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.

Copenhagen – The experimental antibody-drug conjugate inotuzumab ozogamicin was associated with a nearly threefold higher complete remission rate than standard intensive chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia, investigators reported.

Among 218 patients in a phase III clinical trial, rates of combined complete remissions (CR) and complete remission with incomplete recovery of counts (CRi) were 80.7% for patients randomly assigned to receive the anti-CD22 conjugated antibody inotuzumab ozogamicin, compared with 29.4% for patients assigned to receive a standard intensive chemotherapy regimen chosen by investigators (P less than .001).

In addition, among patients who had complete remissions in both groups, significantly more patients in the inotuzumab ozogamicin group had fewer than .01% marrow blasts, a level below the threshold for minimal residual disease (MRD) (78.4% vs. 28.1%, respectively, P less than .001), reported Dr. Hagop Kantarjian, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.

“In my opinion, inotuzumab is well tolerated with appropriate prevention measures, and my hope is that soon in the future, inotuzumab will be used not as a single agent, but in combination with chemotherapy or with other monoclonal antibodies targeting CD19,” he said at the annual congress of the European Hematology Association.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic.  CD22 is expressed on the surface of about 90% of B-cell ALL cells.

Dr. Daniel DeAngelo from the Dana-Farber Cancer Institute in Boston reported that in the same cohort of patients, the first 218 of 326 randomized in the INO-VATE trial, , the co-primary endpoint of CR/CRi by independent review was achieved by 80.7% of patients treated with inotuzumab and 33.3% treated with standard of care.The updated data presented at the meeting also are published online in the New England Journal of Medicine 2016 June doi:10.1056/NEJMoa1509277 .

The phase III trial randomized 326 patients with relapsed/refractory CD22-positive ALL due for salvage 1 or 2 therapy to inotuzumab or standard of care, consisting of either the FLAG regimen (fludarabine (Fludara)/cytarabine (Ara-C)/granulocyte colony-stimulating factor), Ara-C plus mitoxantrone (Novantrone), or high-dose Ara-C. The starting dose for inotuzumab was 1.8 mg/m²/cycle and was reduced to 1.5 mg/m²/cycle once a CR or CRi was achieved. Patients were stratified by duration of first remission, salvage 1 or 2, and age.

The first 218 randomized patients were included in the intention-to-treat CR/CRi analysis, which was modified after excluding 13 patients who refused to start treatment, all in the standard-of-care arm.

The patients’ median age was 47 years (ranging up to 79 years), two-thirds were in salvage 1, and more than half had a remission duration of less than 12 months, an adverse prognostic feature.

Dr. Kantarjian reported that in addition to the superior remission rates seen with inotuzumab ozogamicin, patients on the antibody-drug conjugate had significantly longer duration of remissions, at a median of 4.6 months vs. 3.1 months for patients on chemotherapy (P = .003).

An intention-to-treat survival analysis including all 326 patients randomized in the trial showed that progression-free survival was significantly longer in the inotuzumab ozogamicin group, at a median of 5.0 vs. 1.8 months (hazard ratio .45 P less than .001).

Neil Osterweil/Frontline Medical News

Overall survival was slightly better with inotuzumab, at a median of 7.7 months vs. 6.7 months, but this did not meet the study definition of significantly improved overall survival with a pre-specified boundary of P = .014 or lower.

In the safety population, which included 139 patients assigned to inotuzumab and 120 to chemotherapy who had received at least one dose of the assigned regimen before data cutoff, the most frequent grade 3 or higher non-hematologic adverse events with inotuzumab ozogamicin were liver-related. In all, 13% of patients assigned to inotuzumab in the safety population developed veno-occlusive liver disease of any grade, compared with 1% of those assigned to standard of care.

“This drug showed consistently high activity in several studies, so I think it’s very exciting, The real challenge will be how to proceed, how to incorporate it into clinical trials both in pediatrics and adults,” commented Dr. Shai Izraeli, head of the section of functional genomics and childhood leukemia and cancer research at Sheba Medical Center in Ramat Gan, Israel. Dr. Izraeli was co-moderator of the late-breaking abstract session where the data were presented, but was not involved in the study.

He said in an interview that the challenge for investigators will be to develop clinical trials that combine this agent with different immunotherapies from different companies, which would be a logistical nightmare, “but I think we need to do it.”

The study was funded by Pfizer. Dr. Kantarjian disclosed research support from the company. Dr. Izraeli reported having no relevant disclosures.

Copenhagen – The experimental antibody-drug conjugate inotuzumab ozogamicin was associated with a nearly threefold higher complete remission rate than standard intensive chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia, investigators reported.

