LAS VEGAS – Adhesions occur after just about every abdominal operation, hernia repair in particular, whether they are open or laparoscopic. Small bowel obstructions can result, and management decisions can be complex. What if the patient resolves? Should you offer elective adhesiolysis? If it doesn’t resolve, can the surgery be done laparoscopically or should the procedure be open?

Bradley R. Davis, MD, FACS, discussed some of these options, and the case circumstances that inform the surgeon’s choices at the Annual Minimally Invasive Surgery Symposium by -Global Academy for Medical Education. Dr. Davis is chief of general surgery and of rectal surgery at Carolinas Medical Center, Charlotte, N.C.

Laparoscopic surgeries are associated with significantly lower rates of small bowel obstruction, but it can still happen. More often, patients will have had a previous open surgery, and this should be a selling point for doing first-time surgeries using minimally invasive techniques. “That’s one thing I tell my patients when I see them in the office. There’s a real reduction in adhesive small bowel obstruction and certainly in hernia formation, so there are long-term benefits that I don’t think we talk enough about,” said Dr. Davis.

Although the majority of obstructions are caused by adhesions, some are the result of malignancies or hernias, and Dr. Davis encourages his residents to do exams to determine if a hernia is to blame. “That’s harder and harder to do now that everyone does a CT scan, but that’s always an interesting question to ask a resident,” he said. Inflammatory bowel disease is sometimes also a cause, but that’s rare.

CT scans are the diagnostic mode of choice for small bowel obstructions. Some believe that oral contrast agents may help resolve obstructions, but Dr. Davis mentioned evidence from a study showing that contrast agents don’t change the course of obstructions or reduce laparotomy rates. However, contrast agents can help predict the clinical course of an obstruction. If the contrast agent is present in the colon at 24 hours, then that predicts that the patient will resolve with conservative treatment. “You have a pretty good idea that the patient is going to get better,” said Dr. Davis.

The American Association for the Surgery of Trauma severity grade is helpful for adhesive small bowel obstructions. Grade 2 cases involve intestinal distension and possibly a transition zone, some passage of contrast on follow-up films, and no evidence of intestinal compromise. Grade 3 cases have no distal contrast flow and evidence of complete obstruction or impending bowel compromise. In the latter cases, “we’re scratching our heads wondering whether to take the patient to the operating room. Certainly most of these cases we’ll manage initially nonoperatively, but those patients will end up getting an earlier operation,” said Dr. Davis.

The majority of surgeries are adhesiolysis, sometimes with a bowel resection. Whether or not the surgery can be performed laparoscopically or as an open surgery depends on several factors. If the index operation was done laparoscopically, chances are good that the adhesiolysis can be performed the same way. On the other hand, “if a patient has a known hostile abdomen, I wouldn’t even try. I would basically go straight to an open procedure,” said Dr. Davis.

Generally speaking, though, reoperative surgeries can be attempted laparoscopically and then converted to open procedures if needed, he added. The most common reasons for conversion are dense adhesions and ischemia-related resection.

However, iatrogenic injuries can also occur as a result of trocar access. “Just keep in mind that if you put the trocar into the bowel, the worst thing you can do is take it out because you won’t always find that hole. Just leave the trocar in the bowel, convert to an open procedure, and find the hole and fix it,” said Dr. Davis.

Cases are particularly challenging when the transition zone is in the pelvis. Those procedures are difficult to do laparoscopically because of a difficult angle, and they are more likely to convert to open surgery. “To be honest, that’s not an easy operation to open either, so beware that transition zone in the pelvis can be a difficult case.

“I don’t try to do anything heroic laparoscopically. If you put a camera in and you find it’s going to be a massive adhesiolysis laparoscopically, you might just be better off to open,” said Dr. Davis. In cases like that it can be hard to find the transition zone, which must be identified in order to ensure that the underlying problem is fixed.

An aggressive option in difficult cases is to use a PEEK Port, which starts with a 6-8 cm incision. The surgeon can open up a minimum of disposables and put a hand in to assist the laparoscopic view and determine if the procedure can be completed laparoscopically. “If you encounter extensive adhesions, you just convert to a laparotomy and you haven’t lost any time or spent any money in terms of disposables,” he said.

Dr. Davis had no disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Adhesions occur after just about every abdominal operation, hernia repair in particular, whether they are open or laparoscopic. Small bowel obstructions can result, and management decisions can be complex. What if the patient resolves? Should you offer elective adhesiolysis? If it doesn’t resolve, can the surgery be done laparoscopically or should the procedure be open?

Bradley R. Davis, MD, FACS, discussed some of these options, and the case circumstances that inform the surgeon’s choices at the Annual Minimally Invasive Surgery Symposium by -Global Academy for Medical Education. Dr. Davis is chief of general surgery and of rectal surgery at Carolinas Medical Center, Charlotte, N.C.

