Hematology

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

Lenalidomide can reduce the risk of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM), according to a phase 2/3 trial.

At 3 years, the rate of progression-free survival (PFS) was 91% in SMM patients randomized to lenalidomide and 66% in those randomized to observation.

However, more than half of patients randomized to lenalidomide discontinued treatment because of toxicity.

These results are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Sagar Lonial, MD, of Winship Cancer Institute, Emory University, Atlanta, discussed the results in a press briefing in advance of the meeting.

A prior trial suggested that lenalidomide plus dexamethasone can improve time to MM development and overall survival in patients with high-risk SMM (Mateos MV et al. NEJM 2013). However, inferior imaging was used in this trial, and the addition of dexamethasone hindered researchers’ ability to isolate the effects of lenalidomide, Dr. Lonial said.

With their trial (NCT01169337), Dr. Lonial and colleagues tested lenalidomide alone and screened patients using magnetic resonance imaging.

The trial enrolled patients with intermediate or high-risk SMM in two phases. In phase 2, all 44 patients received lenalidomide at 25 mg daily on days 1-21 of a 28-day cycle. They also received aspirin at 325 mg on days 1-28.

In the phase 3 portion of the trial, 182 patients were randomized to observation or lenalidomide and aspirin at the aforementioned dose and schedule. Patients were stratified according to time since SMM diagnosis – 1 year or less vs. more than 1 year.

Safety

Dr. Lonial said, in general, lenalidomide was “very well tolerated.” However, 80% of patients in phase 2 and 51% in phase 3 discontinued lenalidomide due to toxicity.

The rates of treatment-related adverse events (AEs) in the phase 2 portion were 34.1% for grade 3 AEs, 11.4% for grade 4, and 4.5% for grade 5. In the phase 3 portion, 35.2% of patients had grade 3 treatment-related AEs, and 5.7% had grade 4 treatment-related AEs.

Common AEs in phase 3 were grade 4 neutrophil count decrease (4.5%) and grade 3 infections (20.5%), hypertension (9.1%), fatigue (6.8%), skin AEs (5.7%), dyspnea (5.7%), and hypokalemia (3.4%).
 

Efficacy

“It is worth noting that about 50% of patients had an objective response to lenalidomide in both the phase 2 and the phase 3 trial,” Dr. Lonial said. “I think it’s also important to realize that, in the phase 2 portion of this study, of the 44 patients enrolled, 78% of them did not progress to myeloma with a median follow-up of over 5 years.”

In phase 2, PFS was 98% at 1 year, 87% at 3 years, and 78% at 5 years.

In phase 3, PFS was 98% in the lenalidomide arm and 89% in the observation arm at 1 year. At 2 years, PFS was 93% in the lenalidomide arm and 76% in the observation arm. At 3 years, PFS was 91% in the lenalidomide arm and 66% in the observation arm.

“What’s really quite interesting is that each [risk] group appeared to benefit almost equally from the early intervention of lenalidomide as a single agent,” Dr. Lonial said. “[W]hile the high-risk group may be the target now, this may be a fertile area for investigation in the intermediate-risk group as well.”

Dr. Lonial has relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Oncology, Juno Therapeutics, Merck, Novartis, and Takeda. The trial was funded by the National Institutes of Health.

[email protected]

SOURCE: Lonial S et al. ASCO 2019. Abstract 8001.

The Food and Drug Administration has approved the combination of venetoclax (Venclexta) plus obinutuzumab (Gazyva) for patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

The approval provides a chemotherapy-free, fixed duration treatment. The FDA based the approval on the results of the phase 3 CLL14 trial, which will be presented at the 2019 annual meeting of the American Society of Clinical Oncology.

Researchers randomized 432 patients to either a 12-month duration of venetoclax with a 6-month duration of obinutuzumab or to a 6-month duration of obinutuzumab plus chlorambucil and another 6-month duration of chlorambucil.

The newly approved combination reduced the risk of disease progression or death (progression-free survival as assessed by an independent review committee) by 67%, compared with obinutuzumab/chlorambucil (hazard ratio, 0.33; P less than .0001).

Venetoclax/obinutuzumab also had a higher rate of minimal residual disease negativity in bone marrow and peripheral blood, compared to the other combination, according to Genentech.

The most common adverse reactions of any grade reported for venetoclax/obinutuzumab were neutropenia, diarrhea, fatigue, nausea, anemia, and upper respiratory tract infection.

[email protected]

The Food and Drug Administration has approved the combination of venetoclax (Venclexta) plus obinutuzumab (Gazyva) for patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

The approval provides a chemotherapy-free, fixed duration treatment. The FDA based the approval on the results of the phase 3 CLL14 trial, which will be presented at the 2019 annual meeting of the American Society of Clinical Oncology.