Among 218 patients in a phase III clinical trial, rates of combined complete remissions (CR) and complete remission with incomplete recovery of counts (CRi) were 80.7% for patients randomly assigned to receive the anti-CD22 conjugated antibody inotuzumab ozogamicin, compared with 29.4% for patients assigned to receive a standard intensive chemotherapy regimen chosen by investigators (P less than .001).

In addition, among patients who had complete remissions in both groups, significantly more patients in the inotuzumab ozogamicin group had fewer than .01% marrow blasts, a level below the threshold for minimal residual disease (MRD) (78.4% vs. 28.1%, respectively, P less than .001), reported Dr. Hagop Kantarjian, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.

“In my opinion, inotuzumab is well tolerated with appropriate prevention measures, and my hope is that soon in the future, inotuzumab will be used not as a single agent, but in combination with chemotherapy or with other monoclonal antibodies targeting CD19,” he said at the annual congress of the European Hematology Association.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic.  CD22 is expressed on the surface of about 90% of B-cell ALL cells.

Dr. Daniel DeAngelo from the Dana-Farber Cancer Institute in Boston reported that in the same cohort of patients, the first 218 of 326 randomized in the INO-VATE trial, , the co-primary endpoint of CR/CRi by independent review was achieved by 80.7% of patients treated with inotuzumab and 33.3% treated with standard of care.The updated data presented at the meeting also are published online in the New England Journal of Medicine 2016 June doi:10.1056/NEJMoa1509277 .

The phase III trial randomized 326 patients with relapsed/refractory CD22-positive ALL due for salvage 1 or 2 therapy to inotuzumab or standard of care, consisting of either the FLAG regimen (fludarabine (Fludara)/cytarabine (Ara-C)/granulocyte colony-stimulating factor), Ara-C plus mitoxantrone (Novantrone), or high-dose Ara-C. The starting dose for inotuzumab was 1.8 mg/m²/cycle and was reduced to 1.5 mg/m²/cycle once a CR or CRi was achieved. Patients were stratified by duration of first remission, salvage 1 or 2, and age.

The first 218 randomized patients were included in the intention-to-treat CR/CRi analysis, which was modified after excluding 13 patients who refused to start treatment, all in the standard-of-care arm.

The patients’ median age was 47 years (ranging up to 79 years), two-thirds were in salvage 1, and more than half had a remission duration of less than 12 months, an adverse prognostic feature.

Dr. Kantarjian reported that in addition to the superior remission rates seen with inotuzumab ozogamicin, patients on the antibody-drug conjugate had significantly longer duration of remissions, at a median of 4.6 months vs. 3.1 months for patients on chemotherapy (P = .003).

An intention-to-treat survival analysis including all 326 patients randomized in the trial showed that progression-free survival was significantly longer in the inotuzumab ozogamicin group, at a median of 5.0 vs. 1.8 months (hazard ratio .45 P less than .001).

Neil Osterweil/Frontline Medical News

Overall survival was slightly better with inotuzumab, at a median of 7.7 months vs. 6.7 months, but this did not meet the study definition of significantly improved overall survival with a pre-specified boundary of P = .014 or lower.

In the safety population, which included 139 patients assigned to inotuzumab and 120 to chemotherapy who had received at least one dose of the assigned regimen before data cutoff, the most frequent grade 3 or higher non-hematologic adverse events with inotuzumab ozogamicin were liver-related. In all, 13% of patients assigned to inotuzumab in the safety population developed veno-occlusive liver disease of any grade, compared with 1% of those assigned to standard of care.

“This drug showed consistently high activity in several studies, so I think it’s very exciting, The real challenge will be how to proceed, how to incorporate it into clinical trials both in pediatrics and adults,” commented Dr. Shai Izraeli, head of the section of functional genomics and childhood leukemia and cancer research at Sheba Medical Center in Ramat Gan, Israel. Dr. Izraeli was co-moderator of the late-breaking abstract session where the data were presented, but was not involved in the study.

He said in an interview that the challenge for investigators will be to develop clinical trials that combine this agent with different immunotherapies from different companies, which would be a logistical nightmare, “but I think we need to do it.”

The study was funded by Pfizer. Dr. Kantarjian disclosed research support from the company. Dr. Izraeli reported having no relevant disclosures.

Copenhagen – The experimental antibody-drug conjugate inotuzumab ozogamicin was associated with a nearly threefold higher complete remission rate than standard intensive chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia, investigators reported.

