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Ibrutinib plus carfilzomib active in relapsed multiple myeloma
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
In patients with multiple myeloma who had already undergone multiple lines of therapy, the combination of ibrutinib and carfilzomib with or without dexamethasone produced a favorable rate of response and progression-free survival.
Ibrutinib and carfilzomib combination therapy was also associated with manageable safety in the phase 1 results of the ongoing study, investigators wrote in the journal Leukemia & Lymphoma.
The reported overall response rate in the study was 67%. Median progression-free survival was 7.2 months, which was “encouraging considering the poor outcomes often observed in this group,” Dr. Chari and colleagues wrote.
Carfilzomib, a selective and irreversible proteasome inhibitor, is indicated for patients with previously treated multiple myeloma. Ibrutinib, an orally administered covalent inhibitor of Bruton tyrosine kinase, already has Food and Drug Administration approval for treatment of several B-cell malignancies. Bruton tyrosine kinase is expressed in more than 85% of myeloma tumor cells, according to the researchers, and its signaling may contribute to development of drug resistance.
In an earlier phase 2 study, ibrutinib plus dexamethasone produced a 28% clinical benefit rate and median progression-free survival of 4.6 months. Preclinical data suggest combining ibrutinib and carfilzomib may have a synergistic effect, according to researchers.
To test that hypothesis, Dr. Chari and colleagues conducted a phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy, including bortezomib and an immunomodulatory agent. Among those patients, about three-quarters were refractory to bortezomib and one-quarter had high-risk cytogenetics.
A total of 35 patients in the study received ibrutinib and carfilzomib plus dexamethasone; 8 patients received only ibrutinib and carfilzomib.
Key phase 1 results included the 67% response rate, of which 21% had very good partial response and 2% had stringent complete response. No dose-limiting toxicities were observed.
Both carfilzomib and ibrutinib have known cardiac toxicities, but cardiac adverse events in this study did not reach dose-limiting toxicity criteria and were effectively managed by dose reductions or rechallenge, researchers reported.
Hypertension, anemia, pneumonia, fatigue, diarrhea, and thrombocytopenia were the most common grade 3 events observed. “Ultimately, toxicities and/or treatment discontinuations could be attributed to comorbidities, underlying disease factors, or toxicities due to prior therapies,” the researchers wrote.
Enrollment in phase 2b of the study is ongoing.
Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
SOURCE: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
FROM LEUKEMIA & LYMPHOMA
Key clinical point:
Major finding: The overall response rate was 67%, including a 21% very good partial response and 2% stringent complete response.
Study details: A phase 1 dose-finding study including 43 myeloma patients who had previously received at least two lines of therapy.
Disclosures: Dr. Chari received research funding from Pharmacyclics during the study and grants from other companies outside of the study work.
Source: Chari A et al. Leuk Lymphoma. 2018 Apr 4. doi: 10.1080/10428194.2018.1443337.
Generic melphalan available in US
Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran®, is now available in the US.
Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.
Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.
Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran®, is now available in the US.
Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.
Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.
Fresenius Kabi’s Melphalan Hydrochloride for Injection, a generic version of Alkeran®, is now available in the US.
Melphalan Hydrochloride for Injection is available as a 2-vial kit containing 1 single-dose vial of melphalan hydrochloride equivalent to 50 mg of melphalan and 1 vial of sterile diluent.
Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
For more details on Melphalan Hydrochloride for Injection, see the full prescribing information.
Group identifies novel genes involved in MM development
Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.
The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.
The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.
This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.
There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.
There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.
Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.
The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.
The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.
Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.
The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.
The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.
“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”
Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.
The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.
The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.
This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.
There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.
There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.
Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.
The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.
The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.
Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.
The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.
The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.
“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”
Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.
The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.
The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.
This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.
There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.
There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.
Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.
The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.
The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.
Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.
The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.
The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.
“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.
“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”
Generic antiemetic now available in US
Palonosetron Hydrochloride Injection, a generic alternative to Aloxi®, is now available in the US.
Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.
Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).
In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.
And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.
The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.
Palonosetron Hydrochloride Injection, a generic alternative to Aloxi®, is now available in the US.
Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.
Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).
In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.
And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.
The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.
Palonosetron Hydrochloride Injection, a generic alternative to Aloxi®, is now available in the US.
Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.
Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).
In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.
And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.
The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.
Selinexor receives fast track designation for MM
The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).
The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.
In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.
“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.
About selinexor
Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.
Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.
Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.
In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.
Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.
The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).
The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.
In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.
“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.
About selinexor
Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.
Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.
Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.
In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.
Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.
