User login
FDA approves motixafortide for stem cell mobilization in myeloma
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
The success of autologous stem cell transplantation (ASCT) depends on adequate mobilization of stem cells during the treatment process. Collection of a sufficient number of stem cells to perform two transplantations is recommended. However, in up to 47% of patients, collecting target numbers of hematopoietic stem cells for ASCT after one apheresis session remains a challenge, BioLineRx explained in a press release today, announcing the approval.
The goal of combining motixafortide with filgrastim is to mobilize stem cells more reliably than filgrastim can alone, with fewer days of apheresis sessions and fewer doses of filgrastim.
“We believe [motixafortide] will play a critical role in addressing unmet needs and introduce a new treatment paradigm for” patients with multiple myeloma, CEO Philip Serlin said in the release.
The drug approval was based on the GENESIS trial, which randomized 122 patients to either motixafortide plus filgrastim or placebo plus filgrastim.
BioLineRx said the trial included patients considered representative of the typical multiple myeloma population undergoing ASCT, with a median age of 63 years and with about 70% of patients in both arms of the trial receiving lenalidomide-containing induction therapy.
Motixafortide plus filgrastim enabled 67.5% of patients to achieve the stem cell collection goal of 6 million or more CD34+ cells/kg within two apheresis sessions, versus 9.5% of patients receiving the placebo plus filgrastim regimen. Additionally, 92.5% of patients reached the stem cell collection goal in up to two apheresis sessions in the motixafortide arm and 21.4% in the placebo arm.
However, “the data are descriptive and were not statistically powered nor prespecified. The information should be cautiously interpreted,” the company said.
Serious adverse reactions occurred in 5.4% of patients in the motixafortide arm, including vomiting, injection-site reaction, hypersensitivity reaction, injection-site cellulitis, hypokalemia, and hypoxia. The most common adverse reactions, occurring in more than 20% of patients, were injection site reactions (pain, erythema, and pruritus), pruritus, flushing, and back pain.
Labeling for the subcutaneous injection is available online.
A version of this article first appeared on Medscape.com.
ClonoSEQ Testing for Minimal Residual Disease in Multiple Myeloma: Cleveland VA Experience And Cost Analysis
BACKGROUND
Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).
DISCUSSION
The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.
CONCLUSIONS
An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.
BACKGROUND
Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).
DISCUSSION
The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.
CONCLUSIONS
An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.
BACKGROUND
Minimal residual disease (MRD) testing in myeloma has been shown to be a strong prognostic marker for progression-free and overall survival. Limited data suggest MRD results may also be useful for therapy discontinuation decisions. The clonoSEQ Assay utilizes next generation sequencing involving a bone marrow sample, obtained at the time of diagnosis, to identify patient-specific sequence(s).
DISCUSSION
The same methodology is then applied later to assess for MRD. Although widely adopted at most US academic centers, there has been limited use of MRD across VA centers. In 2022 the Cleveland Louis Stokes VAMC partnered with Adaptive Biotechnologies to develop a process for MRD/clonoSEQ testing in myeloma pts. Hematology, Pathology, Medicine, Administration and Adaptive Biotechnologies representatives met to develop a streamlined process for ordering, sample procurement, billing and result documentation. In 5/2022 the 1st specimen was sent. EQUATE is a national cooperative group trial requiring baseline clono- SEQ testing with a positive sequence ID. Daratumumab hyaluronidase (part of standard treatment) is provided to the institution at no cost on the trial but otherwise would cost the VA $5,797.38/dose. clonoSEQ costs VA $1950/test. There have been 14 specimens sent involving 12 pts: 12 baseline marrow and 2 for MRD (posttransplant). All of the baseline specimens were found to have an identifiable sequence. Both of the MRD tracking specimens were positive. The average turnaround time for clonoSEQ results was 13.2 days (range 7 to 18 days). 4 of the 12 pts with a positive initial clonoSEQ ID qualified for the EQUATE trial but would not have been deemed eligible without the baseline clonoSEQ results. 2 of these pts have enrolled on the trial and started treatment. Costs for 14 clonoSEQ tests: $27,300. Estimated cost savings for the 2 pts enrolled onto EQUATE: $127, 542.36/pt/year= $255,084.72/year. Overall cost savings: $227,784.72.
CONCLUSIONS
An efficient process for baseline and post-treatment (MRD) clonoSEQ testing in myeloma pts was developed. Although expensive, use of this test resulted in significant overall cost savings by allowing enrollment onto a clinical trial. In addition, if studies determine that negative MRD results can guide therapeutic decisions, use of clonoSEQ testing may result in further benefits.
Comparing Outcomes and Toxicities With Standard and Reduced Dose Melphalan in Autologous Stem Cell Transplant Patients With Multiple Myeloma
BACKGROUND
Multiple myeloma, an incurable plasma cell malignancy, has an average age of diagnosis over 65 years. For transplant-eligible patients, high-dose melphalan 200 mg/m2 (MEL200), followed by autologous stem cell rescue (ASCR) is the standard in consolidation therapy. Most clinical trials evaluating MEL200 with ASCR excluded patients over 65 due to concerns for toxicity and treatment-related mortality, leading to use of reduced dose melphalan 140 mg/m2 (MEL140) in clinical practice for older patients. As this dose has limited studies surrounding its reduction, the purpose of this study was to compare outcomes and toxicities of MEL140 in patients over the age of 65 to MEL200 in patients 65 and under.
