ASH 2016

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

SAN DIEGO – For patients with CD30 expressing cutaneous T-cell lymphoma, antibody-drug conjugate therapy with brentuximab vedotin significantly outperformed two standard regimens in the phase III ALCANZA trial.

After a median of 17.5 months of follow-up, 56% of patients receiving brentuximab vedotin had an objective response lasting at least 4 months, versus 13% of patients treated with physician’s choice of methotrexate or bexarotene (P less than .0001), Youn H. Kim, MD, said during an oral presentation at the annual meeting of the American Society of Hematology.

As in past studies, brentuximab vedotin caused high rates of peripheral neuropathy, but more than 80% of cases improved or resolved over time, she said.

This is the first reported phase III trial to convincingly show that a new systemic agent outperformed standard therapies for cutaneous T-cell lymphoma (CTCL), which tend to have inadequate and short-lived efficacy, stated Dr. Kim, of Stanford (Calif.) University. Brentuximab vedotin not only met the primary endpoint, but all other predefined endpoints, including progression-free survival and a quality-of-life measure, she said.

“These compelling results have potential practice-changing implications,” she concluded.

Brentuximab vedotin (Adcetris) targets CD30, which is expressed in skin lesions of about half of patients with CTCL. A protease-cleavable linker attaches an anti-CD30 monoclonal antibody to monomethyl auristatin E, which disrupts microtubules when released into CD30-positive tumor cells (Blood. 2013;122:367). The agent showed clinical activity against CTCL in two previous phase II trials of CTCL.

Accordingly, the international, open-label phase III ALCANZA study enrolled 128 treatment-experienced patients with CD30-expressing mycosis fungoides or primary cutaneous anaplastic large cell lymphoma. Patients were randomly assigned to receive brentuximab vedotin (1.8 mg/kg once every 3 weeks) or physician’s choice of either methotrexate (5 to 50 mg once weekly) or bexarotene (300 mg/m² once daily) for up to 16 3-week cycles, or until disease progression or unacceptable toxicity. Methotrexate or bexarotene were designated “physician’s choice” because they are used worldwide for treating CTCL, according to Dr. Kim.

To capture both the rate and duration of response, researchers defined objective response lasting at least 4 months as the primary endpoint. Brentuximab vedotin more than quadrupled the likelihood of this outcome when compared with the standard CTCL regimens, a trend that spanned key demographic and clinical subgroups, Dr. Kim said.

“All endpoints were highly [statistically] significant,” she further reported. For example, the objective response rate with brentuximab vedotin was 67%, versus 20% for methotrexate or bexarotene. Respective rates of complete response were 16% and 2%, and median durations of progression-free survival were 17 and 4 months, translating to a 73% lower risk of progression or death with brentuximab vedotin (95% confidence interval, 57%-83%). Patients who received brentuximab vedotin also reported about a three-fold greater improvement on the Skindex-29 symptom domain, compared with the physician’s choice group (–29 vs. –9 points; P less than .0001).

The safety profile of brentuximab vedotin resembled that seen in previous studies, Dr. Kim said. Most notably, 67% of patients developed peripheral neuropathy, and 9% developed grade 3 peripheral neuropathy. This usually improved or resolved over about the next 22 months. Diarrhea, fatigue, and vomiting affected about a third of patients on brentuximab vedotin, and about one in four stopped treatment because of adverse events, compared with 8% of the physician’s choice arm. Rates of serious adverse events were 41% and 47%, respectively. One brentuximab vedotin recipient died of multiple organ dysfunction syndrome that investigators attributed to treatment-associated necrosis of peripheral tumors. They identified no other treatment-related deaths.

Seattle Genetics and Takeda funded the trial. Dr. Kim disclosed ties to Takeda and Seattle Genetics, as well as several other pharmaceutical companies.

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – For patients with indolent non-Hodgkin lymphoma, adding the anti-CD20 antibody rituximab to a standard-combination chemotherapy regimen resulted in significant improvements in survival, compared with chemotherapy alone. Obinutuzumab (Gazyva), a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, is being explored in various combinations for the treatment of indolent lymphomas, including follicular lymphoma and marginal zone lymphoma.

