ASCO Annual Meeting 2016
© ASCO/Matt Herp

CHICAGO—Nearly 60% of chronic myeloid leukemia (CML) patients who switch to nilotinib from imatinib maintain treatment-free remission for 48 weeks after stopping treatment, according to a new study, ENESTop, presented at the 2016 ASCO Annual Meeting (abstract 7054). 

Treatment-free remission (TFR)—stopping tyrosine kinase inhibitor therapy after achieving a sustained deep molecular response—is an emerging treatment goal for patients with CML in chronic phase (CML-CP).

Results from Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Complete Molecular Response (ENESTcmr) demonstrated that patients on long-term imatinib who had not achieved MR4.5 were more likely to achieve this response by switching to nilotinib than by remaining on imatinib. 

“This suggests that, compared with remaining on imatinib, switching to nilotinib may enable more of these patients to reach a molecular response level required for attempting to achieve TFR in clinical trials,” said lead author Timothy Hughes, MD, of University of Adelaide in Australia. 

ENESTop is the first study, providing the largest set of prospective TFR data to date, to specifically assess TFR in patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib. 

The trial evaluated 126 patients who were able to achieve a sustained deep molecular response with nilotinib, but not with prior imatinib therapy.

The study met its primary endpoint of the proportion of patients without confirmed loss of MR4.0 or loss of major molecular response (MMR) within 48 weeks of nilotinib discontinuation in the TFR phase. 

Some 57.9% patients who achieved a sustained deep molecular response following at least three years of nilotinib therapy maintained a molecular response 48 weeks after stopping treatment.

Of the 51 patients with confirmed loss of MR4.0 or loss of MMR who restarted nilotinib, 98.0% regained at least MMR, with 94.1% regaining MR4.0 and 92.2% regaining MR4.5. 

By weeks 12 and 13 of treatment reinitiation with nilotinib, half of retreated patients already achieved MR4.0 and MR4.5, respectively. 

One patient entered the treatment reinitiation phase, but did not regain MMR by 20 weeks and discontinued the study. 

“MR4.5 achieved following the switch from imatinib to nilotinib,” Dr Hughes said, “was durable in most patients; more than three quarters of enrolled patients were eligible to enter the TFR phase.”

No new safety signals were observed, Dr Hughes said. Consistent with reports in imatinib-treated patients, the rates of all grade musculoskeletal pain were 42.1% in the first year of the TFR phase versus 14.3% while still taking nilotinib in the consolidation phase. 

Dr Hughes said the results suggest “TFR can be maintained in the majority of patients who achieve a sustained deep molecular response with nilotinib following switch from imatinib.”

He continued, “The results from ENESTop, together with those from ENESTcmr, show that a higher proportion of patients switching to nilotinib achieve MR 4.5, suggesting that a higher proportion of patients switching to nilotinib will achieve TFR compared with patients continuing on imatinib.”

Novartis is the sponsor of ENESTop and the manufacturer of imatinib (Gleevec) and nilotinib (Tasigna). Dr Hughes disclosed that he has received honoraria and research funding from Novartis.

ASCO Annual Meeting 2016
© ASCO/Matt Herp

CHICAGO—Nearly 60% of chronic myeloid leukemia (CML) patients who switch to nilotinib from imatinib maintain treatment-free remission for 48 weeks after stopping treatment, according to a new study, ENESTop, presented at the 2016 ASCO Annual Meeting (abstract 7054). 

Treatment-free remission (TFR)—stopping tyrosine kinase inhibitor therapy after achieving a sustained deep molecular response—is an emerging treatment goal for patients with CML in chronic phase (CML-CP).

Results from Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Complete Molecular Response (ENESTcmr) demonstrated that patients on long-term imatinib who had not achieved MR4.5 were more likely to achieve this response by switching to nilotinib than by remaining on imatinib. 

“This suggests that, compared with remaining on imatinib, switching to nilotinib may enable more of these patients to reach a molecular response level required for attempting to achieve TFR in clinical trials,” said lead author Timothy Hughes, MD, of University of Adelaide in Australia. 

ENESTop is the first study, providing the largest set of prospective TFR data to date, to specifically assess TFR in patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib. 

The trial evaluated 126 patients who were able to achieve a sustained deep molecular response with nilotinib, but not with prior imatinib therapy.

The study met its primary endpoint of the proportion of patients without confirmed loss of MR4.0 or loss of major molecular response (MMR) within 48 weeks of nilotinib discontinuation in the TFR phase. 

Some 57.9% patients who achieved a sustained deep molecular response following at least three years of nilotinib therapy maintained a molecular response 48 weeks after stopping treatment.

Of the 51 patients with confirmed loss of MR4.0 or loss of MMR who restarted nilotinib, 98.0% regained at least MMR, with 94.1% regaining MR4.0 and 92.2% regaining MR4.5. 

By weeks 12 and 13 of treatment reinitiation with nilotinib, half of retreated patients already achieved MR4.0 and MR4.5, respectively. 

One patient entered the treatment reinitiation phase, but did not regain MMR by 20 weeks and discontinued the study. 

“MR4.5 achieved following the switch from imatinib to nilotinib,” Dr Hughes said, “was durable in most patients; more than three quarters of enrolled patients were eligible to enter the TFR phase.”

No new safety signals were observed, Dr Hughes said. Consistent with reports in imatinib-treated patients, the rates of all grade musculoskeletal pain were 42.1% in the first year of the TFR phase versus 14.3% while still taking nilotinib in the consolidation phase. 

Dr Hughes said the results suggest “TFR can be maintained in the majority of patients who achieve a sustained deep molecular response with nilotinib following switch from imatinib.”

He continued, “The results from ENESTop, together with those from ENESTcmr, show that a higher proportion of patients switching to nilotinib achieve MR 4.5, suggesting that a higher proportion of patients switching to nilotinib will achieve TFR compared with patients continuing on imatinib.”

Novartis is the sponsor of ENESTop and the manufacturer of imatinib (Gleevec) and nilotinib (Tasigna). Dr Hughes disclosed that he has received honoraria and research funding from Novartis.

ASCO Annual Meeting 2016
© ASCO/Matt Herp

CHICAGO—Nearly 60% of chronic myeloid leukemia (CML) patients who switch to nilotinib from imatinib maintain treatment-free remission for 48 weeks after stopping treatment, according to a new study, ENESTop, presented at the 2016 ASCO Annual Meeting (abstract 7054). 

Treatment-free remission (TFR)—stopping tyrosine kinase inhibitor therapy after achieving a sustained deep molecular response—is an emerging treatment goal for patients with CML in chronic phase (CML-CP).

Results from Evaluating Nilotinib Efficacy and Safety in Clinical Trials–Complete Molecular Response (ENESTcmr) demonstrated that patients on long-term imatinib who had not achieved MR4.5 were more likely to achieve this response by switching to nilotinib than by remaining on imatinib. 

“This suggests that, compared with remaining on imatinib, switching to nilotinib may enable more of these patients to reach a molecular response level required for attempting to achieve TFR in clinical trials,” said lead author Timothy Hughes, MD, of University of Adelaide in Australia. 

ENESTop is the first study, providing the largest set of prospective TFR data to date, to specifically assess TFR in patients who achieved a sustained deep molecular response after switching from imatinib to nilotinib. 

The trial evaluated 126 patients who were able to achieve a sustained deep molecular response with nilotinib, but not with prior imatinib therapy.

The study met its primary endpoint of the proportion of patients without confirmed loss of MR4.0 or loss of major molecular response (MMR) within 48 weeks of nilotinib discontinuation in the TFR phase. 

Some 57.9% patients who achieved a sustained deep molecular response following at least three years of nilotinib therapy maintained a molecular response 48 weeks after stopping treatment.

Of the 51 patients with confirmed loss of MR4.0 or loss of MMR who restarted nilotinib, 98.0% regained at least MMR, with 94.1% regaining MR4.0 and 92.2% regaining MR4.5. 

By weeks 12 and 13 of treatment reinitiation with nilotinib, half of retreated patients already achieved MR4.0 and MR4.5, respectively. 

One patient entered the treatment reinitiation phase, but did not regain MMR by 20 weeks and discontinued the study. 

“MR4.5 achieved following the switch from imatinib to nilotinib,” Dr Hughes said, “was durable in most patients; more than three quarters of enrolled patients were eligible to enter the TFR phase.”

No new safety signals were observed, Dr Hughes said. Consistent with reports in imatinib-treated patients, the rates of all grade musculoskeletal pain were 42.1% in the first year of the TFR phase versus 14.3% while still taking nilotinib in the consolidation phase. 

Dr Hughes said the results suggest “TFR can be maintained in the majority of patients who achieve a sustained deep molecular response with nilotinib following switch from imatinib.”

He continued, “The results from ENESTop, together with those from ENESTcmr, show that a higher proportion of patients switching to nilotinib achieve MR 4.5, suggesting that a higher proportion of patients switching to nilotinib will achieve TFR compared with patients continuing on imatinib.”

Novartis is the sponsor of ENESTop and the manufacturer of imatinib (Gleevec) and nilotinib (Tasigna). Dr Hughes disclosed that he has received honoraria and research funding from Novartis.

Hagop M. Kantarjian, MD
Photo courtesy of MDACC

In multiple categories, the antibody-drug conjuagate inotuzumab ozogamicin achieved significantly better results than the standard of care in the treatment of adults with acute lymphoblastic leukemia (ALL). 

Patients in the inotuzumab arm experienced a higher rate of complete remissions, a greater frequency of achieving minimal residual disease negativity, and longer progression-free survival and overall survival. 

However, veno-occlusive liver disease occurred more frequently in the inotuzumab-treated patients. 

Inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, received breakthrough designation for ALL from the US Food and Drug Administration last October.

For this phase 3 trial, called INO-VATE, investigators randomized 326 patients to receive inotuzumab or the investigator’s choice of standard therapy. The first 218 patients, 109 in each arm, were included in the intent-to-treat analysis of complete remission.

Hagop M. Kantarjian, MD, of MD Anderson Cancer Center in Houston, Texas, presented the findings at the European Hematology Association meeting as abstract LB2233*. The study was simultaneously published in NEJM. Data cited here are based on the published paper.

Patients had to be 18 years of age or older and had to have relapsed or refractory disease with 5% or more blasts in the bone marrow. They had to be CD22-positive and could be either Philadelphia chromosome positive or negative. Patients had to be scheduled for their first or second salvage therapy. 

No cross-over between the groups was allowed.

The primary endpoints were complete remission including complete remission with incomplete hematologic recovery, and overall survival.

Treatments

Patients in the inotuzumab arm received the drug intravenously at a starting dose of 1.8 mg/m² per cycle for up to 6 cycles. Once a patient achieved complete remission or remission with incomplete hematologic recovery, the dose per cycle was reduced to 1.5 mg/m².

Patients in the standard therapy arm could receive one of three regimens: FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor), cytarabine plus mitoxantrone, or high-dose cytarabine. These regimens were chosen because they are commonly used for the treatment of relapsed or refractory ALL.

Patient characteristics

Patients in both arms were a median age of 47, range 18 – 79. And a little more than a third in each arm were 55 or older. Most patients were white, and about half had an ECOG performance status of 1.

Almost three quarters of the patients in each arm had bone marrow blasts of 50% or more.

Results

Patients in the inotuzumab arm received a median of 3 cycles of therapy and those in the standard therapy arm received a median of 1 cycle. 