Researchers randomized 432 patients to either a 12-month duration of venetoclax with a 6-month duration of obinutuzumab or to a 6-month duration of obinutuzumab plus chlorambucil and another 6-month duration of chlorambucil.

The newly approved combination reduced the risk of disease progression or death (progression-free survival as assessed by an independent review committee) by 67%, compared with obinutuzumab/chlorambucil (hazard ratio, 0.33; P less than .0001).

Venetoclax/obinutuzumab also had a higher rate of minimal residual disease negativity in bone marrow and peripheral blood, compared to the other combination, according to Genentech.

The most common adverse reactions of any grade reported for venetoclax/obinutuzumab were neutropenia, diarrhea, fatigue, nausea, anemia, and upper respiratory tract infection.

[email protected]

The Food and Drug Administration has approved the combination of venetoclax (Venclexta) plus obinutuzumab (Gazyva) for patients with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

The approval provides a chemotherapy-free, fixed duration treatment. The FDA based the approval on the results of the phase 3 CLL14 trial, which will be presented at the 2019 annual meeting of the American Society of Clinical Oncology.

Researchers randomized 432 patients to either a 12-month duration of venetoclax with a 6-month duration of obinutuzumab or to a 6-month duration of obinutuzumab plus chlorambucil and another 6-month duration of chlorambucil.

The newly approved combination reduced the risk of disease progression or death (progression-free survival as assessed by an independent review committee) by 67%, compared with obinutuzumab/chlorambucil (hazard ratio, 0.33; P less than .0001).

Venetoclax/obinutuzumab also had a higher rate of minimal residual disease negativity in bone marrow and peripheral blood, compared to the other combination, according to Genentech.

The most common adverse reactions of any grade reported for venetoclax/obinutuzumab were neutropenia, diarrhea, fatigue, nausea, anemia, and upper respiratory tract infection.

[email protected]

NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.

Jennifer Smith/MDedge News

Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.

Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).

The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).

At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.

QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).

The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).

Reasons for starting second-line treatment varied depending on patients’ phase of disease.

Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).

Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).

Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 10⁹/L and 78% of patients with platelet counts of 20 x 10⁹/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).

On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.

This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.

“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”

Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.

[email protected]

SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.

NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.

Jennifer Smith/MDedge News

Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.

Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).

The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).

At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.

QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).

The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).

Reasons for starting second-line treatment varied depending on patients’ phase of disease.

Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).

Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).

Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 10⁹/L and 78% of patients with platelet counts of 20 x 10⁹/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).

On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.

This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.

“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”

Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.

[email protected]

SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.

NEW ORLEANS – In a survey of pediatric hematologists, quality of life was the most frequently cited reason for starting second-line therapy in children with immune thrombocytopenia.

Jennifer Smith/MDedge News

Quality of life (QOL) was an indication for second-line treatment in nearly three-quarters of patients studied, and it ranked among the top three indications – along with bleeding frequency and bleeding severity – for treatment in more than half of patients.

Kristin A. Shimano, MD, of the department of pediatrics at the University of California, San Francisco, presented these results at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Shimano and colleagues surveyed hematologists treating children in the ICON1 study (Am J Hematol. 2019 Apr 3. doi: 10.1002/ajh.25479).

The study enrolled 120 children receiving second-line immune thrombocytopenia (ITP) treatment at 21 centers. The median age at enrollment was 11.7 years (range, 1.2-17.8 years). About half of patients (53%) had chronic ITP, 31% had persistent ITP, and 16% had newly diagnosed ITP. The median number of prior treatments was three (range, zero to eight).

At study entry, the hematologists were asked to provide reasons that patients required second-line treatment. The list of 12 possible reasons included patient or parent QOL; bleeding severity; bleeding frequency; severity of thrombocytopenia; chronicity of ITP; high baseline activity level; involvement in sports; patient age; distance from medical center; and parent, patient, or physician anxiety. The hematologists were asked to choose all reasons that applied and to rank the top three reasons.

QOL was chosen as a reason to treat in 73% of patients (n = 88). QOL was among the top three reasons in 57% of patients (n = 68) and was the most important reason in 27% of patients (n = 32).

The severity and frequency of bleeding were ranked among the top three indications as well. Bleeding severity was a top indication in 29% of cases (n = 35), and bleeding frequency was a top indication in 40% of cases (n = 48).

Reasons for starting second-line treatment varied depending on patients’ phase of disease.

Bleeding severity was significantly more likely to be an indication for treatment among patients who had newly diagnosed or persistent ITP (69%), rather than chronic ITP (31%; P = .0025). Bleeding frequency was also significantly more likely to be an indication among patients with newly diagnosed or persistent ITP (63% vs. 37%; P = .0054).