METHODS
This single-center institutional review board approved retrospective study was conducted at VA Tennessee Valley Healthcare System. All multiple myeloma patients greater than 18 years of age who received melphalan with ASCR from January 1, 2018, to December 31, 2021, were included. Patients were divided into two arms: age < 65 treated with MEL200 and age >65 treated with MEL140. The primary endpoint was oneyear progression-free survival (PFS). The secondary endpoints were one-year overall survival (OS), treatment related mortality, time to neutrophil engraftment, and toxicities including febrile neutropenia, diarrhea, mucositis, infection, and intensive care unit transfers.
RESULTS
A total of 222 patients were included, 114 patients in the MEL200 arm and 108 patients in the MEL140 arm. The primary endpoint of one-year PFS had no significant difference, with 103 (90.4%) patients in the MEL200 group compared to 99 (91.7%) patients in the MEL140 group (p=0.732). Similarly, there was no statistically significant difference in the secondary endpoint of one-year OS with 112 (98.3%) patients in the MEL200 group compared to 106 (98.2%) in the MEL140 group (p=0.956). Toxicities were similar; however, grade 3 mucositis was higher in the MEL200 arm.
CONCLUSIONS
Our study found no difference in oneyear PFS or one-year OS when comparing MEL140 to MEL200 with minimal differences in regimen-related toxicities. Although not powered to detect statistical difference, results suggests that dose reduction with MEL140 in patients >65 years does not impact one-year PFS when compared to patients <65 receiving standard MEL200.
BACKGROUND
Multiple myeloma, an incurable plasma cell malignancy, has an average age of diagnosis over 65 years. For transplant-eligible patients, high-dose melphalan 200 mg/m2 (MEL200), followed by autologous stem cell rescue (ASCR) is the standard in consolidation therapy. Most clinical trials evaluating MEL200 with ASCR excluded patients over 65 due to concerns for toxicity and treatment-related mortality, leading to use of reduced dose melphalan 140 mg/m2 (MEL140) in clinical practice for older patients. As this dose has limited studies surrounding its reduction, the purpose of this study was to compare outcomes and toxicities of MEL140 in patients over the age of 65 to MEL200 in patients 65 and under.
METHODS
This single-center institutional review board approved retrospective study was conducted at VA Tennessee Valley Healthcare System. All multiple myeloma patients greater than 18 years of age who received melphalan with ASCR from January 1, 2018, to December 31, 2021, were included. Patients were divided into two arms: age < 65 treated with MEL200 and age >65 treated with MEL140. The primary endpoint was oneyear progression-free survival (PFS). The secondary endpoints were one-year overall survival (OS), treatment related mortality, time to neutrophil engraftment, and toxicities including febrile neutropenia, diarrhea, mucositis, infection, and intensive care unit transfers.
RESULTS
A total of 222 patients were included, 114 patients in the MEL200 arm and 108 patients in the MEL140 arm. The primary endpoint of one-year PFS had no significant difference, with 103 (90.4%) patients in the MEL200 group compared to 99 (91.7%) patients in the MEL140 group (p=0.732). Similarly, there was no statistically significant difference in the secondary endpoint of one-year OS with 112 (98.3%) patients in the MEL200 group compared to 106 (98.2%) in the MEL140 group (p=0.956). Toxicities were similar; however, grade 3 mucositis was higher in the MEL200 arm.
CONCLUSIONS
Our study found no difference in oneyear PFS or one-year OS when comparing MEL140 to MEL200 with minimal differences in regimen-related toxicities. Although not powered to detect statistical difference, results suggests that dose reduction with MEL140 in patients >65 years does not impact one-year PFS when compared to patients <65 receiving standard MEL200.
BACKGROUND
Multiple myeloma, an incurable plasma cell malignancy, has an average age of diagnosis over 65 years. For transplant-eligible patients, high-dose melphalan 200 mg/m2 (MEL200), followed by autologous stem cell rescue (ASCR) is the standard in consolidation therapy. Most clinical trials evaluating MEL200 with ASCR excluded patients over 65 due to concerns for toxicity and treatment-related mortality, leading to use of reduced dose melphalan 140 mg/m2 (MEL140) in clinical practice for older patients. As this dose has limited studies surrounding its reduction, the purpose of this study was to compare outcomes and toxicities of MEL140 in patients over the age of 65 to MEL200 in patients 65 and under.
