Leukemia, Myelodysplasia, Transplantation

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers say they have identified biomarkers that may help guide early treatment decisions in patients with acute graft-versus-host disease (GVHD).

The biomarkers, ST2 and REG3-alpha, were measured during the first month of GVHD treatment and proved more accurate than clinical response for predicting 6-month nonrelapse mortality (NRM). In fact, biomarker assessment revealed patients who responded to treatment but had a high risk of NRM and nonresponders who had a low risk of NRM.

The researchers also found that biomarkers changed over the first month of treatment but remained significant predictors of NRM. This suggests that modifying treatment according to biomarker findings at various time points could result in better outcomes for patients.

“We think this is going to transform the way we treat graft-versus-host disease,” said James L.M. Ferrara, MD, DSc, of the Icahn School of Medicine at Mount Sinai, New York.

Dr. Ferrara and Hrishikesh Srinagesh, along with their colleagues at Mount Sinai, have conducted extensive research with these biomarkers and presented some of their findings at the Acute Leukemia Forum of Hemedicus.

Comparing biomarkers and response

In one study, the researchers evaluated 355 patients who had undergone allogeneic hematopoietic stem cell transplant at 1 of 20 Mount Sinai Acute GVHD International Consortium (MAGIC) centers between January 2016 and February 2018. All patients developed acute GVHD and received systemic steroids as treatment.

Patients provided blood samples weekly for the first month of treatment, and concentrations of ST2 and REG3-alpha were measured in each sample. Both biomarker concentrations were used to calculate the biomarker probability of NRM.

“The concentration of those two biomarkers are put into a computer, and we get … a single number, and that gives us the probability of mortality,” Dr. Ferrara said. “[W]e call this the MAGIC algorithm probability, or MAP. And when a MAP is low, the patient has a very low chance of dying from graft-versus-host disease, when it’s intermediate, they have an intermediate risk, and when it’s high, they have a high risk.”

The researchers then compared the MAP and clinical response for their ability to predict 6-month NRM throughout the first month of therapy for acute GVHD.

MAP bests response

After 1 month of therapy, the MAP was more accurate than clinical response for predicting 6-month NRM. The area under the curve was 0.84 and 0.65, respectively (P less than .001).

Likewise, the MAP after 1 week of therapy was more accurate than clinical response at 1 month for predicting 6-month NRM. The area under the curve was 0.80 and 0.65, respectively (P less than .001).

“[T]he clinical responses were good, but not great, at predicting long-term outcome, where the biomarker, the MAP, was significantly better,” Dr. Ferrara said. “[A]t every time point we tested, the biomarkers were better than the clinical responses.”

The researchers also identified subgroups of clinical responders and nonresponders for whom MAP more accurately predicted 6-month NRM.

The team found that 61% of clinical nonresponders were actually low risk according to MAP. And the incidence of 6-month NRM was significantly lower in the MAP-designated low-risk patients than in MAP-designated high-risk patients – 22% and 56%, respectively (P less than .001).

On the other hand, 10% of clinical responders were high risk according to MAP. The incidence of 6-month NRM was significantly higher in the high-risk patients than in the low-risk patients – 40% and 13%, respectively (P less than .001).

Assessing changes over time

The researchers found that patients who were initially high risk by MAP but had not experienced NRM by 6 months had significant decreases in their MAP after 4 weeks of treatment (P = .003). Patients who did experience NRM had a significant increase in their MAP whether their initial MAP was low (P = .007) or high (P = .024).

“What we found was that patients who lived tended to either have low biomarkers at the start of treatment and stay low or start out with high biomarkers and have reductions over the first month of therapy,” Mr. Srinagesh said. “Conversely, patients who tended to do worse were those who had either increases in their biomarkers or stayed high at all time points.”

The researchers identified a threshold – 0.290 – for separating patients by mortality risk.

“Patients who started out above the threshold and then went below it had a 5-fold reduction in mortality, whereas patients who started out below the threshold and rose above it had a 5-fold increase in mortality,” Mr. Srinagesh said.

MAP in clinical trials and practice

Based on these findings and results from related studies, the researchers theorize that MAP would be a better endpoint for clinical trials than clinical response.

At present, there are three trials in which researchers are using MAP as an endpoint to assess the efficacy of treatment for GVHD (NCT02133924, NCT03459040, and NCT03846479). Dr. Ferrara said a fourth trial is set to begin this summer.

Additionally, MAP is being used in clinical practice. A company called Viracor Eurofins Clinical Diagnostics licensed the MAGIC algorithm and provides three related tests for consumer use.

Viracor’s aGVHD Pre-Symptomatic Algorithm assigns patients to high- and low-risk groups based on results from samples collected 7 days after transplant. The aGVHD Symptomatic Onset Algorithm assigns patients to high-, intermediate-, and low-risk groups. The aGVHD Post-Treatment Algorithm, which can be used 7 days or more after GVHD treatment initiation, stratifies steroid-resistant patients into high- or low-risk groups for both NRM and overall survival.

“We are still in early days of figuring out how to use [the biomarker tests], but … what I’ve heard is that people are finding them to be useful in their clinical practice,” Dr. Ferrara said.

Dr. Ferrara has an ownership interest in and receives royalties from Viracor. Mr. Srinagesh reported having no relevant conflicts of interest. The research was supported by grants from the National Cancer Institute and the American Cancer Society.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

For patients with relapsed/refractory chronic lymphocytic leukemia (CLL), long-term treatment with the phosphoinositol 3-kinase inhibitor idelalisib appears safe and effective, according to investigators.

Final results from a phase 3 trial confirmed survival advantages when idelalisib is used in combination with rituximab, reported lead author Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Ore., and colleagues.

During follow-up, which exceeded 5 years in some patients, no new idelalisib-related adverse events were encountered, supporting the safety of long-term use, the investigators noted. The report is in the Journal of Clinical Oncology.

This study was “pivotal” for treating elderly patients with relapsed CLL, the investigators wrote, as these patients previously had few treatment options beyond supportive or palliative care.

Earlier results from the study showed that adding idelalisib to rituximab raised overall response rates from about 15.5% to 83.6% and median progression-free survival from 6.5 months to 19.4 months, resulting in “significantly better clinical outcomes compared with those seen with rituximab alone,” leading to approval by the Food and Drug Administration.

During the primary study, 110 patients received a combination of idelalisib and rituximab, while 108 patients received rituximab and placebo. The median patient age was 71 years, with a median of three lines of prior therapy. The present analysis focused on the 110 patients in the combination group who received at least one dose of idelalisib, whether or not they elected to participate in the extension phase.

After a median follow-up of 18 months, ranging from 0.3 months to 67.6 months, the overall response rate was 85.5% and the median progression-free survival was 20.3 months, both of which are similar to earlier findings. Median overall survival was 40.6 months.

With a median duration of exposure of 16.2 months, the safety analysis revealed no new idelalisib-related adverse events.

However, the investigators pointed out that prolonged therapy often led to diarrhea, which ultimately occurred in about half of patients (46.4%). Roughly equal amounts of patients experienced grade 2 (17.3%) or grade 3 or greater diarrhea (16.4%). In cases of grade 3 or greater diarrhea, steroid therapy was recommended, typically resulting in symptom resolution within 2 weeks; however, “there were insufficient numbers of patients to determine if steroid therapy affected the duration of symptoms,” the investigators wrote.

“The longer-term data presented here confirm the previously reported efficacy of targeting PI3K with idelalisib in patients with relapsed/refractory CLL and support the use of [idelalisib and rituximab] in this patient population with careful management of potential [adverse events],” they wrote.

Gilead Sciences funded the study. Dr. Sharman reported financial relationships with Gilead and other companies.

SOURCE: Sharman JP et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01460.

For patients with relapsed/refractory chronic lymphocytic leukemia (CLL), long-term treatment with the phosphoinositol 3-kinase inhibitor idelalisib appears safe and effective, according to investigators.

Final results from a phase 3 trial confirmed survival advantages when idelalisib is used in combination with rituximab, reported lead author Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Ore., and colleagues.

