cardiac Stage), and NYHA Class I-IIIA. Patients with NYHA Class IIIB and IV were excluded. Patients were randomized to receive bortezomib 1.3 mg/m2 administered subcutaneously, cyclophosphamide 300 mg/m2 (max dose 500 mg) administered orally or intravenously, and dexamethasone 40 mg (or a reduced dose of 20 mg for patients >70 years or body mass index <18.5 or who have hypervolemia, poorly controlled diabetes mellitus or prior intolerance to steroid therapy) administered orally or intravenously on Days 1, 8, 15, and 22 of each 28-day cycle with or without DARZALEX FASPRO 1,800 mg/30,000 units subcutaneously once weekly from weeks 1 to 8, once every 2 weeks from weeks 9 to 24 and once every 4 weeks starting with week 25 until disease progression or a maximum of two years. When DARZALEX FASPRO and dexamethasone were administered on the same day, dexamethasone 20 mg was administered before DARZALEX FASPRO with the remaining dose of dexamethasone administered after DARZALEX FASPRO if applicable. The major efficacy outcome measure was confirmed hematologic complete response (HemCR) rate based on Consensus Criteria as determined by the Independent Review Committee (negative serum and urine immunofixation, involved free light chain level decrease to less than the upper limit of normal, and normal free light chain ratio). Randomization was stratified by Cardiac Stage (European Modification of Mayo 2004 Cardiac Stage) countries that typically offer autologous stem cell transplant (ASCT) for patients with light chain (AL) amyloidosis, and renal function.

A total of 388 patients were randomized: 195 to DARZALEX FASPRO-VCd and 193 to VCd. The median patient age was 64 years (range: 34 to 87 years); 58% were male; 76% White, 17% Asian, and 3% Black or African American; 23% had light chain (AL) amyloidosis Cardiac Stage I, 40% had Stage II, and 37% had Stage IIIA. The median number of organs involved was 2 (range: 1–6) and 66% of patients had 2 or more organs involved. Vital organ involvement was: cardiac 71%, renal 59% and hepatic 8%. The majority (79%) of patients had lambda free light chain disease.

Efficacy results are summarized in Table 24.

Table 24: Efficacy results from ANDROMEDA *
DARZALEX FASPRO-VCd(n=195) VCd(n=193)
VCd=bortezomib-cyclophosphamide-dexamethasone
*
Based on intent-to-treat population
p-value from Cochran Mantel-Haenszel Chi-Squared test.
Major organ deterioration-PFS defined as hematologic progression, major organ (cardiac or renal) deterioration or death
Hematologic complete response (HemCR), n (%) 82 (42%) 26 (13%)
p-value <0.0001
Very good partial response (VGPR), n (%) 71 (36%) 69 (36%)
Partial response (PR), n (%) 26 (13%) 53 (27%)
Hematologic VGPR or better (HemCR + VGPR), n (%) 153 (78%) 95 (49%)
Major organ deterioration progression-free survival , Hazard ratio with 95% CI 0.58 (0.37, 0.92)

The median time to HemCR was 59 days (range: 8 to 299 days) in the DARZALEX FASPRO-VCd arm and 59 days (range: 16 to 340 days) in the VCd arm. The median time to VGPR or better was 17 days (range: 5 to 336 days) in the DARZALEX FASPRO-VCd arm and 25 days (range: 8 to 171 days) in the VCd arm. The median duration of HemCR had not been reached in either arm.

The median follow-up for the study is 11.4 months. Overall survival (OS) data were not mature. A total of 56 deaths were observed [N=27 (13.8%) DARZALEX FASPRO-VCd vs. N=29 (15%) VCd group].

15 REFERENCES

  1. Chapuy, CI, RT Nicholson, MD Aguad, et al., 2015, Resolving the daratumumab interference with blood compatibility testing, Transfusion, 55:1545–1554 (accessible at http://onlinelibrary.wiley.com/doi/10.1111/trf.13069/epdf).

16 HOW SUPPLIED/STORAGE AND HANDLING

DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) injection is a sterile, preservative-free, colorless to yellow, and clear to opalescent solution for subcutaneous use supplied as individually packaged single-dose vials providing 1,800 mg of daratumumab and 30,000 units of hyaluronidase per 15 mL (NDC 57894-503-01).

Store DARZALEX FASPRO vials in a refrigerator at 2ºC to 8ºC (36ºF to 46ºF) in the original carton to protect from light.

Do not freeze or shake.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Hypersensitivity and Other Administration Reactions

Advise patients to seek immediate medical attention for any of the following signs and symptoms of systemic administration-related reactions: itchy, runny or blocked nose; chills, nausea, throat irritation, cough, headache, shortness of breath or difficulty breathing, and blurred vision [see Warnings and Precautions (5.1)].

Cardiac Toxicity in Patients with Light Chain (AL) Amyloidosis

Advise patients to immediately contact their healthcare provider if they have signs or symptoms of cardiac adverse reactions [see Warnings and Precautions (5.2)].