More patients in the inotuzumab arm received treatment for 2 or more cycles (73%) compared to the standard therapy arm (22%), a finding the investigators said was expected.

Dose reductions were more common in the inotuzumab arm (12%) compared with the standard therapy arm (3%). 

More inotuzumab-treated patients discontinued therapy due to achieving complete remission (35%) than in the standard arm (15%).

And fewer patients in the inotuzumab arm (10%) discontinued treatment because of resistant disease than in the standard arm (40%).

Efficacy

The rate of complete remission, including incomplete hematologic recovery, was significantly higher in the inotuzumab group (80.7%) than in the standard group (29.4%), P<0.001.

In both groups, patients who achieved complete remission, including those with incomplete hematologic recovery, did so at the end of cycle 1. 

"Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier,” Dr Kantarjian noted, “and just 18 to 25 percent in those who relapse later." 

"Patients in the inotuzumab ozogamicin study,” he continued, “had remission rates of 58% higher than previously reported, possibly due to patients being treated later in the disease course."

Among the complete responders, significantly more patients achieved minimal residual disease (MRD) negativity in the inotuzumab arm (78.4%) than in the standard therapy group (28.1%), P<0.001.

The median duration of remission was 4.6 months in the inotuzumab arm and 3.1 months in the standard therapy group, P=0.03.

And more patients treated with inotuzumab (41%) proceeded to stem cell transplant directly after treatment than in the standard therapy group (11%), P<0.001.

"Given that stem cell transplant is considered the only curative treatment option,” Dr Kantarjian said, “the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging."

Survival

The intention-to-treat survival analysis included 164 patients in the inotuzumab arm and 162 in the standard therapy arm.

Progression-free survival (PFS) was significantly longer in the inotuzumab arm than in the standard therapy arm, a median of 5.0 months compared to 1.8 months, respectively, P<0.001.

The second primary objective of longer overall survival at the prespecified boundary of P=0.0208 was not met. Median overall survival was 7.7 months in the inotuzumab arm and 6.7 months in the standard therapy group, P=0.04.

Safety

In both treatment groups, the most common hematologic adverse events of any cause occurring during treatment were cytopenias.

Thrombocytopenia of grade 3 or higher was lower in the inotuzumab arm (37%) than in the standard therapy arm (59%).

Febrile neutropenia of grade 3 or higher occurred in 24% of inotuzumab-treated patients compared with 49% of patients in the standard therapy group. 

In the inotuzumab group, the most common non-hematologic adverse events of any grade included nausea (32%), headache (28%), and pyrexia (27%). Grade 3 or higher nausea, headache, and pyrexia occurred in 2%, 1%, and 4%, respectively.

In the standard therapy arm, the most common non-hematologic events of any grade included nausea (47%), pyrexia (43%), and diarrhea (40%). Grade 3 or higher nausea, pyrexia, and diarrhea occurred in 0%, 5%, and 1%, respectively. 

Febrile neutropenia was the most frequently reported serious adverse event, occurring in 12% of the inotuzumab-treated patients and 18% in the standard therapy group.

And liver-related adverse events were more common in the inotuzumab arm. 

The most frequent liver-related adverse event of any grade was increased aspartate aminotransferase level, 20% in the inotuzumab group and 10% in the standard therapy group, hyperbilirubinemia, 15% and 10%, respectively, and increased alanine aminotransferase level, 14% and 11%, respectively. 

Veno-occlusive liver disease (VOD) occurred more frequently with inotuzumab (11%, 15 patients) compared with standard therapy (1%, 1 patient). And cases were reported up to 2 years after randomization. 

Five of the 15 patients developed VOD during or shortly after inotuzumab treatment. No cases of VOD occurred during the administration of standard therapy. 

Seventeen deaths occurred during treatment in the inotuzumab arm and 11 in the standard therapy arm. Four deaths in the inotuzumab group and 2 in the standard therapy group were believed to be treatment-related. 

The study was funded by Pfizer.

*Data in the abstract differ from those published in NEJM.

Hagop M. Kantarjian, MD
Photo courtesy of MDACC

In multiple categories, the antibody-drug conjuagate inotuzumab ozogamicin achieved significantly better results than the standard of care in the treatment of adults with acute lymphoblastic leukemia (ALL). 

Patients in the inotuzumab arm experienced a higher rate of complete remissions, a greater frequency of achieving minimal residual disease negativity, and longer progression-free survival and overall survival. 

However, veno-occlusive liver disease occurred more frequently in the inotuzumab-treated patients. 

Inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, received breakthrough designation for ALL from the US Food and Drug Administration last October.

For this phase 3 trial, called INO-VATE, investigators randomized 326 patients to receive inotuzumab or the investigator’s choice of standard therapy. The first 218 patients, 109 in each arm, were included in the intent-to-treat analysis of complete remission.

Hagop M. Kantarjian, MD, of MD Anderson Cancer Center in Houston, Texas, presented the findings at the European Hematology Association meeting as abstract LB2233*. The study was simultaneously published in NEJM. Data cited here are based on the published paper.

Patients had to be 18 years of age or older and had to have relapsed or refractory disease with 5% or more blasts in the bone marrow. They had to be CD22-positive and could be either Philadelphia chromosome positive or negative. Patients had to be scheduled for their first or second salvage therapy. 

No cross-over between the groups was allowed.

The primary endpoints were complete remission including complete remission with incomplete hematologic recovery, and overall survival.

Treatments

Patients in the inotuzumab arm received the drug intravenously at a starting dose of 1.8 mg/m² per cycle for up to 6 cycles. Once a patient achieved complete remission or remission with incomplete hematologic recovery, the dose per cycle was reduced to 1.5 mg/m².

Patients in the standard therapy arm could receive one of three regimens: FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor), cytarabine plus mitoxantrone, or high-dose cytarabine. These regimens were chosen because they are commonly used for the treatment of relapsed or refractory ALL.

Patient characteristics

Patients in both arms were a median age of 47, range 18 – 79. And a little more than a third in each arm were 55 or older. Most patients were white, and about half had an ECOG performance status of 1.

Almost three quarters of the patients in each arm had bone marrow blasts of 50% or more.

Results

Patients in the inotuzumab arm received a median of 3 cycles of therapy and those in the standard therapy arm received a median of 1 cycle. 

More patients in the inotuzumab arm received treatment for 2 or more cycles (73%) compared to the standard therapy arm (22%), a finding the investigators said was expected.

Dose reductions were more common in the inotuzumab arm (12%) compared with the standard therapy arm (3%). 

More inotuzumab-treated patients discontinued therapy due to achieving complete remission (35%) than in the standard arm (15%).

And fewer patients in the inotuzumab arm (10%) discontinued treatment because of resistant disease than in the standard arm (40%).

Efficacy

The rate of complete remission, including incomplete hematologic recovery, was significantly higher in the inotuzumab group (80.7%) than in the standard group (29.4%), P<0.001.

In both groups, patients who achieved complete remission, including those with incomplete hematologic recovery, did so at the end of cycle 1. 

"Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier,” Dr Kantarjian noted, “and just 18 to 25 percent in those who relapse later." 

"Patients in the inotuzumab ozogamicin study,” he continued, “had remission rates of 58% higher than previously reported, possibly due to patients being treated later in the disease course."

Among the complete responders, significantly more patients achieved minimal residual disease (MRD) negativity in the inotuzumab arm (78.4%) than in the standard therapy group (28.1%), P<0.001.

The median duration of remission was 4.6 months in the inotuzumab arm and 3.1 months in the standard therapy group, P=0.03.

And more patients treated with inotuzumab (41%) proceeded to stem cell transplant directly after treatment than in the standard therapy group (11%), P<0.001.

"Given that stem cell transplant is considered the only curative treatment option,” Dr Kantarjian said, “the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging."

Survival

The intention-to-treat survival analysis included 164 patients in the inotuzumab arm and 162 in the standard therapy arm.

Progression-free survival (PFS) was significantly longer in the inotuzumab arm than in the standard therapy arm, a median of 5.0 months compared to 1.8 months, respectively, P<0.001.

The second primary objective of longer overall survival at the prespecified boundary of P=0.0208 was not met. Median overall survival was 7.7 months in the inotuzumab arm and 6.7 months in the standard therapy group, P=0.04.

Safety

In both treatment groups, the most common hematologic adverse events of any cause occurring during treatment were cytopenias.

Thrombocytopenia of grade 3 or higher was lower in the inotuzumab arm (37%) than in the standard therapy arm (59%).

Febrile neutropenia of grade 3 or higher occurred in 24% of inotuzumab-treated patients compared with 49% of patients in the standard therapy group. 

In the inotuzumab group, the most common non-hematologic adverse events of any grade included nausea (32%), headache (28%), and pyrexia (27%). Grade 3 or higher nausea, headache, and pyrexia occurred in 2%, 1%, and 4%, respectively.

In the standard therapy arm, the most common non-hematologic events of any grade included nausea (47%), pyrexia (43%), and diarrhea (40%). Grade 3 or higher nausea, pyrexia, and diarrhea occurred in 0%, 5%, and 1%, respectively. 

Febrile neutropenia was the most frequently reported serious adverse event, occurring in 12% of the inotuzumab-treated patients and 18% in the standard therapy group.

And liver-related adverse events were more common in the inotuzumab arm. 

The most frequent liver-related adverse event of any grade was increased aspartate aminotransferase level, 20% in the inotuzumab group and 10% in the standard therapy group, hyperbilirubinemia, 15% and 10%, respectively, and increased alanine aminotransferase level, 14% and 11%, respectively. 

Veno-occlusive liver disease (VOD) occurred more frequently with inotuzumab (11%, 15 patients) compared with standard therapy (1%, 1 patient). And cases were reported up to 2 years after randomization. 

Five of the 15 patients developed VOD during or shortly after inotuzumab treatment. No cases of VOD occurred during the administration of standard therapy. 

Seventeen deaths occurred during treatment in the inotuzumab arm and 11 in the standard therapy arm. Four deaths in the inotuzumab group and 2 in the standard therapy group were believed to be treatment-related. 

The study was funded by Pfizer.

*Data in the abstract differ from those published in NEJM.

Hagop M. Kantarjian, MD
Photo courtesy of MDACC

In multiple categories, the antibody-drug conjuagate inotuzumab ozogamicin achieved significantly better results than the standard of care in the treatment of adults with acute lymphoblastic leukemia (ALL). 

Patients in the inotuzumab arm experienced a higher rate of complete remissions, a greater frequency of achieving minimal residual disease negativity, and longer progression-free survival and overall survival. 

However, veno-occlusive liver disease occurred more frequently in the inotuzumab-treated patients. 

Inotuzumab ozogamicin, an anti-CD22 antibody conjugated to calicheamicin, received breakthrough designation for ALL from the US Food and Drug Administration last October.

For this phase 3 trial, called INO-VATE, investigators randomized 326 patients to receive inotuzumab or the investigator’s choice of standard therapy. The first 218 patients, 109 in each arm, were included in the intent-to-treat analysis of complete remission.

Hagop M. Kantarjian, MD, of MD Anderson Cancer Center in Houston, Texas, presented the findings at the European Hematology Association meeting as abstract LB2233*. The study was simultaneously published in NEJM. Data cited here are based on the published paper.