Laparoscopic surgeries are associated with significantly lower rates of small bowel obstruction, but it can still happen. More often, patients will have had a previous open surgery, and this should be a selling point for doing first-time surgeries using minimally invasive techniques. “That’s one thing I tell my patients when I see them in the office. There’s a real reduction in adhesive small bowel obstruction and certainly in hernia formation, so there are long-term benefits that I don’t think we talk enough about,” said Dr. Davis.

Although the majority of obstructions are caused by adhesions, some are the result of malignancies or hernias, and Dr. Davis encourages his residents to do exams to determine if a hernia is to blame. “That’s harder and harder to do now that everyone does a CT scan, but that’s always an interesting question to ask a resident,” he said. Inflammatory bowel disease is sometimes also a cause, but that’s rare.

CT scans are the diagnostic mode of choice for small bowel obstructions. Some believe that oral contrast agents may help resolve obstructions, but Dr. Davis mentioned evidence from a study showing that contrast agents don’t change the course of obstructions or reduce laparotomy rates. However, contrast agents can help predict the clinical course of an obstruction. If the contrast agent is present in the colon at 24 hours, then that predicts that the patient will resolve with conservative treatment. “You have a pretty good idea that the patient is going to get better,” said Dr. Davis.

The American Association for the Surgery of Trauma severity grade is helpful for adhesive small bowel obstructions. Grade 2 cases involve intestinal distension and possibly a transition zone, some passage of contrast on follow-up films, and no evidence of intestinal compromise. Grade 3 cases have no distal contrast flow and evidence of complete obstruction or impending bowel compromise. In the latter cases, “we’re scratching our heads wondering whether to take the patient to the operating room. Certainly most of these cases we’ll manage initially nonoperatively, but those patients will end up getting an earlier operation,” said Dr. Davis.

The majority of surgeries are adhesiolysis, sometimes with a bowel resection. Whether or not the surgery can be performed laparoscopically or as an open surgery depends on several factors. If the index operation was done laparoscopically, chances are good that the adhesiolysis can be performed the same way. On the other hand, “if a patient has a known hostile abdomen, I wouldn’t even try. I would basically go straight to an open procedure,” said Dr. Davis.

Generally speaking, though, reoperative surgeries can be attempted laparoscopically and then converted to open procedures if needed, he added. The most common reasons for conversion are dense adhesions and ischemia-related resection.

However, iatrogenic injuries can also occur as a result of trocar access. “Just keep in mind that if you put the trocar into the bowel, the worst thing you can do is take it out because you won’t always find that hole. Just leave the trocar in the bowel, convert to an open procedure, and find the hole and fix it,” said Dr. Davis.

Cases are particularly challenging when the transition zone is in the pelvis. Those procedures are difficult to do laparoscopically because of a difficult angle, and they are more likely to convert to open surgery. “To be honest, that’s not an easy operation to open either, so beware that transition zone in the pelvis can be a difficult case.

“I don’t try to do anything heroic laparoscopically. If you put a camera in and you find it’s going to be a massive adhesiolysis laparoscopically, you might just be better off to open,” said Dr. Davis. In cases like that it can be hard to find the transition zone, which must be identified in order to ensure that the underlying problem is fixed.

An aggressive option in difficult cases is to use a PEEK Port, which starts with a 6-8 cm incision. The surgeon can open up a minimum of disposables and put a hand in to assist the laparoscopic view and determine if the procedure can be completed laparoscopically. “If you encounter extensive adhesions, you just convert to a laparotomy and you haven’t lost any time or spent any money in terms of disposables,” he said.

Dr. Davis had no disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.

LAS VEGAS – Adhesions occur after just about every abdominal operation, hernia repair in particular, whether they are open or laparoscopic. Small bowel obstructions can result, and management decisions can be complex. What if the patient resolves? Should you offer elective adhesiolysis? If it doesn’t resolve, can the surgery be done laparoscopically or should the procedure be open?

Bradley R. Davis, MD, FACS, discussed some of these options, and the case circumstances that inform the surgeon’s choices at the Annual Minimally Invasive Surgery Symposium by -Global Academy for Medical Education. Dr. Davis is chief of general surgery and of rectal surgery at Carolinas Medical Center, Charlotte, N.C.

Laparoscopic surgeries are associated with significantly lower rates of small bowel obstruction, but it can still happen. More often, patients will have had a previous open surgery, and this should be a selling point for doing first-time surgeries using minimally invasive techniques. “That’s one thing I tell my patients when I see them in the office. There’s a real reduction in adhesive small bowel obstruction and certainly in hernia formation, so there are long-term benefits that I don’t think we talk enough about,” said Dr. Davis.

Although the majority of obstructions are caused by adhesions, some are the result of malignancies or hernias, and Dr. Davis encourages his residents to do exams to determine if a hernia is to blame. “That’s harder and harder to do now that everyone does a CT scan, but that’s always an interesting question to ask a resident,” he said. Inflammatory bowel disease is sometimes also a cause, but that’s rare.

