Omidubicel-onlv (Monograph)

Brand name: Omisirge
Drug class: Cellular Therapy

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Omidubicel-onlv is a nicotinamide modified allogeneic hematopoietic progenitor cell therapy.

Uses for Omidubicel-onlv

Omidubicel-onlv has the following uses:

Omidubicel-onlv is indicated for use in adults and pediatric patients 12 years of age and older with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. Omidubicel-onlv has been designated an orphan drug by FDA for enhancement of cell engraftment and immune reconstitution in patients receiving hematopoietic stem cell transplantation.

Omidubicel-onlv was evaluated in an open-label, multicenter, randomized study (NCT02730299) in patients with hematologic malignancies who were treated with omidubicel transplantation or umbilical cord blood (UCB) transplantation following myeloablative conditioning. Efficacy of omidubicel was established based on time to neutrophil recovery following transplantation and the incidence of Grade 2/3 bacterial or Grade 3 fungal infections (based on the Blood and Marrow Transplant Clinical Trials Network [BMT CTN] grading criteria) through Day 100 following transplantation. Median time to neutrophil recovery was 12 and 22 days, and incidence of Grade 2/3 infections was 39 and 60% in the omidubicel and UCB groups, respectively.

Omidubicel-onlv Dosage and Administration

General

Omidubicel-onlv is available in the following dosage form(s) and strength(s):

A single dose consists of:

• a Cultured Fraction (CF): a minimum of 8.0 × 10⁸ total viable cells of which a minimum of 8.7% is CD34+ cells and a minimum of 9.2 × 10⁷ CD34+ cells

• a Non-cultured Fraction (NF): a minimum of 4.0 × 10⁸ total viable cells with a minimum of 2.4 × 10⁷ CD3+ cells

Administration

For IV use only.

Administer by gravity infusion; central venous access is recommended.

Do not use a leukodepleting filter.

Verify patient's identity upon receipt. Do not open the metal cassettes until time of thaw.

Omidubicel requires thawing and dilution with 2 infusion solution bags prior to administration. Thawing should only take place immediately prior to use.

The thawed and diluted Cultured Fraction (CF) bag must be infused first; the infusion time should not exceed 2 hours from the end of dilution to the end of CF infusion. The thawed and diluted NF bag is infused within 1 hour of safely administering the CF infusion; the infusion time should not exceed 1 hour from the end of dilution to the end of infusion.

The rate of infusion should not exceed a maximum of 10 mL per kg per hour.

Administer under the supervision of a physician experienced in treatment of hematologic malignancies, in centers with expertise in hematopoietic stem cell transplants.

Premedicate the patient approximately 30 to 60 minutes prior to infusion.

Dosage

Pediatric Patients

Dosage in Pediatric Patients 12 Years of Age and Older

A single dose consists of a Cultured Fraction (CF) which contains a minimum of 8.0 × 10⁸ total viable cells of which a minimum of 8.7% is CD34+ cells and a minimum of 9.2 × 10⁷ CD34+ cells, and a Non-cultured Fraction (NF) which contains a minimum of 4.0 × 10⁷ total viable cells with a minimum of 2.4 × 10⁷ CD3+ cells.

Adults

Dosage in Adults

A single dose consists of a Cultured Fraction (CF) which contains a minimum of 8.0 × 10⁸ total viable cells of which a minimum of 8.7% is CD34+ cells and a minimum of 9.2 × 10⁷ CD34+ cells, and a Non-cultured Fraction (NF) which contains a minimum of 4.0 × 10⁷ total viable cells with a minimum of 2.4 × 10⁷ CD3+ cells.

Cautions for Omidubicel-onlv

Contraindications

• Known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40, gentamicin, human serum albumin or bovine material.

Warnings/Precautions

Warnings

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of omidubicel. Reactions include bronchospasm, wheezing, angioedema, pruritis and hives. Serious hypersensitivity reactions, including anaphylaxis, may be due to DMSO, residual gentamicin, Dextran 40, human serum albumin (HSA) and bovine material in omidubicel-onlv.

Omidubicel may contain residual antibiotics if the cord blood donor was exposed to antibiotics in utero. Patients with a history of allergic reactions to antibiotics should be monitored for allergic reactions following omidubicel administration.