Patients had to be 18 years of age or older and had to have relapsed or refractory disease with 5% or more blasts in the bone marrow. They had to be CD22-positive and could be either Philadelphia chromosome positive or negative. Patients had to be scheduled for their first or second salvage therapy. 

No cross-over between the groups was allowed.

The primary endpoints were complete remission including complete remission with incomplete hematologic recovery, and overall survival.

Treatments

Patients in the inotuzumab arm received the drug intravenously at a starting dose of 1.8 mg/m² per cycle for up to 6 cycles. Once a patient achieved complete remission or remission with incomplete hematologic recovery, the dose per cycle was reduced to 1.5 mg/m².

Patients in the standard therapy arm could receive one of three regimens: FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor), cytarabine plus mitoxantrone, or high-dose cytarabine. These regimens were chosen because they are commonly used for the treatment of relapsed or refractory ALL.

Patient characteristics

Patients in both arms were a median age of 47, range 18 – 79. And a little more than a third in each arm were 55 or older. Most patients were white, and about half had an ECOG performance status of 1.

Almost three quarters of the patients in each arm had bone marrow blasts of 50% or more.

Results

Patients in the inotuzumab arm received a median of 3 cycles of therapy and those in the standard therapy arm received a median of 1 cycle. 

More patients in the inotuzumab arm received treatment for 2 or more cycles (73%) compared to the standard therapy arm (22%), a finding the investigators said was expected.

Dose reductions were more common in the inotuzumab arm (12%) compared with the standard therapy arm (3%). 

More inotuzumab-treated patients discontinued therapy due to achieving complete remission (35%) than in the standard arm (15%).

And fewer patients in the inotuzumab arm (10%) discontinued treatment because of resistant disease than in the standard arm (40%).

Efficacy

The rate of complete remission, including incomplete hematologic recovery, was significantly higher in the inotuzumab group (80.7%) than in the standard group (29.4%), P<0.001.

In both groups, patients who achieved complete remission, including those with incomplete hematologic recovery, did so at the end of cycle 1. 

"Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier,” Dr Kantarjian noted, “and just 18 to 25 percent in those who relapse later." 

"Patients in the inotuzumab ozogamicin study,” he continued, “had remission rates of 58% higher than previously reported, possibly due to patients being treated later in the disease course."

Among the complete responders, significantly more patients achieved minimal residual disease (MRD) negativity in the inotuzumab arm (78.4%) than in the standard therapy group (28.1%), P<0.001.

The median duration of remission was 4.6 months in the inotuzumab arm and 3.1 months in the standard therapy group, P=0.03.

And more patients treated with inotuzumab (41%) proceeded to stem cell transplant directly after treatment than in the standard therapy group (11%), P<0.001.

"Given that stem cell transplant is considered the only curative treatment option,” Dr Kantarjian said, “the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging."

Survival

The intention-to-treat survival analysis included 164 patients in the inotuzumab arm and 162 in the standard therapy arm.

Progression-free survival (PFS) was significantly longer in the inotuzumab arm than in the standard therapy arm, a median of 5.0 months compared to 1.8 months, respectively, P<0.001.

The second primary objective of longer overall survival at the prespecified boundary of P=0.0208 was not met. Median overall survival was 7.7 months in the inotuzumab arm and 6.7 months in the standard therapy group, P=0.04.

Safety

In both treatment groups, the most common hematologic adverse events of any cause occurring during treatment were cytopenias.

Thrombocytopenia of grade 3 or higher was lower in the inotuzumab arm (37%) than in the standard therapy arm (59%).

Febrile neutropenia of grade 3 or higher occurred in 24% of inotuzumab-treated patients compared with 49% of patients in the standard therapy group. 

In the inotuzumab group, the most common non-hematologic adverse events of any grade included nausea (32%), headache (28%), and pyrexia (27%). Grade 3 or higher nausea, headache, and pyrexia occurred in 2%, 1%, and 4%, respectively.

In the standard therapy arm, the most common non-hematologic events of any grade included nausea (47%), pyrexia (43%), and diarrhea (40%). Grade 3 or higher nausea, pyrexia, and diarrhea occurred in 0%, 5%, and 1%, respectively. 

Febrile neutropenia was the most frequently reported serious adverse event, occurring in 12% of the inotuzumab-treated patients and 18% in the standard therapy group.

And liver-related adverse events were more common in the inotuzumab arm. 

The most frequent liver-related adverse event of any grade was increased aspartate aminotransferase level, 20% in the inotuzumab group and 10% in the standard therapy group, hyperbilirubinemia, 15% and 10%, respectively, and increased alanine aminotransferase level, 14% and 11%, respectively. 

Veno-occlusive liver disease (VOD) occurred more frequently with inotuzumab (11%, 15 patients) compared with standard therapy (1%, 1 patient). And cases were reported up to 2 years after randomization. 

Five of the 15 patients developed VOD during or shortly after inotuzumab treatment. No cases of VOD occurred during the administration of standard therapy. 

Seventeen deaths occurred during treatment in the inotuzumab arm and 11 in the standard therapy arm. Four deaths in the inotuzumab group and 2 in the standard therapy group were believed to be treatment-related. 

The study was funded by Pfizer.

*Data in the abstract differ from those published in NEJM.

When you travel to Los Angeles for CHEST 2016, October 22 - 26, your intentions will be clear. You’ll want to connect with your colleagues from around the globe, earn CME and MOC, and learn in an innovative, hands-on environment. We’ve got that covered with cutting-edge sessions and a community of innovative problem-solvers. But why travel by yourself when your destination is known for beautiful weather, sandy beaches, amusement parks, and entertainment for the whole family? In LA, your whole family can enjoy a vacation, and you can join in some fun in the sun during your free time or before or after the meeting.

Disney

If you haven’t taken your kids to Disneyland, this may be a great opportunity to visit “the happiest place on earth.” Anaheim, home to Disneyland, is about an hour drive from the Los Angeles Convention Center. Take flight with Dumbo the Elephant, visit the Haunted Mansion, spin around in tea cups, ride Mickey’s Fun Wheel, and much more.

Universal Studios

Located in Hollywood, Universal Studios is only about a half-hour’s drive from the convention center. You’ll enjoy theme park rides and shows, a real working movie studio, and lots of lovable characters. Plus, you can explore a new offering, the mysteries of Hogwarts castle at the Wizarding World of Harry Potter.

Knott’s Berry Farm

This theme park and amusement park is about 50 minutes from the convention center. The park has roller coasters, children’s rides, water rides, and plenty of fun and scary activities to try out during the weeks leading up to Halloween.

Los Angeles Zoo and Botanical Gardens

About 25 minutes from the convention center, the Los Angeles Zoo and Botanical Gardens is home to more than 1,100 mammals, birds, amphibians, and reptiles representing more than 250 different species, of which 29 are endangered. Learn about animals from around the world and their habitats.

California Science Center

Just a 10-minute drive from the convention center, the California Science Center is fun for all ages. The center includes four major exhibits that focus on air and space, technology, commonalities of living organisms, and ecosystems. There is also an educationally focused IMAX theater with a seven-story screen.

CHEST 2016

Los Angeles will energize you with its family-friendly entertainment, and CHEST 2016 will keep you current with the latest developments in chest medicine. Don’t miss out on the opportunity to inspire your patient care. Learn more and register today at chestmeeting.chestnet.org.

When you travel to Los Angeles for CHEST 2016, October 22 - 26, your intentions will be clear. You’ll want to connect with your colleagues from around the globe, earn CME and MOC, and learn in an innovative, hands-on environment. We’ve got that covered with cutting-edge sessions and a community of innovative problem-solvers. But why travel by yourself when your destination is known for beautiful weather, sandy beaches, amusement parks, and entertainment for the whole family? In LA, your whole family can enjoy a vacation, and you can join in some fun in the sun during your free time or before or after the meeting.

Disney

If you haven’t taken your kids to Disneyland, this may be a great opportunity to visit “the happiest place on earth.” Anaheim, home to Disneyland, is about an hour drive from the Los Angeles Convention Center. Take flight with Dumbo the Elephant, visit the Haunted Mansion, spin around in tea cups, ride Mickey’s Fun Wheel, and much more.

Universal Studios

Located in Hollywood, Universal Studios is only about a half-hour’s drive from the convention center. You’ll enjoy theme park rides and shows, a real working movie studio, and lots of lovable characters. Plus, you can explore a new offering, the mysteries of Hogwarts castle at the Wizarding World of Harry Potter.

Knott’s Berry Farm

This theme park and amusement park is about 50 minutes from the convention center. The park has roller coasters, children’s rides, water rides, and plenty of fun and scary activities to try out during the weeks leading up to Halloween.

Los Angeles Zoo and Botanical Gardens

About 25 minutes from the convention center, the Los Angeles Zoo and Botanical Gardens is home to more than 1,100 mammals, birds, amphibians, and reptiles representing more than 250 different species, of which 29 are endangered. Learn about animals from around the world and their habitats.

California Science Center

Just a 10-minute drive from the convention center, the California Science Center is fun for all ages. The center includes four major exhibits that focus on air and space, technology, commonalities of living organisms, and ecosystems. There is also an educationally focused IMAX theater with a seven-story screen.

CHEST 2016

Los Angeles will energize you with its family-friendly entertainment, and CHEST 2016 will keep you current with the latest developments in chest medicine. Don’t miss out on the opportunity to inspire your patient care. Learn more and register today at chestmeeting.chestnet.org.

When you travel to Los Angeles for CHEST 2016, October 22 - 26, your intentions will be clear. You’ll want to connect with your colleagues from around the globe, earn CME and MOC, and learn in an innovative, hands-on environment. We’ve got that covered with cutting-edge sessions and a community of innovative problem-solvers. But why travel by yourself when your destination is known for beautiful weather, sandy beaches, amusement parks, and entertainment for the whole family? In LA, your whole family can enjoy a vacation, and you can join in some fun in the sun during your free time or before or after the meeting.

Disney

If you haven’t taken your kids to Disneyland, this may be a great opportunity to visit “the happiest place on earth.” Anaheim, home to Disneyland, is about an hour drive from the Los Angeles Convention Center. Take flight with Dumbo the Elephant, visit the Haunted Mansion, spin around in tea cups, ride Mickey’s Fun Wheel, and much more.

Universal Studios

Located in Hollywood, Universal Studios is only about a half-hour’s drive from the convention center. You’ll enjoy theme park rides and shows, a real working movie studio, and lots of lovable characters. Plus, you can explore a new offering, the mysteries of Hogwarts castle at the Wizarding World of Harry Potter.

Knott’s Berry Farm

This theme park and amusement park is about 50 minutes from the convention center. The park has roller coasters, children’s rides, water rides, and plenty of fun and scary activities to try out during the weeks leading up to Halloween.

Los Angeles Zoo and Botanical Gardens

About 25 minutes from the convention center, the Los Angeles Zoo and Botanical Gardens is home to more than 1,100 mammals, birds, amphibians, and reptiles representing more than 250 different species, of which 29 are endangered. Learn about animals from around the world and their habitats.

California Science Center

Just a 10-minute drive from the convention center, the California Science Center is fun for all ages. The center includes four major exhibits that focus on air and space, technology, commonalities of living organisms, and ecosystems. There is also an educationally focused IMAX theater with a seven-story screen.

CHEST 2016

Los Angeles will energize you with its family-friendly entertainment, and CHEST 2016 will keep you current with the latest developments in chest medicine. Don’t miss out on the opportunity to inspire your patient care. Learn more and register today at chestmeeting.chestnet.org.