CT scans are the diagnostic mode of choice for small bowel obstructions. Some believe that oral contrast agents may help resolve obstructions, but Dr. Davis mentioned evidence from a study showing that contrast agents don’t change the course of obstructions or reduce laparotomy rates. However, contrast agents can help predict the clinical course of an obstruction. If the contrast agent is present in the colon at 24 hours, then that predicts that the patient will resolve with conservative treatment. “You have a pretty good idea that the patient is going to get better,” said Dr. Davis.

The American Association for the Surgery of Trauma severity grade is helpful for adhesive small bowel obstructions. Grade 2 cases involve intestinal distension and possibly a transition zone, some passage of contrast on follow-up films, and no evidence of intestinal compromise. Grade 3 cases have no distal contrast flow and evidence of complete obstruction or impending bowel compromise. In the latter cases, “we’re scratching our heads wondering whether to take the patient to the operating room. Certainly most of these cases we’ll manage initially nonoperatively, but those patients will end up getting an earlier operation,” said Dr. Davis.

The majority of surgeries are adhesiolysis, sometimes with a bowel resection. Whether or not the surgery can be performed laparoscopically or as an open surgery depends on several factors. If the index operation was done laparoscopically, chances are good that the adhesiolysis can be performed the same way. On the other hand, “if a patient has a known hostile abdomen, I wouldn’t even try. I would basically go straight to an open procedure,” said Dr. Davis.

Generally speaking, though, reoperative surgeries can be attempted laparoscopically and then converted to open procedures if needed, he added. The most common reasons for conversion are dense adhesions and ischemia-related resection.

However, iatrogenic injuries can also occur as a result of trocar access. “Just keep in mind that if you put the trocar into the bowel, the worst thing you can do is take it out because you won’t always find that hole. Just leave the trocar in the bowel, convert to an open procedure, and find the hole and fix it,” said Dr. Davis.

Cases are particularly challenging when the transition zone is in the pelvis. Those procedures are difficult to do laparoscopically because of a difficult angle, and they are more likely to convert to open surgery. “To be honest, that’s not an easy operation to open either, so beware that transition zone in the pelvis can be a difficult case.

“I don’t try to do anything heroic laparoscopically. If you put a camera in and you find it’s going to be a massive adhesiolysis laparoscopically, you might just be better off to open,” said Dr. Davis. In cases like that it can be hard to find the transition zone, which must be identified in order to ensure that the underlying problem is fixed.

An aggressive option in difficult cases is to use a PEEK Port, which starts with a 6-8 cm incision. The surgeon can open up a minimum of disposables and put a hand in to assist the laparoscopic view and determine if the procedure can be completed laparoscopically. “If you encounter extensive adhesions, you just convert to a laparotomy and you haven’t lost any time or spent any money in terms of disposables,” he said.

Dr. Davis had no disclosures. Global Academy for Medical Education and this news organization are owned by the same parent company.

A new screening tool for detecting early psoriatic arthritis in patients with psoriasis that combined the “most discriminative questions” from several other questionnaires performed as well as the Psoriasis Epidemiology Screening Tool (PEST) for detecting the disease.

“The CONTEST questionnaire was developed using the best performing items from three other screening questionnaires in the hope that it would perform better than its originators,” Laura Coates, MBChB, PhD, of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford, England, and her coauthors wrote in the Journal of the European Academy of Dermatology and Venereology. “In development this was partly correct but the current study does not support this – statistically there was no difference between PEST and CONTEST in terms of ability to detect psoriatic arthritis [PsA] in patients with psoriasis.”

designer491/iStock/Getty Images

SOURCE: Coates L et al. J Eur Acad Dermatol Venereol. 2018 Mar 26. doi: 10.1111/jdv.14971.

A new screening tool for detecting early psoriatic arthritis in patients with psoriasis that combined the “most discriminative questions” from several other questionnaires performed as well as the Psoriasis Epidemiology Screening Tool (PEST) for detecting the disease.

“The CONTEST questionnaire was developed using the best performing items from three other screening questionnaires in the hope that it would perform better than its originators,” Laura Coates, MBChB, PhD, of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford, England, and her coauthors wrote in the Journal of the European Academy of Dermatology and Venereology. “In development this was partly correct but the current study does not support this – statistically there was no difference between PEST and CONTEST in terms of ability to detect psoriatic arthritis [PsA] in patients with psoriasis.”

designer491/iStock/Getty Images

SOURCE: Coates L et al. J Eur Acad Dermatol Venereol. 2018 Mar 26. doi: 10.1111/jdv.14971.

A new screening tool for detecting early psoriatic arthritis in patients with psoriasis that combined the “most discriminative questions” from several other questionnaires performed as well as the Psoriasis Epidemiology Screening Tool (PEST) for detecting the disease.