METHODS
This single-center institutional review board approved retrospective study was conducted at VA Tennessee Valley Healthcare System. All multiple myeloma patients greater than 18 years of age who received melphalan with ASCR from January 1, 2018, to December 31, 2021, were included. Patients were divided into two arms: age < 65 treated with MEL200 and age >65 treated with MEL140. The primary endpoint was oneyear progression-free survival (PFS). The secondary endpoints were one-year overall survival (OS), treatment related mortality, time to neutrophil engraftment, and toxicities including febrile neutropenia, diarrhea, mucositis, infection, and intensive care unit transfers.
RESULTS
A total of 222 patients were included, 114 patients in the MEL200 arm and 108 patients in the MEL140 arm. The primary endpoint of one-year PFS had no significant difference, with 103 (90.4%) patients in the MEL200 group compared to 99 (91.7%) patients in the MEL140 group (p=0.732). Similarly, there was no statistically significant difference in the secondary endpoint of one-year OS with 112 (98.3%) patients in the MEL200 group compared to 106 (98.2%) in the MEL140 group (p=0.956). Toxicities were similar; however, grade 3 mucositis was higher in the MEL200 arm.
CONCLUSIONS
Our study found no difference in oneyear PFS or one-year OS when comparing MEL140 to MEL200 with minimal differences in regimen-related toxicities. Although not powered to detect statistical difference, results suggests that dose reduction with MEL140 in patients >65 years does not impact one-year PFS when compared to patients <65 receiving standard MEL200.
FDA approves elranatamab for multiple myeloma
The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.
FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.
The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.
In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.
Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.
Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).
The boxed warning is included in the full prescribing information.
A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.
A version of this article first appeared on Medscape.com.
The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.
FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.
The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.
In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.
Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.
Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).
The boxed warning is included in the full prescribing information.
A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.
A version of this article first appeared on Medscape.com.
The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.
FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.
The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.
In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.
Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.
Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).
The boxed warning is included in the full prescribing information.
A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.
A version of this article first appeared on Medscape.com.
FDA OKs talquetamab, a first-in-class myeloma tx
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Patients must have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The agent, which also received breakthrough and orphan drug designation, is available only through the Tecvayli-Talvey Risk Evaluation and Mitigation Strategy (REMS) because of a boxed warning for life-threatening or fatal cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell–associated neurotoxicity (ICANS), the FDA announced.
Talquetamab-tgvs was evaluated in the single-arm, open-label MonumenTAL-1 study of 187 patients who had previously been treated with at least four prior systemic therapies.
The overall response rate in 100 patients who received a subcutaneous dose of 0.4 mg/kg weekly was 73% and median duration of response was 9.5 months. The overall response rate in 87 patients who received a subcutaneous dose of 0.8 mg/kg biweekly was 73.6%, with about 85% of responders maintaining their response for at least 9 months. In this group, the median duration of response was not estimable.
Patients in the 0.4 mg/kg weekly dose group were treated following two step-up doses in the first week of therapy, and those in the 0.8 mg/kg biweekly group were treated following three step-up doses, until disease progression or unacceptable toxicity.
Adverse reactions occurring in at least 20% of the 339 patients in the safety population included CRS, dysgeusia (foul, metallic taste sensation), nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, decreased weight, dry mouth, pyrexia, xerosis, dysphagia, upper respiratory tract infection, and diarrhea.
Both the weekly 0.4 mg/kg and biweekly 0.8 mg/kg doses are recommended. The full dosing schedule is included in the prescribing information.
The approval follows a series of market withdrawals for other multiple myeloma drugs that initially received accelerated FDA approval. For instance, the FDA recently requested withdrawal of melphalan flufenamide (Pepaxto) after 2021 confirmatory trial results showed an increased risk of death. This agent had received accelerated approval in 2021. GlaxoSmithKline’s blood cancer drugs panobinostat (Farydak) and belantamab mafodotin-blmf (Blenrep) were also withdrawn based on confirmatory trial results.
Continued approval of talquetemab-tgvs for this indication is also contingent on verifying efficacy in confirmatory trials.
The new treatment approach represents a “welcome addition to the myeloma community,” Michael Andreini, president and chief executive officer of the Multiple Myeloma Research Foundation stated in a Janssen press release. “Although options for the treatment of multiple myeloma have expanded significantly in recent years, the disease remains incurable, and therefore, patients are in need of new treatment options.”
Health care professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
A version of this article first appeared on Medscape.com.
Antibody shows promise in preventing GVHD
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
Early, intriguing research suggests that preventing acute graft-versus-host disease (GVHD) in the gut – a potentially life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT) – could be accomplished by the administration of a single antibody that targets the anti-DLL4 Notch signaling pathway, without compromising the stem cell transplant.
“The major surprise was that none of the anti–DLL4-treated animals developed acute gastrointestinal GVHD for the entire duration of the study. This was a remarkable finding, given that intestinal GVHD is otherwise seen in the vast majority of nonhuman primate transplant recipients that receive either no prophylaxis, or prophylaxis with agents other than anti-DLL4 antibodies,” co–senior author Ivan Maillard, MD, PhD, a professor of medicine and vice chief for research in hematology-oncology at the University of Pennsylvania, Philadelphia, said in an interview.
