Dosage & Administration
The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. (
The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day) on Days 1, 3, and 5 of each treatment cycle, administered as an intravenous infusion after dilution
Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity.
Administer pre-infusion medications and supportive treatment, as appropriate, during infusion.
The recommended dosage regimen for each treatment cycle is described below and in Table 1:
| Day | -4 | -3 | -2 | -1 | 0 | 1 | 2 | 3 | 4 | 5 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Subcutaneous GM-CSF | 250 µg/m2/day | 500 µg/m2/day | |||||||||
| Intravenous DANYELZA | 3 mg/kg/day | 3 mg/kg/day | 3 mg/kg/day | ||||||||
Missed Dose
If a DANYELZA dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 µg /m2/day on the first day of the DANYELZA infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. a total of 5 days with 500 µg /m2/day).
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Danyelza Prescribing Information
WARNING: SERIOUS INFUSION-RELATED REACTIONS and NEUROTOXICITY
- Serious Infusion-Related Reactions: DANYELZA can cause serious infusion reactions, including cardiac arrest, anaphylaxis, hypotension, bronchospasm, and stridor. Premedicate prior to each DANYELZA infusion as recommended. Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity(,
2.2 Premedications and Supportive MedicationsPain Management Prior to and During Infusion[see Warnings and Precautions (5.2)]:- Five days prior to the first infusion of DANYELZA in each cycle, initiate a 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin.
- Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion.
- Consider use of ketamine for pain that is not adequately controlled by opioids.
Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting[see Warnings and Precautions (5.1)and Adverse Reactions (6.1)].- Administer intravenous corticosteroids (e.g. methylprednisolone 2 mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to 2 hours prior to the first infusion of DANYELZA. Administer corticosteroid premedication for subsequent infusions if a severe infusion reaction occurred with the previous infusion or during the previous cycle.
- Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion.
,2.3 Dosage Modifications for Adverse ReactionsThe recommended dosage modifications for DANYELZA for adverse reactions are presented in Table 2.
Table 2. Recommended DANYELZA Dosage Modifications for Adverse Reactions Adverse Reaction SeverityBased on Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 Dosage Modifications Infusion-related reactions [see Warnings and Precautions (5.1)]Grade 2
Defined as:
Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours- Reduce DANYELZA infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1.
- Increase infusion rate gradually to rate prior to the event as tolerated.
Grade 3
Defined as:
Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae- Immediately interrupt DANYELZA infusion and monitor closely until recovery to Grade ≤ 2.
- Resume infusion at 50% of the rate prior to the event and increase infusion rate gradually to infusion rate prior to the event as tolerated.
- Permanently discontinue DANYELZA in patients not responding to medical intervention.
Grade 4 infusion-related reactions Defined as:
Life-threatening consequences: urgent intervention indicated
or
Grade 3 or 4 anaphylaxis- Permanently discontinue DANYELZA.
Pain [see Warnings and Precautions (5.2)]Grade 3 unresponsive to maximum supportive measures - Permanently discontinue DANYELZA.
Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2)]All Grades - Permanently discontinue DANYELZA.
Transverse myelitis [see Warnings and Precautions (5.2)]All Grades - Permanently discontinue DANYELZA.
Peripheral neuropathy [see Warnings and Precautions (5.2)]Motor neuropathy: Grade 2 or greater or
Sensory neuropathy: Grade 3 or 4- Permanently discontinue DANYELZA.
Neurological disorders of the eye [see Warnings and Precautions (5.2)]Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living - Withhold DANYELZA until resolution.
- If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms.
- Permanently discontinue DANYELZA if not resolved within 2 weeks or upon recurrence.
Subtotal or total vision loss - Permanently discontinue DANYELZA.
Prolonged urinary retention [see Warnings and Precautions (5.2)]Persisting following discontinuation of opioids - Permanently discontinue DANYELZA.
Myocarditis [see Warnings and Precautions (5.3)]Grade 2 or 3 - Withhold, reduce dose, or permanently discontinue DANYELZA treatment based on severity and duration.