Conversely, QOL was significantly more likely to be an indication for patients with chronic ITP (65%) rather than newly diagnosed or persistent ITP (35%, P = .0056). Sports participation was a more likely indication among patients with chronic ITP as well (75% vs. 26%, P = .017).

Indications for treatment also varied according to baseline platelet counts. For example, QOL was an indication for treatment in 42% of patients with baseline platelet counts less than 10 x 10⁹/L and 78% of patients with platelet counts of 20 x 10⁹/L or greater. So the higher the baseline platelet count, the more likely QOL was an indication for treatment (P = .006).

On the other hand, the importance hematologists placed on QOL did not appear to correlate with actual health-related QOL as assessed by the Kids ITP Tool. There was no difference reported in baseline health-related QOL, according to the tool, in children for whom QOL was ranked versus unranked by hematologists.

This finding suggests physicians may not be adequately assessing the impact of ITP on QOL, Dr. Shimano said.

“Better clinical measures of the impact of ITP on patient quality of life are needed to assess both need for treatment and treatment response,” she said. “Understanding the effects of individual second-line treatments on quality of life is critical for this patient population in order to best tailor therapy for each patient.”

Dr. Shimano reported involvement in an investigator-initiated trial for eltrombopag in children with ITP. The study, which has not yet opened, is funded by Novartis.

[email protected]

SOURCE: Shimano KA et al. ASPHO 2019, Abstract 2012.

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

NEW ORLEANS – Researchers are organizing a master trial in an attempt to improve the treatment of pediatric acute myeloid leukemia (AML).

The Pediatric Acute Leukemia (PedAL) trial is an effort to collect data on all pediatric AML patients. The plan is to use these data to match patients to clinical trials, better understand pediatric AML, and bring new treatments to this population.

E. Anders Kolb, MD, of Nemours Center for Cancer and Blood Disorders in Wilmington, Del., described the initiative at the annual meeting of the American Society of Pediatric Hematology/Oncology.

Dr. Kolb noted that several drugs have been approved to treat adult AML in the last 2 years, but most of them are not approved for use in children.

“What we see in childhood AML is a lot different than what we see in adult AML, and this challenges the paradigm that we have traditionally followed where we use the adult as the 'preclinical model' for pediatric AML,” he said. “I think we are learning more and more that children have a unique disease, unique targets, and need unique therapies.”

The PedAL initiative is an attempt to address these unique needs. PedAL is part of the Leukemia & Lymphoma Society’s Children’s Initiative, and it involves researchers from academic centers and the Children’s Oncology Group.

The PedAL initiative includes preclinical, biomarker, and informatics research, as well as the master clinical trial. The main goal of the master trial is to collect genomic, proteomic, metabolomic, flow cytometry, and clinical data from all children with AML and use these data to match patients to clinical trials.

The PedAL trial will leverage Project:EveryChild, an effort by the Children’s Oncology Group to study every child with cancer. Each child enrolled in this program has an identification number that follows the child through all clinical interventions.

The goal is that Project:EveryChild will capture all pediatric AML patients at the time of diagnosis, although patients can join the project at any time. Then, sequencing, clinical, and other data will be collected from these patients and stored in a data commons.

If patients relapse after standard or other therapies, the GEARBOX algorithm (genomic eligibility algorithm at relapse for better outcomes) can be used to match the patient’s information to clinical trial eligibility criteria and provide a list of appropriate trials.

Dr. Kolb said this process should reduce logistical barriers and get relapsed patients to trials more quickly. Additionally, the data collected through PedAL should help researchers design better trials for pediatric patients with relapsed AML.

“Ultimately, we’ll create the largest data set that will give us a better understanding of all the risks and benefits associated with postrelapse AML,” Dr. Kolb said. “No matter what happens to the patient, no matter where that patient enrolls, we’re going to have the capacity to collect data and present that data to the community for analysis for improved understanding of outcomes.”

Dr. Kolb and his colleagues are already working with researchers in Europe and Japan to make this a global effort and create an international data commons. In addition, the researchers are planning to collaborate with the pharmaceutical industry to unite efforts in pediatric AML drug development.

“We can’t just test drugs in kids because they worked in adults,” Dr. Kolb said. “We really need to maintain the integrity of the science and ask relevant questions in children but do so with the intent to make sure these drugs are licensed for use in kids.”

Dr. Kolb reported having no conflicts of interest. The PedAL trial is sponsored by the Leukemia & Lymphoma Society.

[email protected]

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

NEW ORLEANS – A next-generation sequencing (NGS) test for pathogen detection demonstrated higher sensitivity than conventional testing methods in a cohort of diverse pediatric patients, according to researchers.