In 1956, Margaret Pfrommer, a healthy teenager, became a quadriplegic with limited head control, no use of her upper extremities, no vital capacity. She used a wheelchair the rest of her 42 years.

When she was forced into a nursing home more than a decade later, Margaret’s frustration with her circumstances compelled her to become an advocate for herself and for all those with significant disabilities. She was one of the first to pilot a motorized wheelchair with a “sip-and-puff” mechanism. Her consultation and feedback were instrumental in developing the prototype and other technologies that allowed Margaret and many others with severe disabilities to live independently.

As a champion for improving patient care, Margaret served as president of the Coalition of the Physically Handicapped (COPH), chair of the Citizen’s Council, chair of the Illinois Delegation to the National White House Conference on Handicapped Individuals, chair of the board of directors of Access Living of Metropolitan Chicago, and was a member of the board of directors of the Rehabilitation Engineering and Assistive Technology Society of North America (RESNA).

Margaret also made it her mission to highlight the importance of the clinician and patient relationship. She emphasized understanding the patient and family perspective and respecting their knowledge. Her insistence that patients and clinicians collaborate to determine a most effective care management plan has proven invaluable to many chest medicine professionals.

Margaret died in 1998. Less than a year following her death, Dr. Allen I Goldberg, MD, MBA, Master FCCP, and Eveline A. M. Faure, MD, helped created the Margaret Pfrommer Memorial Lecture in Long-term Mechanical Ventilation. The memorial lecture is partially supported by generous gifts from CHEST and the CHEST Foundation, Post-Polio Health International, and numerous friends of the foundation.

Understanding the patient’s perspective was Margaret’s passion, and through these lectures, we are able to ensure that her legacy lives on for those who champion her effort and admire her dedication. To support the Margaret Pfrommer Memorial Lecture, go to chestnet.org/donate or call 224/521-9517.

In 1956, Margaret Pfrommer, a healthy teenager, became a quadriplegic with limited head control, no use of her upper extremities, no vital capacity. She used a wheelchair the rest of her 42 years.

When she was forced into a nursing home more than a decade later, Margaret’s frustration with her circumstances compelled her to become an advocate for herself and for all those with significant disabilities. She was one of the first to pilot a motorized wheelchair with a “sip-and-puff” mechanism. Her consultation and feedback were instrumental in developing the prototype and other technologies that allowed Margaret and many others with severe disabilities to live independently.

As a champion for improving patient care, Margaret served as president of the Coalition of the Physically Handicapped (COPH), chair of the Citizen’s Council, chair of the Illinois Delegation to the National White House Conference on Handicapped Individuals, chair of the board of directors of Access Living of Metropolitan Chicago, and was a member of the board of directors of the Rehabilitation Engineering and Assistive Technology Society of North America (RESNA).

Margaret also made it her mission to highlight the importance of the clinician and patient relationship. She emphasized understanding the patient and family perspective and respecting their knowledge. Her insistence that patients and clinicians collaborate to determine a most effective care management plan has proven invaluable to many chest medicine professionals.

Margaret died in 1998. Less than a year following her death, Dr. Allen I Goldberg, MD, MBA, Master FCCP, and Eveline A. M. Faure, MD, helped created the Margaret Pfrommer Memorial Lecture in Long-term Mechanical Ventilation. The memorial lecture is partially supported by generous gifts from CHEST and the CHEST Foundation, Post-Polio Health International, and numerous friends of the foundation.

Understanding the patient’s perspective was Margaret’s passion, and through these lectures, we are able to ensure that her legacy lives on for those who champion her effort and admire her dedication. To support the Margaret Pfrommer Memorial Lecture, go to chestnet.org/donate or call 224/521-9517.

In 1956, Margaret Pfrommer, a healthy teenager, became a quadriplegic with limited head control, no use of her upper extremities, no vital capacity. She used a wheelchair the rest of her 42 years.

When she was forced into a nursing home more than a decade later, Margaret’s frustration with her circumstances compelled her to become an advocate for herself and for all those with significant disabilities. She was one of the first to pilot a motorized wheelchair with a “sip-and-puff” mechanism. Her consultation and feedback were instrumental in developing the prototype and other technologies that allowed Margaret and many others with severe disabilities to live independently.

As a champion for improving patient care, Margaret served as president of the Coalition of the Physically Handicapped (COPH), chair of the Citizen’s Council, chair of the Illinois Delegation to the National White House Conference on Handicapped Individuals, chair of the board of directors of Access Living of Metropolitan Chicago, and was a member of the board of directors of the Rehabilitation Engineering and Assistive Technology Society of North America (RESNA).

Margaret also made it her mission to highlight the importance of the clinician and patient relationship. She emphasized understanding the patient and family perspective and respecting their knowledge. Her insistence that patients and clinicians collaborate to determine a most effective care management plan has proven invaluable to many chest medicine professionals.

Margaret died in 1998. Less than a year following her death, Dr. Allen I Goldberg, MD, MBA, Master FCCP, and Eveline A. M. Faure, MD, helped created the Margaret Pfrommer Memorial Lecture in Long-term Mechanical Ventilation. The memorial lecture is partially supported by generous gifts from CHEST and the CHEST Foundation, Post-Polio Health International, and numerous friends of the foundation.

Understanding the patient’s perspective was Margaret’s passion, and through these lectures, we are able to ensure that her legacy lives on for those who champion her effort and admire her dedication. To support the Margaret Pfrommer Memorial Lecture, go to chestnet.org/donate or call 224/521-9517.

CMS has proposed a dramatic change in the methodology used to determine payment to physician offices that provide drugs covered under the Part B Medicare benefit. Under current policy, physician offices are reimbursed at a rate of the average sales price (ASP) +6%. While not exactly a “moneymaker” in the pulmonary space, this policy has been particularly attractive to oncologists who have the opportunity to select expensive medicines that, according to CMS, may overlook very similar, less expensive drugs.

The proposal, in effect a nationwide pilot, reduces the payment to ASP + 3%, plus a $16 administrative fee. The response from the oncology community has been vociferous opposition, and it has garnered significant support on Capitol Hill. But the impact on the pulmonary community has, for the most part, been muted, thanks to uncertainty about the impact such a policy change may trigger. NAMDRC submitted detailed comments to CMS, highlighting concerns that this initiative, which is mandatory and nationwide in scope, could adversely impact the medical care of seniors who suffer from COPD and other related pulmonary diseases. NAMDRC is also concerned about the precedent this policy sets by using limited demonstration authority to change statutory payment policy nationwide.

While NAMDRC supports the goals of developing new health-care delivery methods to increase quality and provide more efficient patient care, it is nevertheless troubled by the Part B drug reimbursement policy proposed by CMS, as it appears to have been created in a vacuum without any input from stakeholders involved, particularly beneficiaries and their physicians. Forcing vulnerable Medicare beneficiaries, many with potentially life-threatening conditions, including COPD, the third leading cause of death in the United States, and asthma, to be exposed to a new mandatory payment initiative that runs the notable risk of impeding access to life-saving therapies runs counter to the initiatives that Congress has put forth.

While NAMDRC understands the need to look seriously at cost issues within our core health programs, we must not subject beneficiaries and their physicians to the problematic choice between practice economics and prescribing the most medically appropriate treatment for each individual patient. As CMS knows, biologic medications for treatment of asthma are likely to take an important role in treatment protocols in the immediate future; one new biologic for asthma was approved recently, and two new biologics in the pipeline are likely to be approved by the end of the year. Beyond asthma, the development of new biologics in the pulmonary field is likely to expand in the foreseeable future.

As noted above, in the proposed rule, CMS expresses concern that the current 6% ASP add-on payment “may encourage the use of more expensive drugs because the 6% add-on generates more revenue for more expensive drugs.” In addition to lacking any data to support this premise, the reimbursement changes contemplated under this model may actually increase overall health-care spending by causing patients to receive care in more expensive settings.

Most importantly, there is no evidence indicating that the payment changes contemplated by the model will improve quality of care and may adversely impact those patients who lose access to their most appropriate treatments. Instead, NAMDRC believes that Medicare beneficiaries would be best served by a more patient-centric approach with appropriate safeguards, while also fostering physician-patient collaboration and ensuring that the unique needs of seniors are met. Therefore, NAMDRC strongly requested that CMS withdraw the proposed rule and obtain meaningful stakeholder input, including from patients and providers, before proceeding with Phase 2 of the proposed pilot.

2017 Educational Conference planning underway: NAMDRC’s 2017 Program Committee is targeting the middle of July for completion of the primary program for the 2017 conference to be held at the Meritage Resort, Napa, CA March 23-25, 2017. For information on the program, visit www.namdrc.org or call the Executive Office at 703/752-4359.

CMS has proposed a dramatic change in the methodology used to determine payment to physician offices that provide drugs covered under the Part B Medicare benefit. Under current policy, physician offices are reimbursed at a rate of the average sales price (ASP) +6%. While not exactly a “moneymaker” in the pulmonary space, this policy has been particularly attractive to oncologists who have the opportunity to select expensive medicines that, according to CMS, may overlook very similar, less expensive drugs.

The proposal, in effect a nationwide pilot, reduces the payment to ASP + 3%, plus a $16 administrative fee. The response from the oncology community has been vociferous opposition, and it has garnered significant support on Capitol Hill. But the impact on the pulmonary community has, for the most part, been muted, thanks to uncertainty about the impact such a policy change may trigger. NAMDRC submitted detailed comments to CMS, highlighting concerns that this initiative, which is mandatory and nationwide in scope, could adversely impact the medical care of seniors who suffer from COPD and other related pulmonary diseases. NAMDRC is also concerned about the precedent this policy sets by using limited demonstration authority to change statutory payment policy nationwide.

While NAMDRC supports the goals of developing new health-care delivery methods to increase quality and provide more efficient patient care, it is nevertheless troubled by the Part B drug reimbursement policy proposed by CMS, as it appears to have been created in a vacuum without any input from stakeholders involved, particularly beneficiaries and their physicians. Forcing vulnerable Medicare beneficiaries, many with potentially life-threatening conditions, including COPD, the third leading cause of death in the United States, and asthma, to be exposed to a new mandatory payment initiative that runs the notable risk of impeding access to life-saving therapies runs counter to the initiatives that Congress has put forth.

While NAMDRC understands the need to look seriously at cost issues within our core health programs, we must not subject beneficiaries and their physicians to the problematic choice between practice economics and prescribing the most medically appropriate treatment for each individual patient. As CMS knows, biologic medications for treatment of asthma are likely to take an important role in treatment protocols in the immediate future; one new biologic for asthma was approved recently, and two new biologics in the pipeline are likely to be approved by the end of the year. Beyond asthma, the development of new biologics in the pulmonary field is likely to expand in the foreseeable future.

As noted above, in the proposed rule, CMS expresses concern that the current 6% ASP add-on payment “may encourage the use of more expensive drugs because the 6% add-on generates more revenue for more expensive drugs.” In addition to lacking any data to support this premise, the reimbursement changes contemplated under this model may actually increase overall health-care spending by causing patients to receive care in more expensive settings.