In this video interview from the annual meeting of the American Society of Hematology, Robert Marcus, FRCP, of King’s College Hospital, London, discussed results of the phase III GALLIUM study, in which patients with untreated follicular lymphoma were randomly assigned to one of three chemotherapy regimens with either obinutuzumab or rituximab. The primary endpoint of investigator-assessed 3-year progression-free survival (PFS) at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio (HR) favoring obinutuzumab of 0.68 (P = .0012).

Respective 3-year overall survival rates at 3 years were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

The GALLIUM trial is sponsored by F. Hoffmann-La Roche. Dr. Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

Attendees at the 2016

ASH Annual Meeting

SAN DIEGO—Interim results of the phase 3 GALLIUM trial suggest an obinutuzumab-based treatment regimen provides a progression-free survival (PFS) benefit over a rituximab-based regimen for patients with previously untreated follicular lymphoma (FL).

According to investigators, patients who received obinutuzumab plus chemotherapy followed by obinutuzumab maintenance had a “clinically meaningful” improvement in PFS, when compared to patients who received rituximab plus chemotherapy followed by rituximab maintenance.

However, there was no significant difference between the treatment arms with regard to overall survival. And the incidence of non-fatal adverse events (AEs) was higher among the patients who received obinutuzumab.

Nevertheless, the data suggest that obinutuzumab-based therapy significantly improves outcomes and should be considered as a first-line treatment for FL, according to Robert Marcus, MBBS, of King’s College Hospital in London, UK.

Dr Marcus presented data from GALLIUM during the plenary session at the 2016 ASH Annual Meeting (abstract 6). GALLIUM is sponsored by Hoffmann-La Roche.

Patients and treatment

The study has enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to obinutuzumab plus chemotherapy followed by obinutuzumab alone for up to 2 years, and half were randomized to rituximab plus chemotherapy followed by rituximab alone for up to 2 years.

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine. The regimens were selected by each participating study site prior to beginning enrollment.

Baseline characteristics were similar between the treatment arms. The median age was about 60 (overall range, 23-88), roughly 40% of patients had high-risk disease, and the median time from diagnosis to randomization was about 1.5 months.

A total of 341 patients in the rituximab arm and 361 patients in the obinutuzumab arm completed maintenance therapy.

The median follow-up was 34.5 months. Maintenance is ongoing in 114 patients—54 on rituximab and 60 on obinutuzumab.

Efficacy

At the end of induction, the overall response rate was 86.9% in the rituximab arm and 88.5% in the obinutuzumab arm. The complete response rates were 23.8% and 19.5%, respectively. And the rates of stable disease were 1.3% and 0.5%, respectively.

The study’s primary endpoint is investigator-assessed PFS. The 3-year PFS rate is 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

According to an independent review committee, the 3-year PFS is 77.9% in the rituximab arm and 81.9% in the obinutuzumab arm (HR=0.71, P=0.0138).

The 3-year overall survival is 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

Safety

The overall incidence of AEs was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of AEs leading to treatment discontinuation was 14.2% and 16.3%, respectively. And the incidence of second neoplasms was 2.7% and 4.7%, respectively.

Grade 5 AEs occurred in 3.4% of patients in the rituximab arm and 4.0% of patients in the obinutuzumab arm. The investigators found that fatal AEs were more common in patients taking bendamustine, regardless of the treatment arm.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Attendees at the 2016

ASH Annual Meeting

SAN DIEGO—Interim results of the phase 3 GALLIUM trial suggest an obinutuzumab-based treatment regimen provides a progression-free survival (PFS) benefit over a rituximab-based regimen for patients with previously untreated follicular lymphoma (FL).

According to investigators, patients who received obinutuzumab plus chemotherapy followed by obinutuzumab maintenance had a “clinically meaningful” improvement in PFS, when compared to patients who received rituximab plus chemotherapy followed by rituximab maintenance.

However, there was no significant difference between the treatment arms with regard to overall survival. And the incidence of non-fatal adverse events (AEs) was higher among the patients who received obinutuzumab.