“The timing was critical,” the authors noted in the study, recently published in Science Translational Medicine. “Intervening before any symptoms of GvHD appear made the long-term protection possible.”
While GVHD may be mild to moderate in chronic forms, acute cases can be serious, if not fatal, and nearly all severe acute GVHD prominently involves the gastrointestinal tract, which can drive activation of pathogenic T cells and potentially lead to tissue damage following allo-HCT.
Systemic corticosteroids are standard first-line treatment for acute GVHD. However, response rates generally range only from 40% to 60%, and there are concerns of side effects. Meanwhile, second-line treatments are of inconsistent benefit.
With previous studies on mice showing benefits of targeting Notch pathway inhibition, particularly DLL4, Dr. Maillard and colleagues further investigated the effects in nonhuman primates that were allo-HCT recipients, using the anti-DLL4 antibody REGN421, which has pharmacokinetic and toxicity information available from previous studies.
The nonhuman primates were treated with one of two dosing regimens: a single dose of REGN421 3 mg/kg at baseline, post HCT, (n = 7) or three weekly doses at days 0, 7 and 14, post transplant (n = 4). Those primates were compared with 11 primates receiving allo-HCT transplants that received supportive care only.
Primates receiving three weekly doses of REGN421 showed antibody concentrations of greater than 2 mcg/mL for more than 30 days post HCT. A single dose of REGN421 was associated with protection from acute GVHD at day 0, while three weekly doses showed protection at day 0, 7, and 14, consistent with an impact of REGN421 during the early phases of T-cell activation.
Compared with animals receiving only supportive care, prophylaxis with REGN421 was associated with delayed acute GVHD onset and lengthened survival.
Of the 11 primates treated with REGN421, none developed clinical signs of gastrointestinal acute GVHD, whereas the majority of those receiving standard care or other preventive interventions did.
“Detailed analysis of acute GVHD clinical presentations in REGN421-treated animals in comparison to no treatment controls revealed near complete protection from GI-acute GvHD with REGN421,” the authors reported.
Furthermore, pathology scores in the gastrointestinal tract were lower with REGN421 treatment, compared with the no-treatment cohort, and the scores matched those of healthy nontransplanted nonhuman primates.
The primates treated with REGN421 did ultimately develop other clinical and pathologic signs of skin, hepatic or pulmonary acute GVHD, but without gastrointestinal disease.
The treatment was not associated with any adverse effects on the allo-HCT, with primates receiving either a single dose or three weekly doses of REGN421 showing rapid donor engraftment after allo-HCT, including high bone marrow, whole blood, and T-cell donor chimerism.
“Reassuringly, short-term systemic DLL4 blockade with REGN421 did not trigger unexpected side effects in our nonhuman primate model, while preserving rapid engraftment as well hematopoietic and immune reconstitution.”
The mechanism preserving the engraftment, described as a “major surprise,” specifically involved DLL4 inhibition blocking the homing of pathogenic T cells to the gut while preserving homing of regulatory T cells that dampen the immune response, Dr. Maillard explained.
“This effect turned out to be at least in part through a posttranslational effect of DLL4/Notch blockade on integrin pairing at the T-cell surface,” he explained. “This was a novel and quite unexpected mechanism of action conserved from mice to nonhuman primates.”
The results are encouraging in terms of translating to humans because of their closer similarities in various physiological factors, Dr. Maillard said.
“The nonhuman primate model of transplantation [offers] a transplantation model very close to what is being performed in humans, as well as the opportunity to study an immune system very similar to that of humans in nonhuman primates,” he said.
Dr. Maillard noted that, while trials in humans are not underway yet, “we are in active discussions about it,” and the team is indeed interested in testing REGN421 itself, with the effects likely to be as a prophylactic strategy.
There are currently no approved anti-DLL4 antibody drugs for use in humans.
“Our approach is mostly promising as a preventive treatment, rather than as a secondary treatment for GVHD, because DLL4/Notch blockade seems most active when applied early after transplantation during the time of initial seeding of the gut by T cells (in mice, we had observed the critical time window for a successful intervention to be within 48 hours of transplantation),” Dr. Maillard said.“There remain questions about which other prophylactic treatments we should ideally combine anti-DLL4 antibodies with.”
Dr. Maillard has received research funding from Regeneron and Genentech and is a member of Garuda Therapeutics’s scientific advisory board.
FROM SCIENCE TRANSLATIONAL MEDICINE
MM: Newest IKEMA results back isatuximab
Median follow up was 44 months in the new update, about 2 additional years past the earlier report.
As in the earlier analysis, adding the anti-CD38 antibody to carfilzomib and dexamethasone brought substantial benefits, including a median progression free survival (PFS) of 35.7 months versus 19.2 months with placebo, as well as a higher rates of complete response (CR, 44.1% vs. 28.5%), minimal residual disease (MRD) negativity (33.5% vs. 15.4%), and MRD negativity CR (26.3% vs. 12.2%).
Although overall survival data are not yet mature, the probability of being alive at 42 months was 66.3% with isatuximab add-on versus 54.5% with placebo.