Most importantly, there is no evidence indicating that the payment changes contemplated by the model will improve quality of care and may adversely impact those patients who lose access to their most appropriate treatments. Instead, NAMDRC believes that Medicare beneficiaries would be best served by a more patient-centric approach with appropriate safeguards, while also fostering physician-patient collaboration and ensuring that the unique needs of seniors are met. Therefore, NAMDRC strongly requested that CMS withdraw the proposed rule and obtain meaningful stakeholder input, including from patients and providers, before proceeding with Phase 2 of the proposed pilot.

2017 Educational Conference planning underway: NAMDRC’s 2017 Program Committee is targeting the middle of July for completion of the primary program for the 2017 conference to be held at the Meritage Resort, Napa, CA March 23-25, 2017. For information on the program, visit www.namdrc.org or call the Executive Office at 703/752-4359.

CMS has proposed a dramatic change in the methodology used to determine payment to physician offices that provide drugs covered under the Part B Medicare benefit. Under current policy, physician offices are reimbursed at a rate of the average sales price (ASP) +6%. While not exactly a “moneymaker” in the pulmonary space, this policy has been particularly attractive to oncologists who have the opportunity to select expensive medicines that, according to CMS, may overlook very similar, less expensive drugs.

The proposal, in effect a nationwide pilot, reduces the payment to ASP + 3%, plus a $16 administrative fee. The response from the oncology community has been vociferous opposition, and it has garnered significant support on Capitol Hill. But the impact on the pulmonary community has, for the most part, been muted, thanks to uncertainty about the impact such a policy change may trigger. NAMDRC submitted detailed comments to CMS, highlighting concerns that this initiative, which is mandatory and nationwide in scope, could adversely impact the medical care of seniors who suffer from COPD and other related pulmonary diseases. NAMDRC is also concerned about the precedent this policy sets by using limited demonstration authority to change statutory payment policy nationwide.

While NAMDRC supports the goals of developing new health-care delivery methods to increase quality and provide more efficient patient care, it is nevertheless troubled by the Part B drug reimbursement policy proposed by CMS, as it appears to have been created in a vacuum without any input from stakeholders involved, particularly beneficiaries and their physicians. Forcing vulnerable Medicare beneficiaries, many with potentially life-threatening conditions, including COPD, the third leading cause of death in the United States, and asthma, to be exposed to a new mandatory payment initiative that runs the notable risk of impeding access to life-saving therapies runs counter to the initiatives that Congress has put forth.

While NAMDRC understands the need to look seriously at cost issues within our core health programs, we must not subject beneficiaries and their physicians to the problematic choice between practice economics and prescribing the most medically appropriate treatment for each individual patient. As CMS knows, biologic medications for treatment of asthma are likely to take an important role in treatment protocols in the immediate future; one new biologic for asthma was approved recently, and two new biologics in the pipeline are likely to be approved by the end of the year. Beyond asthma, the development of new biologics in the pulmonary field is likely to expand in the foreseeable future.

As noted above, in the proposed rule, CMS expresses concern that the current 6% ASP add-on payment “may encourage the use of more expensive drugs because the 6% add-on generates more revenue for more expensive drugs.” In addition to lacking any data to support this premise, the reimbursement changes contemplated under this model may actually increase overall health-care spending by causing patients to receive care in more expensive settings.

Most importantly, there is no evidence indicating that the payment changes contemplated by the model will improve quality of care and may adversely impact those patients who lose access to their most appropriate treatments. Instead, NAMDRC believes that Medicare beneficiaries would be best served by a more patient-centric approach with appropriate safeguards, while also fostering physician-patient collaboration and ensuring that the unique needs of seniors are met. Therefore, NAMDRC strongly requested that CMS withdraw the proposed rule and obtain meaningful stakeholder input, including from patients and providers, before proceeding with Phase 2 of the proposed pilot.

2017 Educational Conference planning underway: NAMDRC’s 2017 Program Committee is targeting the middle of July for completion of the primary program for the 2017 conference to be held at the Meritage Resort, Napa, CA March 23-25, 2017. For information on the program, visit www.namdrc.org or call the Executive Office at 703/752-4359.

Beginning this year, the CPT® code for endobronchial ultrasound (EBUS) 31620 was replaced by three new codes that more accurately describe the procedure as it is currently performed. Codes 31652 and 31653 are reported when EBUS is used for sampling proximal lesions (mediastinal or hilar). Code 31654 is used in identifying more distal lesions. As with other bronchoscopy procedures, the diagnostic code, 31622, is included with these three new codes and the multiple endoscopy rule applies.

CPT code 31652 is utilized when one samples two or fewer proximal locations. CPT code 31653 is utilized when one samples three or more proximal locations. 31652 and 31653 may not be used together; use the code that best describes the work that was done. These two codes include the sampling procedures and, therefore, one does not use CPT codes for sampling, e.g., 31628 or 31629, with either 31652 or 31653. However, if additional procedures are performed on structures distal to the hila, then it is appropriate to use other bronchoscopy codes with 31652 and 31653.

CPT code 31654 is an “add-on” code that is used to identify more peripheral lesions for sampling. As such, it may be used with all of the other bronchoscopy codes.

Unfortunately, when CMS originally published the National Correct Coding Initiative (NCCI) edits for these new codes, there were errors present. NCCI edits are used to instruct CMS payers and clinicians when two distinct CPT codes may or may not be used together. The NCCI edits for 31652 and 31653 published on January 1, 2016, had a value of “0” for all other bronchoscopy codes; this instructed payers to reject any claims for 31652 or 31653 if any other bronchoscopy code was appended. The societies alerted CMS to these problems, and the NCCI edits were corrected. However, these corrections did not take effect until April 1, 2016. It is, therefore, quite possible that some claims will have been rejected by CMS and other carriers from January 1 until March 31. All claims for EBUS procedures during this time should be reviewed and resubmitted if rejected. You have 1 year to resubmit these claims to avoid nonpayment for untimely filing.

Beginning this year, the CPT® code for endobronchial ultrasound (EBUS) 31620 was replaced by three new codes that more accurately describe the procedure as it is currently performed. Codes 31652 and 31653 are reported when EBUS is used for sampling proximal lesions (mediastinal or hilar). Code 31654 is used in identifying more distal lesions. As with other bronchoscopy procedures, the diagnostic code, 31622, is included with these three new codes and the multiple endoscopy rule applies.

CPT code 31652 is utilized when one samples two or fewer proximal locations. CPT code 31653 is utilized when one samples three or more proximal locations. 31652 and 31653 may not be used together; use the code that best describes the work that was done. These two codes include the sampling procedures and, therefore, one does not use CPT codes for sampling, e.g., 31628 or 31629, with either 31652 or 31653. However, if additional procedures are performed on structures distal to the hila, then it is appropriate to use other bronchoscopy codes with 31652 and 31653.

CPT code 31654 is an “add-on” code that is used to identify more peripheral lesions for sampling. As such, it may be used with all of the other bronchoscopy codes.

Unfortunately, when CMS originally published the National Correct Coding Initiative (NCCI) edits for these new codes, there were errors present. NCCI edits are used to instruct CMS payers and clinicians when two distinct CPT codes may or may not be used together. The NCCI edits for 31652 and 31653 published on January 1, 2016, had a value of “0” for all other bronchoscopy codes; this instructed payers to reject any claims for 31652 or 31653 if any other bronchoscopy code was appended. The societies alerted CMS to these problems, and the NCCI edits were corrected. However, these corrections did not take effect until April 1, 2016. It is, therefore, quite possible that some claims will have been rejected by CMS and other carriers from January 1 until March 31. All claims for EBUS procedures during this time should be reviewed and resubmitted if rejected. You have 1 year to resubmit these claims to avoid nonpayment for untimely filing.

Beginning this year, the CPT® code for endobronchial ultrasound (EBUS) 31620 was replaced by three new codes that more accurately describe the procedure as it is currently performed. Codes 31652 and 31653 are reported when EBUS is used for sampling proximal lesions (mediastinal or hilar). Code 31654 is used in identifying more distal lesions. As with other bronchoscopy procedures, the diagnostic code, 31622, is included with these three new codes and the multiple endoscopy rule applies.

CPT code 31652 is utilized when one samples two or fewer proximal locations. CPT code 31653 is utilized when one samples three or more proximal locations. 31652 and 31653 may not be used together; use the code that best describes the work that was done. These two codes include the sampling procedures and, therefore, one does not use CPT codes for sampling, e.g., 31628 or 31629, with either 31652 or 31653. However, if additional procedures are performed on structures distal to the hila, then it is appropriate to use other bronchoscopy codes with 31652 and 31653.

CPT code 31654 is an “add-on” code that is used to identify more peripheral lesions for sampling. As such, it may be used with all of the other bronchoscopy codes.

Unfortunately, when CMS originally published the National Correct Coding Initiative (NCCI) edits for these new codes, there were errors present. NCCI edits are used to instruct CMS payers and clinicians when two distinct CPT codes may or may not be used together. The NCCI edits for 31652 and 31653 published on January 1, 2016, had a value of “0” for all other bronchoscopy codes; this instructed payers to reject any claims for 31652 or 31653 if any other bronchoscopy code was appended. The societies alerted CMS to these problems, and the NCCI edits were corrected. However, these corrections did not take effect until April 1, 2016. It is, therefore, quite possible that some claims will have been rejected by CMS and other carriers from January 1 until March 31. All claims for EBUS procedures during this time should be reviewed and resubmitted if rejected. You have 1 year to resubmit these claims to avoid nonpayment for untimely filing.

LONDON, ENGLAND – Prompt referral to a rheumatologist and early initiation of treatment remain 2 of the 12 key recommendations in the updated European League Against Rheumatism guidelines for early arthritis.

There are now three specific recommendations dealing with referral and diagnosis; four that cover initial drug treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids; two that cover management strategy and monitoring; and three that cover nonpharmacologic interventions, prevention, and patient information and education.

While many of the recommendations have not radically changed, there have been revisions to the wording. In line with other EULAR recommendations for the management of rheumatic disease, the updated early arthritis guidelines also now contain three overarching principles. The first states that the management of early arthritis should aim to achieve the best possible care and emphasizes the need for shared decision making between rheumatologist and patient. The second states that a rheumatologist should be the main specialist looking after a patient with early arthritis, and the third states that a definitive diagnosis should be made only after a careful medical history and clinical examination have been undertaken.

“[The EULAR] recommendations deal especially with early-stage inflammatory arthritis,” said Dr. Bernard Combe of Hôpital Lapeyronie in Montpellier, France, who was the convener of the task force behind the updated guidelines. As such, they are universal for all rheumatologic arthritis conditions when diagnosed early, before they differentiate into more specifics, he said in an interview. That includes progression from early inflammatory arthritis to rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis.

Dr. Combe, who is also professor of rheumatology at Montpellier University and head of the bone and joint diseases department at Montpellier University Hospital, presented the updated EULAR guidance at the European Congress of Rheumatology. He noted that the guidelines were first written almost 10 years ago (Ann Rheum Dis. 2007 Jan;66(1):34-45) and so were in need of an update. A task force of 20 rheumatologists, two patients, and one health care professional representing 12 European countries were involved in the update that adhered to EULAR standard operating procedure of developing guidelines.

Although EULAR had published guidance on the management of arthritis in the intervening years, he said, this had focused more on management, and the aim of the early arthritis guidelines was to cover the “entire spectrum of the management of early inflammatory arthritis.”