The NGS test, which detects sequences of circulating cell-free DNA in plasma, detected pathogens with 92% sensitivity, compared with 64% sensitivity for all conventional testing methods combined (P less than .01).

Jennifer Smith/MDedge News

Results

Of the 100 NGS tests evaluated, 70 were positive for any organism, and 56 of these were deemed clinically relevant.

“What I think is quite remarkable is that, of those clinically relevant organisms, tests on 14, which is 25% of those, were able to identify clinically relevant or pathogenic organisms when no other conventional testing modality was able to identify them,” Dr. Rossoff said. “And these were often in patients who underwent invasive procedures to try to get at the source of their infectious disease.”

In fact, the study included 42 patients who underwent 54 invasive diagnostic procedures, and 32 of those procedures could have been avoided based on positive NGS results, according to Dr. Rossoff and her colleagues.

Dr. Rossoff noted that the most common sites of infection were the bloodstream and respiratory tract, but the NGS test was able to identify pathogens in the bone, skin, cerebrospinal fluid, and urinary tract. She also pointed out that NGS results were available “in a fairly timely manner,” as 86% of test results were available within 48 hours of sample receipt.

Dr. Rossoff and her colleagues did not receive any funding for this study, but they were previously involved in a study funded by Karius, the company that commercialized the NGS test.

[email protected]

SOURCE: Rossoff J et al. ASPHO 2019. Abstract 439.
 

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

The differential diagnosis included psoriasis, drug eruption, and a cutaneous T-cell lymphoma.

A drug eruption could have been due to an over-the-counter medication or supplement, so the lack of improvement from stopping the antihypertensive medication did not rule out this diagnosis. Psoriasis does not always show erythema in persons of color, but these plaques were not typical of psoriasis. (There also were some flat patches that were even less typical of psoriasis.)

The FP performed a 4-mm punch biopsy on one of the hyperpigmented plaques on the abdomen. A 4-mm punch biopsy is generally an ideal method for determining the cause of an unknown skin rash, and it is usually better to choose a lesion on the upper body rather than below the waist if the rash is widespread. (See the Watch & Learn video on “Punch biopsy.”)

The FP also prescribed a 1-pound tub of 0.1% triamcinolone ointment for symptomatic relief as this could help any of the possible diagnoses being considered. The pathology report came back as mycosis fungoides, the most common type of cutaneous T-cell lymphoma.

The patient was sent to Hematology/Oncology for further evaluation and treatment. Mycosis fungoides can have both patches and plaques and frequently involves the trunk more than the extremities (which was the situation in this case). It is important to consider uncommon diagnoses like this in the differential when the initial diagnosis does not appear to be responding to treatment or there is something atypical about the presentation of an expected diagnosis.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Chacon G, Nayar A, Usatine R, Smith M. Cutaneous T-cell lymphoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1124-1131.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the Color Atlas of Family Medicine app by clicking on this link: usatinemedia.com

NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.

Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.

For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.

Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.

The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 10⁹/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 10⁹/L. More than half of patients (57.3%) were male.

The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.

Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”

The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.

[email protected]

NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.

Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.

For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.

Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.

The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 10⁹/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 10⁹/L. More than half of patients (57.3%) were male.

The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.

Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”

The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.

[email protected]

NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.

Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.

For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.

Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.

The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 10⁹/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 10⁹/L. More than half of patients (57.3%) were male.

The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.

Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”

The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.

[email protected]

NEW ORLEANS – Adding gabapentin to standard therapy did not significantly reduce vaso-occlusive pain in most patients with sickle cell disease enrolled in a phase 2 trial.

Jennifer Smith/MDedge News

In the entire cohort, there were no significant differences in pain response between patients who received gabapentin and those who received placebo. However, patients with the HbSS genotype had a significantly greater decrease in pain score from baseline to discharge if they received gabapentin rather than placebo.

Additional studies are needed to confirm these findings because this trial was limited by a small sample size, according to study investigator Latika Puri, MD, of St. Jude Children’s Research Hospital in Memphis. Dr. Puri presented the trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The trial included 86 evaluable patients who had vaso-occlusive pain and a pain score of at least 4. All patients received standard therapy for vaso-occlusive pain and were randomized to receive placebo (n = 44) or a single oral dose of gabapentin at 15 mg/kg (n = 42).

Baseline characteristics were similar between the treatment arms. For the entire cohort, the mean age was 11.8 years (range, 1-21 years), and 51% of patients were male. Forty-four patients had the HbSS genotype, 25 had the HbSC genotype, 8 had HbS/beta⁰-thalassemia, and 9 had other genotypes.

The mean pain score at baseline was 7.8 for the entire cohort, 8.0 for the gabapentin arm, and 7.7 for the placebo arm.