“The CONTEST questionnaire was developed using the best performing items from three other screening questionnaires in the hope that it would perform better than its originators,” Laura Coates, MBChB, PhD, of the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford, England, and her coauthors wrote in the Journal of the European Academy of Dermatology and Venereology. “In development this was partly correct but the current study does not support this – statistically there was no difference between PEST and CONTEST in terms of ability to detect psoriatic arthritis [PsA] in patients with psoriasis.”

designer491/iStock/Getty Images

SOURCE: Coates L et al. J Eur Acad Dermatol Venereol. 2018 Mar 26. doi: 10.1111/jdv.14971.

A 63-year-old man says the 20-year-old rash on his face first appeared one summer. Although it slackens a bit each winter, it flares up again when the weather warms—despite a bevy of OTC and prescription topical treatments.

The patient has consulted many providers, including several dermatologists, who have diagnosed the butterfly rash of lupus. But blood tests failed to bear out that theory, and no one has ever biopsied it.

The patient spent many years working in the sun with minimal to no protection. He denies fever, malaise, joint pain, or other illness. He denies having a similar rash elsewhere on his body.

EXAMINATION
A symmetrical, strikingly red, extensive rash covers most of both sides of the patient’s face. There is epidermal scaling and roughness and large areas of obvious follicular enlargement, atrophy, and telangiectasias.

Punch biopsy shows a multitude of changes: atrophic epithelium, basal vacuolar changes, an intense dermal lymphocytic infiltrate, liquefaction degeneration, and apoptotic keratinocytes. Compact orthokeratosis is noted on the surface, and increased mucin formation in the dermis.

What is the diagnosis?

DLE is the most common type of chronic cutaneous lupus, occurring in about 17 to 48 of every 100,000 people in the general population. It affects far more women than men, mostly those ages 20 to 40. More blacks than whites are affected by DLE, which is thought to be a polygenic autoimmune disease linked to various human leukocyte antigen groups.

DLE affects sun-exposed areas, including the scalp (where it often goes undiagnosed, leading to scarring alopecia). It can also occur in the mouth, manifesting as annular eroded areas. In this patient’s case, the combination of UV exposure and apparent genetic predisposition caused his malady.

Following workup to rule out systemic disease, the patient was started on hydroxychloroquine HCL (200 mg bid) and given strict instructions to protect himself from the sun. This should yield considerable improvement, although the scarring on large sections of his face (eg, the posterior cheeks) will be permanent. He will also be monitored for possible progression to SLE.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a form of chronic cutaneous lupus caused by overexposure to the sun in a genetically susceptible individual.
• Most DLE patients never develop systemic lupus, though it’s far from unknown (17%).
• DLE, an autoimmune disease, is far more common in women (ages 20 – 40) than in men.
• Diagnosis is often made clinically, but biopsy reveals characteristic findings that confirm the disease.
• Besides sun protection, DLE is treated with the oral antimalarial hydroxychloroquine HCL (200 mg bid) and topical steroids as needed.

A 63-year-old man says the 20-year-old rash on his face first appeared one summer. Although it slackens a bit each winter, it flares up again when the weather warms—despite a bevy of OTC and prescription topical treatments.

The patient has consulted many providers, including several dermatologists, who have diagnosed the butterfly rash of lupus. But blood tests failed to bear out that theory, and no one has ever biopsied it.

The patient spent many years working in the sun with minimal to no protection. He denies fever, malaise, joint pain, or other illness. He denies having a similar rash elsewhere on his body.

EXAMINATION
A symmetrical, strikingly red, extensive rash covers most of both sides of the patient’s face. There is epidermal scaling and roughness and large areas of obvious follicular enlargement, atrophy, and telangiectasias.

Punch biopsy shows a multitude of changes: atrophic epithelium, basal vacuolar changes, an intense dermal lymphocytic infiltrate, liquefaction degeneration, and apoptotic keratinocytes. Compact orthokeratosis is noted on the surface, and increased mucin formation in the dermis.

What is the diagnosis?

DLE is the most common type of chronic cutaneous lupus, occurring in about 17 to 48 of every 100,000 people in the general population. It affects far more women than men, mostly those ages 20 to 40. More blacks than whites are affected by DLE, which is thought to be a polygenic autoimmune disease linked to various human leukocyte antigen groups.

DLE affects sun-exposed areas, including the scalp (where it often goes undiagnosed, leading to scarring alopecia). It can also occur in the mouth, manifesting as annular eroded areas. In this patient’s case, the combination of UV exposure and apparent genetic predisposition caused his malady.