Neutropenia

Advise patients to contact their healthcare provider if they have a fever [see Warnings and Precautions (5.3)].

Thrombocytopenia

Advise patients to contact their healthcare provider if they have bruising or bleeding [see Warnings and Precautions (5.4)].

Embryo-Fetal Toxicity

Advise pregnant women of the potential hazard to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5), Use in Specific Populations (8.1, 8.3)].

Advise females of reproductive potential to avoid becoming pregnant during treatment with DARZALEX FASPRO and for 3 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

Advise patients that lenalidomide, thalidomide and pomalidomide have the potential to cause fetal harm and have specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm. Lenalidomide, thalidomide and pomalidomide are only available through a REMS program [see Use in Specific Populations (8.1, 8.3)].

Interference with Laboratory Tests

Advise patients to inform their healthcare provider, including personnel at blood transfusion centers, that they are taking DARZALEX FASPRO, in the event of a planned transfusion [see Warnings and Precautions (5.6)].

Advise patients that DARZALEX FASPRO can affect the results of some tests used to determine complete response in some patients and additional tests may be needed to evaluate response [see Warnings and Precautions (5.7)].

Hepatitis B Virus (HBV) Reactivation

Advise patients to inform healthcare providers if they have ever had or might have a hepatitis B infection and that DARZALEX FASPRO could cause hepatitis B virus to become active again [see Adverse Reactions (6.1)].

Manufactured by:
Janssen Biotech, Inc.
Horsham, PA 19044, USA U.S. License Number 1864

