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HU could save millions of lives in Africa, speaker says
SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.
During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.
Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.
Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.
Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.
“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.
To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.
The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.
The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.
A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.
Results
The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.
Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.
The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).
The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).
The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.
The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).
Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.
*Data in the abstract differ from the presentation and the article.
SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.
During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.
Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.
Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.
Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.
“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.
To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.
The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.
The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.
A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.
Results
The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.
Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.
The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).
The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).
The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.
The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).
Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.
*Data in the abstract differ from the presentation and the article.
SAN DIEGO—Daily hydroxyurea (HU) treatment is feasible, safe, and effective for children with sickle cell disease (SCD) in sub-Saharan Africa, according to a phase 1/2 trial.
During HU treatment, children experienced less vaso-occlusive pain, fewer cases of malaria and other infections, and lower rates of transfusions and death, compared to rates observed in the pretreatment screening phase of the trial.
“Based on that data, we believe that wider access to hydroxyurea for sickle cell anemia has the potential to save millions of lives in Africa,” said Léon Tshilolo, MD, PhD, of Centre Hospitalier Monkole in Kinshasa, Democratic Republic of the Congo.
Dr. Tshilolo reported the data, from the REACH trial (NCT01966731), during the plenary session at the 2018 ASH Annual Meeting (abstract 3*). Data were simultaneously published in The New England Journal of Medicine.
Use of HU has been limited in Africa because of cost, access issues, and challenges associated with laboratory monitoring, according to researchers.
Moreover, most of the efficacy data on HU come from studies conducted in the United States, Europe, and other high-income settings, said senior study author Russell E. Ware, MD, PhD, of Cincinnati Children’s Hospital Center in Ohio.
“Now that there’s data in an African setting, I think this will go a long way to advancing [HU therapy] and encouraging governments, organizations, and pharmaceutical companies to bring it in,” Dr. Ware said.
To collect the data, Drs. Ware and Tshilolo and their colleagues evaluated SCD patients, ages 1 to 10, living in four sub-Saharan African countries—Angola, Democratic Republic of the Congo, Kenya, and Uganda.
The children completed a 2-month pretreatment screening phase designed to capture baseline clinical and laboratory data.
The children were started at 15 mg/kg to 20 mg/kg of HU for 6 months, followed by escalation to the maximum-tolerated dose.
A total of 606 children were treated, 600 of them for 3 months. Treatment is ongoing, but the mean treatment duration at the time of analysis was 29 months.
Results
The average maximum tolerated dose was 22.5 mg/kg/day. Dose-limiting toxicities occurred in 5.1% of the children, which was below the 20% protocol-specified threshold for safety, Dr. Tshilolo said.
Dose-limiting toxicities included severe anemia, reticulocytopenia, neutropenia, and thrombocytopenia. However, there were similar rates of these events during the screening period and the treatment period.
The rate of vaso-occlusive pain during HU treatment was 44.6 events per 100 patient-years, compared with 98.3 events per 100 patient-years in the pretreatment period (incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.37-0.56).
The rate of malaria infection was 22.9 events per 100 patient-years in the HU treatment period, compared to 46.9 events in the pretreatment period (IRR, 0.49; 95% CI, 0.37-0.66).
The rate of nonmalaria infections was 90.0 events per 100 patient-years in the HU treatment period, compared to 142.5 events per 100 patient-years in the pretreatment period (IRR, 0.62; 95% CI, 0.53-0.72).
Dr. Tshilolo said the researchers were “encouraged” by the reduced infection rates, particularly in light of previous concerns that HU could suppress the immune system and put children at risk for malaria.
The rate of transfusion during HU treatment was 14.2 events per 100 patient-years, compared to 43.3 events per 100 patient-years (IRR, 0.33; 95% CI, 0.23 to 0.47).
Death rates were 1.1 per 100 patient-years in the HU treatment period and 3.6 per 100 patient-years in the pretreatment period (IRR, 0.30; 95% CI, 0.10-0.88).