Nevertheless, the data suggest that obinutuzumab-based therapy significantly improves outcomes and should be considered as a first-line treatment for FL, according to Robert Marcus, MBBS, of King’s College Hospital in London, UK.

Dr Marcus presented data from GALLIUM during the plenary session at the 2016 ASH Annual Meeting (abstract 6). GALLIUM is sponsored by Hoffmann-La Roche.

Patients and treatment

The study has enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to obinutuzumab plus chemotherapy followed by obinutuzumab alone for up to 2 years, and half were randomized to rituximab plus chemotherapy followed by rituximab alone for up to 2 years.

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine. The regimens were selected by each participating study site prior to beginning enrollment.

Baseline characteristics were similar between the treatment arms. The median age was about 60 (overall range, 23-88), roughly 40% of patients had high-risk disease, and the median time from diagnosis to randomization was about 1.5 months.

A total of 341 patients in the rituximab arm and 361 patients in the obinutuzumab arm completed maintenance therapy.

The median follow-up was 34.5 months. Maintenance is ongoing in 114 patients—54 on rituximab and 60 on obinutuzumab.

Efficacy

At the end of induction, the overall response rate was 86.9% in the rituximab arm and 88.5% in the obinutuzumab arm. The complete response rates were 23.8% and 19.5%, respectively. And the rates of stable disease were 1.3% and 0.5%, respectively.

The study’s primary endpoint is investigator-assessed PFS. The 3-year PFS rate is 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

According to an independent review committee, the 3-year PFS is 77.9% in the rituximab arm and 81.9% in the obinutuzumab arm (HR=0.71, P=0.0138).

The 3-year overall survival is 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

Safety

The overall incidence of AEs was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of AEs leading to treatment discontinuation was 14.2% and 16.3%, respectively. And the incidence of second neoplasms was 2.7% and 4.7%, respectively.

Grade 5 AEs occurred in 3.4% of patients in the rituximab arm and 4.0% of patients in the obinutuzumab arm. The investigators found that fatal AEs were more common in patients taking bendamustine, regardless of the treatment arm.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Attendees at the 2016

ASH Annual Meeting

SAN DIEGO—Interim results of the phase 3 GALLIUM trial suggest an obinutuzumab-based treatment regimen provides a progression-free survival (PFS) benefit over a rituximab-based regimen for patients with previously untreated follicular lymphoma (FL).

According to investigators, patients who received obinutuzumab plus chemotherapy followed by obinutuzumab maintenance had a “clinically meaningful” improvement in PFS, when compared to patients who received rituximab plus chemotherapy followed by rituximab maintenance.

However, there was no significant difference between the treatment arms with regard to overall survival. And the incidence of non-fatal adverse events (AEs) was higher among the patients who received obinutuzumab.

Nevertheless, the data suggest that obinutuzumab-based therapy significantly improves outcomes and should be considered as a first-line treatment for FL, according to Robert Marcus, MBBS, of King’s College Hospital in London, UK.

Dr Marcus presented data from GALLIUM during the plenary session at the 2016 ASH Annual Meeting (abstract 6). GALLIUM is sponsored by Hoffmann-La Roche.

Patients and treatment

The study has enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to obinutuzumab plus chemotherapy followed by obinutuzumab alone for up to 2 years, and half were randomized to rituximab plus chemotherapy followed by rituximab alone for up to 2 years.

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine. The regimens were selected by each participating study site prior to beginning enrollment.

Baseline characteristics were similar between the treatment arms. The median age was about 60 (overall range, 23-88), roughly 40% of patients had high-risk disease, and the median time from diagnosis to randomization was about 1.5 months.

A total of 341 patients in the rituximab arm and 361 patients in the obinutuzumab arm completed maintenance therapy.

The median follow-up was 34.5 months. Maintenance is ongoing in 114 patients—54 on rituximab and 60 on obinutuzumab.

Efficacy

At the end of induction, the overall response rate was 86.9% in the rituximab arm and 88.5% in the obinutuzumab arm. The complete response rates were 23.8% and 19.5%, respectively. And the rates of stable disease were 1.3% and 0.5%, respectively.