Investigators led by Thomas G. Martin, MD, director of the University of California, San Francisco, myeloma program, noted that median PFS of nearly 3 years “is the longest PFS reported to date with a PI-based regimen in the relapsed MM [multiple myeloma] setting.” The updated results further support the combination “as a standard of care treatment for patients with relapsed MM.”
Overall, the trial adds “another effective triplet in the treatment of patients with” relapsed/refractory MM, Sergio A. Giralt, MD, head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, said when asked for comment. The study was published May 9 in Blood Cancer Journal.
Safety similar to interim analysis
IKEMA randomized 179 patients to isatuximab add-on and 123 to placebo. Patients had relapsed/refractory MM with one to three prior treatment lines. Isatuximab was dosed at10 mg/kg IV in the open-label trial, weekly in the first cycle then biweekly.
The PFS benefit held across various subgroups, including the elderly and others with poor prognoses.
In their write-up, the investigators acknowledged isatuximab’s rival anti-CD38 antibody, daratumumab (Darzalex), which is also approved in the United States for use in combination with carfilzomib and dexamethasone for relapsed/refractory MM after one to three treatment lines.
“Although inter-trial evaluations should be interpreted with caution,” they noted that PFS in the latest analysis of daratumumab’s CANDOR trial in combination with carfilzomib and dexamethasone was shorter than in IKEMA, 28.6 months versus 15.2 months with placebo.
Like efficacy, safety in latest update of IKEMA was similar to that of the interim analysis. However, while there was no difference in the incidence of all-cause serious treatment-emergent adverse events (TEAEs) in the earlier report, the incidence was higher with isatuximab than placebo in the newest findings (70.1% vs. 59.8%).
The investigators said the difference was likely because patients in the isatuximab arm stayed on treatment longer, a median of 94 weeks versus 61.9 weeks in the placebo arm, making adverse events more likely.
The most common, nonhematologic TEAEs were infusion reactions (45.8% in the isatuximab arm vs. 3.3% in the placebo group), diarrhea (39.5% vs. 32%), hypertension (37.9% vs 35.2%), upper respiratory tract infection (37.3% vs 27%), and fatigue (31.6% vs 20.5%).
Grade 3 or higher pneumonia occurred in 18.6% patients in the isatuximab arm versus 12.3% in the placebo group. The incidence of skin cancer was 6.2% with isatuximab versus 3.3%. The incidence of treatment-emergent fatal events remained similar between study arms, 5.6% with isatuximab versus 4.9% with placebo.
The study was funded by Sanofi, maker of isatuximab. Investigators included two Sanofi employees. Others reported a range of ties to the company, including Dr. Martin, who reported research funding and sitting on a Sanofi steering committee.
Median follow up was 44 months in the new update, about 2 additional years past the earlier report.
As in the earlier analysis, adding the anti-CD38 antibody to carfilzomib and dexamethasone brought substantial benefits, including a median progression free survival (PFS) of 35.7 months versus 19.2 months with placebo, as well as a higher rates of complete response (CR, 44.1% vs. 28.5%), minimal residual disease (MRD) negativity (33.5% vs. 15.4%), and MRD negativity CR (26.3% vs. 12.2%).
Although overall survival data are not yet mature, the probability of being alive at 42 months was 66.3% with isatuximab add-on versus 54.5% with placebo.
Investigators led by Thomas G. Martin, MD, director of the University of California, San Francisco, myeloma program, noted that median PFS of nearly 3 years “is the longest PFS reported to date with a PI-based regimen in the relapsed MM [multiple myeloma] setting.” The updated results further support the combination “as a standard of care treatment for patients with relapsed MM.”
Overall, the trial adds “another effective triplet in the treatment of patients with” relapsed/refractory MM, Sergio A. Giralt, MD, head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, said when asked for comment. The study was published May 9 in Blood Cancer Journal.
Safety similar to interim analysis
IKEMA randomized 179 patients to isatuximab add-on and 123 to placebo. Patients had relapsed/refractory MM with one to three prior treatment lines. Isatuximab was dosed at10 mg/kg IV in the open-label trial, weekly in the first cycle then biweekly.
The PFS benefit held across various subgroups, including the elderly and others with poor prognoses.
In their write-up, the investigators acknowledged isatuximab’s rival anti-CD38 antibody, daratumumab (Darzalex), which is also approved in the United States for use in combination with carfilzomib and dexamethasone for relapsed/refractory MM after one to three treatment lines.
“Although inter-trial evaluations should be interpreted with caution,” they noted that PFS in the latest analysis of daratumumab’s CANDOR trial in combination with carfilzomib and dexamethasone was shorter than in IKEMA, 28.6 months versus 15.2 months with placebo.
Like efficacy, safety in latest update of IKEMA was similar to that of the interim analysis. However, while there was no difference in the incidence of all-cause serious treatment-emergent adverse events (TEAEs) in the earlier report, the incidence was higher with isatuximab than placebo in the newest findings (70.1% vs. 59.8%).