Dr. Tshilolo reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Cincinnati Children’s Research Foundation, along with nonfinancial support from Bristol-Myers Squibb. Dr. Ware reported grants from the National Institutes of Health/National Heart, Lung, and Blood Institute and Bristol-Myers Squibb.
*Data in the abstract differ from the presentation and the article.
Triplet demonstrates activity in relapsed/refractory MM
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
SAN DIEGO—A three-drug combination produced “deep and durable” responses in patients with relapsed/refractory multiple myeloma (MM), according to a speaker at the 2018 ASH Annual Meeting.
Selinexor, dexamethasone, and daratumumab produced a response rate of 73% when given at the recommended dosing schedule to MM patients who had received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent.
Most responders had a very good partial response (VGPR), but there were no complete responses. At a median follow-up of 7.7 months, the median progression-free survival had not been reached.
The most common grade 3/4 adverse events (AEs) in this trial were hematologic toxicities.
Cristina J. Gasparetto, MD, of Duke University Medical Center in Durham, North Carolina, presented these results, from the phase 1/2 STOMP trial (NCT02343042), as abstract 599.*
Patients
As of November 15, the trial had enrolled 28 MM patients. At baseline, their median age was 68 (range, 44-77). There were 14 males and 14 females. The median time from diagnosis to study treatment was 5.9 years (range, <1 to 12.9 years).
Patients had received a median of 3 (range, 2 to 10) prior treatment regimens.
All 28 patients had received a proteasome inhibitor, and 61% of them (n=17) were refractory to the treatment. All 28 patients had also received an immunomodulatory drug, and 64% of them (n=18) were refractory to it.
Seventy-nine percent (n=22) of patients had undergone an autologous transplant, and 7% (n=2) had received prior daratumumab.
Treatment
Patients were treated in two concurrent cohorts.
One cohort included 25 patients who received selinexor at 100 mg once-weekly (QW), dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
The other cohort included three patients who received selinexor at 60 mg twice-weekly (BIW), dexamethasone at 20 mg BIW, and daratumumab at 16 mg/kg QW.
The recommended phase 2 dose and schedule was selinexor at 100 mg QW, dexamethasone at 40 mg QW, and daratumumab at 16 mg/kg QW.
Safety
Among patients who received the recommended phase 2 dosing schedule, common treatment-related AEs included:
- Nausea (60%)
- Diarrhea (32%)
- Anorexia (28%)
- Vomiting (24%)
- Dysgeusia (20%)
- Fatigue (48%)
- Hyponatremia (28%)
- Insomnia (24%)
- Blurred vision (24%)
- Thrombocytopenia (64%)
- Anemia (48%)
- Leukopenia (44%)
- Neutropenia (44%)
- Lymphopenia (20%).
“[T]he weekly dose was better tolerated [with] only a couple of patients with grade 3 [gastrointestinal] toxicity,” Dr Gasparetto noted.
The most common grade 3/4 AEs were thrombocytopenia (44%), anemia (28%), leukopenia (28%), and neutropenia (24%). There were no grade 5 AEs.
Efficacy
The median follow-up was 7.7 months, and the median time on study was 5.8 months.
Twenty-six patients were evaluable for response, as two patients withdrew consent prior to follow-up.
The overall response rate was 73% (n=19), which includes seven very good partial responses (VGPRs) and 12 partial responses (PRs). Two patients had a minimal response, four had stable disease, and one progressed.
Among patients with a PR or better, the median time on treatment was 7.3 months. The median time to response was 1 month.
Three VGPRs are ongoing, but four patients who achieved a VGPR progressed.
Six PRs are ongoing, and one patient with a PR progressed. Other reasons for treatment discontinuation among patients with a PR included transplant (n=1), AE (n=1), patient decision (n=2), and hospice (n=1).
One patient with a minimal response progressed, and one discontinued treatment due to an AE.
The median progression-free survival was not reached.
“Selinexor in combination with dara and dexa appears to be highly active, producing deep and durable responses in the relapsed setting,” Dr. Gasparetto said.