Following workup to rule out systemic disease, the patient was started on hydroxychloroquine HCL (200 mg bid) and given strict instructions to protect himself from the sun. This should yield considerable improvement, although the scarring on large sections of his face (eg, the posterior cheeks) will be permanent. He will also be monitored for possible progression to SLE.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a form of chronic cutaneous lupus caused by overexposure to the sun in a genetically susceptible individual.
• Most DLE patients never develop systemic lupus, though it’s far from unknown (17%).
• DLE, an autoimmune disease, is far more common in women (ages 20 – 40) than in men.
• Diagnosis is often made clinically, but biopsy reveals characteristic findings that confirm the disease.
• Besides sun protection, DLE is treated with the oral antimalarial hydroxychloroquine HCL (200 mg bid) and topical steroids as needed.

A 63-year-old man says the 20-year-old rash on his face first appeared one summer. Although it slackens a bit each winter, it flares up again when the weather warms—despite a bevy of OTC and prescription topical treatments.

The patient has consulted many providers, including several dermatologists, who have diagnosed the butterfly rash of lupus. But blood tests failed to bear out that theory, and no one has ever biopsied it.

The patient spent many years working in the sun with minimal to no protection. He denies fever, malaise, joint pain, or other illness. He denies having a similar rash elsewhere on his body.

EXAMINATION
A symmetrical, strikingly red, extensive rash covers most of both sides of the patient’s face. There is epidermal scaling and roughness and large areas of obvious follicular enlargement, atrophy, and telangiectasias.

Punch biopsy shows a multitude of changes: atrophic epithelium, basal vacuolar changes, an intense dermal lymphocytic infiltrate, liquefaction degeneration, and apoptotic keratinocytes. Compact orthokeratosis is noted on the surface, and increased mucin formation in the dermis.

What is the diagnosis?

DLE is the most common type of chronic cutaneous lupus, occurring in about 17 to 48 of every 100,000 people in the general population. It affects far more women than men, mostly those ages 20 to 40. More blacks than whites are affected by DLE, which is thought to be a polygenic autoimmune disease linked to various human leukocyte antigen groups.

DLE affects sun-exposed areas, including the scalp (where it often goes undiagnosed, leading to scarring alopecia). It can also occur in the mouth, manifesting as annular eroded areas. In this patient’s case, the combination of UV exposure and apparent genetic predisposition caused his malady.

Following workup to rule out systemic disease, the patient was started on hydroxychloroquine HCL (200 mg bid) and given strict instructions to protect himself from the sun. This should yield considerable improvement, although the scarring on large sections of his face (eg, the posterior cheeks) will be permanent. He will also be monitored for possible progression to SLE.

TAKE-HOME LEARNING POINTS

• Discoid lupus erythematosus (DLE) is a form of chronic cutaneous lupus caused by overexposure to the sun in a genetically susceptible individual.
• Most DLE patients never develop systemic lupus, though it’s far from unknown (17%).
• DLE, an autoimmune disease, is far more common in women (ages 20 – 40) than in men.
• Diagnosis is often made clinically, but biopsy reveals characteristic findings that confirm the disease.
• Besides sun protection, DLE is treated with the oral antimalarial hydroxychloroquine HCL (200 mg bid) and topical steroids as needed.

After treatment with blinatumomab, most patients with minimal residual disease–positive acute lymphoblastic leukemia (ALL) achieved complete MRD response, according to results of a single-arm phase 2 study.

Achieving complete MRD response was associated with significantly longer relapse-free and overall survival in the patients, who were already in hematologic complete remission, researchers reported in the journal Blood.

“Our results suggest that targeted treatment in early stages of MRD is a viable therapeutic strategy for patients with B-cell precursor ALL and that it should also be evaluated in other hematologic malignancies,” Nicola Gökbuget, MD, University Hospital, Frankfurt, Germany, and her coauthors wrote.

This is the first international multicenter study to specifically enroll MRD-positive ALL patients and evaluate them for an MRD-based primary outcome in a cohort of MRD-positive ALL patients, according to the authors.

Preemptively treating low but measurable disease in ALL in remission, instead of waiting for overt relapse, is a strategy that may prolong overall survival, Dr. Gökbuget and her colleagues said in describing the rationale for their study. While there is no standard therapy yet for ALL patients with detectable MRD after intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) is recommended, based on data that it may improve outcomes in patients with persistent MRD. However, other studies suggest detectable MRD before HSCT is associated with higher relapse rates, and many patients relapse while waiting for HSCT, the researchers noted.

To test an MRD-directed treatment strategy, Dr. Gökbuget and colleagues at 46 centers in Europe and Russia conducted an open-label, single-arm, phase 2 study including 116 patients with B-cell precursor ALL in hematologic complete remission. Patients in the study received up to four cycles of blinatumomab, a bispecific, T cell–engager antibody construct that enables T cells to recognize and eliminate CD19-positive cells.

Of 113 evaluable patients, 88 (78%) achieved complete MRD response after one cycle, the primary end point of the study. Relapse-free survival at 18 months was estimated at 54% and median overall survival was 36.5 months in the subset of 110 patients with Philadelphia chromosome–negative ALL in hematologic remission.