The investigators said the difference was likely because patients in the isatuximab arm stayed on treatment longer, a median of 94 weeks versus 61.9 weeks in the placebo arm, making adverse events more likely.
The most common, nonhematologic TEAEs were infusion reactions (45.8% in the isatuximab arm vs. 3.3% in the placebo group), diarrhea (39.5% vs. 32%), hypertension (37.9% vs 35.2%), upper respiratory tract infection (37.3% vs 27%), and fatigue (31.6% vs 20.5%).
Grade 3 or higher pneumonia occurred in 18.6% patients in the isatuximab arm versus 12.3% in the placebo group. The incidence of skin cancer was 6.2% with isatuximab versus 3.3%. The incidence of treatment-emergent fatal events remained similar between study arms, 5.6% with isatuximab versus 4.9% with placebo.
The study was funded by Sanofi, maker of isatuximab. Investigators included two Sanofi employees. Others reported a range of ties to the company, including Dr. Martin, who reported research funding and sitting on a Sanofi steering committee.
Median follow up was 44 months in the new update, about 2 additional years past the earlier report.
As in the earlier analysis, adding the anti-CD38 antibody to carfilzomib and dexamethasone brought substantial benefits, including a median progression free survival (PFS) of 35.7 months versus 19.2 months with placebo, as well as a higher rates of complete response (CR, 44.1% vs. 28.5%), minimal residual disease (MRD) negativity (33.5% vs. 15.4%), and MRD negativity CR (26.3% vs. 12.2%).
Although overall survival data are not yet mature, the probability of being alive at 42 months was 66.3% with isatuximab add-on versus 54.5% with placebo.
Investigators led by Thomas G. Martin, MD, director of the University of California, San Francisco, myeloma program, noted that median PFS of nearly 3 years “is the longest PFS reported to date with a PI-based regimen in the relapsed MM [multiple myeloma] setting.” The updated results further support the combination “as a standard of care treatment for patients with relapsed MM.”
Overall, the trial adds “another effective triplet in the treatment of patients with” relapsed/refractory MM, Sergio A. Giralt, MD, head of the division of hematologic malignancies at Memorial Sloan Kettering Cancer Center, New York, said when asked for comment. The study was published May 9 in Blood Cancer Journal.
Safety similar to interim analysis
IKEMA randomized 179 patients to isatuximab add-on and 123 to placebo. Patients had relapsed/refractory MM with one to three prior treatment lines. Isatuximab was dosed at10 mg/kg IV in the open-label trial, weekly in the first cycle then biweekly.
The PFS benefit held across various subgroups, including the elderly and others with poor prognoses.
In their write-up, the investigators acknowledged isatuximab’s rival anti-CD38 antibody, daratumumab (Darzalex), which is also approved in the United States for use in combination with carfilzomib and dexamethasone for relapsed/refractory MM after one to three treatment lines.
“Although inter-trial evaluations should be interpreted with caution,” they noted that PFS in the latest analysis of daratumumab’s CANDOR trial in combination with carfilzomib and dexamethasone was shorter than in IKEMA, 28.6 months versus 15.2 months with placebo.
Like efficacy, safety in latest update of IKEMA was similar to that of the interim analysis. However, while there was no difference in the incidence of all-cause serious treatment-emergent adverse events (TEAEs) in the earlier report, the incidence was higher with isatuximab than placebo in the newest findings (70.1% vs. 59.8%).
The investigators said the difference was likely because patients in the isatuximab arm stayed on treatment longer, a median of 94 weeks versus 61.9 weeks in the placebo arm, making adverse events more likely.
The most common, nonhematologic TEAEs were infusion reactions (45.8% in the isatuximab arm vs. 3.3% in the placebo group), diarrhea (39.5% vs. 32%), hypertension (37.9% vs 35.2%), upper respiratory tract infection (37.3% vs 27%), and fatigue (31.6% vs 20.5%).
Grade 3 or higher pneumonia occurred in 18.6% patients in the isatuximab arm versus 12.3% in the placebo group. The incidence of skin cancer was 6.2% with isatuximab versus 3.3%. The incidence of treatment-emergent fatal events remained similar between study arms, 5.6% with isatuximab versus 4.9% with placebo.
The study was funded by Sanofi, maker of isatuximab. Investigators included two Sanofi employees. Others reported a range of ties to the company, including Dr. Martin, who reported research funding and sitting on a Sanofi steering committee.
FROM BLOOD CANCER JOURNAL
ESMO helps hematologists assess new cancer drugs
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
It consists of 11 2- to 3-page forms with checklists to grade treatment trials on the extent to which they meet efficacy and safety thresholds. Each of the 11 forms covers a specific trial scenario, such as a randomized controlled trial with curative intent or a trial of a therapy that is not likely to be curative with a primary endpoint of overall survival.
Treatments with curative intent are graded A, B, or C, while treatments in the noncurative setting are graded on a descending scale from 5 to 1. Scores of A and B in the curative setting and 5 and 4 in the noncurative setting represent substantial benefit.