She reported relationships with Takeda, Janssen, Celgene, and Bristol-Myers Squibb. The trial is sponsored by Karyopharm Therapeutics.
*Data in the presentation differ from the abstract.
Two-drug combo deemed ‘very promising’ for PMBCL
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
ALL regimens clear disease in kids with MPAL
SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.
In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).
Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.
Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).
The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.
Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.
Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.
Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).
The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.
Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.
Survival
The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.
In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.
“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.
The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.
The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.
In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).
There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.
“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.
In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.
“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.
He disclosed no conflicts of interest.
* Data in the presentation differ from the abstract.
SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.
In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).
Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.
Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).
The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.
Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.
Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.
Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).
The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.
Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.
Survival
The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.
In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.
“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.
The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.
The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.
In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).
There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.
“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.
In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.
“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.
He disclosed no conflicts of interest.
* Data in the presentation differ from the abstract.
SAN DIEGO—Pediatric patients with mixed phenotype acute leukemia (MPAL) can achieve minimal residual disease (MRD) negativity with acute lymphoblastic leukemia (ALL)-directed chemotherapy, according to new research.
In a retrospective study, most pediatric MPAL patients who received ALL-directed chemotherapy achieved an MRD-negative complete response (CR).
Ninety-three percent of patients achieved a CR at the end of induction with an ALL regimen, 70% were MRD-negative at the end of induction, and 86% were MRD-negative at the end of induction or consolidation.
Etan Orgel, MD, of the University of Southern California, Los Angeles, presented these findings at the ASH 2018 Annual Meeting (abstract 558*).
The study included 94 patients aged 1-21 years who met World Health Organization MPAL criteria and were treated between 2008 and 2016 at one of six U.S. institutions.
Most patients had B/Myeloid phenotype (89%, n=84), 10% (n=9) had T/Myeloid, and 1% (n=1) had B/T phenotype.
Eighty-seven patients (93%) received ALL induction, and 83 (89%) continued on ALL therapy after induction.
Ninety-three percent (81/87) of patients treated with an ALL induction regimen had a CR at the end of induction. One patient died during induction, and six had induction failures, defined as either disease progression (n=2) or MRD of 5% or greater (n=4).
The MRD-negative rates, defined as MRD less than 0.01%, were 70% (59/84) at the end of induction and 86% (68/79) at the end of induction or consolidation.
Twelve of 14 patients (86%) who were MRD-positive at the end of induction and continued on ALL therapy achieved MRD negativity at the end of consolidation.
Survival
The researchers assessed 5-year survival in patients who received an ALL regimen but did not go on to transplant.
In these patients, the 5-year event-free survival (EFS) was 75%, and the 5-year overall survival (OS) was 89%, “thus demonstrating that, for a majority of patients, transplant in first remission may not be necessary,” Dr. Orgel said.
“[T]his is very different from the approach used at many adult centers and many of the adult recommendations,” he added.
The 5-year EFS rate was 80% in patients who were MRD-negative at the end of induction and 52% in patients who were MRD-positive at the end of induction. Five-year OS rates were 91% and 84%, respectively.
The 5-year EFS rate was 77% in patients who were MRD-negative at the end of consolidation and was unavailable in the three patients who were MRD-positive. The 5-year OS rates were 89% and not available, respectively.
In a multivariable analysis, MRD was the strongest predictor of EFS (hazard ratio [HR]=3.5) and OS (HR=4.6).
There was a trend toward earlier failure and worse OS (HR=4.49, P=0.074) for T-lineage-containing MPAL.
“That indicates that this might be a group that needs careful scrutiny of which form of ALL therapy they receive,” Dr. Orgel said.
In closing, he said this research suggests that ALL therapy without transplant may be sufficient to treat most patients with pediatric MPAL. However, he noted that clinical trials are necessary to prospectively validate MRD thresholds at end of induction and consolidation and to establish the threshold for favorable survival.
“Future research should explore either intensification of therapy or different therapies for patients with persistent MRD,” Dr. Orgel said.