Infusion Reactions

Infusion reactions occurred following omidubicel infusion, including hypertension, mucosal inflammation, dysphagia, dyspnea, vomiting and gastrointestinal toxicity. Premedication with antipyretics, histamine antagonists, and corticosteroids may reduce the incidence and intensity of infusion reactions.

In patients transplanted with omidubicel-onlv in clinical trials, 47% (55/117) patients had an infusion reaction of any severity. Grade 3-4 infusion reactions were reported in 15% (18/117) patients.

Infusion reactions may begin within minutes of the start of infusion of omidubicel, although symptoms may continue to intensify and not peak for several hours after the completion of the infusion. Monitor patients for signs and symptoms of infusion reactions during and after omidubicel administration. When a reaction occurs, pause the infusion and institute supportive care as needed.

Graft-versus-Host Disease

Acute and chronic GvHD, including life-threatening and fatal cases, occurred following treatment with omidubicel-onlv. In patients transplanted with omidubicel, Grade II-IV acute GvHD was reported in 58% (68/117). Grade III-IV acute GvHD was reported in 17% (20/117) of patients and chronic GvHD occurred in 35% (41/117) of patients. Acute GvHD manifests as maculopapular rash, gastrointestinal symptoms, and elevated bilirubin. Patients treated with omidubicel should receive immunosuppressive drugs to decrease the risk of GvHD, be monitored for signs and symptoms of GvHD, and treated if GvHD develops.

Engraftment Syndrome

Engraftment syndrome may occur because omidubicel is derived from umbilical cord blood. Monitor patients for unexplained fever, rash, hypoxemia, weight gain, and pulmonary infiltrates in the peri-engraftment period. Treat with corticosteroids as soon as engraftment syndrome is recognized to ameliorate symptoms. If untreated, engraftment syndrome may progress to multiorgan failure and death.

Graft Failure

Primary graft failure occurred in 3% (4/117) of patients in omidubicel-onlv clinical trials. Primary graft failure, which may be fatal, is defined as failure to achieve an absolute neutrophil count greater than 500 per microliter blood by Day 42 after transplantation. Immunologic rejection is the primary cause of graft failure. Patients should be monitored for laboratory evidence of hematopoietic recovery.

Malignancies of Donor Origin

Two patients treated with omidubicel-onlv developed post-transplant lymphoproliferative disorder (PTLD) in the second-year post-transplant. PTLD manifests as a lymphoma-like disease favoring non-nodal sites. PTLD is usually fatal if not treated. The etiology is thought to be donor lymphoid cells transformed by Epstein-Barr virus (EBV). Serial monitoring of blood for EBV DNA may be warranted in patients with persistent cytopenias.

One patient treated with omidubicel-onlv developed a donor-cell derived myelodysplastic syndrome (MDS) during the fourth-year post-transplant. The natural history is presumed to be the same as that for de novo MDS. Monitor life-long for secondary malignancies.

In the event that a secondary malignancy occurs, contact Gamida Cell at (844) 477-7478.

Transmission of Serious Infections

Transmission of infectious disease may occur because omidubicel is derived from umbilical cord blood. Disease may be caused by known or unknown infectious agents. Donors are screened for increased risk of infection with human immunodeficiency virus (HIV), human T-cell lymphotropic virus (HTLV), hepatitis B virus (HBV), hepatitis C virus (HCV), T. pallidum, West Nile Virus (WNV), transmissible spongiform encephalopathy (TSE) agents, vaccinia, and Zika virus (for umbilical cord blood collected since March 2016). Donors are also screened for clinical evidence of sepsis, and communicable disease risks associated with xenotransplantation. Maternal blood samples are tested for HIV types 1 and 2, HTLV types I and II, HBV, HCV, T. pallidum, and WNV. There may be an effect on the reliability of the sterility test results if the cord blood donor was exposed to antibiotics in utero. Omidubicel is tested for sterility, endotoxin, and mycoplasma. These measures do not totally eliminate the risk of transmitting these or other transmissible infectious diseases and disease agents.