The US Food and Drug Administration (FDA) has granted fast track designation to selinexor for the treatment of patients with penta-refractory multiple myeloma (MM).
The patients must have received at least 3 prior lines of therapy that included an alkylating agent, a glucocorticoid, bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.
In addition, the patients must have disease that is refractory to at least 1 proteasome inhibitor, at least 1 immunomodulatory agent, glucocorticoids, daratumumab, and the patients’ most recent therapy.
“The designation of fast track for selinexor represents important recognition by the FDA of the potential of this anticancer agent to address the significant unmet need in the treatment of patients with penta-refractory myeloma that has continued to progress despite available therapies,” said Sharon Shacham, PhD, founder, president, and chief scientific officer of Karyopharm Therapeutics Inc., the company developing selinexor.
The FDA’s fast track drug development program is designed to expedite clinical development and submission of new drug applications for medicines with the potential to treat serious or life-threatening conditions and address unmet medical needs.
Fast track designation facilitates frequent interactions with the FDA review team, including meetings to discuss all aspects of development to support a drug’s approval, and also provides the opportunity to submit sections of a new drug application on a rolling basis as data become available.
About selinexor
Selinexor (formerly KPT-330) is a first-in-class, oral selective inhibitor of nuclear export compound.
Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to apoptosis in cancer cells while largely sparing normal cells.
Selinexor is currently being evaluated in several clinical trials across multiple cancer indications.
In the phase 2 STORM trial, researchers are testing selinexor in combination with low-dose dexamethasone for patients with penta-refractory MM. Karyopharm Therapeutics plans to report top-line data from this study at the end of this month.
Trials of selinexor were placed on partial clinical hold in mid-March last year due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.
Age and race affect access to myeloma treatment
Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.
Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.
The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.
“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.
Racial and socioeconomic barriers should also be addressed, they added.
The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.
Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).
Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.
“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.
The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.
Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.
Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.
SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.
Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.
Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.
The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.
“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.
Racial and socioeconomic barriers should also be addressed, they added.
The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.
Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).
Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.
“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.
The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.
Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.
Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.
SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.
Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.
Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.
The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.
“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.
Racial and socioeconomic barriers should also be addressed, they added.
The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.
Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).
Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.
“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.
The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.
Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.
Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.
SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.
FROM CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA
Key clinical point:
Major finding: Factors significantly associated with no systemic treatment included older age (adjusted odds ratio, 1.07 per year), African American descent (aOR, 1.26), and dual Medicare-Medicaid enrollment (aOR, 1.21).
Study details: A retrospective cohort analysis including data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011.
Disclosures: The research was supported by the National Cancer Institute. The investigators reported having no financial disclosures.
Source: Fakhri B et al. Clin Lymphoma Myeloma Leuk. Mar 2018;18(3):219-24.
Screening may reduce prevalence of MM
Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.
Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.
The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.
However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.
“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.
Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.
The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.
The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.
Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.
A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.
“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.
Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.
Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.
The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.
However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.
“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.
Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.
The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.
The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.
Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.
A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.
“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.
Targeted screening could potentially reduce the prevalence of multiple myeloma (MM), according to research published in JCO Clinical Cancer Informatics.
Researchers found that screening for monoclonal gammopathy of undetermined significance (MGUS) might reduce the risk of MM in individuals with a high lifetime risk of MGUS, which includes men, African Americans, and people with a family history of MM.
The researchers said patients who screen positive for MGUS could seek medical care early and try strategies such as aspirin, metformin, or weight reduction to potentially reduce their risk of progression from MGUS to MM.
However, additional studies are needed to confirm the effectiveness of aspirin, metformin, and weight-loss strategies in preventing MGUS progression.
“Screening for MGUS may have significant benefits by lowering the incidence of multiple myeloma, provided that effective and non-toxic interventions can be identified,” said study author Philipp Altrock, PhD, of Moffitt Cancer Center in Tampa, Florida.
Dr Altrock and his colleagues performed a series of computational modeling experiments to determine the best screening strategies in different groups of patients. The goal was to determine when screening should begin, how often it should occur, and in which individuals it could be most effective.
The researchers designed their model to predict the progression of MGUS to MM, the changes in MGUS and MM prevalence, and the annual follow-up mortality due to disease.
The team found evidence to suggest that screening strategies could reduce the risk of progression and the prevalence of MM. This effect was more pronounced in individuals who had a higher risk of MGUS.
Modeling suggested the prevalence of MM could be reduced by 19% in patients who begin screening at age 55 and have follow-up screening every 6 years.
A similar reduction in prevalence could also be achieved by starting screening at age 65 and following up every 2 years.