Among 218 patients in a phase III clinical trial, rates of combined complete remissions (CR) and complete remission with incomplete recovery of counts (CRi) were 80.7% for patients randomly assigned to receive the anti-CD22 conjugated antibody inotuzumab ozogamicin, compared with 29.4% for patients assigned to receive a standard intensive chemotherapy regimen chosen by investigators (P less than .001).

In addition, among patients who had complete remissions in both groups, significantly more patients in the inotuzumab ozogamicin group had fewer than .01% marrow blasts, a level below the threshold for minimal residual disease (MRD) (78.4% vs. 28.1%, respectively, P less than .001), reported Dr. Hagop Kantarjian, professor in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.

“In my opinion, inotuzumab is well tolerated with appropriate prevention measures, and my hope is that soon in the future, inotuzumab will be used not as a single agent, but in combination with chemotherapy or with other monoclonal antibodies targeting CD19,” he said at the annual congress of the European Hematology Association.

Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody conjugated to calicheamicin, a cytotoxic antibiotic.  CD22 is expressed on the surface of about 90% of B-cell ALL cells.

Dr. Daniel DeAngelo from the Dana-Farber Cancer Institute in Boston reported that in the same cohort of patients, the first 218 of 326 randomized in the INO-VATE trial, , the co-primary endpoint of CR/CRi by independent review was achieved by 80.7% of patients treated with inotuzumab and 33.3% treated with standard of care.The updated data presented at the meeting also are published online in the New England Journal of Medicine 2016 June doi:10.1056/NEJMoa1509277 .

The phase III trial randomized 326 patients with relapsed/refractory CD22-positive ALL due for salvage 1 or 2 therapy to inotuzumab or standard of care, consisting of either the FLAG regimen (fludarabine (Fludara)/cytarabine (Ara-C)/granulocyte colony-stimulating factor), Ara-C plus mitoxantrone (Novantrone), or high-dose Ara-C. The starting dose for inotuzumab was 1.8 mg/m²/cycle and was reduced to 1.5 mg/m²/cycle once a CR or CRi was achieved. Patients were stratified by duration of first remission, salvage 1 or 2, and age.

The first 218 randomized patients were included in the intention-to-treat CR/CRi analysis, which was modified after excluding 13 patients who refused to start treatment, all in the standard-of-care arm.

The patients’ median age was 47 years (ranging up to 79 years), two-thirds were in salvage 1, and more than half had a remission duration of less than 12 months, an adverse prognostic feature.

Dr. Kantarjian reported that in addition to the superior remission rates seen with inotuzumab ozogamicin, patients on the antibody-drug conjugate had significantly longer duration of remissions, at a median of 4.6 months vs. 3.1 months for patients on chemotherapy (P = .003).

An intention-to-treat survival analysis including all 326 patients randomized in the trial showed that progression-free survival was significantly longer in the inotuzumab ozogamicin group, at a median of 5.0 vs. 1.8 months (hazard ratio .45 P less than .001).

Neil Osterweil/Frontline Medical News

Overall survival was slightly better with inotuzumab, at a median of 7.7 months vs. 6.7 months, but this did not meet the study definition of significantly improved overall survival with a pre-specified boundary of P = .014 or lower.

In the safety population, which included 139 patients assigned to inotuzumab and 120 to chemotherapy who had received at least one dose of the assigned regimen before data cutoff, the most frequent grade 3 or higher non-hematologic adverse events with inotuzumab ozogamicin were liver-related. In all, 13% of patients assigned to inotuzumab in the safety population developed veno-occlusive liver disease of any grade, compared with 1% of those assigned to standard of care.

“This drug showed consistently high activity in several studies, so I think it’s very exciting, The real challenge will be how to proceed, how to incorporate it into clinical trials both in pediatrics and adults,” commented Dr. Shai Izraeli, head of the section of functional genomics and childhood leukemia and cancer research at Sheba Medical Center in Ramat Gan, Israel. Dr. Izraeli was co-moderator of the late-breaking abstract session where the data were presented, but was not involved in the study.

He said in an interview that the challenge for investigators will be to develop clinical trials that combine this agent with different immunotherapies from different companies, which would be a logistical nightmare, “but I think we need to do it.”

The study was funded by Pfizer. Dr. Kantarjian disclosed research support from the company. Dr. Izraeli reported having no relevant disclosures.

Chicago – Survivors of childhood cancers face several later risks from treatment, and investigators presented studies evaluating risks in three specific areas – secondary neoplasms, premature menopause, and neurocognitive function – at the annual meeting of the American Society of Clinical Oncology.