The updated recommendations start and end with patient-centered statements, he observed. The first notes that patients with any joint swelling associated with pain or stiffness should be referred to and seen by a rheumatologist within 6 weeks of the onset of symptoms. The final recommendation deals with patient information and education about the disease, and programs aiming to help patients cope with pain, disability, and ensure their continued ability to work and participate in their usual social activities.

The concept of early identification and treatment is not new, Dr. Combe observed, but there is so much more evidence in support of initiating DMARD therapy within the first 3 months of referral, even if patients do not fulfill classification criteria for a specific inflammatory rheumatic disease.

In terms of diagnosis, the recommendations now hinge on performing a thorough clinical examination and using ultrasonography to confirm the presence of arthritis if needed. Magnetic resonance imaging (MRI) is no longer recommended in this initial diagnostic work up. This is due to the cost and often lack of widespread access in all European countries, Dr. Combe said. MRI might be considered later, however, if a diagnosis cannot be reached. Assessment of the number of swollen joints, acute phase reactants, and antibody tests (rheumatoid factor and anti-citrullinated protein antibody) also might be of use at this point.

Among the various DMARDs, methotrexate is recommended as the “anchor drug”; it should be used as part of the first treatment strategy in patients who are at risk of persistent disease, unless it contraindicated. The goal of treatment with DMARDs is to achieve clinical remission. Regular monitoring of disease activity, side effects, and comorbidities should be performed alongside their use. Regular monitoring of all pharmacologic therapy should include assessment of tender and swollen joint counts, global health assessments by the patient and the physician, and acute phase reactants.

As for NSAIDs, they are recommended for symptomatic relief, but “at the minimum effective dose for the shortest time possible.” The risks for gastrointestinal, renal, and cardiovascular complications should be carefully weighed against the likely benefits. Glucocorticoids also are recommended for reducing pain and swelling, and structural progression, but again these need to be used at the lowest possible dose and for no more than 6 months to avoid potential long-term side effects.

A recommendation on nonpharmacologic interventions also is included, which states that physical exercise and occupational therapy should be considered as adjunctive therapy.

In addition, the task force came up with a list of 10 research questions that need to be answered, which included items on risk prediction, optimal treatment combinations, and dosing regimens.

As with other EULAR guidelines, a flow chart is included that summarizes the recommendations to help guide physicians on when and how to treat, when to adapt dosing or change medication, and other treatments and approaches to consider.

There is a new recommendation on prevention highlighting the importance of smoking cessation, dental care, weight control, vaccination, and managing comorbidities.

Once the guidelines have been finalized, they will be published in the EULAR journal, Annals of the Rheumatic Diseases, later in the year.

Dr. Combe has received research grants and honoraria from Pfizer, Roche-Chugai, and UCB, and honoraria from Bristol-Myers Squibb, Janssen, Eli Lilly, Merck Sharpe and Dohme, and Novartis.

LONDON, ENGLAND – Prompt referral to a rheumatologist and early initiation of treatment remain 2 of the 12 key recommendations in the updated European League Against Rheumatism guidelines for early arthritis.

There are now three specific recommendations dealing with referral and diagnosis; four that cover initial drug treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids; two that cover management strategy and monitoring; and three that cover nonpharmacologic interventions, prevention, and patient information and education.

While many of the recommendations have not radically changed, there have been revisions to the wording. In line with other EULAR recommendations for the management of rheumatic disease, the updated early arthritis guidelines also now contain three overarching principles. The first states that the management of early arthritis should aim to achieve the best possible care and emphasizes the need for shared decision making between rheumatologist and patient. The second states that a rheumatologist should be the main specialist looking after a patient with early arthritis, and the third states that a definitive diagnosis should be made only after a careful medical history and clinical examination have been undertaken.

“[The EULAR] recommendations deal especially with early-stage inflammatory arthritis,” said Dr. Bernard Combe of Hôpital Lapeyronie in Montpellier, France, who was the convener of the task force behind the updated guidelines. As such, they are universal for all rheumatologic arthritis conditions when diagnosed early, before they differentiate into more specifics, he said in an interview. That includes progression from early inflammatory arthritis to rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis.

Dr. Combe, who is also professor of rheumatology at Montpellier University and head of the bone and joint diseases department at Montpellier University Hospital, presented the updated EULAR guidance at the European Congress of Rheumatology. He noted that the guidelines were first written almost 10 years ago (Ann Rheum Dis. 2007 Jan;66(1):34-45) and so were in need of an update. A task force of 20 rheumatologists, two patients, and one health care professional representing 12 European countries were involved in the update that adhered to EULAR standard operating procedure of developing guidelines.

Although EULAR had published guidance on the management of arthritis in the intervening years, he said, this had focused more on management, and the aim of the early arthritis guidelines was to cover the “entire spectrum of the management of early inflammatory arthritis.”

The updated recommendations start and end with patient-centered statements, he observed. The first notes that patients with any joint swelling associated with pain or stiffness should be referred to and seen by a rheumatologist within 6 weeks of the onset of symptoms. The final recommendation deals with patient information and education about the disease, and programs aiming to help patients cope with pain, disability, and ensure their continued ability to work and participate in their usual social activities.

The concept of early identification and treatment is not new, Dr. Combe observed, but there is so much more evidence in support of initiating DMARD therapy within the first 3 months of referral, even if patients do not fulfill classification criteria for a specific inflammatory rheumatic disease.

In terms of diagnosis, the recommendations now hinge on performing a thorough clinical examination and using ultrasonography to confirm the presence of arthritis if needed. Magnetic resonance imaging (MRI) is no longer recommended in this initial diagnostic work up. This is due to the cost and often lack of widespread access in all European countries, Dr. Combe said. MRI might be considered later, however, if a diagnosis cannot be reached. Assessment of the number of swollen joints, acute phase reactants, and antibody tests (rheumatoid factor and anti-citrullinated protein antibody) also might be of use at this point.

Among the various DMARDs, methotrexate is recommended as the “anchor drug”; it should be used as part of the first treatment strategy in patients who are at risk of persistent disease, unless it contraindicated. The goal of treatment with DMARDs is to achieve clinical remission. Regular monitoring of disease activity, side effects, and comorbidities should be performed alongside their use. Regular monitoring of all pharmacologic therapy should include assessment of tender and swollen joint counts, global health assessments by the patient and the physician, and acute phase reactants.

As for NSAIDs, they are recommended for symptomatic relief, but “at the minimum effective dose for the shortest time possible.” The risks for gastrointestinal, renal, and cardiovascular complications should be carefully weighed against the likely benefits. Glucocorticoids also are recommended for reducing pain and swelling, and structural progression, but again these need to be used at the lowest possible dose and for no more than 6 months to avoid potential long-term side effects.

A recommendation on nonpharmacologic interventions also is included, which states that physical exercise and occupational therapy should be considered as adjunctive therapy.

In addition, the task force came up with a list of 10 research questions that need to be answered, which included items on risk prediction, optimal treatment combinations, and dosing regimens.

As with other EULAR guidelines, a flow chart is included that summarizes the recommendations to help guide physicians on when and how to treat, when to adapt dosing or change medication, and other treatments and approaches to consider.

There is a new recommendation on prevention highlighting the importance of smoking cessation, dental care, weight control, vaccination, and managing comorbidities.

Once the guidelines have been finalized, they will be published in the EULAR journal, Annals of the Rheumatic Diseases, later in the year.

Dr. Combe has received research grants and honoraria from Pfizer, Roche-Chugai, and UCB, and honoraria from Bristol-Myers Squibb, Janssen, Eli Lilly, Merck Sharpe and Dohme, and Novartis.

LONDON, ENGLAND – Prompt referral to a rheumatologist and early initiation of treatment remain 2 of the 12 key recommendations in the updated European League Against Rheumatism guidelines for early arthritis.

There are now three specific recommendations dealing with referral and diagnosis; four that cover initial drug treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and glucocorticoids; two that cover management strategy and monitoring; and three that cover nonpharmacologic interventions, prevention, and patient information and education.

While many of the recommendations have not radically changed, there have been revisions to the wording. In line with other EULAR recommendations for the management of rheumatic disease, the updated early arthritis guidelines also now contain three overarching principles. The first states that the management of early arthritis should aim to achieve the best possible care and emphasizes the need for shared decision making between rheumatologist and patient. The second states that a rheumatologist should be the main specialist looking after a patient with early arthritis, and the third states that a definitive diagnosis should be made only after a careful medical history and clinical examination have been undertaken.

“[The EULAR] recommendations deal especially with early-stage inflammatory arthritis,” said Dr. Bernard Combe of Hôpital Lapeyronie in Montpellier, France, who was the convener of the task force behind the updated guidelines. As such, they are universal for all rheumatologic arthritis conditions when diagnosed early, before they differentiate into more specifics, he said in an interview. That includes progression from early inflammatory arthritis to rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis.

Dr. Combe, who is also professor of rheumatology at Montpellier University and head of the bone and joint diseases department at Montpellier University Hospital, presented the updated EULAR guidance at the European Congress of Rheumatology. He noted that the guidelines were first written almost 10 years ago (Ann Rheum Dis. 2007 Jan;66(1):34-45) and so were in need of an update. A task force of 20 rheumatologists, two patients, and one health care professional representing 12 European countries were involved in the update that adhered to EULAR standard operating procedure of developing guidelines.

Although EULAR had published guidance on the management of arthritis in the intervening years, he said, this had focused more on management, and the aim of the early arthritis guidelines was to cover the “entire spectrum of the management of early inflammatory arthritis.”

The updated recommendations start and end with patient-centered statements, he observed. The first notes that patients with any joint swelling associated with pain or stiffness should be referred to and seen by a rheumatologist within 6 weeks of the onset of symptoms. The final recommendation deals with patient information and education about the disease, and programs aiming to help patients cope with pain, disability, and ensure their continued ability to work and participate in their usual social activities.

The concept of early identification and treatment is not new, Dr. Combe observed, but there is so much more evidence in support of initiating DMARD therapy within the first 3 months of referral, even if patients do not fulfill classification criteria for a specific inflammatory rheumatic disease.

In terms of diagnosis, the recommendations now hinge on performing a thorough clinical examination and using ultrasonography to confirm the presence of arthritis if needed. Magnetic resonance imaging (MRI) is no longer recommended in this initial diagnostic work up. This is due to the cost and often lack of widespread access in all European countries, Dr. Combe said. MRI might be considered later, however, if a diagnosis cannot be reached. Assessment of the number of swollen joints, acute phase reactants, and antibody tests (rheumatoid factor and anti-citrullinated protein antibody) also might be of use at this point.

Among the various DMARDs, methotrexate is recommended as the “anchor drug”; it should be used as part of the first treatment strategy in patients who are at risk of persistent disease, unless it contraindicated. The goal of treatment with DMARDs is to achieve clinical remission. Regular monitoring of disease activity, side effects, and comorbidities should be performed alongside their use. Regular monitoring of all pharmacologic therapy should include assessment of tender and swollen joint counts, global health assessments by the patient and the physician, and acute phase reactants.

As for NSAIDs, they are recommended for symptomatic relief, but “at the minimum effective dose for the shortest time possible.” The risks for gastrointestinal, renal, and cardiovascular complications should be carefully weighed against the likely benefits. Glucocorticoids also are recommended for reducing pain and swelling, and structural progression, but again these need to be used at the lowest possible dose and for no more than 6 months to avoid potential long-term side effects.