He disclosed no conflicts of interest.
* Data in the presentation differ from the abstract.
Data support apixaban for cancer-associated VTE, doc says
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
Regimen provides survival benefit in PTCL
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
Ixazomib improves PFS after ASCT in MM
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
SAN DIEGO—Ixazomib improved progression-free survival (PFS) following autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (MM) in the TOURMALINE-MM3 trial.
The oral proteasome inhibitor improved PFS by 39% compared to placebo.
In addition, treatment with ixazomib was well tolerated, and there was a low discontinuation rate.
TOURMALINE-MM3 is the first-ever randomized, double-blind, placebo-controlled study of a proteasome inhibitor used as maintenance after ASCT, according to Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece.
Dr. Dimopoulos presented results from the trial at the 2018 ASH Annual Meeting (abstract 301).
He said the results suggest ixazomib represents a new treatment option for maintenance after ASCT in MM.
“Proteasome inhibitors have a different mechanism of action and may provide an alternative to lenalidomide,” Dr. Dimopoulos said.
He noted that ixazomib has a manageable toxicity profile and “convenient” weekly oral dosing, making it “well suited” for maintenance.
The TOURMALINE-MM3 study (NCT02181413) included 656 MM patients randomized post-ASCT to receive weekly ixazomib or placebo for up to 2 years.
The median PFS was 26.5 months for ixazomib and 21.3 months for placebo (hazard ratio=0.720; 95% confidence interval, 0.582-0.890; P=0.002).
At a median follow-up of 31 months, the median overall survival has not been reached in either treatment arm.
The discontinuation rate due to adverse events was 7% for ixazomib and 5% for placebo.
Ixazomib was associated with “low toxicity,” Dr Dimopoulos said, and there was no difference in the rates of new primary malignancies, at 3% in both arms.
When asked by an attendee whether ixazomib would become the standard of care for younger MM patients in this setting, Dr. Dimopoulos said the results show that ixazomib “is an option for patients, especially for those where a physician may believe that a proteasome inhibitor may be indicated.”
However, when pressed to comment on how ixazomib compares with lenalidomide for maintenance, Dr. Dimopoulos remarked that current maintenance studies are moving in the direction of combining therapies.
“I think that instead of saying, ‘Is ixazomib better than lenalidomide or vice-versa,’ it is better to see how one may combine those drugs in subsets of patients or even combine these drugs with other agents,” he said.
A manuscript describing results of the TOURMALINE-MM3 study is in press at The Lancet, with an expected online publication date of December 10, Dr. Dimopoulos said.
TOURMALINE-MM3 is sponsored by Takeda (Millennium), the maker of ixazomib.
Dr. Dimopoulos reported honoraria and consultancy with Janssen, Takeda Pharmaceuticals, Amgen, Bristol-Myers Squibb, and Celgene.
Update shows durable responses in rel/ref DLBCL
SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.
Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.
Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.
At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.
In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).
Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.
As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.
Fifty-four percent of patients who had achieved PR converted to CR.
The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 64%.
The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.
Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc.
SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.
Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.
Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.
At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.
In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).
Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.
As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.
Fifty-four percent of patients who had achieved PR converted to CR.
The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 64%.
The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.
Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc.
SAN DIEGO—An updated analysis of the JULIET trial showed that tisagenlecleucel produced a high rate of durable responses in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
After a median follow-up of 19 months, two-thirds of adults with relapsed/refractory DLBCL who had early responses to the chimeric antigen receptor (CAR) T-cell therapy remained in remission with no evidence of minimal residual disease.
“Since the previous report, no new deaths have been reported due to any cause other than patient disease progression, no treatment-related mortality was seen throughout the study, and there were three early deaths, all related to lymphoma that progressed,” said study investigator Richard Thomas Maziarz, MD, of Oregon Health & Science University’s Knight Cancer Institute in Portland.
Dr. Maziarz and his colleagues reported the updated study results at the 2018 ASH Annual Meeting (abstract 1684). Results were published simultaneously in The New England Journal of Medicine. Data reported here are based on the ASH data.