Discussant Paul Nathan, M.D., of The Hospital for Sick Children in Toronto, said “the whole purpose” of research in this area “is to start to understand the predictors and modifiers of late effects” and then to design risk assessment tools and interventions to reduce long-term toxicity. These interventions include modification of chemotherapy and radiation doses, protective strategies, and disease risk stratification to adjust intensity of therapies.

Other strategies are to use behavioral interventions directed at improving compliance with follow-up to detect problems earlier and the use of real-time monitoring, such as with smart phones or fitness trackers. He said one limitation of this sort of research and implementing interventions to reduce late toxicities is that “you need time to document long-term outcomes.” So tracking newer therapies, such as proton beam radiation, small molecule drugs, and immunotherapy, is “going to take time, perhaps decades, before you understand their impact on patients.”

Risk of secondary neoplasms reduced

Risk-stratifying of disease “has allowed us to make attempts to minimize late effects by modifying therapy over time in certain subgroups of lower-risk patients,” said Dr. Lucie Turcotte of the University of Minnesota in Minneapolis.

To study the effects of these changes, she determined the risk of certain subsequent malignant or benign neoplasms over three periods of therapeutic exposure among 23,603 5-year survivors of childhood cancers diagnosed at less than 21 years of age from 1970 to 1999, drawing from the cohort of the Childhood Cancer Survivor Study (CCSS). The CCSS represents about 20% of childhood cancer survivors in the United States for the study period.

Over the decades of 1970-1979, 1980-1989, and 1990-1999, the use of any radiation went from 77% to 58% to 41%, respectively. Cranial radiation for acute lymphoblastic leukemia (ALL) decreased from 85% to 19%, abdominal radiation for Wilms tumor from 78% to 43%, and chest radiotherapy for Hodgkin lymphoma from 87% to 61%. The proportion of children receiving alkylating agents, anthracyclines, and epipodophyllotoxins went up, but the cumulative doses went down (N Engl J Med. 2016 Mar 3;374(9):833-42).

Dr. Nathan said today, almost no child gets cranial radiation for ALL. “So we’ve slowly learned that our treatments are toxic, and we’ve certainly done what we can to change them.”

But have these changes made a difference? Dr. Turcotte found that survivors remain at increased risk of a secondary neoplasm, but the risk was lower for children treated in later time periods.

Dr. Nathan pointed to Dr. Turcotte’s data showing that the incidence of subsequent malignant neoplasms decreased from 1970 to 1999 by 7% for each 5-year era (15-year risk: 2.3% to 1.6%; P = .001; number needed to treat, NNT = 143). Similarly, non-melanoma skin cancer 15-year risk decreased from 0.7% to 0.1% (P less than .001; NNT = 167). The NNT’s are “certainly important, but these are not major differences over time,” Dr. Nathan said. Knowing the impact of newer, targeted therapeutic approaches will take some time.

Predicting risk of premature menopause

Also using the CCSS data, Dr. Jennifer Levine of Columbia University Medical Center, New York, N.Y., studied the prevalence of and risk factors for nonsurgical premature menopause (NSPM), defined as cessation of menses prior to age 40 years, as well as the effect on reproductive outcomes for survivors of childhood cancers.

Dr. Nathan said when a child is first diagnosed with cancer, seldom does the issue of fertility come up early in the discussion, “but when you treat young adults who are survivors, the number one thing they talk about often is fertility. And so doing a better job in predicting who is at risk for infertility is clearly a priority for survivorship research.”

He said the development of the cyclophosphamide equivalent dose (CED) by D.M Green et al. (Pediatr Blood Cancer. 2014 Jan;61(1):53-67) has been very helpful for quantifying alkylating agent exposure to make comparisons between studies. The goal is to develop a risk assessment tool to be able to tell patients and families their fertility risk based on demographics, therapy, and biomarkers.

Being able to evaluate risk is critically important because for girls, oocyte or ovarian harvesting or even transvaginal ultrasound is highly invasive, and these procedures should be recommended only if their risk for infertility is very high.

Dr. Levine studied 2,930 female cancer survivors diagnosed at a median age of 6 years between 1979 and 1986 and a median age at follow-up of 34 years, who were compared with 1,399 healthy siblings. Of the survivor cohort, 110 developed NSPM at a median age of 32 years, and the prevalence of NSPM at age 40 years for the entire cohort was 9.1%, giving a relative risk of NSPM of 10.5 compared with siblings, who had a 0.9% NSPM prevalence at age 40.