Grade 4 - Permanently discontinue DANYELZA.
Hypertension [see Warnings and Precautions (5.4)]Grade 3 - Withhold DANYELZA or pause infusion until recovery to ≤ Grade 2.
- Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms.
- Permanently discontinue DANYELZA in patients not responding to medical intervention.
Grade 4 - Permanently discontinue DANYELZA.
Orthostatic hypotension [see Warnings and precautions (5.5)]All grades - Withhold DANYELZA until recovery to Grade ≤ 1.
- If resolved within 1 week, restart DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles.
- If not resolved within 1 week, permanently discontinue DANYELZA.
Other Adverse Reactions [see Adverse Reactions (6.1)]Grade 3 - Withhold DANYELZA until recovery to Grade ≤ 2.
- If resolved to Grade ≤ 2 resume DANYELZA at same rate.
- Permanently discontinue DANYELZA if not resolved to Grade ≤2 within 2 weeks.
Grade 4 - Permanently discontinue DANYELZA.
,4 CONTRAINDICATIONSDANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis
[see Warnings and Precautions (5.1)].History of severe hypersensitivity reaction to naxitamab-gqgk.
).5.1 Serious Infusion-Related ReactionsDANYELZA can cause serious infusion reactions requiring urgent intervention including fluid resuscitation, administration of bronchodilators and corticosteroids, intensive care unit admission, infusion rate reduction or interruption of DANYELZA infusion. Infusion-related reactions included hypotension, bronchospasm, hypoxia, and stridor
[see Adverse Reactions (6.1)].Serious infusion-related reactions occurred in 4% of patients in Study 201 and in 18% of patients in Study 12-230. Infusion-related reactions of any Grade occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Hypotension of any grade occurred in 100% of patients in Study 201 and 89% of patients in Study 12-230.
In Study 201, 68% of patients experienced Grade 3 or 4 infusion reactions; and in Study 12-230, 32% of patients experienced Grade 3 or 4 infusion reactions. Anaphylaxis occurred in 12% of patients and 2 patients (8%) permanently discontinued DANYELZA due to anaphylaxis in Study 201. One patient in Study 12-230 (1.4%) experienced a Grade 4 cardiac arrest 1.5 hours following completion of DANYELZA infusion.
In Study 201, infusion reactions generally occurred within 24 hours of completing a DANYELZA infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion of DANYELZA in each cycle. Eighty percent of patients required reduction in infusion rate and 80% of patients had an infusion interrupted for at least one infusion-related reaction.
Caution is advised in patients with pre-existing cardiac disease, as this may exacerbate the risk of severe hypotension.
Premedicate with an antihistamine, acetaminophen, an H2 antagonist and corticosteroid as recommended
[see Dosage and Administration (2.2)].Monitor patients closely for signs and symptoms of infusion reactions during and for at least 2 hours following completion of each DANYELZA infusion in a setting where cardiopulmonary resuscitation medication and equipment are available.Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity and institute appropriate medical management as needed
[see Dosage and Administration (2.3)and Contraindications (4)]. - Neurotoxicity: DANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome (RPLS). Premedicate to treat neuropathic pain as recommended. Permanently discontinue DANYELZA based on the adverse reaction and severity (,
2.2 Premedications and Supportive MedicationsPain Management Prior to and During Infusion[see Warnings and Precautions (5.2)]:- Five days prior to the first infusion of DANYELZA in each cycle, initiate a 12-day course (Day -4 through Day 7) of prophylactic medication for neuropathic pain, such as gabapentin.
- Administer oral opioids 45-60 minutes prior to initiation of each DANYELZA infusion and additional intravenous opioids as needed for breakthrough pain during the infusion.
- Consider use of ketamine for pain that is not adequately controlled by opioids.
Premedication: Reduce Risk of Infusion-Related Reactions and Nausea/Vomiting[see Warnings and Precautions (5.1)and Adverse Reactions (6.1)].- Administer intravenous corticosteroids (e.g. methylprednisolone 2 mg/kg with maximum dose of 80 mg or equivalent corticosteroid dose) 30 minutes to 2 hours prior to the first infusion of DANYELZA. Administer corticosteroid premedication for subsequent infusions if a severe infusion reaction occurred with the previous infusion or during the previous cycle.