For the entire cohort, there was no significant difference in pain response between the gabapentin and placebo arms.

The proportion of patients who experienced a greater than 33% decrease in pain from baseline to 3 hours posttreatment was 67% in the gabapentin arm and 59% in the placebo arm (P = .23). The proportion of patients who experienced a greater than 33% decrease from baseline to discharge from the acute care clinic was 75% and 61%, respectively (P = .18).

In the entire cohort, decreases in pain scores from baseline to 3 hours posttreatment were not significantly different between the gabapentin and placebo arms, at 1.3 and 0.7, respectively (P = .74). Likewise, decreases in pain scores from baseline to discharge were not significantly different, at 1.6 and 0.8 (P = .38).

Among patients who had the HbSS genotype, there was a significantly greater decrease in pain score from baseline to discharge in the gabapentin arm than in the placebo arm, 5.9 versus 3.6 (P = .03). However, there were no other significant differences in pain response for the HbSS subgroup.

There were no significant differences in opioid consumption or hospitalization for the HbSS subgroup or the entire cohort. For the entire cohort, the mean morphine equivalent dose from baseline to 3 hours posttreatment was 0.16 mg/kg in the gabapentin arm and 0.17 mg/kg in the placebo arm (P = .89). For the HbSS subgroup, the mean dose was 0.16 mg/kg and 0.15 mg/kg, respectively (P = .93).

In the entire cohort, 24% of patients in the gabapentin arm and 27% of those in the placebo arm were hospitalized (P = .71). In the HbSS subgroup, hospitalizations occurred in 11% and 35% (P = .15).

Dr. Puri pointed out several challenges that led to limitations in this study. Specifically, the investigators had to obtain patient consent while delivering standard treatment, while patients were in pain and distress, and from patients who had already received opioids and were sleepy. Additionally, gabapentin had to be delivered within 1 hour of opioid administration, and a lack of after-hours staff limited enrollment.

“These challenges led to one of our biggest limitations, which was a small sample size, leading to a limited power to observe real differences,” Dr. Puri said. “We also defined a very short time period of evaluation for the primary outcomes; that was 3 hours from the gabapentin dose or placebo dose. This limited our capability to see real differences if they existed.”

Dr. Puri said additional studies with larger sample sizes are needed to confirm these findings. She added that efforts to better characterize pain in sickle cell disease could reveal patients who may benefit from gabapentin because they have a neuropathic component to their pain.

The trial was sponsored by St. Jude Children’s Research Hospital in collaboration with Scan|Design Foundation. Dr. Puri did not provide disclosure information at the meeting.
 

[email protected]

SOURCE: Puri L et al. ASPHO 2019, Abstract 2011.

NEW ORLEANS – Adding gabapentin to standard therapy did not significantly reduce vaso-occlusive pain in most patients with sickle cell disease enrolled in a phase 2 trial.

Jennifer Smith/MDedge News

In the entire cohort, there were no significant differences in pain response between patients who received gabapentin and those who received placebo. However, patients with the HbSS genotype had a significantly greater decrease in pain score from baseline to discharge if they received gabapentin rather than placebo.

Additional studies are needed to confirm these findings because this trial was limited by a small sample size, according to study investigator Latika Puri, MD, of St. Jude Children’s Research Hospital in Memphis. Dr. Puri presented the trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The trial included 86 evaluable patients who had vaso-occlusive pain and a pain score of at least 4. All patients received standard therapy for vaso-occlusive pain and were randomized to receive placebo (n = 44) or a single oral dose of gabapentin at 15 mg/kg (n = 42).

Baseline characteristics were similar between the treatment arms. For the entire cohort, the mean age was 11.8 years (range, 1-21 years), and 51% of patients were male. Forty-four patients had the HbSS genotype, 25 had the HbSC genotype, 8 had HbS/beta⁰-thalassemia, and 9 had other genotypes.

The mean pain score at baseline was 7.8 for the entire cohort, 8.0 for the gabapentin arm, and 7.7 for the placebo arm.

For the entire cohort, there was no significant difference in pain response between the gabapentin and placebo arms.

The proportion of patients who experienced a greater than 33% decrease in pain from baseline to 3 hours posttreatment was 67% in the gabapentin arm and 59% in the placebo arm (P = .23). The proportion of patients who experienced a greater than 33% decrease from baseline to discharge from the acute care clinic was 75% and 61%, respectively (P = .18).

In the entire cohort, decreases in pain scores from baseline to 3 hours posttreatment were not significantly different between the gabapentin and placebo arms, at 1.3 and 0.7, respectively (P = .74). Likewise, decreases in pain scores from baseline to discharge were not significantly different, at 1.6 and 0.8 (P = .38).