During follow-up, which exceeded 5 years in some patients, no new idelalisib-related adverse events were encountered, supporting the safety of long-term use, the investigators noted. The report is in the Journal of Clinical Oncology.

This study was “pivotal” for treating elderly patients with relapsed CLL, the investigators wrote, as these patients previously had few treatment options beyond supportive or palliative care.

Earlier results from the study showed that adding idelalisib to rituximab raised overall response rates from about 15.5% to 83.6% and median progression-free survival from 6.5 months to 19.4 months, resulting in “significantly better clinical outcomes compared with those seen with rituximab alone,” leading to approval by the Food and Drug Administration.

During the primary study, 110 patients received a combination of idelalisib and rituximab, while 108 patients received rituximab and placebo. The median patient age was 71 years, with a median of three lines of prior therapy. The present analysis focused on the 110 patients in the combination group who received at least one dose of idelalisib, whether or not they elected to participate in the extension phase.

After a median follow-up of 18 months, ranging from 0.3 months to 67.6 months, the overall response rate was 85.5% and the median progression-free survival was 20.3 months, both of which are similar to earlier findings. Median overall survival was 40.6 months.

With a median duration of exposure of 16.2 months, the safety analysis revealed no new idelalisib-related adverse events.

However, the investigators pointed out that prolonged therapy often led to diarrhea, which ultimately occurred in about half of patients (46.4%). Roughly equal amounts of patients experienced grade 2 (17.3%) or grade 3 or greater diarrhea (16.4%). In cases of grade 3 or greater diarrhea, steroid therapy was recommended, typically resulting in symptom resolution within 2 weeks; however, “there were insufficient numbers of patients to determine if steroid therapy affected the duration of symptoms,” the investigators wrote.

“The longer-term data presented here confirm the previously reported efficacy of targeting PI3K with idelalisib in patients with relapsed/refractory CLL and support the use of [idelalisib and rituximab] in this patient population with careful management of potential [adverse events],” they wrote.

Gilead Sciences funded the study. Dr. Sharman reported financial relationships with Gilead and other companies.

SOURCE: Sharman JP et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01460.

For patients with relapsed/refractory chronic lymphocytic leukemia (CLL), long-term treatment with the phosphoinositol 3-kinase inhibitor idelalisib appears safe and effective, according to investigators.

Final results from a phase 3 trial confirmed survival advantages when idelalisib is used in combination with rituximab, reported lead author Jeff P. Sharman, MD, of Willamette Valley Cancer Institute and Research Center in Springfield, Ore., and colleagues.

During follow-up, which exceeded 5 years in some patients, no new idelalisib-related adverse events were encountered, supporting the safety of long-term use, the investigators noted. The report is in the Journal of Clinical Oncology.

This study was “pivotal” for treating elderly patients with relapsed CLL, the investigators wrote, as these patients previously had few treatment options beyond supportive or palliative care.

Earlier results from the study showed that adding idelalisib to rituximab raised overall response rates from about 15.5% to 83.6% and median progression-free survival from 6.5 months to 19.4 months, resulting in “significantly better clinical outcomes compared with those seen with rituximab alone,” leading to approval by the Food and Drug Administration.

During the primary study, 110 patients received a combination of idelalisib and rituximab, while 108 patients received rituximab and placebo. The median patient age was 71 years, with a median of three lines of prior therapy. The present analysis focused on the 110 patients in the combination group who received at least one dose of idelalisib, whether or not they elected to participate in the extension phase.

After a median follow-up of 18 months, ranging from 0.3 months to 67.6 months, the overall response rate was 85.5% and the median progression-free survival was 20.3 months, both of which are similar to earlier findings. Median overall survival was 40.6 months.

With a median duration of exposure of 16.2 months, the safety analysis revealed no new idelalisib-related adverse events.

However, the investigators pointed out that prolonged therapy often led to diarrhea, which ultimately occurred in about half of patients (46.4%). Roughly equal amounts of patients experienced grade 2 (17.3%) or grade 3 or greater diarrhea (16.4%). In cases of grade 3 or greater diarrhea, steroid therapy was recommended, typically resulting in symptom resolution within 2 weeks; however, “there were insufficient numbers of patients to determine if steroid therapy affected the duration of symptoms,” the investigators wrote.

“The longer-term data presented here confirm the previously reported efficacy of targeting PI3K with idelalisib in patients with relapsed/refractory CLL and support the use of [idelalisib and rituximab] in this patient population with careful management of potential [adverse events],” they wrote.

Gilead Sciences funded the study. Dr. Sharman reported financial relationships with Gilead and other companies.

SOURCE: Sharman JP et al. J Clin Oncol. 2019 Apr 17. doi: 10.1200/JCO.18.01460.

Tagraxofusp demonstrated efficacy in a phase 2 trial of patients with previously treated or untreated blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The overall response rate was 90% in previously untreated patients who received the highest dose of tagraxofusp and 67% in patients with relapsed/refractory BPDCN.

The researchers wrote that capillary leak syndrome (CLS) was an important adverse event in this trial, as it caused two deaths. However, the researchers developed strategies that appear to mitigate the risk of CLS in patients taking tagraxofusp.

Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues conducted the trial and reported the results in the New England Journal of Medicine.

The trial included 47 patients – 32 with previously untreated BPDCN and 15 with relapsed/refractory BPDCN. The patients’ median age at baseline was 70 years and 83% were men.

Three patients (all previously untreated) received tagraxofusp at 7 mcg/kg per day, and 44 patients received a 12 mcg/kg per day dose. All patients were treated on days 1-5 of a 21-day cycle.

Response and survival

In the 29 previously untreated patients who received the 12 mcg/kg dose of tagraxofusp, the overall response rate was 90%. The rate of complete response plus clinical complete response in these patients was 72%.

In the 15 patients with relapsed/refractory BPDCN, the overall response rate was 67%, and the rate of complete response plus clinical complete response was 33%.

A total of 14 patients, 13 of whom had previously untreated BPDCN, went on to transplant.

In the 29 previously untreated patients, the median overall survival was not reached at a median follow-up of 25 months. The overall survival rate was 62% at 12 months, 59% at 18 months, and 52% at 24 months.

In the 15 previously treated patients, the median overall survival was 8.5 months.

Safety

Common adverse events in this trial were ALT increase (64%), AST increase (60%), hypoalbuminemia (55%), peripheral edema (51%), thrombocytopenia (49%), nausea (45%), pyrexia (45%), and fatigue (45%).

Among the 44 patients who received the 12 mcg/kg dose of tagraxofusp, 8 (18%) developed CLS. Six patients had grade 2 CLS, one had grade 4, and one had grade 5. There was an additional CLS-related death in a patient who received tagraxofusp at 7 mcg/kg.


After the first death, the trial protocol was amended to reduce CLS risk. Inclusion criteria were changed so that patients must have normal cardiac function, adequate kidney function, and serum albumin of at least 3.2 g/dL. Additionally, the researchers began monitoring patients’ weight, albumin levels, and kidney function. The team withheld tagraxofusp if patients experienced rapid weight gain or if their serum albumin or systolic blood pressure fell too low.

The trial was sponsored by Stemline Therapeutics. The researchers reported relationships with Stemline and other companies.

[email protected]

SOURCE: Pemmaraju N et al. N Engl J Med. 2019; 380:1628-37.

Tagraxofusp demonstrated efficacy in a phase 2 trial of patients with previously treated or untreated blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The overall response rate was 90% in previously untreated patients who received the highest dose of tagraxofusp and 67% in patients with relapsed/refractory BPDCN.

The researchers wrote that capillary leak syndrome (CLS) was an important adverse event in this trial, as it caused two deaths. However, the researchers developed strategies that appear to mitigate the risk of CLS in patients taking tagraxofusp.

Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues conducted the trial and reported the results in the New England Journal of Medicine.

The trial included 47 patients – 32 with previously untreated BPDCN and 15 with relapsed/refractory BPDCN. The patients’ median age at baseline was 70 years and 83% were men.