On the form for RCTs with curative intent, for instance, a survival improvement of 5% or more garners an A but an improvement of less than 3% gets a C. Scores are also annotated for serious acute and/or persistent toxicity if present.
The tool, dubbed the ESMO-MCBS:H (European Society for Medical Oncology Magnitude of Clinical Benefit Scale: Hematology), is explained in an article published in Annals of Oncology. The evaluation forms are available online.
The idea behind the work is to help health care professionals and others to more “accurately assess the value of and prioritise therapies for patients with blood cancers. For clinicians, ESMO-MCBS:H will aid in their clinical decision-making and in the development of evidence-based practice and guidelines,” ESMO said in a press release.
To develop ESMO-MCBS:H, the group tailored its tool for evaluating solid tumor therapies, the ESMO-MCBS, to account for the sometimes different endpoints used in hematologic malignancy trials and the very indolent nature of some blood cancers, such as follicular lymphoma, which hampers development of mature data.
Specific changes include adding a new evaluation form to grade single-arm trials with curative intent, such as those used for CAR-T-cell therapies; incorporating molecular surrogate endpoints used in CML trials; and adding a way to grade outcomes for indolent cancers, among others.
The development process included applying the solid tumor tool to 80 blood cancer studies to identify shortcomings and improve its applicability. The final tool was field tested with 51 international experts from EHA and ESMO who largely agreed on the reasonableness of the trial scores.
ESMO said it expects ESMO-MCBS:H will be useful. The solid tumor tool, first published in 2015, is used by the World Health Organization to screen medications for its essential medicines list as well as by ESMO to generate guidelines and oncology centers across Europe to help with resource allocation decisions.
FROM ANNALS OF ONCOLOGY
Multiprong strategy makes clinical trials less White
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
CHICAGO – Clinical trials are so White. Only a small percentage of eligible patients participate in clinical trials in the first place, and very few come from racial and ethnic minority groups.
For example, according to the Food and Drug Administration, in trials that resulted in drug approvals from 2017 to 2020, only 2%-5% of participants were Black patients.
When clinical trials lack diverse patient populations, those who are left out have fewer opportunities to get new therapies. Moreover, the scope of the research is limited by smaller phenotypic and genotypic samples, and the trial results are applicable only to more homogeneous patient groups.
There has been a push to include more underrepresented patients in clinical trials. One group reported its success in doing so here at the annual meeting of the American Society of Clinical Oncology.
a period that included a pandemic-induced hiatus in clinical trials in general.
Alliance member Electra D. Paskett, PhD, from the College of Public Health at the Ohio State University in Columbus, presented accrual data from 117 trials led by the Alliance from 2014 to 2022.
During this period, accrual of racial and ethnic minority patients increased from 13.6% to 25.3% for cancer treatment trials and from 13% to 21.5% for cancer control trials.
Overall, the recruitment program resulted in an absolute increase from 13.5 % to 23.6% of underrepresented populations, which translated into a relative 74.8% improvement.
“We’re focusing now on monitoring accrual of women, rural populations, younger AYAs [adolescents and young adults] and older patients, and we’ll see what strategies we need to implement,” Dr. Packett told this news organization.
The Alliance has implemented a real-time accrual dashboard on its website that allows individual sites to review accrual by trial and overall for all of the identified underrepresented populations, she noted.
Program to increase underrepresented patient accrual
The impetus for the program to increase enrollment of underrepresented patients came from the goal set by Monica M. Bertagnolli, MD, group chair of the Alliance from 2011 to 2022 and currently the director of the U.S. National Cancer Institute.
“Our leader, Dr. Bertagnolli, set out a group-wide goal for accrual of underrepresented minorities to our trials of 20%, and that gave us permission to implement a whole host of new strategies,” Dr. Paskett said in an interview.
“These strategies follow the Accrual of Clinical Trials framework, which essentially says that the interaction between the patient and the provider for going on a clinical trial is not just an interaction between the patient and provider but recognizes, for example, that the provider has coworkers and they have norms and beliefs and attitudes, and the patient comes from a family with their own values. And then there are system-level barriers, and there are community barriers that all relate to this interaction about going on a trial,” Dr. Packett said.
What works?
The study was presented as a poster at the meeting. During the poster discussion session, comoderator Victoria S. Blinder, MD, from Memorial Sloan Kettering Cancer Center in New York, asked Dr. Paskett, “If you had a certain amount of money and you really wanted to use that resource to focus on one area, where would you put that resource?”
“I’m going to violate the rules of your question,” Dr. Paskett replied.
“You cannot change this problem by focusing on one thing, and that’s what we showed in our Alliance poster, and what I’ve said is based on over 30 years of work in this area,” she said.
She cited what she considered as the two most important components for improving accrual of underrepresented populations: a commitment by leadership to a recruitment goal, and the development of protocols with specific accrual goals for minority populations.
Still, those are only two components of a comprehensive program that includes the aforementioned accrual goal set by Dr. Bertagnolli, as well as the following:
- Funding of minority junior investigators and research that focuses on issues of concern to underrepresented populations.