The study’s primary endpoint is investigator-assessed PFS. The 3-year PFS rate is 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

According to an independent review committee, the 3-year PFS is 77.9% in the rituximab arm and 81.9% in the obinutuzumab arm (HR=0.71, P=0.0138).

The 3-year overall survival is 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

Safety

The overall incidence of AEs was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of AEs leading to treatment discontinuation was 14.2% and 16.3%, respectively. And the incidence of second neoplasms was 2.7% and 4.7%, respectively.

Grade 5 AEs occurred in 3.4% of patients in the rituximab arm and 4.0% of patients in the obinutuzumab arm. The investigators found that fatal AEs were more common in patients taking bendamustine, regardless of the treatment arm.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Harry Erba, MD, PhD

© Todd Buchanan 2016

SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.

In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.

The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).

The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.

Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.

The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.

Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m² and daunorubicin at 60 mg/m²) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.

A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.

Results

The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.

Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).

Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.

None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.

A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).

The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.

There was a hint of additional benefit as well, he added.

“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”

MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.

Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017.

*Information presented at the meeting differs from the abstract.

Harry Erba, MD, PhD

© Todd Buchanan 2016

SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.

In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.

The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).

The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.

Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.

The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.

Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m² and daunorubicin at 60 mg/m²) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.

A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.

Results

The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.

Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).

Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.

None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.

A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).

The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.

There was a hint of additional benefit as well, he added.

“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”

MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.

Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017.

*Information presented at the meeting differs from the abstract.

Harry Erba, MD, PhD

© Todd Buchanan 2016

SAN DIEGO—A targeted therapy combined with standard chemotherapy can produce rapid, deep remissions in patients with newly diagnosed acute myeloid leukemia (AML), according to research presented at the 2016 ASH Annual Meeting.

In this phase 1b study, investigators tested vadastuximab talirine, an antibody drug conjugate targeting CD33, in combination with 7+3 chemotherapy—a continuous infusion of cytarabine for 7 days plus daunorubicin for 3 days.

The combination produced a high rate of response, which included minimal residual disease (MRD)-negative complete remissions (CRs).

The treatment also resulted in “acceptable” on-target myelosuppression and non-hematologic adverse events (AEs) similar to what would be expected with 7+3 alone, according to study investigator Harry Erba, MD, PhD, of the University of Alabama at Birmingham.

Dr Erba presented these results in abstract 211.* The research was sponsored by Seattle Genetics, Inc.

The study included 42 newly diagnosed AML patients with a median age of 45.5. Half the patients had intermediate-risk karyotypes, 36% had adverse karyotypes, and 17% had secondary AML.

Patients received escalating doses of vadastuximab talirine (10+10 mcg/kg [n=4] and 20+10 mcg/kg [n=38]) in combination with 7+3 induction (cytarabine at 100 mg/m² and daunorubicin at 60 mg/m²) on days 1 and 4 of a 28-day treatment cycle. Responses were assessed on days 15 and 28.

A second induction regimen and post-remission therapies were prescribed according to investigator choice and did not include vadastuximab talirine.

Results

The maximum tolerated dose of vadastuximab talirine was 20+10 mcg/kg.

Hematologic treatment-related AEs included febrile neutropenia (43%, grade 1-3), thrombocytopenia (38%, grade 3-4), anemia (24%, grade 3), and neutropenia (17%, grade 3-4).

Non-hematologic treatment-related AEs included nausea (17%), fatigue (14%), diarrhea (7%), and decreased appetite (7%). All of these AEs were grade 1-2.

None of the patients experienced infusion-related reactions, veno-occlusive disease, or significant liver damage.

A total of 76% of patients responded to treatment, with 60% percent achieving a CR and 17% achieving a CR with incomplete blood count recovery (CRi).

The 76% response rate is close to what would be expected for a well-chosen population fit for a clinical trial, Dr Erba said.

There was a hint of additional benefit as well, he added.

“The first hint was that 30 out of the 32 patients [who achieved a CR/CRi] required only 1 round of chemotherapy to achieve that remission,” Dr Erba said. “This also suggested that deeper remissions may be possible.”