- Administer an antihistamine, an H2 antagonist, acetaminophen and an antiemetic 30 minutes prior to each infusion.
,2.3 Dosage Modifications for Adverse ReactionsThe recommended dosage modifications for DANYELZA for adverse reactions are presented in Table 2.
Table 2. Recommended DANYELZA Dosage Modifications for Adverse Reactions Adverse Reaction SeverityBased on Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 Dosage Modifications Infusion-related reactions [see Warnings and Precautions (5.1)]Grade 2
Defined as:
Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤24 hours- Reduce DANYELZA infusion rate to 50% of previous rate and monitor closely until recovery to Grade ≤ 1.
- Increase infusion rate gradually to rate prior to the event as tolerated.
Grade 3
Defined as:
Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae- Immediately interrupt DANYELZA infusion and monitor closely until recovery to Grade ≤ 2.
- Resume infusion at 50% of the rate prior to the event and increase infusion rate gradually to infusion rate prior to the event as tolerated.
- Permanently discontinue DANYELZA in patients not responding to medical intervention.
Grade 4 infusion-related reactions Defined as:
Life-threatening consequences: urgent intervention indicated
or
Grade 3 or 4 anaphylaxis- Permanently discontinue DANYELZA.
Pain [see Warnings and Precautions (5.2)]Grade 3 unresponsive to maximum supportive measures - Permanently discontinue DANYELZA.
Reversible posterior leukoencephalopathy syndrome (RPLS) [see Warnings and Precautions (5.2)]All Grades - Permanently discontinue DANYELZA.
Transverse myelitis [see Warnings and Precautions (5.2)]All Grades - Permanently discontinue DANYELZA.
Peripheral neuropathy [see Warnings and Precautions (5.2)]Motor neuropathy: Grade 2 or greater or
Sensory neuropathy: Grade 3 or 4- Permanently discontinue DANYELZA.
Neurological disorders of the eye [see Warnings and Precautions (5.2)]Grade 2 to 4 resulting in decreased visual acuity or limiting activities of daily living - Withhold DANYELZA until resolution.
- If resolved resume DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms, gradually increase DANYELZA to dose prior to onset of symptoms.
- Permanently discontinue DANYELZA if not resolved within 2 weeks or upon recurrence.
Subtotal or total vision loss - Permanently discontinue DANYELZA.
Prolonged urinary retention [see Warnings and Precautions (5.2)]Persisting following discontinuation of opioids - Permanently discontinue DANYELZA.
Myocarditis [see Warnings and Precautions (5.3)]Grade 2 or 3 - Withhold, reduce dose, or permanently discontinue DANYELZA treatment based on severity and duration.
Grade 4 - Permanently discontinue DANYELZA.
Hypertension [see Warnings and Precautions (5.4)]Grade 3 - Withhold DANYELZA or pause infusion until recovery to ≤ Grade 2.
- Resume infusion at 50% of prior rate; if tolerated without recurrence of symptoms, gradually increase DANYELZA to rate prior to onset of symptoms.
- Permanently discontinue DANYELZA in patients not responding to medical intervention.
Grade 4 - Permanently discontinue DANYELZA.
Orthostatic hypotension [see Warnings and precautions (5.5)]All grades - Withhold DANYELZA until recovery to Grade ≤ 1.
- If resolved within 1 week, restart DANYELZA at 50% of the prior dose; if tolerated without recurrence of symptoms after completion of next cycle, resume to recommended dose for subsequent cycles.
- If not resolved within 1 week, permanently discontinue DANYELZA.
Other Adverse Reactions [see Adverse Reactions (6.1)]Grade 3 - Withhold DANYELZA until recovery to Grade ≤ 2.
- If resolved to Grade ≤ 2 resume DANYELZA at same rate.
- Permanently discontinue DANYELZA if not resolved to Grade ≤2 within 2 weeks.