A recommendation on nonpharmacologic interventions also is included, which states that physical exercise and occupational therapy should be considered as adjunctive therapy.

In addition, the task force came up with a list of 10 research questions that need to be answered, which included items on risk prediction, optimal treatment combinations, and dosing regimens.

As with other EULAR guidelines, a flow chart is included that summarizes the recommendations to help guide physicians on when and how to treat, when to adapt dosing or change medication, and other treatments and approaches to consider.

There is a new recommendation on prevention highlighting the importance of smoking cessation, dental care, weight control, vaccination, and managing comorbidities.

Once the guidelines have been finalized, they will be published in the EULAR journal, Annals of the Rheumatic Diseases, later in the year.

Dr. Combe has received research grants and honoraria from Pfizer, Roche-Chugai, and UCB, and honoraria from Bristol-Myers Squibb, Janssen, Eli Lilly, Merck Sharpe and Dohme, and Novartis.

NEW ORLEANS – The second trial involving a sub-dermal matchstick-size osmotic mini-pump that releases exenatide over 6 months in people who have poorly controlled type 2 diabetes achieved superior blood glucose levels and weight loss after a year, compared with sitagliptin alone, Dr. Julio Rosenstock reported at the annual scientific sessions of the American Diabetes Association.

Dr. Rosenstock, director of the Dallas Diabetes and Endocrine Center, reported on the findings of the study, known as FREEDOM-2. The study randomized 535 adults with poorly controlled type 2 diabetes to either the mini-pump, known as the ITCA 650, that releases 60 μg of exenatide a day, or 100 mg of daily sitagliptin. This is a follow-on trial to FREEDOM-1 that compared the ICTA 650 mini-pump to twice-daily exenatide in people with type 2 diabetes who were taking metformin (Diabetes Care. 2013 Sep;36[9]:2559-65). All participants in FREEDOM-2 had been on metformin greater than or equal to 1,500 mg daily and had HbA1c greater than or equal to 7.5%.

©Boarding1Now/Thinkstock

“The continuous subcutaneous delivery of exenatide with ICTA 650 is a novel approach to improve glycemic control, ensuring adherence and consistent delivery of therapy for 6-12 months for people with type 2 diabetes,” Dr. Rosenstock said. The ICTA recipients first received a dose of 20 μg of exenatide daily for the first 12 weeks, then had that increased to 60 μg for the remainder of the study.

After 1 year, average reduction in HbA1c was 1.5% with ITCA 650 vs. 0.8% with sitagliptin, Dr. Rosenstock said. Sixty-one percent of those in the ITCA 650 group achieved greater than 0.5% reductions in HbA1c and more than 2 kg loss in body weight after a year, compared with 28% of the sitagliptin group.

Overall, the patients who receive the ITCA 650 achieved an average body weight reduction of 4 kg vs. 1.3 kg for the sitagliptin patients. Again, 61% of the ITCA patients achieved target HbA1c of less than 7% vs. 42% of the sitagliptin group. Rescue therapy was required in 15% with ITCA 650 and 35% with sitagliptin, and minor hypoglycemia occurred in 4.2% with ITCA 650 vs. 1.9% with sitagliptin.

The ICTA 650 group did have a higher incidence of adverse events, Dr. Rosenstock said, 82% vs. 74%. These included side effects at the application site like hematoma, bleeding, infection, or pain, as well as gastrointestinal (GI) problems such as nausea and vomiting. “The GI adverse events were similar to what we have seen with other GLP-1 receptor agonists,” Dr. Rosenstock said. “The incidence of nausea spiked at the initial insertion and then when we increased the dose from 20 μg to 60 μg, but the second time the ICTA 650 was replaced for 60 μg dosing, the nausea rates did not spike.” The ICTA 650 group had a discontinuation rate of 1%.

Each mini-pump inserted in the FREEDOM-2 trial had a duration of 6 months, but Dr. Rosenstock said the goal is to achieve extended-release dosing with a single mini-pump for 2 years.

Dr. Rosenstock disclosed he serves on the advisory panels of Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo Co., Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Sanofi U.S., and Takeda Pharmaceutical Company; and that he has received research support from Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Pfizer, Roche Pharmaceuticals, Sanofi U.S. and Takeda.

NEW ORLEANS – The second trial involving a sub-dermal matchstick-size osmotic mini-pump that releases exenatide over 6 months in people who have poorly controlled type 2 diabetes achieved superior blood glucose levels and weight loss after a year, compared with sitagliptin alone, Dr. Julio Rosenstock reported at the annual scientific sessions of the American Diabetes Association.

Dr. Rosenstock, director of the Dallas Diabetes and Endocrine Center, reported on the findings of the study, known as FREEDOM-2. The study randomized 535 adults with poorly controlled type 2 diabetes to either the mini-pump, known as the ITCA 650, that releases 60 μg of exenatide a day, or 100 mg of daily sitagliptin. This is a follow-on trial to FREEDOM-1 that compared the ICTA 650 mini-pump to twice-daily exenatide in people with type 2 diabetes who were taking metformin (Diabetes Care. 2013 Sep;36[9]:2559-65). All participants in FREEDOM-2 had been on metformin greater than or equal to 1,500 mg daily and had HbA1c greater than or equal to 7.5%.

©Boarding1Now/Thinkstock

“The continuous subcutaneous delivery of exenatide with ICTA 650 is a novel approach to improve glycemic control, ensuring adherence and consistent delivery of therapy for 6-12 months for people with type 2 diabetes,” Dr. Rosenstock said. The ICTA recipients first received a dose of 20 μg of exenatide daily for the first 12 weeks, then had that increased to 60 μg for the remainder of the study.

After 1 year, average reduction in HbA1c was 1.5% with ITCA 650 vs. 0.8% with sitagliptin, Dr. Rosenstock said. Sixty-one percent of those in the ITCA 650 group achieved greater than 0.5% reductions in HbA1c and more than 2 kg loss in body weight after a year, compared with 28% of the sitagliptin group.

Overall, the patients who receive the ITCA 650 achieved an average body weight reduction of 4 kg vs. 1.3 kg for the sitagliptin patients. Again, 61% of the ITCA patients achieved target HbA1c of less than 7% vs. 42% of the sitagliptin group. Rescue therapy was required in 15% with ITCA 650 and 35% with sitagliptin, and minor hypoglycemia occurred in 4.2% with ITCA 650 vs. 1.9% with sitagliptin.

The ICTA 650 group did have a higher incidence of adverse events, Dr. Rosenstock said, 82% vs. 74%. These included side effects at the application site like hematoma, bleeding, infection, or pain, as well as gastrointestinal (GI) problems such as nausea and vomiting. “The GI adverse events were similar to what we have seen with other GLP-1 receptor agonists,” Dr. Rosenstock said. “The incidence of nausea spiked at the initial insertion and then when we increased the dose from 20 μg to 60 μg, but the second time the ICTA 650 was replaced for 60 μg dosing, the nausea rates did not spike.” The ICTA 650 group had a discontinuation rate of 1%.

Each mini-pump inserted in the FREEDOM-2 trial had a duration of 6 months, but Dr. Rosenstock said the goal is to achieve extended-release dosing with a single mini-pump for 2 years.

Dr. Rosenstock disclosed he serves on the advisory panels of Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo Co., Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Sanofi U.S., and Takeda Pharmaceutical Company; and that he has received research support from Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Pfizer, Roche Pharmaceuticals, Sanofi U.S. and Takeda.

NEW ORLEANS – The second trial involving a sub-dermal matchstick-size osmotic mini-pump that releases exenatide over 6 months in people who have poorly controlled type 2 diabetes achieved superior blood glucose levels and weight loss after a year, compared with sitagliptin alone, Dr. Julio Rosenstock reported at the annual scientific sessions of the American Diabetes Association.

Dr. Rosenstock, director of the Dallas Diabetes and Endocrine Center, reported on the findings of the study, known as FREEDOM-2. The study randomized 535 adults with poorly controlled type 2 diabetes to either the mini-pump, known as the ITCA 650, that releases 60 μg of exenatide a day, or 100 mg of daily sitagliptin. This is a follow-on trial to FREEDOM-1 that compared the ICTA 650 mini-pump to twice-daily exenatide in people with type 2 diabetes who were taking metformin (Diabetes Care. 2013 Sep;36[9]:2559-65). All participants in FREEDOM-2 had been on metformin greater than or equal to 1,500 mg daily and had HbA1c greater than or equal to 7.5%.

©Boarding1Now/Thinkstock

“The continuous subcutaneous delivery of exenatide with ICTA 650 is a novel approach to improve glycemic control, ensuring adherence and consistent delivery of therapy for 6-12 months for people with type 2 diabetes,” Dr. Rosenstock said. The ICTA recipients first received a dose of 20 μg of exenatide daily for the first 12 weeks, then had that increased to 60 μg for the remainder of the study.

After 1 year, average reduction in HbA1c was 1.5% with ITCA 650 vs. 0.8% with sitagliptin, Dr. Rosenstock said. Sixty-one percent of those in the ITCA 650 group achieved greater than 0.5% reductions in HbA1c and more than 2 kg loss in body weight after a year, compared with 28% of the sitagliptin group.

Overall, the patients who receive the ITCA 650 achieved an average body weight reduction of 4 kg vs. 1.3 kg for the sitagliptin patients. Again, 61% of the ITCA patients achieved target HbA1c of less than 7% vs. 42% of the sitagliptin group. Rescue therapy was required in 15% with ITCA 650 and 35% with sitagliptin, and minor hypoglycemia occurred in 4.2% with ITCA 650 vs. 1.9% with sitagliptin.

The ICTA 650 group did have a higher incidence of adverse events, Dr. Rosenstock said, 82% vs. 74%. These included side effects at the application site like hematoma, bleeding, infection, or pain, as well as gastrointestinal (GI) problems such as nausea and vomiting. “The GI adverse events were similar to what we have seen with other GLP-1 receptor agonists,” Dr. Rosenstock said. “The incidence of nausea spiked at the initial insertion and then when we increased the dose from 20 μg to 60 μg, but the second time the ICTA 650 was replaced for 60 μg dosing, the nausea rates did not spike.” The ICTA 650 group had a discontinuation rate of 1%.

Each mini-pump inserted in the FREEDOM-2 trial had a duration of 6 months, but Dr. Rosenstock said the goal is to achieve extended-release dosing with a single mini-pump for 2 years.

Dr. Rosenstock disclosed he serves on the advisory panels of Boehringer Ingelheim Pharmaceuticals, Daiichi-Sankyo Co., Eli Lilly and Company, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Sanofi U.S., and Takeda Pharmaceutical Company; and that he has received research support from Amylin Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, MannKind Corporation, Merck & Co., Novartis, Novo Nordisk, Pfizer, Roche Pharmaceuticals, Sanofi U.S. and Takeda.

Copenhagen – Among older adults with acute myeloid leukemia, the combination of a drug-antibody conjugate and hypomethylating therapy was associated with high complete remission rates.

In a phase I study of 53 patients (median age 75 years) with AML, the combination of vadastuximab talirine and a hypomethylating agent (HMA), either azacitidine or decitabine, was associated in 49 efficacy-evaluable patients with a 71% rate of composite complete remission (CR) and complete remission with incomplete recovery of counts (CRi), reported Dr. Amir Fathi from the Massachusetts General Hospital Cancer Center in Boston.