- Establishment of work groups that focus on specific populations with the Alliance health disparities committee.
- Translation of informational materials for patients.
- Opening studies at National Cancer Institute Community. Oncology Research Program–designated minority underserved sites.
- Real-time monitoring of accrual demographics by the Alliance and at the trial site.
- Closing protocol enrollment to majority populations.
- Increasing the study sample sizes to enroll additional minority participants and to allow for subgroup analyses.
The study was funded by the National Institutes of Health. Dr. Packett and Dr. Blinder reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023
CBSM phone app eases anxiety, depression in cancer patients
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
CHICAGO – One-third of patients with cancer also experience anxiety or depression, and an estimated 70% of the 18 million patients with cancer and cancer survivors in the US experience emotional symptoms, including fear of recurrence.
Despite many having these symptoms, few patients with cancer have access to psycho-oncologic support.
A digital cognitive-behavioral stress management (CBSM) application may help to ease some of the burden, reported Allison Ramiller, MPH, of Blue Note Therapeutics in San Francisco, which developed the app version of the program.
In addition, patients assigned to the CBSM app were twice as likely as control persons to report that their symptoms were “much” or “very much” improved after using the app for 12 weeks, Ms. Ramiller reported at an oral abstract session at the annual meeting of the American Society of Clinical Oncology (ASCO).
However, the investigators did not report baseline characteristics of patients in each of the study arms, which might have helped to clarify the depth of the effects they saw.
The CBSM program was developed by Michael H. Antoni, PhD, and colleagues in the University of Miami Health System. It is based on cognitive-behavioral therapy but also includes stress management and relaxation techniques to help patients cope with cancer-specific stress.
“”It has been clinically validated and shown to benefit patients with cancer,” Ms. Ramiller said. “However, access is a problem,” she said.
“There aren’t enough qualified, trained providers for the need, and patients with cancer encounter barriers to in-person participation, including things like transportation or financial barriers. So to overcome this, we developed a digitized version of CBSM,” she explained.
Impressive and elegant
“Everything about [the study] I thought was very impressive, very elegant, very nicely done,” said invited discussant Raymond U. Osarogiagbon, MBBS, FACP, chief scientist at Baptist Memorial Health Care Corp in Memphis, Tenn.
“They showed efficacy, they showed safety – very nice – user friendliness – very good. Certainly they look like they’re trying to address a highly important, unmet need in a very elegant way. Certainly, they pointed out it needs longer follow-up to see sustainability. We need to see will this work in other settings. Will this be cost-effective? You’ve gotta believe it probably will be,” he said.
CBSM has previously been shown to help patients with cancer reduce stress, improve general and cancer-specific quality of life at various stages of treatment, reduce symptom burden, and improve coping skills, Ms. Ramiller said.
To see whether these benefits could be conveyed digitally rather than in face-to-face encounters, Ms. Ramiller and colleagues worked with Dr. Antoni to develop the CBSM app.
Patients using the app received therapeutic content over 10 sessions with audio, video, and interactive tools that mimicked the sessions they would have received during in-person interventions.
They then compared the app against the control educational app in the randomized, decentralized RESTORE study.
High-quality control
Ms. Ramiller said that the control app set “a high bar.”
“The control also offered 10 interactive self-guided sessions. Both treatment apps were professionally designed and visually similar in styling, and they were presented as digital therapeutic-specific for cancer patients. And they were also in a match condition, meaning they received the same attention from study staff and cadence of reminders, but importantly, only the intervention app was based on CBSM,” she explained.
A total of 449 patients with cancers of stage I–III who were undergoing active systemic treatment or were planning to undergo such treatment within 6 months were randomly assigned to the CBSM app or the control app.
The CBSM app was superior to the control app for the primary outcome of anxiety reduction over baseline, as measured at 4, 8 and 12 weeks by the Patient-Reported Outcomes Measurement Information System Anxiety Scale (PROMIS-A) (beta = -.03; P = .019).
CBSM was also significantly better than the control app for the secondary endpoints of reducing symptoms of depression, as measured by the PROMIS-D scale (beta = -.02, P = .042), and also at increasing the percentage of patients who reported improvement in anxiety and depression symptoms on the Patient Global Impression of Change instrument (P < .001)
An extension study of the durability of the effects at 3 and 6 months is underway.
The investigators noted that the incremental cost of management of anxiety or depression is greater than $17,000 per patient per year.
“One of the big promises of a digital therapeutic like this is that it could potentially reduce costs,” Ms. Ramiller told the audience, but she acknowledged, “More work is really needed, however, to directly test the potential savings.”
The RESTORE study is funded by Blue Note Therapeutics. Dr. Osarogiagbon owns stock in Gilead, Lilly, and Pfizer, has received honoraria from Biodesix and Medscape, and has a consulting or advisory role for the American Cancer Society AstraZeneca, Genentech/Roche, LUNGevity, National Cancer Institute, and Triptych Health Partners.
A version of this article originally appeared on Medscape.com.
AT ASCO 2023