JULIET then
In the phase 2, single-arm trial, investigators enrolled adults with DLBCL who had relapsed or were refractory after two or more prior lines of therapy and who were either ineligible for hematopoietic stem cell transplant (HSCT) or who experienced disease progression after HSCT.
Interim results of the study were previously reported at the 22nd Congress of the European Hematology Association in 2017.
At that meeting, Gilles Salles, MD, PhD, of the University of Lyon in France, presented results of an analysis of available efficacy data on 51 patients with at least 3 months of follow-up.
In this population, the best overall response rate (ORR) was 59%. Three-month ORR was 45%, consisting of 37% complete responses (CR) and 8% partial responses (PR).
Relapse-free survival at 6 months was 79%, and all patients who had responses at 3 months continued to have responses at the time of data cutoff.
JULIET now
The current analysis was completed after a median time from infusion to data cutoff of 19 months as of May 21, 2018. The analysis included 115 patients who received CAR T-cell infusions, 99 of whom were evaluable for efficacy.
As reported at ASH, the best ORR, the primary endpoint, was 54%, comprised of 40% CR and 13% PR.
Fifty-four percent of patients who had achieved PR converted to CR.
The response rates were consistent across all subgroups, regardless of age, sex, previous response status, International Prognostic Index score at enrollment, prior therapy, molecular subtype, and other factors.
Estimated relapse-free survival 12 months after documentation of an initial response was 64%.
The median duration of response had not been reached at the time of data cutoff, and the median overall survival had not been reached for patients with a CR.
Median overall survival in this heavily pretreated population as a whole (all patients who received CAR T-cell infusions) was 11.1 months and not reached for patients in CR.
Adverse events of special interest included grade 3 or 4 cytokine release syndrome (CRS) in 23% of patients, prolonged cytopenia in 34%, infections in 19%, neurologic events in 11%, febrile neutropenia in 15%, and tumor lysis syndrome in 2%.
There were no deaths attributable to the treatment, CRS, or to cerebral edema, a complication of CAR T-cell therapy that appears to be related to the costimulatory molecule used in various constructs.
The JULIET trial is supported by Novartis. Dr. Maziarz disclosed honoraria, consultancy fees, and/or research funding from Novartis, Incyte, Juno Therapeutics, and Kite Therapeutics as well as patents/royalties from Athersys, Inc.
Luspatercept reduced transfusion burden in MDS patients
SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.
Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.
And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.
Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.
Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.
The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.
The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).
The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).
The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).
The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).
“This was a very clean drug and a very safe drug,” Dr. List said.
The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.
The PACE study also included a small number of patients who had not previously received an ESA.
Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.
“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.
Dr. List reported research funding from Celgene.
SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.
Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.
And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.
Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.
Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.
The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.
The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).
The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).
The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).
The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).
“This was a very clean drug and a very safe drug,” Dr. List said.
The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.
The PACE study also included a small number of patients who had not previously received an ESA.
Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.
“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.
Dr. List reported research funding from Celgene.
SAN DIEGO—Results of the randomized, phase 3 Medalist trial show that the erythroid maturation agent luspatercept can reduce transfusion burden in patients with anemia due to myelodysplastic syndromes (MDS) and ring sideroblasts.
Almost 38% of luspatercept-treated patients achieved red blood cell (RBC) transfusion independence for 8 weeks or more, compared with 13% of patients receiving placebo.
And 28% of luspatercept-treated patients achieved transfusion independence for 12 weeks or more, compared to 8% in the placebo group.
Investigators reported these results as abstract 1 at the 2018 ASH Annual Meeting.
Treatment with luspatercept was “very well tolerated,” and responses were durable, with approximately 40% of patients remaining transfusion-free after 1 year of therapy, said senior investigator Alan F. List, MD, of Moffitt Cancer Center in Tampa, Florida, during a press conference at the meeting.
The first-in-class erythroid maturation agent is being developed as a treatment for anemia related to MDS and beta-thalassemia, Dr. List said.