SOURCE: Gökbuget N et al. Blood. 2018 Apr 5;131(14):1522-31.

After treatment with blinatumomab, most patients with minimal residual disease–positive acute lymphoblastic leukemia (ALL) achieved complete MRD response, according to results of a single-arm phase 2 study.

Achieving complete MRD response was associated with significantly longer relapse-free and overall survival in the patients, who were already in hematologic complete remission, researchers reported in the journal Blood.

“Our results suggest that targeted treatment in early stages of MRD is a viable therapeutic strategy for patients with B-cell precursor ALL and that it should also be evaluated in other hematologic malignancies,” Nicola Gökbuget, MD, University Hospital, Frankfurt, Germany, and her coauthors wrote.

This is the first international multicenter study to specifically enroll MRD-positive ALL patients and evaluate them for an MRD-based primary outcome in a cohort of MRD-positive ALL patients, according to the authors.

Preemptively treating low but measurable disease in ALL in remission, instead of waiting for overt relapse, is a strategy that may prolong overall survival, Dr. Gökbuget and her colleagues said in describing the rationale for their study. While there is no standard therapy yet for ALL patients with detectable MRD after intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) is recommended, based on data that it may improve outcomes in patients with persistent MRD. However, other studies suggest detectable MRD before HSCT is associated with higher relapse rates, and many patients relapse while waiting for HSCT, the researchers noted.

To test an MRD-directed treatment strategy, Dr. Gökbuget and colleagues at 46 centers in Europe and Russia conducted an open-label, single-arm, phase 2 study including 116 patients with B-cell precursor ALL in hematologic complete remission. Patients in the study received up to four cycles of blinatumomab, a bispecific, T cell–engager antibody construct that enables T cells to recognize and eliminate CD19-positive cells.

Of 113 evaluable patients, 88 (78%) achieved complete MRD response after one cycle, the primary end point of the study. Relapse-free survival at 18 months was estimated at 54% and median overall survival was 36.5 months in the subset of 110 patients with Philadelphia chromosome–negative ALL in hematologic remission.

SOURCE: Gökbuget N et al. Blood. 2018 Apr 5;131(14):1522-31.

After treatment with blinatumomab, most patients with minimal residual disease–positive acute lymphoblastic leukemia (ALL) achieved complete MRD response, according to results of a single-arm phase 2 study.

Achieving complete MRD response was associated with significantly longer relapse-free and overall survival in the patients, who were already in hematologic complete remission, researchers reported in the journal Blood.

“Our results suggest that targeted treatment in early stages of MRD is a viable therapeutic strategy for patients with B-cell precursor ALL and that it should also be evaluated in other hematologic malignancies,” Nicola Gökbuget, MD, University Hospital, Frankfurt, Germany, and her coauthors wrote.

This is the first international multicenter study to specifically enroll MRD-positive ALL patients and evaluate them for an MRD-based primary outcome in a cohort of MRD-positive ALL patients, according to the authors.

Preemptively treating low but measurable disease in ALL in remission, instead of waiting for overt relapse, is a strategy that may prolong overall survival, Dr. Gökbuget and her colleagues said in describing the rationale for their study. While there is no standard therapy yet for ALL patients with detectable MRD after intensive chemotherapy, hematopoietic stem cell transplantation (HSCT) is recommended, based on data that it may improve outcomes in patients with persistent MRD. However, other studies suggest detectable MRD before HSCT is associated with higher relapse rates, and many patients relapse while waiting for HSCT, the researchers noted.

To test an MRD-directed treatment strategy, Dr. Gökbuget and colleagues at 46 centers in Europe and Russia conducted an open-label, single-arm, phase 2 study including 116 patients with B-cell precursor ALL in hematologic complete remission. Patients in the study received up to four cycles of blinatumomab, a bispecific, T cell–engager antibody construct that enables T cells to recognize and eliminate CD19-positive cells.

Of 113 evaluable patients, 88 (78%) achieved complete MRD response after one cycle, the primary end point of the study. Relapse-free survival at 18 months was estimated at 54% and median overall survival was 36.5 months in the subset of 110 patients with Philadelphia chromosome–negative ALL in hematologic remission.

SOURCE: Gökbuget N et al. Blood. 2018 Apr 5;131(14):1522-31.

Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Is rosacea a red flag for more dangerous conditions? MedPAC wants to curb low-value care. Statins cut sepsis patients’ risk of death. And why reading aloud to kids can cut hyperactivity.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

As more hospitalized patients develop infections that are immune to antibiotics, researchers are looking into new preventive therapies. National Institute of Allergy and Infectious-supported researchers are studying monoclonal antibodies and their effects on Pseudomonas aeruginosa (P aeruginosa) and Staphylococcus aureus (S aureus), which are among the antibiotic-resistant bacteria that the World Health Organization says pose the greatest risk to human health.