Three patients (all previously untreated) received tagraxofusp at 7 mcg/kg per day, and 44 patients received a 12 mcg/kg per day dose. All patients were treated on days 1-5 of a 21-day cycle.

Response and survival

In the 29 previously untreated patients who received the 12 mcg/kg dose of tagraxofusp, the overall response rate was 90%. The rate of complete response plus clinical complete response in these patients was 72%.

In the 15 patients with relapsed/refractory BPDCN, the overall response rate was 67%, and the rate of complete response plus clinical complete response was 33%.

A total of 14 patients, 13 of whom had previously untreated BPDCN, went on to transplant.

In the 29 previously untreated patients, the median overall survival was not reached at a median follow-up of 25 months. The overall survival rate was 62% at 12 months, 59% at 18 months, and 52% at 24 months.

In the 15 previously treated patients, the median overall survival was 8.5 months.

Safety

Common adverse events in this trial were ALT increase (64%), AST increase (60%), hypoalbuminemia (55%), peripheral edema (51%), thrombocytopenia (49%), nausea (45%), pyrexia (45%), and fatigue (45%).

Among the 44 patients who received the 12 mcg/kg dose of tagraxofusp, 8 (18%) developed CLS. Six patients had grade 2 CLS, one had grade 4, and one had grade 5. There was an additional CLS-related death in a patient who received tagraxofusp at 7 mcg/kg.


After the first death, the trial protocol was amended to reduce CLS risk. Inclusion criteria were changed so that patients must have normal cardiac function, adequate kidney function, and serum albumin of at least 3.2 g/dL. Additionally, the researchers began monitoring patients’ weight, albumin levels, and kidney function. The team withheld tagraxofusp if patients experienced rapid weight gain or if their serum albumin or systolic blood pressure fell too low.

The trial was sponsored by Stemline Therapeutics. The researchers reported relationships with Stemline and other companies.

[email protected]

SOURCE: Pemmaraju N et al. N Engl J Med. 2019; 380:1628-37.

Tagraxofusp demonstrated efficacy in a phase 2 trial of patients with previously treated or untreated blastic plasmacytoid dendritic cell neoplasm (BPDCN).

The overall response rate was 90% in previously untreated patients who received the highest dose of tagraxofusp and 67% in patients with relapsed/refractory BPDCN.

The researchers wrote that capillary leak syndrome (CLS) was an important adverse event in this trial, as it caused two deaths. However, the researchers developed strategies that appear to mitigate the risk of CLS in patients taking tagraxofusp.

Naveen Pemmaraju, MD, of the University of Texas MD Anderson Cancer Center, Houston, and his colleagues conducted the trial and reported the results in the New England Journal of Medicine.

The trial included 47 patients – 32 with previously untreated BPDCN and 15 with relapsed/refractory BPDCN. The patients’ median age at baseline was 70 years and 83% were men.

Three patients (all previously untreated) received tagraxofusp at 7 mcg/kg per day, and 44 patients received a 12 mcg/kg per day dose. All patients were treated on days 1-5 of a 21-day cycle.

Response and survival

In the 29 previously untreated patients who received the 12 mcg/kg dose of tagraxofusp, the overall response rate was 90%. The rate of complete response plus clinical complete response in these patients was 72%.

In the 15 patients with relapsed/refractory BPDCN, the overall response rate was 67%, and the rate of complete response plus clinical complete response was 33%.

A total of 14 patients, 13 of whom had previously untreated BPDCN, went on to transplant.

In the 29 previously untreated patients, the median overall survival was not reached at a median follow-up of 25 months. The overall survival rate was 62% at 12 months, 59% at 18 months, and 52% at 24 months.

In the 15 previously treated patients, the median overall survival was 8.5 months.

Safety

Common adverse events in this trial were ALT increase (64%), AST increase (60%), hypoalbuminemia (55%), peripheral edema (51%), thrombocytopenia (49%), nausea (45%), pyrexia (45%), and fatigue (45%).

Among the 44 patients who received the 12 mcg/kg dose of tagraxofusp, 8 (18%) developed CLS. Six patients had grade 2 CLS, one had grade 4, and one had grade 5. There was an additional CLS-related death in a patient who received tagraxofusp at 7 mcg/kg.


After the first death, the trial protocol was amended to reduce CLS risk. Inclusion criteria were changed so that patients must have normal cardiac function, adequate kidney function, and serum albumin of at least 3.2 g/dL. Additionally, the researchers began monitoring patients’ weight, albumin levels, and kidney function. The team withheld tagraxofusp if patients experienced rapid weight gain or if their serum albumin or systolic blood pressure fell too low.

The trial was sponsored by Stemline Therapeutics. The researchers reported relationships with Stemline and other companies.

[email protected]

SOURCE: Pemmaraju N et al. N Engl J Med. 2019; 380:1628-37.

GLASGOW – Many patients receiving tyrosine kinase inhibitors (TKIs) are taking complementary therapies or eating foods that interfere with TKI metabolism, based on results of a British survey of patients with chronic myeloid leukemia.

©Ls9907/Thinkstockphotos.com

About one out of three patients with chronic myeloid leukemia (CML) reported taking complementary medicines, according to lead author David Sparksman, MD, of Norfolk and Norwich (England) University Hospital, and his colleagues.

Only a minority of patients were aware of the potential for dietary interactions with TKIs. However, even knowing the potential risk, about a quarter of patients still didn’t exclude these foods from their diets.

“These worrying results are unlikely to be confined to patients with CML,” the investigators wrote in an abstract presented at the annual meeting of the British Society for Haematology. “TKIs are used in the treatment of many other haematological malignancies.”

Because TKIs are metabolized by cytochrome P450 enzymes, inhibition of these enzymes by complementary therapies and foods may alter metabolism, and therefore, safety and efficacy of TKIs, according to the investigators.

“Use of complementary medicines and belief in their effectiveness is common,” the investigators wrote. “In a recent YouGov poll, 51% of those asked believed herbal medicine to be an effective treatment for illness.”

To investigate the prevalence of these beliefs and practices in a subset of cancer patients, the investigators identified 78 patients with CML undergoing follow-up at Norfolk and Norwich University Hospital. The median age of patients was 60 years. Eleven patients were excluded because they were not receiving a TKI and 6 patients declined to participate, leaving 61 patients in the final survey group.

Of these respondents, 41% had considered taking a complementary therapy and 34% were actively doing so. Further questioning revealed that about half of the patients taking a complementary medicine (52%) were taking a drug with known potential to interact with their TKI. Of these 11 patients, 5 were taking a complementary drug that would reduce serum concentrations of their TKI, potentially making it less effective. Conversely, six patients were taking a complementary drug that would increase serum concentrations, potentially increasing the risk of TKI side effects.

About 39% of respondents were aware of possible dietary interactions with TKIs, such as grapefruit. “Surprisingly,” the investigators said, 25% of patients with this knowledge still included such foods in their diet.

Dietary questioning revealed that among the patients who were unaware of food interactions, 67% were consuming foods that interact with TKIs.

Considering these results, the investigators offered some advice on patient communication and management.

“The use of complementary medicine should be discussed with all patients when starting TKIs and written information given to patients should highlight the potential dangers posed by substances which many patients currently regard as harmless,” thy wrote. “Since most patients will remain on treatment for many years, re-discussion about food and drug interactions should take place periodically to remind them of the potential risks.”

The investigators reported having no conflicts of interest.

GLASGOW – Many patients receiving tyrosine kinase inhibitors (TKIs) are taking complementary therapies or eating foods that interfere with TKI metabolism, based on results of a British survey of patients with chronic myeloid leukemia.

©Ls9907/Thinkstockphotos.com

About one out of three patients with chronic myeloid leukemia (CML) reported taking complementary medicines, according to lead author David Sparksman, MD, of Norfolk and Norwich (England) University Hospital, and his colleagues.

Only a minority of patients were aware of the potential for dietary interactions with TKIs. However, even knowing the potential risk, about a quarter of patients still didn’t exclude these foods from their diets.

“These worrying results are unlikely to be confined to patients with CML,” the investigators wrote in an abstract presented at the annual meeting of the British Society for Haematology. “TKIs are used in the treatment of many other haematological malignancies.”