Grade 4 - Permanently discontinue DANYELZA.
).5.2 NeurotoxicityDANYELZA can cause severe neurotoxicity, including severe neuropathic pain, transverse myelitis, and reversible posterior leukoencephalopathy syndrome.
Pain
Pain, including abdominal pain, bone pain, neck pain, and extremity pain, occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Grade 3 pain occurred in 72% of patients in Study 201. One patient in Study 201 (4%) required interruption of an infusion due to pain. Pain typically began during the infusion of DANYELZA and lasted a median of less than one day in Study 201 (range less than one day and up to 62 days)
[see Adverse Reactions (6.1)].Premedicate with drugs that treat neuropathic pain (e.g., gabapentin) and oral opioids. Administer intravenous opioids as needed for breakthrough pain
[see Dosage and Administration (2.2)].Permanently discontinue DANYELZA based on severity[see Dosage and Administration (2.3)].Transverse Myelitis
Transverse myelitis has occurred with DANYELZA. Permanently discontinue DANYELZA in patients who develop transverse myelitis
[see Dosage and Administration (2.3)].Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Reversible posterior leukoencephalopathy syndrome (RPLS) (also known as posterior reversible encephalopathy syndrome or PRES) occurred in 2 (2.8%) patients in Study 12-230. Events occurred 2 and 7 days following completion of the first cycle of DANYELZA. Monitor blood pressure during and following DANYELZA infusion and assess for neurologic symptoms
[see Warnings and Precautions (5.3)]. Permanently discontinue DANYELZA in case of symptomatic RPLS[see Dosage and Administration (2.3)and Adverse Reactions (6.1)].Peripheral Neuropathy
Peripheral neuropathy, including peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, and neuralgia, occurred in 32% of patients in Study 201 and in 25% of patients in Study 12-230. Most signs and symptoms of neuropathy began on the day of the infusion and neuropathy lasted a median of 5.5 days (range 0 to 22 days) in Study 201 and 0 days (range 0 to 22 days) in Study 12-230
[see Adverse Reactions (6.1)].Permanently discontinue DANYELZA based on severity
[see Dosage and Administration (2.3)].Neurological Disorders of the Eye
Neurological disorders of the eye including unequal pupils, blurred vision, accommodation disorder, mydriasis, visual impairment, and photophobia occurred in 24% of patients in Study 201 and 19% of patients in Study 12-230. Neurological disorders of the eye lasted a median of 17 days (range 0 to 84 days) in Study 201 with two patients (8%) experiencing an event that had not resolved at the time of data cutoff, and a median of 1 day (range less than one day to 21 days) in Study 12-230. Permanently discontinue DANYELZA based on severity
[see Dosage and Administration (2.3)and Adverse Reactions (6.1)].Prolonged Urinary Retention
Urinary retention occurred in 1 (4%) patient in Study 201 and in 3 patients (4%) in Study 12-230. All events in both studies occurred on the day of an infusion of DANYELZA and lasted between 0 and 24 days. Permanently discontinue DANYELZA in patients with urinary retention that does not resolve following discontinuation of opioids
[see Dosage and Administration (2.3)and Adverse Reactions (6.1)].
DANYELZA is indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy.
This indication is approved under accelerated approval based on overall response rate and duration of response
The efficacy of DANYELZA in combination with GM-CSF was evaluated in two open-label, single arm trials in patients with high-risk neuroblastoma with refractory or relapsed disease in the bone or bone marrow, Study 201 and Study 12-230.
Study 201
The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 201 (NCT03363373), a multicenter open-label, single arm trial, in a subpopulation of patients who had refractory or relapsed high-risk neuroblastoma in the bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg on Days 1, 3 and 5 of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on Days 1 to 5. Preplanned radiation to the primary site was allowed.
The major efficacy outcome measure was overall response rate (ORR) according to the revised International Neuroblastoma Response Criteria (INRC), as determined by independent pathology and imaging review and confirmed by at least one subsequent assessment. An additional efficacy outcome measure was duration of response (DOR).