The monoclonal antibodies can be administered along with standard antibiotic therapy. Monoclonal antibodies have been used in cancer, Ebola, and respiratory syncytial virus but rarely have been used to target bacterial pathogens, National Institute of Health says.

One trial, EVADE, will evaluate the safety of the investigational medicine MEDI3902 and whether it can prevent pneumonia caused by P aeruginosa. The other study, SAATELLITE, will test the safety and efficacy of another investigational medicine, suvratoxumab, against S aureus. The researchers hope to enroll 30 patients from 15 intensive care units.

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Micrograph showing DLBCL

New research helps explain why some patients with diffuse large B-cell lymphoma (DLBCL) respond well to immunochemotherapy and others do not.

Researchers analyzed samples from nearly 600 DLBCL patients and identified 4 new genetic subtypes of the disease.

Patients with 2 of these subtypes had overall survival (OS) rates that were roughly twice as high as OS rates in patients with the other 2 subtypes.

Louis M. Staudt, MD, PhD, of the National Cancer Institute in Bethesda, Maryland, and his colleagues described these findings in NEJM.

The researchers noted that the current subtypes of DLBCL—germinal center B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL—are associated with OS after treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).

Patients with ABC DLBCL have a much lower OS rate, on average, than patients with GCB DLBCL. However, even in the GCB subgroup, many patients relapse after treatment.

“The first question we wanted to tackle was whether there were other molecular features of the tumors that could help us explain why some people were well-served by chemotherapy,” Dr Staudt said.

“And the second, related question was, if we could understand who was not responding well to treatment, could we understand the genetics of these tumors to suggest new potential therapies beyond chemotherapy? The answer to both questions was ‘yes.’”

Dr Staudt and his colleagues analyzed tumor samples from 574 patients with DLBCL, performing exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to find recurrent aberrations.

The team also developed an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations.

In this way, they identified 4 genetic subtypes:

• MCD, which was named based on the co-occurrence of MYD88L265P and CD79B mutations
• BN2, whose name was based on the presence of BCL6 fusions and NOTCH2 mutations
• N1, named for NOTCH1 mutations
• EZB, named for EZH2 mutations and BCL2 translocations.

The researchers said aberrations in multiple genes distinguished each of these subtypes from other DLBCLs, and the subtypes differed phenotypically.

Patients with BN2 or EZB subtypes had much higher OS rates after receiving R-CHOP than patients with MCD or N1 subtypes. The predicted 5-year OS rates were 26% for MCD patients, 36% for N1 patients, 65% for BN2 patients, and 68% for EZB patients.

The researchers said they found evidence to suggest that MCD and BN2 DLBCLs rely on chronic active B-cell receptor signaling that is amenable to therapeutic inhibition.

The team also noted that some of the subtypes they identified can be found in both ABC and GCB DLBCLs. For example, a patient could have ABC DLBCL, which is associated with a lower OS rate after R-CHOP, but also have the BN2 genetic subtype that responds well to R-CHOP.

“This shows we’ve gone beyond where we were,” Dr Staudt said. “Before, even with our most advanced molecular diagnosis, we would have said all ABC tumors are the ‘bad’ type, and they need to be treated aggressively.”

“Now, we can implement this kind of classification and say that, even if a patient has the ‘bad’ ABC type, they have the ‘good’ genetic type, BN2. So there’s a much better chance of chemotherapy curing the disease.”

Data from this study will be shared through the National Cancer Institute’s Genomic Data Commons to make it available for future research.

Dr Staudt said he and his colleagues hope their new molecular classification will be used in clinical trials so that DLBCL treatment can move toward more targeted therapies.

“The goal is to find the right drug for the right person at the right time,” Dr Staudt said. “And we feel this genetic understanding of diffuse lymphoma is a step forward in precision therapy.”

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Lab mouse

Preclinical results support clinical testing of an experimental agent in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), according to researchers.

The agent, ALRN-6924, was shown to combat AML and MDS by restoring activity of the tumor-suppressing protein p53.

ALRN-6924 exhibited antileukemic activity in AML cells and mouse models of the disease, as well as in a patient with MDS and excess leukemic blasts who received the drug on a compassionate-use basis.

These results, published in Science Translational Medicine, have led to a phase 1 trial of ALRN-6924 in patients with AML or MDS.

ALRN-6924 was developed by Aileron Therapeutics Inc., to target p53 by inhibiting 2 naturally occurring proteins, MDMX and MDM2. Overexpression of these proteins inactivates p53, allowing cancer cells to multiply unchecked.

In the current study, researchers set out to confirm ALRN-6924’s mechanism of action and determine the efficacy of the drug in AML/MDS. This work was supported, in part, by grants from Aileron Therapeutics Inc., and the National Institutes of Health.

The researchers did find that ALRN-6924 targets both MDMX and MDM2, blocking their interaction with p53 in AML cells.