Among patients who had the HbSS genotype, there was a significantly greater decrease in pain score from baseline to discharge in the gabapentin arm than in the placebo arm, 5.9 versus 3.6 (P = .03). However, there were no other significant differences in pain response for the HbSS subgroup.

There were no significant differences in opioid consumption or hospitalization for the HbSS subgroup or the entire cohort. For the entire cohort, the mean morphine equivalent dose from baseline to 3 hours posttreatment was 0.16 mg/kg in the gabapentin arm and 0.17 mg/kg in the placebo arm (P = .89). For the HbSS subgroup, the mean dose was 0.16 mg/kg and 0.15 mg/kg, respectively (P = .93).

In the entire cohort, 24% of patients in the gabapentin arm and 27% of those in the placebo arm were hospitalized (P = .71). In the HbSS subgroup, hospitalizations occurred in 11% and 35% (P = .15).

Dr. Puri pointed out several challenges that led to limitations in this study. Specifically, the investigators had to obtain patient consent while delivering standard treatment, while patients were in pain and distress, and from patients who had already received opioids and were sleepy. Additionally, gabapentin had to be delivered within 1 hour of opioid administration, and a lack of after-hours staff limited enrollment.

“These challenges led to one of our biggest limitations, which was a small sample size, leading to a limited power to observe real differences,” Dr. Puri said. “We also defined a very short time period of evaluation for the primary outcomes; that was 3 hours from the gabapentin dose or placebo dose. This limited our capability to see real differences if they existed.”

Dr. Puri said additional studies with larger sample sizes are needed to confirm these findings. She added that efforts to better characterize pain in sickle cell disease could reveal patients who may benefit from gabapentin because they have a neuropathic component to their pain.

The trial was sponsored by St. Jude Children’s Research Hospital in collaboration with Scan|Design Foundation. Dr. Puri did not provide disclosure information at the meeting.
 

[email protected]

SOURCE: Puri L et al. ASPHO 2019, Abstract 2011.

NEW ORLEANS – Adding gabapentin to standard therapy did not significantly reduce vaso-occlusive pain in most patients with sickle cell disease enrolled in a phase 2 trial.

Jennifer Smith/MDedge News

In the entire cohort, there were no significant differences in pain response between patients who received gabapentin and those who received placebo. However, patients with the HbSS genotype had a significantly greater decrease in pain score from baseline to discharge if they received gabapentin rather than placebo.

Additional studies are needed to confirm these findings because this trial was limited by a small sample size, according to study investigator Latika Puri, MD, of St. Jude Children’s Research Hospital in Memphis. Dr. Puri presented the trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.

The trial included 86 evaluable patients who had vaso-occlusive pain and a pain score of at least 4. All patients received standard therapy for vaso-occlusive pain and were randomized to receive placebo (n = 44) or a single oral dose of gabapentin at 15 mg/kg (n = 42).

Baseline characteristics were similar between the treatment arms. For the entire cohort, the mean age was 11.8 years (range, 1-21 years), and 51% of patients were male. Forty-four patients had the HbSS genotype, 25 had the HbSC genotype, 8 had HbS/beta⁰-thalassemia, and 9 had other genotypes.

The mean pain score at baseline was 7.8 for the entire cohort, 8.0 for the gabapentin arm, and 7.7 for the placebo arm.

For the entire cohort, there was no significant difference in pain response between the gabapentin and placebo arms.

The proportion of patients who experienced a greater than 33% decrease in pain from baseline to 3 hours posttreatment was 67% in the gabapentin arm and 59% in the placebo arm (P = .23). The proportion of patients who experienced a greater than 33% decrease from baseline to discharge from the acute care clinic was 75% and 61%, respectively (P = .18).

In the entire cohort, decreases in pain scores from baseline to 3 hours posttreatment were not significantly different between the gabapentin and placebo arms, at 1.3 and 0.7, respectively (P = .74). Likewise, decreases in pain scores from baseline to discharge were not significantly different, at 1.6 and 0.8 (P = .38).

Among patients who had the HbSS genotype, there was a significantly greater decrease in pain score from baseline to discharge in the gabapentin arm than in the placebo arm, 5.9 versus 3.6 (P = .03). However, there were no other significant differences in pain response for the HbSS subgroup.

There were no significant differences in opioid consumption or hospitalization for the HbSS subgroup or the entire cohort. For the entire cohort, the mean morphine equivalent dose from baseline to 3 hours posttreatment was 0.16 mg/kg in the gabapentin arm and 0.17 mg/kg in the placebo arm (P = .89). For the HbSS subgroup, the mean dose was 0.16 mg/kg and 0.15 mg/kg, respectively (P = .93).