“Luspatercept is a potential new therapy that we think could be very effective in patients with lower-risk MDS with ring sideroblasts who are red blood cell transfusion-dependent,” Dr. List affirmed.
Luspatercept is a soluble receptor chimera that binds to an array of ligands in the TGF-β superfamily, which is known to be very important in suppressing erythropoiesis in patients with MDS, Dr. List noted.
The Medalist study (NCT02631070) included patients with very low-, low-, or intermediate-risk disease and ring sideroblasts who were RBC transfusion-dependent and were refractory to, unresponsive to, or ineligible for first-line treatment with an erythropoiesis-stimulating agent (ESA).
A total of 153 patients were randomized to receive luspatercept at 1.0 mg/kg, administered subcutaneously every 21 days for at least 24 weeks, while 76 were randomized to placebo every 21 days.
The primary endpoint was the proportion of patients achieving RBC transfusion independence for at least 8 weeks during the first 24 weeks of treatment.
The primary endpoint was achieved by 37.9% of luspatercept-treated patients and 13.2% of placebo-treated patients (P<0.0001).
The luspatercept-treated patients also had a higher rate of erythroid response compared with the placebo group, at 52.9% and 11.8%, respectively (P<0.0001).
The investigators reported no differences in treatment-emergent adverse events, severe adverse events, or frequency of progression of acute myeloid leukemia (AML).
The safety profile was consistent with that of the phase 2 PACE-MDS study, which included treatment-related grade 3 myalgia (2%), increased blast cell count (2%), and general physical health deterioration (2%).
“This was a very clean drug and a very safe drug,” Dr. List said.
The decision to study luspatercept in patients with ring sideroblasts was based on results of the phase 2 PACE study showing a higher response rate in that subset of MDS patients, according to Dr. List.
The PACE study also included a small number of patients who had not previously received an ESA.
Currently underway is a phase 3 trial (NCT03682536) investigating luspatercept in ESA-naïve lower-risk MDS patients with anemia who require RBC transfusions.
Luspatercept would be a useful therapy to have in clinic for patients with ring sideroblasts, which represent about 25% of patients overall, according to MDS expert David Steensma, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, Massachusetts.
“It’s been 12 years since we had an FDA-approved drug in MDS, and there have been 7 in acute myeloid leukemia in the last year and a half, so it’s our turn, I think,” said Dr. Steensma, who moderated the press conference.
The Medalist study was sponsored by Celgene in collaboration with Acceleron Pharma, Inc.
Dr. List reported research funding from Celgene.
New VTE guidelines include over 150 recommendations
The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).
The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.
Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.
An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.
The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.
Prevention
For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.
Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.
But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.
For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.
The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.
The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.
Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.
And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.
People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.
Diagnosis
For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.
For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.
The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.
Management
Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.
But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.
The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.
The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.
For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.
The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.
ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.
The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.
At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:
Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.
The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).
The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.
Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.
An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.
The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.
Prevention
For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.
Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.
But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.
For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.
The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.
The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.
Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.
And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.
People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.
Diagnosis
For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.
For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.
The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.
Management
Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.
But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.
The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.
The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.
For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.
The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.
ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.
The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.
At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:
Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.
The American Society of Hematology (ASH) has released a new set of guidelines for the prevention, diagnosis, and management of venous thromboembolism (VTE).
The new guidelines contain more than 150 individual recommendations, including sections devoted to managing VTE during pregnancy and in pediatric patients.
Guideline highlights cited by some of the writing panel include a high reliance on low-molecular-weight heparin (LMWH) as the preferred treatment for many patients, reliance on the D-dimer test to rule out VTE in patients with a low pretest probability of disease, and reliance on the 4Ts score to identify patients with heparin-induced thrombocytopenia.
An updated set of VTE guidelines were needed because clinicians now have a “greater understanding of risk factors” for VTE as well as having “more options available for treating VTE, including new medications,” Adam C. Cuker, MD, of the University of Pennsylvania in Philadelphia and co-chair of the guideline-writing group, said during a webcast to unveil the new guidelines.