She found that exposure to alkylating agents and older age at diagnosis put childhood cancer survivors at increased risk of NSPM, which was associated with lower rates of pregnancy and live births after age 31 years. The greatest risk of NSPM occurred if the cyclophosphamide equivalent dose was greater than 6000 mg/m² (odds ratio = 3.6 compared with no CED); if there had been any radiation to the ovaries (less than 5 Gy: OR = 4.0; 5 Gy or more: OR = 20.4); or if the age at diagnosis was greater than 14 years (OR = 2.3).

Women with NSPM, compared with survivors without NSPM, were less likely ever to be pregnant (OR = 0.41) or to have a live birth after age 30 (OR = 0.35). However, these outcomes were no different between the ages of 21 and 30. Dr. Levine said this information can assist clinicians in counseling their patients about the risk for early menopause and planning for alternative reproductive means, such as oocyte or embryo harvesting and preservation.

Neurocognitive functioning after treatment

Dr. Wei Liu of St. Jude Children’s Research Hospital, Memphis, Tenn., studied the neurocognitive function of long-term survivors of ALL.

Dr. Nathan called ALL “the paradigm for how we’ve sort of learned and adjusted how we treat patients based on late effects.” Early on, the disease was treated with craniospinal radiation and intrathecal chemotherapy, and while patients survived, it became obvious that they suffered neurocognitive and endocrine problems, growth abnormalities, and secondary malignancies. These findings forced a reevaluatuon of treatments, leading to elimination of spinal radiation, reduction of cranial radiation dose, intensification of systemic therapy, including methotrexate, and risk stratification allowing modification of therapies.

Survival was sustained, but long-term outcomes were still based on children treated with radiation. So long-term cognitive consequences in the more modern era of therapy were unknown. Only recently have adult cohorts become available who were treated in the chemotherapy-only era.

Dr. Liu studied 159 ALL survivors who had been treated with chemotherapy alone at a mean age of 9.2 years. The follow-up was at a median of 7.6 years off therapy at a mean age of 13.7 years. At the end of the chemotherapy protocol, patients completed tests of sustained attention, and parents rated survivors’ behavior on standard scales.

She found that for these childhood cancer survivors, sustained attention and behavior functioning at the end of chemotherapy predicted long-term attention and processing speed outcomes. Only exposure to chemotherapy, and not end-of-therapy function, predicted that survivors would have poor executive function of fluency and flexibility at long-term follow up.

Dr. Nathan praised the investigators for their foresight to collect data on the methotrexate area under the curve, number of triple intrathecal therapies (cytarabine, methotrexate, and hydrocortisone), and neurocognitive functioning at the end of chemotherapy. “What’s clear is that chemotherapy alone can lead to neurocognitive late effects,” he said. “But what’s also important is that not all late effects can be predicted by end of therapy assessments.” These late effects appear to evolve over time, so ongoing assessments are needed.

Dr. Turcotte, Dr. Liu, Dr. Levine, and Dr. Nathan each reported no financial disclosures.

Chicago – Survivors of childhood cancers face several later risks from treatment, and investigators presented studies evaluating risks in three specific areas – secondary neoplasms, premature menopause, and neurocognitive function – at the annual meeting of the American Society of Clinical Oncology.

Discussant Paul Nathan, M.D., of The Hospital for Sick Children in Toronto, said “the whole purpose” of research in this area “is to start to understand the predictors and modifiers of late effects” and then to design risk assessment tools and interventions to reduce long-term toxicity. These interventions include modification of chemotherapy and radiation doses, protective strategies, and disease risk stratification to adjust intensity of therapies.

Other strategies are to use behavioral interventions directed at improving compliance with follow-up to detect problems earlier and the use of real-time monitoring, such as with smart phones or fitness trackers. He said one limitation of this sort of research and implementing interventions to reduce late toxicities is that “you need time to document long-term outcomes.” So tracking newer therapies, such as proton beam radiation, small molecule drugs, and immunotherapy, is “going to take time, perhaps decades, before you understand their impact on patients.”

Risk of secondary neoplasms reduced

Risk-stratifying of disease “has allowed us to make attempts to minimize late effects by modifying therapy over time in certain subgroups of lower-risk patients,” said Dr. Lucie Turcotte of the University of Minnesota in Minneapolis.

To study the effects of these changes, she determined the risk of certain subsequent malignant or benign neoplasms over three periods of therapeutic exposure among 23,603 5-year survivors of childhood cancers diagnosed at less than 21 years of age from 1970 to 1999, drawing from the cohort of the Childhood Cancer Survivor Study (CCSS). The CCSS represents about 20% of childhood cancer survivors in the United States for the study period.