Because TKIs are metabolized by cytochrome P450 enzymes, inhibition of these enzymes by complementary therapies and foods may alter metabolism, and therefore, safety and efficacy of TKIs, according to the investigators.

“Use of complementary medicines and belief in their effectiveness is common,” the investigators wrote. “In a recent YouGov poll, 51% of those asked believed herbal medicine to be an effective treatment for illness.”

To investigate the prevalence of these beliefs and practices in a subset of cancer patients, the investigators identified 78 patients with CML undergoing follow-up at Norfolk and Norwich University Hospital. The median age of patients was 60 years. Eleven patients were excluded because they were not receiving a TKI and 6 patients declined to participate, leaving 61 patients in the final survey group.

Of these respondents, 41% had considered taking a complementary therapy and 34% were actively doing so. Further questioning revealed that about half of the patients taking a complementary medicine (52%) were taking a drug with known potential to interact with their TKI. Of these 11 patients, 5 were taking a complementary drug that would reduce serum concentrations of their TKI, potentially making it less effective. Conversely, six patients were taking a complementary drug that would increase serum concentrations, potentially increasing the risk of TKI side effects.

About 39% of respondents were aware of possible dietary interactions with TKIs, such as grapefruit. “Surprisingly,” the investigators said, 25% of patients with this knowledge still included such foods in their diet.

Dietary questioning revealed that among the patients who were unaware of food interactions, 67% were consuming foods that interact with TKIs.

Considering these results, the investigators offered some advice on patient communication and management.

“The use of complementary medicine should be discussed with all patients when starting TKIs and written information given to patients should highlight the potential dangers posed by substances which many patients currently regard as harmless,” thy wrote. “Since most patients will remain on treatment for many years, re-discussion about food and drug interactions should take place periodically to remind them of the potential risks.”

The investigators reported having no conflicts of interest.

GLASGOW – Many patients receiving tyrosine kinase inhibitors (TKIs) are taking complementary therapies or eating foods that interfere with TKI metabolism, based on results of a British survey of patients with chronic myeloid leukemia.

©Ls9907/Thinkstockphotos.com

About one out of three patients with chronic myeloid leukemia (CML) reported taking complementary medicines, according to lead author David Sparksman, MD, of Norfolk and Norwich (England) University Hospital, and his colleagues.

Only a minority of patients were aware of the potential for dietary interactions with TKIs. However, even knowing the potential risk, about a quarter of patients still didn’t exclude these foods from their diets.

“These worrying results are unlikely to be confined to patients with CML,” the investigators wrote in an abstract presented at the annual meeting of the British Society for Haematology. “TKIs are used in the treatment of many other haematological malignancies.”

Because TKIs are metabolized by cytochrome P450 enzymes, inhibition of these enzymes by complementary therapies and foods may alter metabolism, and therefore, safety and efficacy of TKIs, according to the investigators.

“Use of complementary medicines and belief in their effectiveness is common,” the investigators wrote. “In a recent YouGov poll, 51% of those asked believed herbal medicine to be an effective treatment for illness.”

To investigate the prevalence of these beliefs and practices in a subset of cancer patients, the investigators identified 78 patients with CML undergoing follow-up at Norfolk and Norwich University Hospital. The median age of patients was 60 years. Eleven patients were excluded because they were not receiving a TKI and 6 patients declined to participate, leaving 61 patients in the final survey group.

Of these respondents, 41% had considered taking a complementary therapy and 34% were actively doing so. Further questioning revealed that about half of the patients taking a complementary medicine (52%) were taking a drug with known potential to interact with their TKI. Of these 11 patients, 5 were taking a complementary drug that would reduce serum concentrations of their TKI, potentially making it less effective. Conversely, six patients were taking a complementary drug that would increase serum concentrations, potentially increasing the risk of TKI side effects.

About 39% of respondents were aware of possible dietary interactions with TKIs, such as grapefruit. “Surprisingly,” the investigators said, 25% of patients with this knowledge still included such foods in their diet.

Dietary questioning revealed that among the patients who were unaware of food interactions, 67% were consuming foods that interact with TKIs.

Considering these results, the investigators offered some advice on patient communication and management.

“The use of complementary medicine should be discussed with all patients when starting TKIs and written information given to patients should highlight the potential dangers posed by substances which many patients currently regard as harmless,” thy wrote. “Since most patients will remain on treatment for many years, re-discussion about food and drug interactions should take place periodically to remind them of the potential risks.”

The investigators reported having no conflicts of interest.

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. — A model that mimics the recommender system used by Netflix and Amazon can help predict outcomes of lenalidomide treatment in patients with non–deletion 5q (non-del[5q]) myelodysplastic syndromes (MDS), according to new research.

The model was used to identify genomic biomarkers that were associated with resistance or response to lenalidomide. Researchers found these associations in 39% of patients with non-del(5q) MDS, and the model predicted response or resistance with 82% accuracy.

Yazan Madanat, MD, of the Cleveland Clinic, and his colleagues presented these findings at the Acute Leukemia Forum of Hemedicus.

Dr. Madanat explained that his group’s model is similar to the recommender system used by Netflix and Amazon, which makes suggestions for new products based on customers’ past behavior. Dr. Madanat and his colleagues used their model to show that patients with certain molecular or cytogenetic abnormalities are likely to respond or not respond to lenalidomide.

The researchers began by looking at 139 patients who had received at least two cycles of lenalidomide treatment. There were 118 patients with MDS, and 108 who had received lenalidomide monotherapy. However, the team focused on the 100 patients who had non-del(5q) MDS, 58 of whom had normal karyotype (NK) and 19 of whom had complex karyotype (CK).

The model revealed several combinations of genomic/cytogenetic abnormalities that could predict resistance to lenalidomide, including the following:

• DNMT3A and SF3B1
• EZH2 and NK
• ASXL1, TET2, and NK
• STAG2, IDH1/2, and NK
• TP53, del(5q), and CK
• BCOR/BCORL1 and NK
• JAK2, TET2, and NK
• U2AF1, +/– ETV6, and NK

However, only the following two combinations could predict response to lenalidomide:

• DDX41 and NK
• MECOM and KDM6A/B

These combinations could be applied to 39% of the patients with non-del(5q) MDS, and the model predicted response or resistance to lenalidomide with 82% accuracy.

Although the biomarkers were found in only a subset of patients, Dr. Madanat said these findings may help physicians tailor therapy for MDS patients, given the high level of accuracy the researchers observed.

“It’s really important to validate the results in a prospective manner and to ensure that we’re able to apply them clinically and potentially change the way we’re treating our patients,” he added.

Dr. Madanat and his colleagues reported having no relevant conflicts of interest.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – A five-drug regimen was deemed safe in patients with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndromes (MDS), and it appeared to be effective regardless of patients’ FLT3 status.

Researchers tested this regimen – sorafenib plus granulocyte colony–stimulating factor (G-CSF), cladribine, high-dose cytarabine, and mitoxantrone (GCLAM) – in a phase 1 trial.

Kelsey-Leigh Garcia, a clinical research coordinator at Seattle Cancer Care Alliance, and her colleagues presented the results at the Acute Leukemia Forum of Hemedicus.

“The background for doing this study was our institutional results of GCLAM [Leukemia. 2018 Nov;32(11):2352-62] that showed a higher minimal residual disease–negative complete response rate than 7+3 [cytarabine continuously for 7 days, along with short infusions of an anthracycline on each of the first 3 days] and an international study by Röllig that showed the addition of sorafenib to 7+3 increased event-free survival versus [7+3 and] placebo [Lancet Oncol. 2015 Dec;16(16):1691-9],” Ms. Garcia said.

“GCLAM is the standard backbone at our institution, and we wanted to ask the question, ‘If we add sorafenib, can this improve upon the results of GCLAM?’ ” said Anna Halpern, MD, a hematologist-oncologist at the University of Washington, Seattle and principal investigator of the phase 1 trial.