“This high remission rate in this traditionally high risk group and difficult to treat population is very compelling. Response rates were higher, and were achieved more quickly than would be expected from historical data associated with HMA therapy alone,” he said at a briefing at the annual congress of the European Hematology Association.

Many older patients with AML may not be able to withstand the rigors of cytotoxic chemotherapy, and these patients are often treated with hypomethylating agents or other low-intensity therapies, Dr. Fathi said.

Vadastuximab talirine is an antibody-drug conjugate designed to deliver a cytotoxic agent to myeloid leukemia cells, and in preclinical studies has been shown to enhance the cytotoxic effects of HMAs when given in combination.

Dr. Fathi reported preliminary data on 53 patients enrolled in a phase 1 study of the safety, tolerability, pharmacokinetics, and antileukemic activity of vadastuximab in combination with an HMA.

Neil Osterweil/Frontline Medical News

They enrolled adults with good performance status (Eastern Cooperative Oncology Group 0 or 1) who had CD33-positive AML and had declined intensive chemotherapy. They were given vadastuximab 10 mg/kg in an outpatient intravenous basis every 4 weeks on the fifth day of a 5-day HMA regimen,

Patients who were observed to have a clinical benefit could continue on treatment until relapse or unacceptable toxicity.

Of the 53 patients enrolled, 19 had adverse cytogenetic risk, and 30 had intermediate risk. The majority of patients (48) had not previously been treated for AML, and 5 had received prior low-intensity therapy for the myelodysplastic syndrome.

A total of 49 patients had sufficient data for the efficacy evaluation, and among these patients the composite CR/CRi rate was 71%; the rates of CR/CRi were similar whether the partner HMA was azacitadine or decitabine.

The overall response rate was 76%, with responses seem among higher-risk patients, including remissions in 16 of 22 patients with underlying myelodysplasia, and in 15 of 18 patients with adverse cytogenetics.

In addition, 8 of 19 patients with a CR, and 5 of 15 with a CRi met the definition for minimal residual disease.

Dr. Fathi reported early overall survival results, which he noted were still evolving. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months after a median follow-up of 12.58 months.

The median relapse free-survival was 7.7 months. As of last follow-up, 27 patients were alive and remained on study.

The 30-day mortality rate was 2%, and the 60-day rate was 8%.

The most common treatment-related adverse events of any grade occurring in 20% or more of patients were fatigue, thrombocytopenia, nausea, febrile neutropenia, constipation, and anemia

The most common grade 3 or greater treatment-emergent adverse events were febrile neutropenia, thrombocytopenia, neutropenia, anemia, and fatigue.

In an interview, Dr. Fathi said that he has been very encouraged by the results thus far.

“This is a traditionally high-risk patient population. Even with a conventional induction cytotoxic chemotherapy, rates of remission in this population are relatively lower, so if the remission rates pan out in a larger population, I would say it competes and possibly supersedes what you would expect in an older population,” Dr. Fathi said.

Asked whether it might be possible to boost outcomes further with additional therapies, he said that “I’m not sure if there is much more improvement over what we are already seeing; a rate of 70-something percent among older adults with AML is quite good.”

“I like this ‘Trojan-horse’ approach to treating AML,” commented Dr. Anton Hagenbeek, professor of hematology at the Academic Medical Center, University of Amsterdam, who moderated the briefing.

A randomized phase III trial of vadastuximab talirine and HMA therapy is currently enrolling patients.

The study was funded by Seattle Genetics. Dr. Fathi reported no relevant disclosures.

Copenhagen – Among older adults with acute myeloid leukemia, the combination of a drug-antibody conjugate and hypomethylating therapy was associated with high complete remission rates.

In a phase I study of 53 patients (median age 75 years) with AML, the combination of vadastuximab talirine and a hypomethylating agent (HMA), either azacitidine or decitabine, was associated in 49 efficacy-evaluable patients with a 71% rate of composite complete remission (CR) and complete remission with incomplete recovery of counts (CRi), reported Dr. Amir Fathi from the Massachusetts General Hospital Cancer Center in Boston.

“This high remission rate in this traditionally high risk group and difficult to treat population is very compelling. Response rates were higher, and were achieved more quickly than would be expected from historical data associated with HMA therapy alone,” he said at a briefing at the annual congress of the European Hematology Association.

Many older patients with AML may not be able to withstand the rigors of cytotoxic chemotherapy, and these patients are often treated with hypomethylating agents or other low-intensity therapies, Dr. Fathi said.

Vadastuximab talirine is an antibody-drug conjugate designed to deliver a cytotoxic agent to myeloid leukemia cells, and in preclinical studies has been shown to enhance the cytotoxic effects of HMAs when given in combination.

Dr. Fathi reported preliminary data on 53 patients enrolled in a phase 1 study of the safety, tolerability, pharmacokinetics, and antileukemic activity of vadastuximab in combination with an HMA.

Neil Osterweil/Frontline Medical News

They enrolled adults with good performance status (Eastern Cooperative Oncology Group 0 or 1) who had CD33-positive AML and had declined intensive chemotherapy. They were given vadastuximab 10 mg/kg in an outpatient intravenous basis every 4 weeks on the fifth day of a 5-day HMA regimen,

Patients who were observed to have a clinical benefit could continue on treatment until relapse or unacceptable toxicity.

Of the 53 patients enrolled, 19 had adverse cytogenetic risk, and 30 had intermediate risk. The majority of patients (48) had not previously been treated for AML, and 5 had received prior low-intensity therapy for the myelodysplastic syndrome.

A total of 49 patients had sufficient data for the efficacy evaluation, and among these patients the composite CR/CRi rate was 71%; the rates of CR/CRi were similar whether the partner HMA was azacitadine or decitabine.

The overall response rate was 76%, with responses seem among higher-risk patients, including remissions in 16 of 22 patients with underlying myelodysplasia, and in 15 of 18 patients with adverse cytogenetics.

In addition, 8 of 19 patients with a CR, and 5 of 15 with a CRi met the definition for minimal residual disease.

Dr. Fathi reported early overall survival results, which he noted were still evolving. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months after a median follow-up of 12.58 months.

The median relapse free-survival was 7.7 months. As of last follow-up, 27 patients were alive and remained on study.

The 30-day mortality rate was 2%, and the 60-day rate was 8%.

The most common treatment-related adverse events of any grade occurring in 20% or more of patients were fatigue, thrombocytopenia, nausea, febrile neutropenia, constipation, and anemia

The most common grade 3 or greater treatment-emergent adverse events were febrile neutropenia, thrombocytopenia, neutropenia, anemia, and fatigue.

In an interview, Dr. Fathi said that he has been very encouraged by the results thus far.

“This is a traditionally high-risk patient population. Even with a conventional induction cytotoxic chemotherapy, rates of remission in this population are relatively lower, so if the remission rates pan out in a larger population, I would say it competes and possibly supersedes what you would expect in an older population,” Dr. Fathi said.

Asked whether it might be possible to boost outcomes further with additional therapies, he said that “I’m not sure if there is much more improvement over what we are already seeing; a rate of 70-something percent among older adults with AML is quite good.”

“I like this ‘Trojan-horse’ approach to treating AML,” commented Dr. Anton Hagenbeek, professor of hematology at the Academic Medical Center, University of Amsterdam, who moderated the briefing.

A randomized phase III trial of vadastuximab talirine and HMA therapy is currently enrolling patients.

The study was funded by Seattle Genetics. Dr. Fathi reported no relevant disclosures.

Copenhagen – Among older adults with acute myeloid leukemia, the combination of a drug-antibody conjugate and hypomethylating therapy was associated with high complete remission rates.

In a phase I study of 53 patients (median age 75 years) with AML, the combination of vadastuximab talirine and a hypomethylating agent (HMA), either azacitidine or decitabine, was associated in 49 efficacy-evaluable patients with a 71% rate of composite complete remission (CR) and complete remission with incomplete recovery of counts (CRi), reported Dr. Amir Fathi from the Massachusetts General Hospital Cancer Center in Boston.

“This high remission rate in this traditionally high risk group and difficult to treat population is very compelling. Response rates were higher, and were achieved more quickly than would be expected from historical data associated with HMA therapy alone,” he said at a briefing at the annual congress of the European Hematology Association.

Many older patients with AML may not be able to withstand the rigors of cytotoxic chemotherapy, and these patients are often treated with hypomethylating agents or other low-intensity therapies, Dr. Fathi said.

Vadastuximab talirine is an antibody-drug conjugate designed to deliver a cytotoxic agent to myeloid leukemia cells, and in preclinical studies has been shown to enhance the cytotoxic effects of HMAs when given in combination.

Dr. Fathi reported preliminary data on 53 patients enrolled in a phase 1 study of the safety, tolerability, pharmacokinetics, and antileukemic activity of vadastuximab in combination with an HMA.

Neil Osterweil/Frontline Medical News

They enrolled adults with good performance status (Eastern Cooperative Oncology Group 0 or 1) who had CD33-positive AML and had declined intensive chemotherapy. They were given vadastuximab 10 mg/kg in an outpatient intravenous basis every 4 weeks on the fifth day of a 5-day HMA regimen,

Patients who were observed to have a clinical benefit could continue on treatment until relapse or unacceptable toxicity.

Of the 53 patients enrolled, 19 had adverse cytogenetic risk, and 30 had intermediate risk. The majority of patients (48) had not previously been treated for AML, and 5 had received prior low-intensity therapy for the myelodysplastic syndrome.

A total of 49 patients had sufficient data for the efficacy evaluation, and among these patients the composite CR/CRi rate was 71%; the rates of CR/CRi were similar whether the partner HMA was azacitadine or decitabine.

The overall response rate was 76%, with responses seem among higher-risk patients, including remissions in 16 of 22 patients with underlying myelodysplasia, and in 15 of 18 patients with adverse cytogenetics.

In addition, 8 of 19 patients with a CR, and 5 of 15 with a CRi met the definition for minimal residual disease.

Dr. Fathi reported early overall survival results, which he noted were still evolving. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months after a median follow-up of 12.58 months.

The median relapse free-survival was 7.7 months. As of last follow-up, 27 patients were alive and remained on study.

The 30-day mortality rate was 2%, and the 60-day rate was 8%.

The most common treatment-related adverse events of any grade occurring in 20% or more of patients were fatigue, thrombocytopenia, nausea, febrile neutropenia, constipation, and anemia

The most common grade 3 or greater treatment-emergent adverse events were febrile neutropenia, thrombocytopenia, neutropenia, anemia, and fatigue.

In an interview, Dr. Fathi said that he has been very encouraged by the results thus far.

“This is a traditionally high-risk patient population. Even with a conventional induction cytotoxic chemotherapy, rates of remission in this population are relatively lower, so if the remission rates pan out in a larger population, I would say it competes and possibly supersedes what you would expect in an older population,” Dr. Fathi said.

Asked whether it might be possible to boost outcomes further with additional therapies, he said that “I’m not sure if there is much more improvement over what we are already seeing; a rate of 70-something percent among older adults with AML is quite good.”

“I like this ‘Trojan-horse’ approach to treating AML,” commented Dr. Anton Hagenbeek, professor of hematology at the Academic Medical Center, University of Amsterdam, who moderated the briefing.

A randomized phase III trial of vadastuximab talirine and HMA therapy is currently enrolling patients.

The study was funded by Seattle Genetics. Dr. Fathi reported no relevant disclosures.