MRD assessments using a sensitive flow cytometric assay revealed that 25 of the 32 patients (78%) who achieved a CR/CRi were MRD-negative.

Dr Erba said a randomized, phase 2 trial of vadastuximab talirine plus 7+3 versus 7+3 alone is planned for the first quarter of 2017.

*Information presented at the meeting differs from the abstract.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Obinutuzumab, a second-generation anti-CD20 antibody touted as the heir apparent to rituximab, offered a progression-free survival (PFS) edge over rituximab when combined with standard chemotherapy in patients with previously untreated advanced follicular lymphoma.

attended the presentation of the GALLIUM data at a plenary session during the American Society of Hematology annual meeting indicated that despite the data, they weren’t ready to make a switch to the newer, costlier antibody.

“I feel that it is not convincing for practice-changing,” said Kanti R. Rai, MD, professor of medicine and molecular medicine at Hofstra University, Hempstead, N.Y.

“Unless we have evidence of a survival advantage in indolent disease, progression-free survivorship is not an adequate reason to jump to another antibody,” he said in an interview.

In GALLIUM, the primary endpoint of investigator-assessed 3-year PFS at a median follow-up of 34.5 months was 80% for patients with follicular lymphoma treated with obinutuzumab and one of three standard chemotherapy regimens, compared with 73.3% for patients treated with rituximab and chemotherapy. This difference translated into a hazard ratio of 0.68 favoring obinutuzumab (P = .0012).

Respective 3-year overall survival rates were similar, however, at 94% and 92.1% (HR, 0.75; P = .21).

Indolent lymphoma trial

The GALLIUM trial is a phase III study comparing obinutuzumab with rituximab when paired with one of three standard chemotherapy regimens for indolent non-Hodgkin lymphomas, including follicular lymphoma and splenic, nodal, or extranodal marginal zone lymphoma. Dr. Marcus presented data on patients with follicular lymphoma only.

The antibodies were delivered in combination with either CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone; 33.1% of patients), CVP (cyclophosphamide, vincristine, prednisone; 9.8%) or bendamustine alone (B; 57.1%) as the chemotherapy backbone. The choice of regimen was at the discretion of the treating center.

A total of 1,202 patients with follicular lymphoma were enrolled and randomized to treatment and were included in an intention-to-treat analysis.

The treatment arms were well balanced with regard to distribution of patients characteristics, with approximately 21% in each arm having Follicular Lymphoma International Prognostic Index low-risk disease; 37% having intermediate-risk disease; and 34% having high-risk disease.

Roughly half of patients in each arm had bone marrow involvement, and two-thirds had extranodal involvement.

Obinutuzumab was dosed 1,000 mg IV on days 1, 8, and 15 of cycle one, and either on day 1 of cycles two through eight every 3 weeks, or every 4 weeks during cycles two through six.

Overall response rates at the end of induction were 86.9% with rituximab and 88.5% with obinutuzumab, with complete responses of 23.8% and 19.5%, respectively.

As noted before, investigator-assessed PFS favored obinutuzumab, as did PFS assessed by independent reviewer, at 81.9% vs. 77.9% for rituximab (HR, 0.71; P = .0138).

The newer antibody also had a slight edge in time to new treatment, with 87.1% of patients on obinutuzumab not starting on new therapy, compared with 81.2% of patients on rituximab.

More bendamustine deaths

Nearly all patients in each arm had an adverse event, with grade 3 or greater events occurring in 74.6% of patients on obinutuzumab vs. 67.8% on rituximab. Rates of neutropenia, leukopenia, febrile neutropenia, infusion reactions, and thrombocytopenia were all slightly higher with obinutuzumab. Grade 3 or greater infections occurred in 20% with obinutuzumab, compared with 15.6% with rituximab.

“What we did note, however, was a high level of mortality in patients receiving either obinutuzumab-based therapy or rituximab-based therapy, which were no different between the two arms and were somewhat higher than one might expect from patients receiving induction treatment in follicular lymphoma. Hence, we did a more detailed analysis of safety by treatment regimen,” Dr. Marcus said.