The trial (NCT02728050) included 47 patients, 39 with AML and 8 with MDS. Patients were aged 60 years or younger and had a median age of 48. They had a median treatment-related mortality score of 1.76 (range, 0.19-12.26). A total of 11 patients (23%) had FLT3-ITD, and 4 (9%) had FLT3-TKD.

Treatment and toxicity

For induction, patients received G-CSF at 5 mcg/kg on days 0-5, cladribine at 5 mg/m² on days 1-5, and cytarabine at 2 g/m² on days 1-5. Mitoxantrone was given at 10 mg/m², 12 mg/m², 15 mg/m², or 18 mg/m² on days 1-3. Sorafenib was given at 200 mg twice daily, 400 mg in the morning and 200 mg in the afternoon, or 400 mg b.i.d. on days 10-19.

For consolidation, patients could receive up to four cycles of G-CSF, cladribine, and cytarabine plus sorafenib on days 8-27. Patients who did not proceed to transplant could receive 12 months of sorafenib as maintenance therapy.

There were four dose-limiting toxicities.

• Grade 4 intracranial hemorrhage with mitoxantrone at 12 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 prolonged count recovery with mitoxantrone at 15 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 4 sepsis, Sweet syndrome, and Bell’s palsy with mitoxantrone at 18 mg/m² and sorafenib at 200 mg b.i.d.
• Grade 3 cardiomyopathy and acute pericarditis with mitoxantrone at 18 mg/m² and sorafenib at 400 mg b.i.d.

However, these toxicities did not define the maximum-tolerated dose. Therefore, the recommended phase 2 dose of mitoxantrone is 18 mg/m², and the recommended phase 2 dose of sorafenib is 400 mg b.i.d.

There were no grade 5 treatment-related adverse events. Grade 3 events included febrile neutropenia (90%), maculopapular rash (20%), infections (10%), hand-foot syndrome (2%), and diarrhea (1%). Grade 4 events included sepsis, intracranial hemorrhage, and oral mucositis (all 1%).

Response and survival

Among the 46 evaluable patients, 83% achieved a complete response, 78% had a minimal residual disease–negative complete response, and 4% had a minimal residual disease–negative complete response with incomplete count recovery. A morphological leukemia-free state was achieved by 4% of patients, and 8% had resistant disease.

Fifty-nine percent of patients went on to transplant. The median overall survival had not been reached at a median follow-up of 10 months.

The researchers compared outcomes in this trial with outcomes in a cohort of patients who had received GCLAM alone, and there were no significant differences in overall survival or event-free survival.

“The trial wasn’t powered, necessarily, for efficacy, but we compared these results to our historical cohort of medically matched and age-matched patients treated with GCLAM alone and, so far, found no differences in survival between the two groups,” Dr. Halpern said.

She noted, however, that follow-up was short in the sorafenib trial, and it included patients treated with all dose levels of sorafenib and mitoxantrone.

A phase 2 study of sorafenib plus GCLAM in newly diagnosed AML or high-risk MDS is now underway.

Dr. Halpern and Ms. Garcia reported that they had no conflicts of interest. The phase 1 trial was sponsored by the University of Washington in collaboration with the National Cancer Institute, and funding was provided by Bayer.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

Studies that look at the relationship between environment and childhood leukemia usually consider exposure at only a single residential address, such as the child’s home at birth or at time of diagnosis, say researchers from University of California and University of Southern California. But residential mobility, they contend, can have an impact on a number of relevant factors.

For instance, mobility can affect selection through the availability of data; cases are usually required to reside and be diagnosed in the same geographic area. It can affect exposure to electromagnetic fields and overhead power lines.  Residential mobility can also function as a marker for other risk factors for childhood leukemia, such as maternal place of birth and younger maternal age at birth, as well as increased exposure to viruses or other infections potentially linked to higher leukemia risk. Finally, the type of dwelling can affect not only exposure but exposure assessment. Mobile homes and apartments, for instance, are more likely to lead to poor geographic information system (GIS) matching of the residential address.

The researchers hoped with their study to “disentangle the effect of mobility.” Using the California Power Lines Study, they analyzed data from 4,879 childhood leukemia patients born in California and diagnosed between 1988 and 2008.

Many childhood leukemia cases were mobile, the researchers found: 2,982 (61%) children changed residence between birth and diagnosis. Of those who moved, 618 stayed within 2 km of their birth home; 1,992 moved outside of their birth neighborhood. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status.

However, the effects of distance to power lines and magnetic field exposure on childhood leukemia were similar for a subset of residentially stable cases, and overall results were unchanged when the researchers controlled for proxies of mobility (except for dwelling). They found an OR for childhood leukemia of 1.44 for those whose birth residence was within 50 m of a 200+ kV line, and an OR of 1.50 for the highest exposure of calculated fields, compared with 1.62 and 1.71, respectively, among children who stayed in place.

While they believe their findings on mobility are relevant to other environmental exposures and other childhood outcome studies, the researchers conclude that confounding by mobility is an unlikely explanation for the associations observed between power lines exposure and childhood leukemia.

Studies that look at the relationship between environment and childhood leukemia usually consider exposure at only a single residential address, such as the child’s home at birth or at time of diagnosis, say researchers from University of California and University of Southern California. But residential mobility, they contend, can have an impact on a number of relevant factors.

For instance, mobility can affect selection through the availability of data; cases are usually required to reside and be diagnosed in the same geographic area. It can affect exposure to electromagnetic fields and overhead power lines.  Residential mobility can also function as a marker for other risk factors for childhood leukemia, such as maternal place of birth and younger maternal age at birth, as well as increased exposure to viruses or other infections potentially linked to higher leukemia risk. Finally, the type of dwelling can affect not only exposure but exposure assessment. Mobile homes and apartments, for instance, are more likely to lead to poor geographic information system (GIS) matching of the residential address.

The researchers hoped with their study to “disentangle the effect of mobility.” Using the California Power Lines Study, they analyzed data from 4,879 childhood leukemia patients born in California and diagnosed between 1988 and 2008.

Many childhood leukemia cases were mobile, the researchers found: 2,982 (61%) children changed residence between birth and diagnosis. Of those who moved, 618 stayed within 2 km of their birth home; 1,992 moved outside of their birth neighborhood. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status.

However, the effects of distance to power lines and magnetic field exposure on childhood leukemia were similar for a subset of residentially stable cases, and overall results were unchanged when the researchers controlled for proxies of mobility (except for dwelling). They found an OR for childhood leukemia of 1.44 for those whose birth residence was within 50 m of a 200+ kV line, and an OR of 1.50 for the highest exposure of calculated fields, compared with 1.62 and 1.71, respectively, among children who stayed in place.

While they believe their findings on mobility are relevant to other environmental exposures and other childhood outcome studies, the researchers conclude that confounding by mobility is an unlikely explanation for the associations observed between power lines exposure and childhood leukemia.

Studies that look at the relationship between environment and childhood leukemia usually consider exposure at only a single residential address, such as the child’s home at birth or at time of diagnosis, say researchers from University of California and University of Southern California. But residential mobility, they contend, can have an impact on a number of relevant factors.

For instance, mobility can affect selection through the availability of data; cases are usually required to reside and be diagnosed in the same geographic area. It can affect exposure to electromagnetic fields and overhead power lines.  Residential mobility can also function as a marker for other risk factors for childhood leukemia, such as maternal place of birth and younger maternal age at birth, as well as increased exposure to viruses or other infections potentially linked to higher leukemia risk. Finally, the type of dwelling can affect not only exposure but exposure assessment. Mobile homes and apartments, for instance, are more likely to lead to poor geographic information system (GIS) matching of the residential address.

The researchers hoped with their study to “disentangle the effect of mobility.” Using the California Power Lines Study, they analyzed data from 4,879 childhood leukemia patients born in California and diagnosed between 1988 and 2008.

Many childhood leukemia cases were mobile, the researchers found: 2,982 (61%) children changed residence between birth and diagnosis. Of those who moved, 618 stayed within 2 km of their birth home; 1,992 moved outside of their birth neighborhood. Children who moved tended to be older, lived in housing other than single-family homes, had younger mothers and fewer siblings, and were of lower socioeconomic status.