For patent information: www.janssenpatents.com

© 2021 Janssen Pharmaceutical Companies

PATIENT INFORMATIONDARZALEX (Dar’-zah-lex) FASPRO® (Fas-pro)(daratumumab and hyaluronidase-fihj)injection, for subcutaneous use
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 11/2022
DARZALEX FASPRO may be used with other medicines called lenalidomide, thalidomide or pomalidomide. You should also read the Medication Guide that comes with lenalidomide, thalidomide or pomalidomide if you use DARZALEX FASPRO with these medicines.
What is DARZALEX FASPRO? DARZALEX FASPRO is a prescription medicine used to treat adult patients with multiple myeloma:
  • in combination with the medicines bortezomib, melphalan and prednisone, in people with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant).
  • in combination with the medicines lenalidomide and dexamethasone in people with newly diagnosed multiple myeloma who cannot receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant) and in people whose multiple myeloma has come back or did not respond to treatment, who have received at least one prior medicine to treat multiple myeloma.
  • in combination with the medicines bortezomib, thalidomide, and dexamethasone in newly diagnosed people who are eligible to receive a type of stem cell transplant that uses their own stem cells (autologous stem cell transplant).
  • in combination with the medicines bortezomib and dexamethasone in people who have received at least one prior medicine to treat multiple myeloma.
  • in combination with the medicines pomalidomide and dexamethasone in people who have received at least one prior medicine including lenalidomide and a proteasome inhibitor to treat multiple myeloma.
  • in combination with the medicines carfilzomib and dexamethasone in people whose multiple myeloma has come back or did not respond to treatment who have received one to three prior medicines to treat multiple myeloma.
  • alone in people who have received at least three prior medicines, including a proteasome inhibitor and an immunomodulatory agent, or did not respond to a proteasome inhibitor and an immunomodulatory agent.
DARZALEX FASPRO is a prescription medicine also used in combination with the medicines bortezomib, cyclophosphamide and dexamethasone in patients with newly diagnosed light chain (AL) amyloidosis.It is not known if DARZALEX FASPRO is safe and effective in children.
Do not receive DARZALEX FASPRO if you have a history of a severe allergic reaction to daratumumab, hyaluronidase or any of the ingredients in DARZALEX FASPRO. See the end of this leaflet for a complete list of ingredients in DARZALEX FASPRO.
Before you receive DARZALEX FASPRO, tell your healthcare provider about all of your medical conditions, including if you:
  • have a history of breathing problems.
  • have had shingles (herpes zoster).
  • have ever had or might now have a hepatitis B infection as DARZALEX FASPRO could cause hepatitis B virus to become active again. Your healthcare provider will check you for signs of this infection before, during and for some time after treatment with DARZALEX FASPRO. Tell your healthcare provider right away if you get worsening tiredness or yellowing of your skin or white part of your eyes.
  • are pregnant or plan to become pregnant. DARZALEX FASPRO may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with DARZALEX FASPRO.
    • Females who are able to become pregnant should use an effective method of birth control (contraception) during treatment and for 3 months after your last dose of DARZALEX FASPRO. Talk to your healthcare provider about birth control methods that you can use during this time.
    • Before starting DARZALEX FASPRO in combination with lenalidomide, thalidomide or pomalidomide, females and males must agree to the instructions in the lenalidomide, thalidomide or pomalidomide REMS program.
      • The lenalidomide, thalidomide and pomalidomide REMS have more information about effective methods of birth control, pregnancy testing, and blood donation for females who can become pregnant.
      • For males who have female partners who can become pregnant, there is information in the lenalidomide, thalidomide and pomalidomide REMS about sperm donation and how lenalidomide, thalidomide and pomalidomide can pass into human semen.
  • are breastfeeding or plan to breastfeed. It is not known if DARZALEX FASPRO passes into your breast milk. You should not breastfeed during treatment with DARZALEX FASPRO. Talk to your healthcare provider about the best way to feed your baby during treatment with DARZALEX FASPRO.
Before you receive DARZALEX FASPRO for light chain (AL) amyloidosis, tell your healthcare provider if you have a history of heart problems. DARZALEX FASPRO should not be used in light chain (AL) amyloidosis patients with highly advanced heart disease outside of clinical trials.Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
How will I receive DARZALEX FASPRO?
  • DARZALEX FASPRO may be given alone or together with other medicines used to treat multiple myeloma.
  • DARZALEX FASPRO will be given to you by your healthcare provider as an injection under the skin, in the stomach area (abdomen).
  • DARZALEX FASPRO is injected over 3 to 5 minutes.
  • Your healthcare provider will decide the time between doses as well as how many treatments you will receive.
  • Your healthcare provider will give you medicines before each dose of DARZALEX FASPRO and after each dose of DARZALEX FASPRO to help reduce the risk of serious allergic reactions and other reactions due to release of certain substances by your body (systemic).
If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.
What are the possible side effects of DARZALEX FASPRO?DARZALEX FASPRO may cause serious reactions, including:
  • Serious allergic reactions and other severe injection-related reactions. Serious allergic reactions and reactions due to release of certain substances by your body (systemic) that can lead to death, can happen with DARZALEX FASPRO. Your healthcare provider may temporarily stop or completely stop treatment with DARZALEX FASPRO if you have a serious reaction. Tell your healthcare provider or get medical help right away if you get any of these symptoms during or after an injection of DARZALEX FASPRO.
  • shortness of breath or trouble breathing
  • dizziness or lightheadedness (hypotension)
  • cough
  • wheezing
  • heart beating faster than usual
  • low oxygen in the blood (hypoxia)
  • throat tightness or irritation
  • runny or stuffy nose
  • headache
  • itching
  • high blood pressure
  • eye pain
  • nausea
  • vomiting
  • chills
  • fever
  • chest pain
  • blurred vision
  • Injection site reactions. Skin reactions at or near the injection site (local), including injection site reactions, can happen with DARZALEX FASPRO. Symptoms at the site of injection may include itching, swelling, bruising, pain, rash, bleeding, or redness of the skin. These reactions sometimes happen more than 24 hours after an injection of DARZALEX FASPRO.
  • Heart problems in people with light chain (AL) amyloidosis. Heart problems, in some cases fatal, have occurred. Your healthcare provider will monitor you closely during treatment with DARZALEX FASPRO. Call your healthcare provider right away if you get any of the following symptoms: chest pain, feeling faint, swollen legs, shortness of breath, or abnormal heart rhythm.
  • Decreases in blood cell counts. DARZALEX FASPRO can decrease white blood cell counts which help fight infections and blood cells called platelets which help to clot blood. Decreases in blood cell counts are common with DARZALEX FASPRO, but can be severe. Your healthcare provider will check your blood cell counts during treatment with DARZALEX FASPRO. Tell your healthcare provider if you develop fever or have signs of bruising or bleeding.
  • Changes in blood tests. DARZALEX FASPRO can affect the results of blood tests to match your blood type. These changes can last for up to 6 months after your final dose of DARZALEX FASPRO. Your healthcare provider will do blood tests to match your blood type before you start treatment with DARZALEX FASPRO. Tell all of your healthcare providers that you are being treated with DARZALEX FASPRO before receiving blood transfusions.
The most common side effects of DARZALEX FASPRO when used alone include: cold-like symptoms (upper respiratory infection) and decreased red blood cell counts.The most common side effects of DARZALEX FASPRO used in combination therapy include:
  • tiredness
  • nausea
  • diarrhea
  • shortness of breath
  • trouble sleeping
  • headache
  • fever
  • cough
  • muscle spasms
  • back pain
  • vomiting
  • high blood pressure
  • cold-like symptoms (upper respiratory infection)
  • nerve damage causing tingling, numbness, or pain
  • constipation
  • lung infection (pneumonia)
  • swollen hands, ankles, or feet
  • decreased red blood cell counts
These are not all the possible side effects of DARZALEX FASPRO.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of DARZALEX FASPRO. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about DARZALEX FASPRO that is written for health professionals.
What are the ingredients in DARZALEX FASPRO? Active ingredient: daratumumab and hyaluronidase-fihj Inactive ingredients: L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol, and water for injection. Manufactured by: Janssen Biotech, Inc., Horsham, PA 19044 USALicense Number 1864 For patent information: www.janssenpatents.com@2021 Janssen Pharmaceutical CompaniesFor more information, call 1-800-526-7736 or go to www.DARZALEXFASPRO.com.

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