Over the decades of 1970-1979, 1980-1989, and 1990-1999, the use of any radiation went from 77% to 58% to 41%, respectively. Cranial radiation for acute lymphoblastic leukemia (ALL) decreased from 85% to 19%, abdominal radiation for Wilms tumor from 78% to 43%, and chest radiotherapy for Hodgkin lymphoma from 87% to 61%. The proportion of children receiving alkylating agents, anthracyclines, and epipodophyllotoxins went up, but the cumulative doses went down (N Engl J Med. 2016 Mar 3;374(9):833-42).

Dr. Nathan said today, almost no child gets cranial radiation for ALL. “So we’ve slowly learned that our treatments are toxic, and we’ve certainly done what we can to change them.”

But have these changes made a difference? Dr. Turcotte found that survivors remain at increased risk of a secondary neoplasm, but the risk was lower for children treated in later time periods.

Dr. Nathan pointed to Dr. Turcotte’s data showing that the incidence of subsequent malignant neoplasms decreased from 1970 to 1999 by 7% for each 5-year era (15-year risk: 2.3% to 1.6%; P = .001; number needed to treat, NNT = 143). Similarly, non-melanoma skin cancer 15-year risk decreased from 0.7% to 0.1% (P less than .001; NNT = 167). The NNT’s are “certainly important, but these are not major differences over time,” Dr. Nathan said. Knowing the impact of newer, targeted therapeutic approaches will take some time.

Predicting risk of premature menopause

Also using the CCSS data, Dr. Jennifer Levine of Columbia University Medical Center, New York, N.Y., studied the prevalence of and risk factors for nonsurgical premature menopause (NSPM), defined as cessation of menses prior to age 40 years, as well as the effect on reproductive outcomes for survivors of childhood cancers.

Dr. Nathan said when a child is first diagnosed with cancer, seldom does the issue of fertility come up early in the discussion, “but when you treat young adults who are survivors, the number one thing they talk about often is fertility. And so doing a better job in predicting who is at risk for infertility is clearly a priority for survivorship research.”

He said the development of the cyclophosphamide equivalent dose (CED) by D.M Green et al. (Pediatr Blood Cancer. 2014 Jan;61(1):53-67) has been very helpful for quantifying alkylating agent exposure to make comparisons between studies. The goal is to develop a risk assessment tool to be able to tell patients and families their fertility risk based on demographics, therapy, and biomarkers.

Being able to evaluate risk is critically important because for girls, oocyte or ovarian harvesting or even transvaginal ultrasound is highly invasive, and these procedures should be recommended only if their risk for infertility is very high.

Dr. Levine studied 2,930 female cancer survivors diagnosed at a median age of 6 years between 1979 and 1986 and a median age at follow-up of 34 years, who were compared with 1,399 healthy siblings. Of the survivor cohort, 110 developed NSPM at a median age of 32 years, and the prevalence of NSPM at age 40 years for the entire cohort was 9.1%, giving a relative risk of NSPM of 10.5 compared with siblings, who had a 0.9% NSPM prevalence at age 40.

She found that exposure to alkylating agents and older age at diagnosis put childhood cancer survivors at increased risk of NSPM, which was associated with lower rates of pregnancy and live births after age 31 years. The greatest risk of NSPM occurred if the cyclophosphamide equivalent dose was greater than 6000 mg/m² (odds ratio = 3.6 compared with no CED); if there had been any radiation to the ovaries (less than 5 Gy: OR = 4.0; 5 Gy or more: OR = 20.4); or if the age at diagnosis was greater than 14 years (OR = 2.3).

Women with NSPM, compared with survivors without NSPM, were less likely ever to be pregnant (OR = 0.41) or to have a live birth after age 30 (OR = 0.35). However, these outcomes were no different between the ages of 21 and 30. Dr. Levine said this information can assist clinicians in counseling their patients about the risk for early menopause and planning for alternative reproductive means, such as oocyte or embryo harvesting and preservation.

Neurocognitive functioning after treatment

Dr. Wei Liu of St. Jude Children’s Research Hospital, Memphis, Tenn., studied the neurocognitive function of long-term survivors of ALL.

Dr. Nathan called ALL “the paradigm for how we’ve sort of learned and adjusted how we treat patients based on late effects.” Early on, the disease was treated with craniospinal radiation and intrathecal chemotherapy, and while patients survived, it became obvious that they suffered neurocognitive and endocrine problems, growth abnormalities, and secondary malignancies. These findings forced a reevaluatuon of treatments, leading to elimination of spinal radiation, reduction of cranial radiation dose, intensification of systemic therapy, including methotrexate, and risk stratification allowing modification of therapies.