However, the effects of distance to power lines and magnetic field exposure on childhood leukemia were similar for a subset of residentially stable cases, and overall results were unchanged when the researchers controlled for proxies of mobility (except for dwelling). They found an OR for childhood leukemia of 1.44 for those whose birth residence was within 50 m of a 200+ kV line, and an OR of 1.50 for the highest exposure of calculated fields, compared with 1.62 and 1.71, respectively, among children who stayed in place.

While they believe their findings on mobility are relevant to other environmental exposures and other childhood outcome studies, the researchers conclude that confounding by mobility is an unlikely explanation for the associations observed between power lines exposure and childhood leukemia.

NEWPORT BEACH, CALIF. – Researchers have shown they can identify transgender leukemia patients by detecting gender-karyotype mismatches, but some transgender patients may be overlooked with this method.

The researchers’ work also highlights how little we know about transgender patients with leukemia and other cancers.

Alison Alpert, MD, of the University of Rochester (N.Y.) Medical Center, and her colleagues conducted this research and presented their findings in a poster at the Acute Leukemia Forum of Hemedicus.

“There’s almost no data about transgender people with cancer ... in terms of prevalence or anything else,” Dr. Alpert noted. “And because we don’t know which patients with cancer are transgender, we can’t begin to answer any of the other big questions for patients.”

Specifically, it’s unclear what kinds of cancer transgender patients have, if there are health disparities among transgender patients, if it is safe to continue hormone therapy during cancer treatment, and if it is possible to do transition-related surgeries in the context of cancer care.

With this in mind, Dr. Alpert and her colleagues set out to identify transgender patients by detecting gender-karyotype mismatches. The team analyzed data on patients with acute myeloid leukemia (AML) or myelodysplastic syndromes enrolled in five Southwest Oncology Group (SWOG) trials.

Of the 1,748 patients analyzed, six (0.3%) had a gender-karyotype mismatch. Five patients had a 46,XY karyotype and identified as female, and one patient had a 46,XX karyotype and identified as male.

“Some transgender patients have their gender identity accurately reflected in the electronic medical record, [but] some transgender patients probably don’t,” Dr. Alpert noted. “So we identified some, but probably not all, and probably not even most, transgender patients with leukemia in this cohort.”

All six of the transgender patients identified had AML, and all were white. They ranged in age from 18 to 57 years. Four patients had achieved a complete response to therapy, and two had refractory disease.

Four patients, including one who was refractory, were still alive at last follow-up. The remaining two patients, including one who had achieved a complete response, had died.

The transgender patients identified in this analysis represent a very small percentage of the population studied, Dr. Alpert noted. Therefore, the researchers could not draw any conclusions about transgender patients with AML.

“Mostly, what we did was, we pointed out how little information we have,” Dr. Alpert said. “Oncologists don’t routinely collect gender identity information, and this information doesn’t exist in cooperative group databases either.”

“But going forward, what probably really needs to happen is that oncologists need to ask their patients whether they are transgender or not. And then, ideally, consent forms for large cooperative groups like SWOG would include gender identity data, and then we would be able to answer some of our other questions and better counsel our patients.”

Dr. Alpert and her colleagues are hoping to gain insights regarding transgender patients with lymphoma as well. The researchers are analyzing the lymphoma database at the University of Rochester Medical Center, which includes about 2,200 patients.

The team is attempting to identify transgender lymphoma patients using gender-karyotype mismatch as well as other methods, including assessing patients’ medication and surgical histories, determining whether patients have any aliases, and looking for the word “transgender” in patient charts.

“Given that the country is finally starting to talk about transgender patients, their health disparities, and their needs and experiences, it’s really time that we start collecting this data,” Dr. Alpert said.

“[I]f we are able to start to collect this data, it can help us build relationships with our patients, improve their care and outcomes, and, hopefully, be able to better counsel them about hormones and surgery.”

Dr. Alpert and her colleagues did not disclose any conflicts of interest.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers have shown they can identify transgender leukemia patients by detecting gender-karyotype mismatches, but some transgender patients may be overlooked with this method.

The researchers’ work also highlights how little we know about transgender patients with leukemia and other cancers.

Alison Alpert, MD, of the University of Rochester (N.Y.) Medical Center, and her colleagues conducted this research and presented their findings in a poster at the Acute Leukemia Forum of Hemedicus.

“There’s almost no data about transgender people with cancer ... in terms of prevalence or anything else,” Dr. Alpert noted. “And because we don’t know which patients with cancer are transgender, we can’t begin to answer any of the other big questions for patients.”

Specifically, it’s unclear what kinds of cancer transgender patients have, if there are health disparities among transgender patients, if it is safe to continue hormone therapy during cancer treatment, and if it is possible to do transition-related surgeries in the context of cancer care.

With this in mind, Dr. Alpert and her colleagues set out to identify transgender patients by detecting gender-karyotype mismatches. The team analyzed data on patients with acute myeloid leukemia (AML) or myelodysplastic syndromes enrolled in five Southwest Oncology Group (SWOG) trials.

Of the 1,748 patients analyzed, six (0.3%) had a gender-karyotype mismatch. Five patients had a 46,XY karyotype and identified as female, and one patient had a 46,XX karyotype and identified as male.

“Some transgender patients have their gender identity accurately reflected in the electronic medical record, [but] some transgender patients probably don’t,” Dr. Alpert noted. “So we identified some, but probably not all, and probably not even most, transgender patients with leukemia in this cohort.”

All six of the transgender patients identified had AML, and all were white. They ranged in age from 18 to 57 years. Four patients had achieved a complete response to therapy, and two had refractory disease.

Four patients, including one who was refractory, were still alive at last follow-up. The remaining two patients, including one who had achieved a complete response, had died.

The transgender patients identified in this analysis represent a very small percentage of the population studied, Dr. Alpert noted. Therefore, the researchers could not draw any conclusions about transgender patients with AML.

“Mostly, what we did was, we pointed out how little information we have,” Dr. Alpert said. “Oncologists don’t routinely collect gender identity information, and this information doesn’t exist in cooperative group databases either.”

“But going forward, what probably really needs to happen is that oncologists need to ask their patients whether they are transgender or not. And then, ideally, consent forms for large cooperative groups like SWOG would include gender identity data, and then we would be able to answer some of our other questions and better counsel our patients.”

Dr. Alpert and her colleagues are hoping to gain insights regarding transgender patients with lymphoma as well. The researchers are analyzing the lymphoma database at the University of Rochester Medical Center, which includes about 2,200 patients.

The team is attempting to identify transgender lymphoma patients using gender-karyotype mismatch as well as other methods, including assessing patients’ medication and surgical histories, determining whether patients have any aliases, and looking for the word “transgender” in patient charts.

“Given that the country is finally starting to talk about transgender patients, their health disparities, and their needs and experiences, it’s really time that we start collecting this data,” Dr. Alpert said.

“[I]f we are able to start to collect this data, it can help us build relationships with our patients, improve their care and outcomes, and, hopefully, be able to better counsel them about hormones and surgery.”

Dr. Alpert and her colleagues did not disclose any conflicts of interest.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – Researchers have shown they can identify transgender leukemia patients by detecting gender-karyotype mismatches, but some transgender patients may be overlooked with this method.

The researchers’ work also highlights how little we know about transgender patients with leukemia and other cancers.

Alison Alpert, MD, of the University of Rochester (N.Y.) Medical Center, and her colleagues conducted this research and presented their findings in a poster at the Acute Leukemia Forum of Hemedicus.

“There’s almost no data about transgender people with cancer ... in terms of prevalence or anything else,” Dr. Alpert noted. “And because we don’t know which patients with cancer are transgender, we can’t begin to answer any of the other big questions for patients.”

Specifically, it’s unclear what kinds of cancer transgender patients have, if there are health disparities among transgender patients, if it is safe to continue hormone therapy during cancer treatment, and if it is possible to do transition-related surgeries in the context of cancer care.