Testing of maternal and infant donor blood is also performed for evidence of donor infection due to cytomegalovirus (CMV).

Test results may be found on the container label and/or in accompanying records.

Product manufacturing includes bovine-derived reagents. While all animal-derived reagents are tested for animal viruses, bacteria, fungi, and mycoplasma before use, these measures do not eliminate the risk of transmitting these or other transmissible infectious diseases and disease agents.

Transmission of Rare Genetic Diseases

Omidubicel may transmit rare genetic diseases involving the hematopoietic system because it is derived from umbilical cord blood. Cord blood donors have been screened to exclude donors with sickle cell anemia, and anemias due to abnormalities in hemoglobins C, D, and E. Because of the age of the donor at the time cord blood collection takes place, the ability to exclude rare genetic diseases is severely limited.

Specific Populations

Pregnancy

There are no available data with omidubicel use in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with omidubicel-onlv to assess whether it can cause fetal harm when administered to a pregnant woman.

Omidubicel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In the United States (U.S.) general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

There is no information regarding the presence of omidubicel in human milk, the effect on the breastfed infant, and the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omidubicel and any potential adverse effects on the breastfed infant from omidubicel or from the underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy status of females with reproductive potential should be verified. Sexually-active females of reproductive potential should have a pregnancy test prior to starting the conditioning regimen for omidubicel.

See the prescribing information for the medications used for conditioning for information on the need for effective contraception in patients who receive a conditioning regimen.

There are insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with omidubicel.

There are no data on the effect of omidubicel on fertility.

Pediatric Use

The safety and efficacy of omidubicel-onlv have been established in adolescents (12 years to less than 17 years). The efficacy and safety outcomes in Study NCT02730299 suggest consistent efficacy and safety across age groups.

Safety and efficacy of omidubicel-onlv in pediatric patients below the age of 12 have not been established.

Geriatric Use

Clinical studies of omidubicel-onlv did not include patients aged 65 and over; therefore, it cannot be determined whether patients 65 years and over respond differently from younger patients.

Common Adverse Effects

The most common adverse reactions (incidence > 20%) are infections, GvHD, and infusion reaction.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments.

No drug interaction studies have been performed with omidubicel.

Actions

Mechanism of Action

Omidubicel is a nicotinamide (NAM) modified allogeneic hematopoietic progenitor cell therapy derived from cord blood used as an allogeneic stem cell donor source. Omidubicel-onlv is manufactured utilizing a proprietary NAM based technology producing enriched hematopoietic progenitor cells (HPCs).

NAM technology overcomes the induction of accelerated proliferation, differentiation, cellular stress and signaling pathways that are typically activated when HPCs are removed from their natural environment.

Ex-vivo culturing of cord blood derived HPCs in the presence of NAM leads to preservation of their stemness, homing to the bone marrow (BM) and retained engraftment capacity as demonstrated by rapid neutrophil engraftment and multi lineage immune reconstitution as observed in the clinical trials with omidubicel.

Advice to Patients

• Hypersensitivity Reactions: Report immediately any signs and symptoms of hypersensitivity reactions including wheezing, swelling, itching, or hives.

• Infusion Reactions: Report immediately any signs and symptoms of infusion reactions including fever, chills, fatigue, tachycardia, hypoxia, severe nausea, severe vomiting, diarrhea, muscle pain, joint pain, low blood pressure, high blood pressure, or dizziness/lightheadedness.

• Graft-versus-Host-Disease: Report immediately any signs and symptoms suggestive of graft vs host disease, including rash, diarrhea or yellowing of the eyes.

• Engraftment Syndrome: Report immediately any signs and symptoms suggestive of engraftment syndrome including fever, rash, or unexplained weight gain.

• Graft Failure: Advise patients that primary graft failure, which may be fatal, can occur.

• Malignancies of Donor Origin: Advise patients of the need to contact Gamida Cell at (844)-477-7478 if they are diagnosed with a secondary malignancy after treatment with omidubicel.

• Transmission of Serious Infections: Advise patients of the risk of transmission of infectious disease.

• Transmission of Rare Genetic Diseases: Advise patients of the risk of transmission of rare genetic diseases.

Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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