There were more deaths among patients treated with bendamustine (5.6% for patients in the B-obinutuzumab cohort, and 4.4% of patients in the B-rituximab cohort) vs. 1.6% and 2.0%, respectively, for patients on CHOP, and 1.6 and 1.8% for patients on CVP.

Dose effect?

John P. Leonard, MD, from Cornell University, New York , who introduced Dr. Marcus, commented that PFS may not be the ideal endpoint for patients with follicular lymphoma.

He pointed out that in trials comparing rituximab with obinutuzumab for other diseases, results have been mixed, with obinutuzumab showing superiority in chronic lymphocytic leukemia, but in data presented elsewhere at ASH 2016, obinutuzumab was not superior to rituximab for treatment of diffuse large B-cell lymphoma.

“One question is whether obinutuzumab, which is generally administered at a higher mg dose to patients, is in fact a better antibody or if it is in fact a dose effect,” he said.

In response to a similar question following his presentation, Dr. Marcus replied that, despite sharing a target, the two antibodies are different, with different mechanisms of action. He also noted that there is no evidence to suggest that rituximab potency would be greater in follicular lymphoma if it were given at higher doses.

The GALLIUM trial is sponsored by Hoffmann-La Roche, Dr, Marcus disclosed consulting with and receiving honoraria from the company, and relationships with other companies.

SAN DIEGO – Rising rates of pediatric venous thromboembolism in the United States underscore the need to carefully weigh the risks and benefits of placing central lines, Julie Jaffray, MD, said at the annual meeting of the American Society of Hematology.

Peripherally inserted central catheters (PICCs) are especially likely to lead to deep vein thrombosis in children, said Dr. Jaffray of Children’s Hospital Los Angeles, University of Southern California. Children and adolescents who received PICCs had about fourfold the rate of this outcome in the next 6 months as did those who received tunneled lines, based on interim results from her first-in-kind, prospective multicenter observational study.

Amy Karon

Earlier research has shown that the placement of PICCs approximately doubled at Children’s Hospital Los Angeles between 2005 and 2012, while the use of tunneled lines remained constant at a much-lower rate, Dr. Jaffray noted.

To better understand how central lines contribute to pediatric thrombotic events, she and her associates at the Children’s Hospital of Philadelphia and Texas Children’s Hospital in Houston are studying patients aged 6 months to 18 years who had these devices placed at their centers starting in 2013. To parse out risk factors, the investigators are analyzing numerous relevant keywords from nursing notes and other parts of electronic health records.

As of October 2016, the study included 1,096 patients who received a total of 1,233 central lines related to the treatment of cancer, infection, and other serious conditions. Among 827 PICC recipients, the 6-month cumulative rate of venous thromboembolism was 7.5%. In contrast, only 406 patients received tunneled lines, and only 2% developed venous thromboembolism (P = .004).

But tunneled lines had their own risks. About 16% of recipients developed CLABSI within 6 months, compared with 9% of children who received PICCs (P = .005). The overall rate of CLABSI was 12%, Dr. Jaffray noted.

Thromboses were identified a median of 15 days after PICC placement and 40 days after tunneled line placement, she said. Children with leukemia, other cancers, and congenital heart disease were at significantly increased risk of venous thromboembolism, as were children who received multilumen catheters, she noted.

Ongoing analyses should lead to new guidelines on pediatric catheter selection, insertion techniques, and the prophylactic use of anticoagulation or antiseptics, Dr. Jaffray said. She also is planning a separate study of children younger than 6 months, to examine their unique coagulation systems, she added.

The conclusion at this point is that two-thirds of this cohort received PICCs instead of tunneled lines, and 85% of venous thromboembolism episodes occurred in PICC recipients, Dr. Jaffray emphasized. “Due to their ease of insertion, PICCs are being placed at increasing rates in some pediatric centers, [and] this may be the leading factor for the increasing incidence of pediatric venous thromboembolism,” she commented. “A lot of us pediatric treaters aren’t necessarily giving anticoagulation for an incidental clot, but I think this is something we certainly need to look at. And maybe if we can choose the patients who are at highest risk of VTE, we can consider prophylactic anticoagulation in those kids.”