With this in mind, Dr. Alpert and her colleagues set out to identify transgender patients by detecting gender-karyotype mismatches. The team analyzed data on patients with acute myeloid leukemia (AML) or myelodysplastic syndromes enrolled in five Southwest Oncology Group (SWOG) trials.

Of the 1,748 patients analyzed, six (0.3%) had a gender-karyotype mismatch. Five patients had a 46,XY karyotype and identified as female, and one patient had a 46,XX karyotype and identified as male.

“Some transgender patients have their gender identity accurately reflected in the electronic medical record, [but] some transgender patients probably don’t,” Dr. Alpert noted. “So we identified some, but probably not all, and probably not even most, transgender patients with leukemia in this cohort.”

All six of the transgender patients identified had AML, and all were white. They ranged in age from 18 to 57 years. Four patients had achieved a complete response to therapy, and two had refractory disease.

Four patients, including one who was refractory, were still alive at last follow-up. The remaining two patients, including one who had achieved a complete response, had died.

The transgender patients identified in this analysis represent a very small percentage of the population studied, Dr. Alpert noted. Therefore, the researchers could not draw any conclusions about transgender patients with AML.

“Mostly, what we did was, we pointed out how little information we have,” Dr. Alpert said. “Oncologists don’t routinely collect gender identity information, and this information doesn’t exist in cooperative group databases either.”

“But going forward, what probably really needs to happen is that oncologists need to ask their patients whether they are transgender or not. And then, ideally, consent forms for large cooperative groups like SWOG would include gender identity data, and then we would be able to answer some of our other questions and better counsel our patients.”

Dr. Alpert and her colleagues are hoping to gain insights regarding transgender patients with lymphoma as well. The researchers are analyzing the lymphoma database at the University of Rochester Medical Center, which includes about 2,200 patients.

The team is attempting to identify transgender lymphoma patients using gender-karyotype mismatch as well as other methods, including assessing patients’ medication and surgical histories, determining whether patients have any aliases, and looking for the word “transgender” in patient charts.

“Given that the country is finally starting to talk about transgender patients, their health disparities, and their needs and experiences, it’s really time that we start collecting this data,” Dr. Alpert said.

“[I]f we are able to start to collect this data, it can help us build relationships with our patients, improve their care and outcomes, and, hopefully, be able to better counsel them about hormones and surgery.”

Dr. Alpert and her colleagues did not disclose any conflicts of interest.

The Acute Leukemia Forum is organized by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The evolving treatment of acute myeloid leukemia (AML) was highlighted at the Acute Leukemia Forum of Hemedicus.

In a video interview, Martin Tallman, MD, of Memorial Sloan Kettering Cancer Center in New York, discussed several meeting presentations on the treatment of AML.

In his presentation, Craig Jordan, PhD, of the University of Colorado at Denver, Aurora, explained how the combination of venetoclax and azacitidine appears to target leukemic stem cells in AML.

Courtney DiNardo, MD, of the University of Texas MD Anderson Cancer Center, Houston, presented information on novel agents for AML, including antibody-drug conjugates; bispecific therapies; checkpoint inhibitors; and inhibitors of IDH1/2, MCL1, and MDM2.

Richard Larson, MD, of the University of Chicago, explored the possibility of an individualized approach to postremission therapy in AML.

Frederick Appelbaum, MD, of Fred Hutchinson Cancer Research Center in Seattle, showed that various maintenance therapies given after allogeneic hematopoietic stem cell transplant (HSCT) have not proven beneficial for AML patients.

Richard Jones, MD, of Johns Hopkins Medicine in Baltimore, presented data showing that post-HSCT cyclophosphamide has made haploidentical transplants safer and more effective for AML patients.

And James Ferrara, MD, of the Icahn School of Medicine at Mount Sinai, New York, detailed research showing that biomarkers of graft-versus-host disease can predict nonrelapse mortality after HSCT.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The evolving treatment of acute myeloid leukemia (AML) was highlighted at the Acute Leukemia Forum of Hemedicus.

In a video interview, Martin Tallman, MD, of Memorial Sloan Kettering Cancer Center in New York, discussed several meeting presentations on the treatment of AML.

In his presentation, Craig Jordan, PhD, of the University of Colorado at Denver, Aurora, explained how the combination of venetoclax and azacitidine appears to target leukemic stem cells in AML.

Courtney DiNardo, MD, of the University of Texas MD Anderson Cancer Center, Houston, presented information on novel agents for AML, including antibody-drug conjugates; bispecific therapies; checkpoint inhibitors; and inhibitors of IDH1/2, MCL1, and MDM2.

Richard Larson, MD, of the University of Chicago, explored the possibility of an individualized approach to postremission therapy in AML.

Frederick Appelbaum, MD, of Fred Hutchinson Cancer Research Center in Seattle, showed that various maintenance therapies given after allogeneic hematopoietic stem cell transplant (HSCT) have not proven beneficial for AML patients.

Richard Jones, MD, of Johns Hopkins Medicine in Baltimore, presented data showing that post-HSCT cyclophosphamide has made haploidentical transplants safer and more effective for AML patients.

And James Ferrara, MD, of the Icahn School of Medicine at Mount Sinai, New York, detailed research showing that biomarkers of graft-versus-host disease can predict nonrelapse mortality after HSCT.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The evolving treatment of acute myeloid leukemia (AML) was highlighted at the Acute Leukemia Forum of Hemedicus.

In a video interview, Martin Tallman, MD, of Memorial Sloan Kettering Cancer Center in New York, discussed several meeting presentations on the treatment of AML.

In his presentation, Craig Jordan, PhD, of the University of Colorado at Denver, Aurora, explained how the combination of venetoclax and azacitidine appears to target leukemic stem cells in AML.

Courtney DiNardo, MD, of the University of Texas MD Anderson Cancer Center, Houston, presented information on novel agents for AML, including antibody-drug conjugates; bispecific therapies; checkpoint inhibitors; and inhibitors of IDH1/2, MCL1, and MDM2.

Richard Larson, MD, of the University of Chicago, explored the possibility of an individualized approach to postremission therapy in AML.

Frederick Appelbaum, MD, of Fred Hutchinson Cancer Research Center in Seattle, showed that various maintenance therapies given after allogeneic hematopoietic stem cell transplant (HSCT) have not proven beneficial for AML patients.

Richard Jones, MD, of Johns Hopkins Medicine in Baltimore, presented data showing that post-HSCT cyclophosphamide has made haploidentical transplants safer and more effective for AML patients.

And James Ferrara, MD, of the Icahn School of Medicine at Mount Sinai, New York, detailed research showing that biomarkers of graft-versus-host disease can predict nonrelapse mortality after HSCT.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The combination of ruxolitinib and decitabine will not proceed to a phase 3 trial in patients with accelerated or blast phase myeloproliferative neoplasms (MPNs).

The combination demonstrated activity and tolerability in a phase 2 trial, but outcomes were not optimal, according to Raajit K. Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

“[P]erhaps the outcomes might be favorable compared to standard induction chemotherapy regimens,” Dr. Rampal said. “Nonetheless, it’s clear that we still have a lot of work to do, and the outcomes are not optimal in these patients.”

However, Dr. Rampal and his colleagues are investigating the possibility of combining ruxolitinib and decitabine with other agents to treat patients with accelerated or blast phase MPNs.

Dr. Rampal and his colleagues presented results from the phase 2 trial in a poster at the Acute Leukemia Forum of Hemedicus.

The trial (NCT02076191) enrolled 25 patients, 10 with accelerated phase MPN (10%-19% blasts) and 15 with blast phase MPN (at least 20% blasts). The patients’ median age was 71 years.

Patients had a median disease duration of 72.9 months. Six patients (25%) had received prior ruxolitinib, and two (8.3%) had received prior decitabine.

Treatment and safety

For the first cycle, patients received decitabine at 20 mg/m² per day on days 8-12 and ruxolitinib at 25 mg twice a day on days 1-35. For subsequent cycles, patients received the same dose of decitabine on days 1-5 and ruxolitinib at 10 mg twice a day on days 6-28. Patients were treated until progression, withdrawal, or unacceptable toxicity.