Of the 22 patients included in the efficacy analysis, 64% had refractory disease and 36% had relapsed disease; the median age was 5 years (range 3 to 10 years), 59% were male; 45% were White, 50% were Asian and 5% were Black. MYCN amplification was present in 14% of patients and 86% of patients were International Neuroblastoma Staging System (INSS) stage 4 at time of diagnosis. Disease sites included 59% in the bone only, 9% in bone marrow only, and 32% in both. Prior therapies included surgery (91%), chemotherapy (95%), radiation (36%), autologous stem cell transplant (ASCT) (18%), and anti-GD2 antibody treatment (18%).
Efficacy results for Study 201 are described in Table 8.
| DANYELZA with GM-CSF (n=22) | |
|---|---|
| CI = confidence interval NE: not estimable. | |
Overall response rateOverall response rate is defined as a complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow.(95% CI) | 45% (24%, 68%) |
| Complete response rate | 36% |
| Partial response rate | 9% |
Duration of response | |
| Median (95% CI), months | 6.2 (4.9, NE) |
| Responders with DOR ≥ 6 months | 30% |
In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=4), one patient demonstrated a confirmed complete response and no patients demonstrated a partial response.
Study 12-230
The efficacy of DANYELZA in combination with GM-CSF was evaluated in Study 12-230 (NCT01757626), a single center, open-label, single arm trial, in a subpopulation of patients who had relapsed or refractory high-risk neuroblastoma in bone or bone marrow and demonstrated a partial response, minor response, or stable disease to prior therapy. Patients with progressive disease were excluded. All patients received at least one systemic therapy to treat disease outside of the bone or bone marrow prior to enrollment. Patients were required to have received at least one dose of DANYELZA at a dose of 3 mg/kg or greater per infusion and have evaluable disease at baseline according to independent review per the revised INRC.
Patients received DANYELZA 9 mg/kg/cycle administered as three separate intravenous infusions of 3 mg/kg (on Days 1, 3 and 5) in the first week of each cycle. Patients received GM-CSF subcutaneously at 250 µg/m2/day on Days -4 to 0 and at 500 µg/m2/day on Days 1 to 5. Radiation to non-target bony lesions and soft tissue lesions was permitted at the investigator's discretion; assessment of response excluded sites that received radiation. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by independent pathology and imaging review according to the revised INRC and confirmed by at least one subsequent assessment.
Of the 38 patients included in the efficacy analysis, 55% had relapsed neuroblastoma and 45% had refractory disease; 50% were male, the median age was 5 years (range 2 to 23 years), 74% were White, 8% Asian and 5% were Black, 5% Native American/American Indian/Alaska Native, 3% other races and 5% was not available. MYCN-amplification was present in 16% of patients and most patients were International Neuroblastoma Staging System (INSS) stage 4 (95%). Fifty percent (50%) of patients had disease involvement in the bone only, 11% only in bone marrow, and 39% in both. Prior therapies included surgery (100%), chemotherapy (100%), radiation (47%), autologous stem cell transplant (ASCT) (42%), and anti-GD2 antibody treatment (58%).
Efficacy results are provided in Table 9.
| DANYELZA with GM-CSF (n=38) | |
|---|---|
| CI = confidence interval | |
Overall response rateOverall response rate is defined as a complete or partial response according to the revised INRC (2017) that was confirmed by at least one subsequent assessment. Responses were observed in the bone, bone marrow, or both bone and bone marrow.(95% CI) | 34% (20%, 51%) |
| Complete response rate | 26% |
| Partial response rate | 8% |
Duration of Response | |
| Responders with DOR ≥ 6 months | 23% |
In an exploratory analysis in the subset of patients previously treated with an anti-GD2 antibody (n=22), the ORR was 18% (95% CI 5%, 40%), with no patients having a documented response of 6 months or greater.