Survival was sustained, but long-term outcomes were still based on children treated with radiation. So long-term cognitive consequences in the more modern era of therapy were unknown. Only recently have adult cohorts become available who were treated in the chemotherapy-only era.

Dr. Liu studied 159 ALL survivors who had been treated with chemotherapy alone at a mean age of 9.2 years. The follow-up was at a median of 7.6 years off therapy at a mean age of 13.7 years. At the end of the chemotherapy protocol, patients completed tests of sustained attention, and parents rated survivors’ behavior on standard scales.

She found that for these childhood cancer survivors, sustained attention and behavior functioning at the end of chemotherapy predicted long-term attention and processing speed outcomes. Only exposure to chemotherapy, and not end-of-therapy function, predicted that survivors would have poor executive function of fluency and flexibility at long-term follow up.

Dr. Nathan praised the investigators for their foresight to collect data on the methotrexate area under the curve, number of triple intrathecal therapies (cytarabine, methotrexate, and hydrocortisone), and neurocognitive functioning at the end of chemotherapy. “What’s clear is that chemotherapy alone can lead to neurocognitive late effects,” he said. “But what’s also important is that not all late effects can be predicted by end of therapy assessments.” These late effects appear to evolve over time, so ongoing assessments are needed.

Dr. Turcotte, Dr. Liu, Dr. Levine, and Dr. Nathan each reported no financial disclosures.

Chicago – Survivors of childhood cancers face several later risks from treatment, and investigators presented studies evaluating risks in three specific areas – secondary neoplasms, premature menopause, and neurocognitive function – at the annual meeting of the American Society of Clinical Oncology.

Discussant Paul Nathan, M.D., of The Hospital for Sick Children in Toronto, said “the whole purpose” of research in this area “is to start to understand the predictors and modifiers of late effects” and then to design risk assessment tools and interventions to reduce long-term toxicity. These interventions include modification of chemotherapy and radiation doses, protective strategies, and disease risk stratification to adjust intensity of therapies.

Other strategies are to use behavioral interventions directed at improving compliance with follow-up to detect problems earlier and the use of real-time monitoring, such as with smart phones or fitness trackers. He said one limitation of this sort of research and implementing interventions to reduce late toxicities is that “you need time to document long-term outcomes.” So tracking newer therapies, such as proton beam radiation, small molecule drugs, and immunotherapy, is “going to take time, perhaps decades, before you understand their impact on patients.”

Risk of secondary neoplasms reduced

Risk-stratifying of disease “has allowed us to make attempts to minimize late effects by modifying therapy over time in certain subgroups of lower-risk patients,” said Dr. Lucie Turcotte of the University of Minnesota in Minneapolis.

To study the effects of these changes, she determined the risk of certain subsequent malignant or benign neoplasms over three periods of therapeutic exposure among 23,603 5-year survivors of childhood cancers diagnosed at less than 21 years of age from 1970 to 1999, drawing from the cohort of the Childhood Cancer Survivor Study (CCSS). The CCSS represents about 20% of childhood cancer survivors in the United States for the study period.

Over the decades of 1970-1979, 1980-1989, and 1990-1999, the use of any radiation went from 77% to 58% to 41%, respectively. Cranial radiation for acute lymphoblastic leukemia (ALL) decreased from 85% to 19%, abdominal radiation for Wilms tumor from 78% to 43%, and chest radiotherapy for Hodgkin lymphoma from 87% to 61%. The proportion of children receiving alkylating agents, anthracyclines, and epipodophyllotoxins went up, but the cumulative doses went down (N Engl J Med. 2016 Mar 3;374(9):833-42).

Dr. Nathan said today, almost no child gets cranial radiation for ALL. “So we’ve slowly learned that our treatments are toxic, and we’ve certainly done what we can to change them.”

But have these changes made a difference? Dr. Turcotte found that survivors remain at increased risk of a secondary neoplasm, but the risk was lower for children treated in later time periods.

Dr. Nathan pointed to Dr. Turcotte’s data showing that the incidence of subsequent malignant neoplasms decreased from 1970 to 1999 by 7% for each 5-year era (15-year risk: 2.3% to 1.6%; P = .001; number needed to treat, NNT = 143). Similarly, non-melanoma skin cancer 15-year risk decreased from 0.7% to 0.1% (P less than .001; NNT = 167). The NNT’s are “certainly important, but these are not major differences over time,” Dr. Nathan said. Knowing the impact of newer, targeted therapeutic approaches will take some time.