“Regular screening of MGUS candidates should start as early as possible, with biannual follow-up, and focus on high-risk individuals, especially with a family history of multiple myeloma or in groups with a strong indication of MGUS progression,” Dr Altrock said.
European Commission expands denosumab indication
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
The , making it is available for the prevention of skeletal-related events in adults with multiple myeloma and other advanced malignancies involving bone.
The European approval is based on the monoclonal antibody’s strong performance in a phase 3, international trial looking specifically at prevention of skeletal-related events in multiple myeloma patients.
During the trial, the drug demonstrated noninferiority to zoledronic acid in delaying the time to first skeletal-related event (hazard ratio, 0.98, 95% confidence interval: 0.85-1.14), according to Amgen, which markets denosumab. The median time to first skeletal-related event was 22.8 months for denosumab versus 24.0 months for zoledronic acid.
The denosumab indication was expanded to include prevention of skeletal-related events by the Food and Drug Administration in the United States in January 2018.
EC expands indication for denosumab to MM
The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).
The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).
Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.
Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.
Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.
In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.
Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).
All patients also received investigators’ choice of first-line MM therapy.
The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).
There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.
But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.
The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).
The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).
Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.
Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.
Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.
In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.
Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).
All patients also received investigators’ choice of first-line MM therapy.
The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).
There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.
But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.
The European Commission (EC) has approved an expanded indication for denosumab (Xgeva).
The drug is now approved for the prevention of skeletal-related events (SREs) in adults with advanced malignancies involving bone, which includes patients with multiple myeloma (MM).
Approval from the EC provides a centralized marketing authorization with unified labeling in all member countries of the European Union.
Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
Denosumab was previously approved by the EC to prevent SREs—defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression—in adults with bone metastases from solid tumors.
Denosumab also received EC approval for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity.
The EC’s approval for denosumab in MM patients is based on data from the ’482 study, which were recently published in The Lancet Oncology.
In this phase 3 trial, denosumab proved non-inferior to zoledronic acid for delaying SREs in patients with newly diagnosed MM and bone disease.
Researchers randomized 1718 patients to receive subcutaneous denosumab at 120 mg and intravenous placebo every 4 weeks (n=859) or intravenous zoledronic acid at 4 mg (adjusted for renal function at baseline) and subcutaneous placebo every 4 weeks (n=859).
All patients also received investigators’ choice of first-line MM therapy.
The median time to first on-study SRE was 22.8 months for patients in the denosumab arm and 24 months for those in the zoledronic acid arm (hazard ratio=0.98; 95% confidence interval: 0.85-1.14; P for non-inferiority=0.010).
There were fewer renal treatment-emergent adverse events in the denosumab arm than the zoledronic acid arm—10% and 17%, respectively.
But there were more hypocalcemia adverse events in the denosumab arm than the zoledronic acid arm—17% and 12%, respectively.
CHMP supports expanded approval for fosaprepitant
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).
The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.
Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.
As it is in adults, fosaprepitant would be given to children as part of combination therapy.
The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.
Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.
Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).
The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.
Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.
As it is in adults, fosaprepitant would be given to children as part of combination therapy.
The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.
Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.
Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).
The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended changing the terms of marketing authorization for fosaprepitant (Ivemend).
The product is already approved in the European Union (EU) for the prevention of acute and delayed nausea and vomiting associated with moderately or highly emetogenic cancer chemotherapy in adults.
Now, the CHMP is recommending that fosaprepitant be authorized for the same indication in pediatric patients age 6 months and older.
As it is in adults, fosaprepitant would be given to children as part of combination therapy.
The CHMP’s opinion on fosaprepitant will be reviewed by the European Commission (EC).
If the EC agrees with the CHMP, the commission will grant a centralized marketing authorization that will be valid in the EU. Norway, Iceland, and Liechtenstein will make corresponding decisions on the basis of the EC’s decision.
The EC typically makes a decision within 67 days of the CHMP’s recommendation.
Merck Sharp & Dohme Corp., the company developing fosaprepitant, has conducted a phase 2 trial assessing the pharmacokinetics, pharmacodynamics, safety, and tolerability of fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in children.
Patients ages 2 to 17 were randomized to receive 1 of 4 doses of fosaprepitant (0.4 mg/kg, 1.2 mg/kg, 3 mg/kg, and 5 mg/kg) or placebo in cycle 1. All patients also received ondansetron, with or without dexamethasone. Patients ages 0 to 11 were invited to participate in optional cycles 2 to 6, during which they received fosaprepitant at 3 mg/kg or 5 mg/kg.
Results from this trial have been posted on its clinicaltrials.gov page (NCT01697579).