The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day), administered as an intravenous infusion after dilution on Days 1, 3, and 5 of each treatment cycle. Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity. Administer GM-CSF subcutaneously prior to and during each treatment cycle as recommended. (
The recommended dosage of DANYELZA is 3 mg/kg/day (up to 150 mg/day) on Days 1, 3, and 5 of each treatment cycle, administered as an intravenous infusion after dilution
Treatment cycles are repeated every 4 weeks until complete response or partial response, followed by 5 additional cycles every 4 weeks. Subsequent cycles may be repeated every 8 weeks. Discontinue DANYELZA and GM-CSF for disease progression or unacceptable toxicity.
Administer pre-infusion medications and supportive treatment, as appropriate, during infusion.
The recommended dosage regimen for each treatment cycle is described below and in Table 1:
- Days -4 to 0: administer GM-CSF 250 µg/m2/day by subcutaneous injection, beginning 5 days prior to DANYELZA infusion.
- Days 1 to 5: administer GM-CSF 500 µg/m2/day by subcutaneous injection. Administer at least 1 hour prior to DANYELZA administration on Days 1, 3, and 5.
- Days, 1, 3, and 5: administer DANYELZA 3 mg/kg/day (up to 150 mg/day) by intravenous infusion.
| Day | -4 | -3 | -2 | -1 | 0 | 1 | 2 | 3 | 4 | 5 | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Subcutaneous GM-CSF | 250 µg/m2/day | 500 µg/m2/day | |||||||||
| Intravenous DANYELZA | 3 mg/kg/day | 3 mg/kg/day | 3 mg/kg/day | ||||||||
Missed Dose
If a DANYELZA dose is missed, administer the missed dose the following week by Day 10. Administer GM-CSF 500 µg /m2/day on the first day of the DANYELZA infusion, and on the day before and on the day of the second and third infusion, respectively (i.e. a total of 5 days with 500 µg /m2/day).
Injection: 40 mg/10 mL (4 mg/mL) clear to slightly opalescent and colorless to slightly yellow solution in a single-dose vial.
Lactation: Advise not to breastfeed. (
Risk Summary
There are no data on the presence of naxitamab-gqgk in human milk or its effects on the breastfed child, or on milk production, however, human IgG is present in human milk. Because of the potential for serious adverse reactions in a breastfed child from DANYELZA, advise women not to breastfeed during treatment and for 2 months after the last dose of DANYELZA.
DANYELZA is contraindicated in patients with a history of severe hypersensitivity reaction to naxitamab-gqgk. Reactions have included anaphylaxis
DANYELZA can cause serious infusion reactions requiring urgent intervention including fluid resuscitation, administration of bronchodilators and corticosteroids, intensive care unit admission, infusion rate reduction or interruption of DANYELZA infusion. Infusion-related reactions included hypotension, bronchospasm, hypoxia, and stridor
Serious infusion-related reactions occurred in 4% of patients in Study 201 and in 18% of patients in Study 12-230. Infusion-related reactions of any Grade occurred in 100% of patients in Study 201 and 94% of patients in Study 12-230. Hypotension of any grade occurred in 100% of patients in Study 201 and 89% of patients in Study 12-230.
In Study 201, 68% of patients experienced Grade 3 or 4 infusion reactions; and in Study 12-230, 32% of patients experienced Grade 3 or 4 infusion reactions. Anaphylaxis occurred in 12% of patients and 2 patients (8%) permanently discontinued DANYELZA due to anaphylaxis in Study 201. One patient in Study 12-230 (1.4%) experienced a Grade 4 cardiac arrest 1.5 hours following completion of DANYELZA infusion.
In Study 201, infusion reactions generally occurred within 24 hours of completing a DANYELZA infusion, most often within 30 minutes of initiation. Infusion reactions were most frequent during the first infusion of DANYELZA in each cycle. Eighty percent of patients required reduction in infusion rate and 80% of patients had an infusion interrupted for at least one infusion-related reaction.
Caution is advised in patients with pre-existing cardiac disease, as this may exacerbate the risk of severe hypotension.
Premedicate with an antihistamine, acetaminophen, an H2 antagonist and corticosteroid as recommended
Reduce the rate, interrupt infusion, or permanently discontinue DANYELZA based on severity and institute appropriate medical management as needed