Dr. Jaffray did not report funding sources and had no relevant financial disclosures.

SAN DIEGO – Rising rates of pediatric venous thromboembolism in the United States underscore the need to carefully weigh the risks and benefits of placing central lines, Julie Jaffray, MD, said at the annual meeting of the American Society of Hematology.

Peripherally inserted central catheters (PICCs) are especially likely to lead to deep vein thrombosis in children, said Dr. Jaffray of Children’s Hospital Los Angeles, University of Southern California. Children and adolescents who received PICCs had about fourfold the rate of this outcome in the next 6 months as did those who received tunneled lines, based on interim results from her first-in-kind, prospective multicenter observational study.

Amy Karon

Earlier research has shown that the placement of PICCs approximately doubled at Children’s Hospital Los Angeles between 2005 and 2012, while the use of tunneled lines remained constant at a much-lower rate, Dr. Jaffray noted.

To better understand how central lines contribute to pediatric thrombotic events, she and her associates at the Children’s Hospital of Philadelphia and Texas Children’s Hospital in Houston are studying patients aged 6 months to 18 years who had these devices placed at their centers starting in 2013. To parse out risk factors, the investigators are analyzing numerous relevant keywords from nursing notes and other parts of electronic health records.

As of October 2016, the study included 1,096 patients who received a total of 1,233 central lines related to the treatment of cancer, infection, and other serious conditions. Among 827 PICC recipients, the 6-month cumulative rate of venous thromboembolism was 7.5%. In contrast, only 406 patients received tunneled lines, and only 2% developed venous thromboembolism (P = .004).

But tunneled lines had their own risks. About 16% of recipients developed CLABSI within 6 months, compared with 9% of children who received PICCs (P = .005). The overall rate of CLABSI was 12%, Dr. Jaffray noted.

Thromboses were identified a median of 15 days after PICC placement and 40 days after tunneled line placement, she said. Children with leukemia, other cancers, and congenital heart disease were at significantly increased risk of venous thromboembolism, as were children who received multilumen catheters, she noted.

Ongoing analyses should lead to new guidelines on pediatric catheter selection, insertion techniques, and the prophylactic use of anticoagulation or antiseptics, Dr. Jaffray said. She also is planning a separate study of children younger than 6 months, to examine their unique coagulation systems, she added.

The conclusion at this point is that two-thirds of this cohort received PICCs instead of tunneled lines, and 85% of venous thromboembolism episodes occurred in PICC recipients, Dr. Jaffray emphasized. “Due to their ease of insertion, PICCs are being placed at increasing rates in some pediatric centers, [and] this may be the leading factor for the increasing incidence of pediatric venous thromboembolism,” she commented. “A lot of us pediatric treaters aren’t necessarily giving anticoagulation for an incidental clot, but I think this is something we certainly need to look at. And maybe if we can choose the patients who are at highest risk of VTE, we can consider prophylactic anticoagulation in those kids.”

Dr. Jaffray did not report funding sources and had no relevant financial disclosures.

SAN DIEGO – Rising rates of pediatric venous thromboembolism in the United States underscore the need to carefully weigh the risks and benefits of placing central lines, Julie Jaffray, MD, said at the annual meeting of the American Society of Hematology.

Peripherally inserted central catheters (PICCs) are especially likely to lead to deep vein thrombosis in children, said Dr. Jaffray of Children’s Hospital Los Angeles, University of Southern California. Children and adolescents who received PICCs had about fourfold the rate of this outcome in the next 6 months as did those who received tunneled lines, based on interim results from her first-in-kind, prospective multicenter observational study.

Amy Karon

Earlier research has shown that the placement of PICCs approximately doubled at Children’s Hospital Los Angeles between 2005 and 2012, while the use of tunneled lines remained constant at a much-lower rate, Dr. Jaffray noted.

To better understand how central lines contribute to pediatric thrombotic events, she and her associates at the Children’s Hospital of Philadelphia and Texas Children’s Hospital in Houston are studying patients aged 6 months to 18 years who had these devices placed at their centers starting in 2013. To parse out risk factors, the investigators are analyzing numerous relevant keywords from nursing notes and other parts of electronic health records.