The team said ALRN-6924 inhibited proliferation by inducing cell-cycle arrest and apoptosis in AML cell lines and AML patient cells, including leukemic stem cell-enriched populations.

“This is important because AML is driven by stem cells, and, if you don’t target stem cells, the disease will come back very quickly,” said study author Ulrich Steidl, MD, PhD, of Albert Einstein College of Medicine in Bronx, New York.

The researchers also found that ALRN-6924 greatly increased survival in a mouse model of AML. The median survival was 34 days in vehicle-treated control mice, 83 days in mice that received ALRN-6924 at 20 mg/kg twice a week, and 151 days in mice that received ALRN-6924 at 20 mg/kg three times a week.

“This is a very striking response,” Dr Steidl said. “Most experimental drugs for leukemia achieve an increase in survival of only a few days in these preclinical models. Even more importantly, ALRN-6924 effectively cured about 40% of the treated mice, meaning they were disease-free more than 1 year after treatment, essentially a lifetime for a mouse.”

Finally, the researchers assessed the effects of ALRN-6924 in a patient who had high-risk MDS with excess leukemic blasts.

The team found the p53 protein “was rapidly induced” in CD34+ leukemic blasts but not in healthy lymphocytes. And ALRN-6924 reduced the number of malignant cells circulating in the blood.

“This test was not designed to assess the efficacy of the drug in humans,” Dr Steidl noted. “That has to be done in a proper clinical trial. Our goal was to determine whether it can hit the desired target in human cells in a clinical setting, which it did in this individual.”

ALRN-6924 is a stapled alpha-helical peptide, a class of drugs whose helical structure is stabilized using hydrocarbon “staples.” The stapling prevents the peptides from being degraded by enzymes before reaching their intended target. ALRN-6924 is the first stapled peptide therapeutic to be tested in patients.

In the phase 1 trial (NCT02909972), researchers are testing ALRN-6924 in patients with relapsed/refractory AML or advanced MDS.

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Micrograph showing MM

Researchers have identified novel genes involved in the development of multiple myeloma (MM), according to a paper published in Leukemia.

The team’s analyses revealed regions of coding and non-coding DNA that appear to drive MM development.

The researchers analyzed whole-exome sequencing data from 804 MM patients and whole-genome sequencing data from 765 MM patients.

This revealed 16 novel genes that were disrupted in coding regions of DNA and 15 novel genes disrupted in non-coding regions.

There were 5 genes disrupted by structural variants in coding regions—CD96, PRDM1, FBXW7, MAP3K14, and CCND2.

There were also 11 genes disrupted by single nucleotide variants (SNVs) and indels in coding regions—BAX, C8orf86, FAM154B, FTL, HIST1H4H, LEMD2, PABPC1, RPN1, RPS3A, SGPP1, and TBC1D29.

Among the novel genes disrupted by mutations in non-coding regions was NBPF1, a promoter disrupted by SNVs. The researchers noted that NBPF1 is directly regulated by NF-κB, and the NF-κB pathway is recurrently affected in MM.

The team also identified 7 cis-regulatory elements (CREs) disrupted by SNVs—CALCB, COBLL1, HOXB3, ST6GAL1, PAX5, ATP13A2, and TPRG1.

The researchers said the SNVs in PAX5 and HOXB3 reduced gene expression, suggesting PAX5 and HOXB3 function as tumor suppressors in MM. On the other hand, the SNVs in ST6GAL1 increased gene expression, which may contribute to the aberrant immunoglobulin-G glycosylation seen in MM.

Finally, there were 7 CREs disrupted by copy number variations—MYC, PLD4, KDM3B, SP110, RAB36, PACS2, and TEX22.

The researchers noted that, with the exception of MYC, these genes reside close to regions of common structural variation, so their relevance in MM is not clear.

The team also said it’s well known that MYC is upregulated in MM through gene amplification or translocation, but this research shows that MYC can be dysregulated by alternative mechanisms.

“We need smarter, kinder treatments for myeloma that are more tailored to each person’s cancer,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

“Exhaustive genetic research like this is helping us to make that possible. Our findings should now open up new avenues for discovering treatments that target the genes driving myeloma.”

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.

Photo from Business Wire

Palonosetron Hydrochloride Injection, a generic alternative to Aloxi^®, is now available in the US.

Fresenius Kabi’s Palonosetron Hydrochloride Injection is a 5-HT3 serotonin receptor that is approved for the prevention of nausea and vomiting in certain adults.

Palonosetron Hydrochloride Injection is available in a single-dose vial (0.25 mg per 5 mL).

In the US, Palonosetron Hydrochloride Injection is approved for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

The drug is also approved for the prevention of acute nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

And Palonosetron Hydrochloride Injection is approved for the prevention of post-operative nausea and vomiting for up to 24 hours after surgery. Efficacy beyond 24 hours has not been demonstrated.

The full prescribing information for Palonosetron Hydrochloride Injection can be found on the Fresenius Kabi website.