The guidelines, released on November 27, took more than 3 years to develop, an effort that began in 2015.
Prevention
For preventing VTE in hospitalized medical patients, the guidelines recommend initial assessment of the patient’s risk for both VTE and bleeding.
Patients with a high bleeding risk who need VTE prevention should preferentially receive mechanical prophylaxis, either compression stockings or pneumatic sleeves.
But in patients with a high VTE risk and an “acceptable” bleeding risk, prophylaxis with an anticoagulant is preferred over mechanical measures, said Mary Cushman, MD, of the University of Vermont in Burlington and member of the guideline writing group.
For prevention of VTE in medical inpatients, LMWH is preferred over unfractionated heparin because of its once-daily dosing and fewer complications, Dr. Cushman said.
The panel also endorsed LMWH over a direct-acting oral anticoagulant (DOAC), both during hospitalization and following discharge.
The guidelines for prevention in medical patients explicitly “recommended against” using a DOAC “over other treatments” both for hospitalized medical patients and after discharge. The guidelines further recommend against extended prophylaxis after discharge with any other anticoagulant.
Another important take-away from the prevention section is a statement that combining both mechanical and medical prophylaxis is not needed for medical inpatients.
And once patients are discharged, they have no need for compression stockings or aspirin on a long plane trip if their risk for thrombosis is not elevated.
People with a “substantially increased” thrombosis risk “may benefit” from compression stockings or treatment with LMWH, Dr. Cushman said.
Diagnosis
For diagnosis, Wendy Lim, MD, of McMaster University in Hamilton, Ontario, Canada, highlighted the need for first categorizing patients as having a low or high probability for VTE, a judgment that can aid the accuracy of the diagnosis and that helps avoid unnecessary testing.
For patients with low pretest probability, the guidelines recommend the D-dimer test as the best first step. Further testing isn’t needed when the D-dimer is negative, Dr. Lim noted.
The guidelines also recommend using ventilation-perfusion scintigraphy (V/Q scan) for imaging a pulmonary embolism over a CT scan, which uses more radiation. But V/Q scans are not ideal for assessing older patients or patients with lung disease, Dr. Lim cautioned.
Management
Management of VTE should occur, when feasible, through a specialized anticoagulation management service center, which can provide care that is best suited to the complexities of anticoagulation therapy.
But it’s a level of care that many U.S. patients don’t currently receive and, hence, is an area ripe for growth, said Daniel M. Witt, PharmD, of the University of Utah in Salt Lake City.
The guidelines recommend against bridging therapy with LMWH for most patients who need to stop warfarin when undergoing an invasive procedure.
The guidelines also call for “thoughtful” use of anticoagulant reversal agents, and they advise that patients who survive a major bleed while on anticoagulation should often resume the anticoagulant once they are stabilized.
For patients who develop heparin-induced thrombocytopenia, the 4Ts score is the best way to make a more accurate diagnosis and boost the prospects for recovery, according to Dr. Cuker, lead author of a paper on the subject published in Blood.
The guidelines cite several agents now available to treat this common complication, which affects about 1% of the 12 million Americans treated each year with heparin, argatroban, bivalirudin, danaparoid, fondaparinux, apixaban, dabigatran, edoxaban, and rivaroxaban.
ASH has a VTE website with links to detailed information for each of the guideline subcategories: prophylaxis for medical patients, diagnosis, anticoagulation therapy, heparin-induced thrombocytopenia, VTE in pregnancy, and VTE in children.
The website indicates that additional guidelines will soon be released on managing VTE in patients with cancer, in patients with thrombophilia, and for prophylaxis in surgical patients, as well as further information on treatment. A spokesperson for ASH said these additional documents will post sometime in 2019.
At the time of the release, the guidelines panel published the following six articles in the journal Blood Advances that detail the guidelines and their documentation relating to VTE and:
Drs. Cushman, Lim, and Witt reported having no relevant disclosures. Dr. Cuker reported receiving research support from T2 Biosystems.