As of October 2016, the study included 1,096 patients who received a total of 1,233 central lines related to the treatment of cancer, infection, and other serious conditions. Among 827 PICC recipients, the 6-month cumulative rate of venous thromboembolism was 7.5%. In contrast, only 406 patients received tunneled lines, and only 2% developed venous thromboembolism (P = .004).

But tunneled lines had their own risks. About 16% of recipients developed CLABSI within 6 months, compared with 9% of children who received PICCs (P = .005). The overall rate of CLABSI was 12%, Dr. Jaffray noted.

Thromboses were identified a median of 15 days after PICC placement and 40 days after tunneled line placement, she said. Children with leukemia, other cancers, and congenital heart disease were at significantly increased risk of venous thromboembolism, as were children who received multilumen catheters, she noted.

Ongoing analyses should lead to new guidelines on pediatric catheter selection, insertion techniques, and the prophylactic use of anticoagulation or antiseptics, Dr. Jaffray said. She also is planning a separate study of children younger than 6 months, to examine their unique coagulation systems, she added.

The conclusion at this point is that two-thirds of this cohort received PICCs instead of tunneled lines, and 85% of venous thromboembolism episodes occurred in PICC recipients, Dr. Jaffray emphasized. “Due to their ease of insertion, PICCs are being placed at increasing rates in some pediatric centers, [and] this may be the leading factor for the increasing incidence of pediatric venous thromboembolism,” she commented. “A lot of us pediatric treaters aren’t necessarily giving anticoagulation for an incidental clot, but I think this is something we certainly need to look at. And maybe if we can choose the patients who are at highest risk of VTE, we can consider prophylactic anticoagulation in those kids.”

Dr. Jaffray did not report funding sources and had no relevant financial disclosures.

SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.

SAN DIEGO – After more than four decades of near stagnation in the treatment of patients with acute myeloid leukemia (AML), investigators are beginning to identify drugs that can produce rapid and deep complete remissions, which recent evidence suggests are associated with prolonged survival.

In this video interview at the annual meeting of the American Society of Hematology, Harry P. Erba, MD, PhD, professor of medicine, University of Alabama, Birmingham, describes the early results of one such agent, a novel antibody drug conjugate called vadastuximab talirine, or 33A for short. In the phase Ib clinical trial of induction therapy for newly diagnosed AML, a combination of standard 7+3 induction chemotherapy with cytarabine and daunorubicin plus 33A was associated with a 76% composite rate of complete remissions or complete remissions with incomplete recovery of platelets.

SAN DIEGO – After more than four decades of near stagnation in the treatment of patients with acute myeloid leukemia (AML), investigators are beginning to identify drugs that can produce rapid and deep complete remissions, which recent evidence suggests are associated with prolonged survival.

In this video interview at the annual meeting of the American Society of Hematology, Harry P. Erba, MD, PhD, professor of medicine, University of Alabama, Birmingham, describes the early results of one such agent, a novel antibody drug conjugate called vadastuximab talirine, or 33A for short. In the phase Ib clinical trial of induction therapy for newly diagnosed AML, a combination of standard 7+3 induction chemotherapy with cytarabine and daunorubicin plus 33A was associated with a 76% composite rate of complete remissions or complete remissions with incomplete recovery of platelets.

SAN DIEGO – After more than four decades of near stagnation in the treatment of patients with acute myeloid leukemia (AML), investigators are beginning to identify drugs that can produce rapid and deep complete remissions, which recent evidence suggests are associated with prolonged survival.

In this video interview at the annual meeting of the American Society of Hematology, Harry P. Erba, MD, PhD, professor of medicine, University of Alabama, Birmingham, describes the early results of one such agent, a novel antibody drug conjugate called vadastuximab talirine, or 33A for short. In the phase Ib clinical trial of induction therapy for newly diagnosed AML, a combination of standard 7+3 induction chemotherapy with cytarabine and daunorubicin plus 33A was associated with a 76% composite rate of complete remissions or complete remissions with incomplete recovery of platelets.