Predicting risk of premature menopause

Also using the CCSS data, Dr. Jennifer Levine of Columbia University Medical Center, New York, N.Y., studied the prevalence of and risk factors for nonsurgical premature menopause (NSPM), defined as cessation of menses prior to age 40 years, as well as the effect on reproductive outcomes for survivors of childhood cancers.

Dr. Nathan said when a child is first diagnosed with cancer, seldom does the issue of fertility come up early in the discussion, “but when you treat young adults who are survivors, the number one thing they talk about often is fertility. And so doing a better job in predicting who is at risk for infertility is clearly a priority for survivorship research.”

He said the development of the cyclophosphamide equivalent dose (CED) by D.M Green et al. (Pediatr Blood Cancer. 2014 Jan;61(1):53-67) has been very helpful for quantifying alkylating agent exposure to make comparisons between studies. The goal is to develop a risk assessment tool to be able to tell patients and families their fertility risk based on demographics, therapy, and biomarkers.

Being able to evaluate risk is critically important because for girls, oocyte or ovarian harvesting or even transvaginal ultrasound is highly invasive, and these procedures should be recommended only if their risk for infertility is very high.

Dr. Levine studied 2,930 female cancer survivors diagnosed at a median age of 6 years between 1979 and 1986 and a median age at follow-up of 34 years, who were compared with 1,399 healthy siblings. Of the survivor cohort, 110 developed NSPM at a median age of 32 years, and the prevalence of NSPM at age 40 years for the entire cohort was 9.1%, giving a relative risk of NSPM of 10.5 compared with siblings, who had a 0.9% NSPM prevalence at age 40.

She found that exposure to alkylating agents and older age at diagnosis put childhood cancer survivors at increased risk of NSPM, which was associated with lower rates of pregnancy and live births after age 31 years. The greatest risk of NSPM occurred if the cyclophosphamide equivalent dose was greater than 6000 mg/m² (odds ratio = 3.6 compared with no CED); if there had been any radiation to the ovaries (less than 5 Gy: OR = 4.0; 5 Gy or more: OR = 20.4); or if the age at diagnosis was greater than 14 years (OR = 2.3).

Women with NSPM, compared with survivors without NSPM, were less likely ever to be pregnant (OR = 0.41) or to have a live birth after age 30 (OR = 0.35). However, these outcomes were no different between the ages of 21 and 30. Dr. Levine said this information can assist clinicians in counseling their patients about the risk for early menopause and planning for alternative reproductive means, such as oocyte or embryo harvesting and preservation.

Neurocognitive functioning after treatment

Dr. Wei Liu of St. Jude Children’s Research Hospital, Memphis, Tenn., studied the neurocognitive function of long-term survivors of ALL.

Dr. Nathan called ALL “the paradigm for how we’ve sort of learned and adjusted how we treat patients based on late effects.” Early on, the disease was treated with craniospinal radiation and intrathecal chemotherapy, and while patients survived, it became obvious that they suffered neurocognitive and endocrine problems, growth abnormalities, and secondary malignancies. These findings forced a reevaluatuon of treatments, leading to elimination of spinal radiation, reduction of cranial radiation dose, intensification of systemic therapy, including methotrexate, and risk stratification allowing modification of therapies.

Survival was sustained, but long-term outcomes were still based on children treated with radiation. So long-term cognitive consequences in the more modern era of therapy were unknown. Only recently have adult cohorts become available who were treated in the chemotherapy-only era.

Dr. Liu studied 159 ALL survivors who had been treated with chemotherapy alone at a mean age of 9.2 years. The follow-up was at a median of 7.6 years off therapy at a mean age of 13.7 years. At the end of the chemotherapy protocol, patients completed tests of sustained attention, and parents rated survivors’ behavior on standard scales.

She found that for these childhood cancer survivors, sustained attention and behavior functioning at the end of chemotherapy predicted long-term attention and processing speed outcomes. Only exposure to chemotherapy, and not end-of-therapy function, predicted that survivors would have poor executive function of fluency and flexibility at long-term follow up.

Dr. Nathan praised the investigators for their foresight to collect data on the methotrexate area under the curve, number of triple intrathecal therapies (cytarabine, methotrexate, and hydrocortisone), and neurocognitive functioning at the end of chemotherapy. “What’s clear is that chemotherapy alone can lead to neurocognitive late effects,” he said. “But what’s also important is that not all late effects can be predicted by end of therapy assessments.” These late effects appear to evolve over time, so ongoing assessments are needed.

Dr. Turcotte, Dr. Liu, Dr. Levine, and Dr. Nathan each reported no financial disclosures.