In the entire cohort, 24% of patients in the gabapentin arm and 27% of those in the placebo arm were hospitalized (P = .71). In the HbSS subgroup, hospitalizations occurred in 11% and 35% (P = .15).

Dr. Puri pointed out several challenges that led to limitations in this study. Specifically, the investigators had to obtain patient consent while delivering standard treatment, while patients were in pain and distress, and from patients who had already received opioids and were sleepy. Additionally, gabapentin had to be delivered within 1 hour of opioid administration, and a lack of after-hours staff limited enrollment.

“These challenges led to one of our biggest limitations, which was a small sample size, leading to a limited power to observe real differences,” Dr. Puri said. “We also defined a very short time period of evaluation for the primary outcomes; that was 3 hours from the gabapentin dose or placebo dose. This limited our capability to see real differences if they existed.”

Dr. Puri said additional studies with larger sample sizes are needed to confirm these findings. She added that efforts to better characterize pain in sickle cell disease could reveal patients who may benefit from gabapentin because they have a neuropathic component to their pain.

The trial was sponsored by St. Jude Children’s Research Hospital in collaboration with Scan|Design Foundation. Dr. Puri did not provide disclosure information at the meeting.
 

[email protected]

SOURCE: Puri L et al. ASPHO 2019, Abstract 2011.

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

[email protected]

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

[email protected]

Hospitals could get a payment bump for administering chimeric antigen receptor (CAR) T-cell therapies under a proposed rule issued by the Centers for Medicare & Medicaid Services.

Penn Medicine

The proposal calls for raising the new technology add-on payment (NTAP) associated with the therapies from 50% of the technology to 65%, an increase from $186,500 to $242,450.

Beginning with discharges on Oct. 1, 2019, if discharge costs involving a new medical service or technology exceed the full Medicare Severity Diagnosis-Related Group (DRG) payment, Medicare would make an add-on payment of either 65% of the cost of the new medical service or technology, or 65% of the amount by which the costs of the case exceed the standard DRG payment, whichever is less.

Roy Silverstein, MD, president of the American Society of Hematology, said the group was pleased that the CMS is examining its existing payment policies to identify more realistic ways to account for the costs of administering CAR T-cell therapies.

“While ASH had originally suggested a higher [new technology] payment, any increase is an improvement,” Dr. Silverstein said in a statement. “While the proposal from CMS is promising, it is not a one-stop solution for making CAR T more accessible to patients. Just as these therapies are innovative, it is going to take some innovation on the part of CMS to develop a plan that equitably compensates providers and institutions so that offering the therapy is sustainable.”

The agency’s proposal follows an August 2018 final rule by the CMS that set a new payment scheme for inpatient administration of two CAR T-cell therapies. The rule categorized CAR T-cell therapies under the umbrella of the renamed Medicare Severity–Diagnosis Related Groups (MS-DRG) 016 – Autologous Bone Marrow Transplant with CC/MCC or T-cell Immunotherapy – and assigned ICD-10 PCS procedure codes XW033C3 and XW043C3 to the use of axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah) in the inpatient setting for fiscal year 2019, which began in October 2018.

In April 2018, the CMS announced payment rates for outpatient administration of the two drugs, settling on $395,380 for axicabtagene ciloleucel and $500,839 for tisagenlecleucel. The two medications have list prices of $373,000 and $475,000, respectively.

In February 2019, the CMS also proposed to cover CAR T-cell therapy for cancer patients participating in clinical trials that study the treatment’s effectiveness. A final decision on the proposal is expected in May 2019.

In the current proposal, the CMS acknowledged requests calling for the agency to create a new MS-DRG for procedures involving CAR T-cell therapies to improve payment in the inpatient setting. However, the agency declined to create a new MS-DRG for CAR T-cell cases, writing that the move is premature given the relative newness of CAR T-cell therapy and the agency’s proposal to continue new technology add-on payments for fiscal 2020 for Kymriah and Yescarta.

However, the agency is requesting public comments on whether, in light of additional experience with billing and payment for cases involving CAR T-cell therapies to Medicare patients, the CMS should consider using a specific cost-to-charge ratio for ICD-10-PCS procedure codes used to report the performance of procedures involving CAR T-cell therapies.

Comments on the proposed rule will be accepted until June 24.

[email protected]

To the Editor: I read with great interest the article “Aleukemic leukemia cutis” by Abraham et al,¹ as we recently had a case of this at my institution. The case is unique and quite intriguing; however, I found the pathologic description confusing and imprecise.

The authors state, “The findings were consistent with leukemic T cells with monocytic differentiation.”¹ This is based on their findings that the tumor cells expressed CD4, CD43, CD68, and lysozyme. However, the cells were negative for CD30, ALK-1, CD2, and CD3.