“The adverse events we saw in this study were typical for this population, including fevers, mostly neutropenic fevers, as well as anemia and thrombocytopenia,” Dr. Rampal said.

Nonhematologic adverse events (AEs) included fatigue, abdominal pain, pneumonia, diarrhea, dizziness, and constipation. Hematologic AEs included anemia, neutropenia, febrile neutropenia, and thrombocytopenia.

Response and survival

Eighteen patients were evaluable for response. Four patients were not evaluable because they withdrew from the study due to secondary AEs and completed one cycle of therapy or less, two patients did not have circulating blasts at baseline, and one patient refused further treatment.

Among the evaluable patients, nine (50%) achieved a partial response, including four patients with accelerated phase MPN and five with blast phase MPN.

Two patients (11.1%), one with accelerated phase MPN and one with blast phase MPN, achieved a complete response with incomplete count recovery.

The remaining seven patients (38.9%), five with blast phase MPN and two with accelerated phase MPN, did not respond.

The median overall survival was 7.6 months for the entire cohort, 9.7 months for patients with blast phase MPN, and 5.8 months for patients with accelerated phase MPN.

Based on these results, Dr. Rampal and his colleagues theorized that ruxolitinib plus decitabine might be improved by the addition of other agents. The researchers are currently investigating this possibility.

“The work for this trial really came out of preclinical work in the laboratory where we combined these drugs and saw efficacy in murine models,” Dr. Rampal said. “So we’re going back to the drawing board and looking at those again to see, ‘Can we come up with new rational combinations?’ ”

Dr. Rampal and his colleagues reported having no conflicts of interest. Their study was supported by the National Institutes of Health, the National Cancer Institute, and Incyte Corporation.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The combination of ruxolitinib and decitabine will not proceed to a phase 3 trial in patients with accelerated or blast phase myeloproliferative neoplasms (MPNs).

The combination demonstrated activity and tolerability in a phase 2 trial, but outcomes were not optimal, according to Raajit K. Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

“[P]erhaps the outcomes might be favorable compared to standard induction chemotherapy regimens,” Dr. Rampal said. “Nonetheless, it’s clear that we still have a lot of work to do, and the outcomes are not optimal in these patients.”

However, Dr. Rampal and his colleagues are investigating the possibility of combining ruxolitinib and decitabine with other agents to treat patients with accelerated or blast phase MPNs.

Dr. Rampal and his colleagues presented results from the phase 2 trial in a poster at the Acute Leukemia Forum of Hemedicus.

The trial (NCT02076191) enrolled 25 patients, 10 with accelerated phase MPN (10%-19% blasts) and 15 with blast phase MPN (at least 20% blasts). The patients’ median age was 71 years.

Patients had a median disease duration of 72.9 months. Six patients (25%) had received prior ruxolitinib, and two (8.3%) had received prior decitabine.

Treatment and safety

For the first cycle, patients received decitabine at 20 mg/m² per day on days 8-12 and ruxolitinib at 25 mg twice a day on days 1-35. For subsequent cycles, patients received the same dose of decitabine on days 1-5 and ruxolitinib at 10 mg twice a day on days 6-28. Patients were treated until progression, withdrawal, or unacceptable toxicity.

“The adverse events we saw in this study were typical for this population, including fevers, mostly neutropenic fevers, as well as anemia and thrombocytopenia,” Dr. Rampal said.

Nonhematologic adverse events (AEs) included fatigue, abdominal pain, pneumonia, diarrhea, dizziness, and constipation. Hematologic AEs included anemia, neutropenia, febrile neutropenia, and thrombocytopenia.

Response and survival

Eighteen patients were evaluable for response. Four patients were not evaluable because they withdrew from the study due to secondary AEs and completed one cycle of therapy or less, two patients did not have circulating blasts at baseline, and one patient refused further treatment.

Among the evaluable patients, nine (50%) achieved a partial response, including four patients with accelerated phase MPN and five with blast phase MPN.

Two patients (11.1%), one with accelerated phase MPN and one with blast phase MPN, achieved a complete response with incomplete count recovery.

The remaining seven patients (38.9%), five with blast phase MPN and two with accelerated phase MPN, did not respond.

The median overall survival was 7.6 months for the entire cohort, 9.7 months for patients with blast phase MPN, and 5.8 months for patients with accelerated phase MPN.

Based on these results, Dr. Rampal and his colleagues theorized that ruxolitinib plus decitabine might be improved by the addition of other agents. The researchers are currently investigating this possibility.

“The work for this trial really came out of preclinical work in the laboratory where we combined these drugs and saw efficacy in murine models,” Dr. Rampal said. “So we’re going back to the drawing board and looking at those again to see, ‘Can we come up with new rational combinations?’ ”

Dr. Rampal and his colleagues reported having no conflicts of interest. Their study was supported by the National Institutes of Health, the National Cancer Institute, and Incyte Corporation.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]

NEWPORT BEACH, CALIF. – The combination of ruxolitinib and decitabine will not proceed to a phase 3 trial in patients with accelerated or blast phase myeloproliferative neoplasms (MPNs).

The combination demonstrated activity and tolerability in a phase 2 trial, but outcomes were not optimal, according to Raajit K. Rampal, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

“[P]erhaps the outcomes might be favorable compared to standard induction chemotherapy regimens,” Dr. Rampal said. “Nonetheless, it’s clear that we still have a lot of work to do, and the outcomes are not optimal in these patients.”

However, Dr. Rampal and his colleagues are investigating the possibility of combining ruxolitinib and decitabine with other agents to treat patients with accelerated or blast phase MPNs.

Dr. Rampal and his colleagues presented results from the phase 2 trial in a poster at the Acute Leukemia Forum of Hemedicus.

The trial (NCT02076191) enrolled 25 patients, 10 with accelerated phase MPN (10%-19% blasts) and 15 with blast phase MPN (at least 20% blasts). The patients’ median age was 71 years.

Patients had a median disease duration of 72.9 months. Six patients (25%) had received prior ruxolitinib, and two (8.3%) had received prior decitabine.

Treatment and safety

For the first cycle, patients received decitabine at 20 mg/m² per day on days 8-12 and ruxolitinib at 25 mg twice a day on days 1-35. For subsequent cycles, patients received the same dose of decitabine on days 1-5 and ruxolitinib at 10 mg twice a day on days 6-28. Patients were treated until progression, withdrawal, or unacceptable toxicity.

“The adverse events we saw in this study were typical for this population, including fevers, mostly neutropenic fevers, as well as anemia and thrombocytopenia,” Dr. Rampal said.

Nonhematologic adverse events (AEs) included fatigue, abdominal pain, pneumonia, diarrhea, dizziness, and constipation. Hematologic AEs included anemia, neutropenia, febrile neutropenia, and thrombocytopenia.

Response and survival

Eighteen patients were evaluable for response. Four patients were not evaluable because they withdrew from the study due to secondary AEs and completed one cycle of therapy or less, two patients did not have circulating blasts at baseline, and one patient refused further treatment.

Among the evaluable patients, nine (50%) achieved a partial response, including four patients with accelerated phase MPN and five with blast phase MPN.

Two patients (11.1%), one with accelerated phase MPN and one with blast phase MPN, achieved a complete response with incomplete count recovery.

The remaining seven patients (38.9%), five with blast phase MPN and two with accelerated phase MPN, did not respond.

The median overall survival was 7.6 months for the entire cohort, 9.7 months for patients with blast phase MPN, and 5.8 months for patients with accelerated phase MPN.

Based on these results, Dr. Rampal and his colleagues theorized that ruxolitinib plus decitabine might be improved by the addition of other agents. The researchers are currently investigating this possibility.

“The work for this trial really came out of preclinical work in the laboratory where we combined these drugs and saw efficacy in murine models,” Dr. Rampal said. “So we’re going back to the drawing board and looking at those again to see, ‘Can we come up with new rational combinations?’ ”

Dr. Rampal and his colleagues reported having no conflicts of interest. Their study was supported by the National Institutes of Health, the National Cancer Institute, and Incyte Corporation.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

[email protected]