First, I must contest the authors’ claim that “the cells co-expressed T-cell markers (CD4 and CD43)”: CD4 and CD43 are not specific for T cells and are almost invariably seen on monocytes, especially in acute monoblastic/monocytic leukemia (AMoL; also known as M5 in the French-American-British classification system).^2,3 Therefore, the immunophenotype is perfect for an AMoL, but since there was no significant blood or bone marrow involvement and it was limited to the skin, this would best fit with a myeloid sarcoma, which frequently has a monocytic immunoprofile.^3,4

Additionally, this would not be a mixed-phenotype acute leukemia, T/myeloid, not otherwise specified, as that requires positivity for cytoplasmic CD3 or surface CD3, and that was conspicuously absent.⁵ Therefore, the appropriate workup and treatment should have essentially followed the course for acute myeloid leukemia,⁴ which is unclear from the present report as there is no mention of a molecular workup (eg, for FLT3 and NPM1 mutations). This would, in turn, have important treatment and prognostic implications.⁶

The reason for my comments is to bring to light the importance of exact pathologic diagnosis, especially when dealing with leukemia. We currently have a host of treatment options and prognostic tools for the various types of acute myeloid leukemia, but only when a clear and precise pathologic diagnosis is given.⁵

To the Editor: I read with great interest the article “Aleukemic leukemia cutis” by Abraham et al,¹ as we recently had a case of this at my institution. The case is unique and quite intriguing; however, I found the pathologic description confusing and imprecise.

The authors state, “The findings were consistent with leukemic T cells with monocytic differentiation.”¹ This is based on their findings that the tumor cells expressed CD4, CD43, CD68, and lysozyme. However, the cells were negative for CD30, ALK-1, CD2, and CD3.

First, I must contest the authors’ claim that “the cells co-expressed T-cell markers (CD4 and CD43)”: CD4 and CD43 are not specific for T cells and are almost invariably seen on monocytes, especially in acute monoblastic/monocytic leukemia (AMoL; also known as M5 in the French-American-British classification system).^2,3 Therefore, the immunophenotype is perfect for an AMoL, but since there was no significant blood or bone marrow involvement and it was limited to the skin, this would best fit with a myeloid sarcoma, which frequently has a monocytic immunoprofile.^3,4

Additionally, this would not be a mixed-phenotype acute leukemia, T/myeloid, not otherwise specified, as that requires positivity for cytoplasmic CD3 or surface CD3, and that was conspicuously absent.⁵ Therefore, the appropriate workup and treatment should have essentially followed the course for acute myeloid leukemia,⁴ which is unclear from the present report as there is no mention of a molecular workup (eg, for FLT3 and NPM1 mutations). This would, in turn, have important treatment and prognostic implications.⁶

The reason for my comments is to bring to light the importance of exact pathologic diagnosis, especially when dealing with leukemia. We currently have a host of treatment options and prognostic tools for the various types of acute myeloid leukemia, but only when a clear and precise pathologic diagnosis is given.⁵

To the Editor: I read with great interest the article “Aleukemic leukemia cutis” by Abraham et al,¹ as we recently had a case of this at my institution. The case is unique and quite intriguing; however, I found the pathologic description confusing and imprecise.

The authors state, “The findings were consistent with leukemic T cells with monocytic differentiation.”¹ This is based on their findings that the tumor cells expressed CD4, CD43, CD68, and lysozyme. However, the cells were negative for CD30, ALK-1, CD2, and CD3.

First, I must contest the authors’ claim that “the cells co-expressed T-cell markers (CD4 and CD43)”: CD4 and CD43 are not specific for T cells and are almost invariably seen on monocytes, especially in acute monoblastic/monocytic leukemia (AMoL; also known as M5 in the French-American-British classification system).^2,3 Therefore, the immunophenotype is perfect for an AMoL, but since there was no significant blood or bone marrow involvement and it was limited to the skin, this would best fit with a myeloid sarcoma, which frequently has a monocytic immunoprofile.^3,4

Additionally, this would not be a mixed-phenotype acute leukemia, T/myeloid, not otherwise specified, as that requires positivity for cytoplasmic CD3 or surface CD3, and that was conspicuously absent.⁵ Therefore, the appropriate workup and treatment should have essentially followed the course for acute myeloid leukemia,⁴ which is unclear from the present report as there is no mention of a molecular workup (eg, for FLT3 and NPM1 mutations). This would, in turn, have important treatment and prognostic implications.⁶

The reason for my comments is to bring to light the importance of exact pathologic diagnosis, especially when dealing with leukemia. We currently have a host of treatment options and prognostic tools for the various types of acute myeloid leukemia, but only when a clear and precise pathologic diagnosis is given.⁵