A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

[email protected]

A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

[email protected]

A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

[email protected]

BOSTON – Patients with rosacea, particularly the erythrotelangiectatic form, are considered good candidates for treatment with lasers and light therapies, but for acne, treatments with these therapies are still in the development stage.

For acne, treatments that are being studied include those that target the sebaceous glands, according to Mathew M. Avram, MD, who spoke about laser and light therapies for acne and rosacea at the American Academy of Dermatology summer meeting.

Light therapies for rosacea

Oxyhemoglobin in the blood absorbs light from lasers at wavelengths of about 595 nm (pulsed dye laser) and 532 nm (KTP laser), creating heat that helps destroy capillaries that contribute to the appearance of rosacea. Over a period of 3-4 weeks, the vessels are resorbed, and facial redness diminishes.

Patients with rosacea that are expected to do best with laser therapy are those with telangiectasia. Laser therapy is also effective for background redness but will be less effective for people with the papules associated with rosacea and “almost not effective at all for preventing flushing,” Dr. Avram said in an interview at the meeting.

Intense pulsed light (IPL) is another modality for treating rosacea. As with lasers, the mode of action is heating of certain structures and chromophores, causing their destruction and resorption, but unlike lasers, IPL output is broad spectrum and can be modified using filters.

With IPL, “basically, the endpoint that you want to see is transient purpural change, just a fleeting period of some black and blue, or if you’re treating vessels, you want to see vessel clearance when you’re firing the laser or the intense pulsed light,” said Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston.

On-screen settings of laser or IPL devices are essential, “but ultimately, if you want to have an effective treatment you really have to see what’s happening to your target … you need to pay attention to clinical endpoints, which is seeing that black and blue or that vessel clearance, not just paying attention to what’s on the screen.”

With IPL, too much pressure can compress vessels and blanch the skin, resulting in a less effective treatment, he added. He noted that tissue graying, whitening, or contraction indicates overly aggressive treatment, with the risk of scarring.

Certain factors can reduce the efficacy of IPL treatments of rosacea. Dr. Avram recommended against treating tanned skin and pointed out that anemic patients may benefit less from this approach since less hemoglobin presents a less-absorptive target for the treatments. He also advised particular caution when treating darker skin phototypes. But the most common factor that may make these treatments less effective is when a patient is on any type of anticoagulant, including NSAIDs or warfarin (Coumadin), because the mechanism of action is immediate microvascular hemorrhage, thrombosis, and eventual resorption.

For best results, Dr. Avram advises “appropriate overlap with the laser” to get an even and uniform improvement in the redness, with about a 15% overlap. Spacing laser spots too far apart can result in “foot printing,” the appearance of clearance in the areas of the laser pulse, but not in areas immediately around it “so it looks almost polka dotted.” After treatments, all patients should avoid the sun, he added.

What’s ahead for acne treatment

Until now, laser and light-based treatments for acne, “have provided inconsistent benefits for patients and all too often disappointing results,” Dr. Avram said in the interview. But several developments on the horizon may offer more effective therapies based on completely different technologies than are currently available. “Each of these therapies will be targeting the sebaceous glands in order to provide improved treatment for acne.”

One is a cryolysis device that uses cooling to selectively target lipids in the sebaceous glands. (Cryolysis is similar to cryolipolysis, which uses cooling to target fat cells.) The lipid-filled adipocytes are more sensitive to cold than is the water-rich dermis, thereby preserving the surrounding structures. There are also laser wavelengths that are absorbed by lipids, one of which is at about 1720 nm. In this case, heating rather than cooling targets the lipids.

Another technology in development is the use of nanoparticles coated with elements such as gold that are massaged through the skin into the sebaceous glands. Laser treatment with multiple different wavelengths targets the nanoparticles, heating them within the sebaceous glands, resulting in improvements in acne. In this case, treatment does not depend on the absorption spectrum of lipids. Clinical trials of this approach are now underway.

It is too early to tell which of these technologies is going to be effective or what potential side effects may occur. “However, the exciting news is that there will be multiple different technologies” designed to improve acne by targeting the sebaceous gland, and there is “the promise of potentially more effective noninvasive treatments that don’t require topical medications or oral medications,” Dr. Avram said.

For these potential new treatments, some objective outcome measure is needed to judge their efficacy. Right now, all that can be said is that they target the sebaceous gland, and clinical work still needs to be done to determine whether they will be effective, the degree of effectiveness, and how to optimize treatment, he noted.

Dr. Avram reported financial relationships with Cytrellis Biosystems, Invasix, Kythera, Masters of Aesthetics, Sciton, Zalea, and Zeltiq Aesthetics.

BOSTON – Patients with rosacea, particularly the erythrotelangiectatic form, are considered good candidates for treatment with lasers and light therapies, but for acne, treatments with these therapies are still in the development stage.

For acne, treatments that are being studied include those that target the sebaceous glands, according to Mathew M. Avram, MD, who spoke about laser and light therapies for acne and rosacea at the American Academy of Dermatology summer meeting.

Light therapies for rosacea

Oxyhemoglobin in the blood absorbs light from lasers at wavelengths of about 595 nm (pulsed dye laser) and 532 nm (KTP laser), creating heat that helps destroy capillaries that contribute to the appearance of rosacea. Over a period of 3-4 weeks, the vessels are resorbed, and facial redness diminishes.

Patients with rosacea that are expected to do best with laser therapy are those with telangiectasia. Laser therapy is also effective for background redness but will be less effective for people with the papules associated with rosacea and “almost not effective at all for preventing flushing,” Dr. Avram said in an interview at the meeting.

Intense pulsed light (IPL) is another modality for treating rosacea. As with lasers, the mode of action is heating of certain structures and chromophores, causing their destruction and resorption, but unlike lasers, IPL output is broad spectrum and can be modified using filters.

With IPL, “basically, the endpoint that you want to see is transient purpural change, just a fleeting period of some black and blue, or if you’re treating vessels, you want to see vessel clearance when you’re firing the laser or the intense pulsed light,” said Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston.

On-screen settings of laser or IPL devices are essential, “but ultimately, if you want to have an effective treatment you really have to see what’s happening to your target … you need to pay attention to clinical endpoints, which is seeing that black and blue or that vessel clearance, not just paying attention to what’s on the screen.”

With IPL, too much pressure can compress vessels and blanch the skin, resulting in a less effective treatment, he added. He noted that tissue graying, whitening, or contraction indicates overly aggressive treatment, with the risk of scarring.

Certain factors can reduce the efficacy of IPL treatments of rosacea. Dr. Avram recommended against treating tanned skin and pointed out that anemic patients may benefit less from this approach since less hemoglobin presents a less-absorptive target for the treatments. He also advised particular caution when treating darker skin phototypes. But the most common factor that may make these treatments less effective is when a patient is on any type of anticoagulant, including NSAIDs or warfarin (Coumadin), because the mechanism of action is immediate microvascular hemorrhage, thrombosis, and eventual resorption.

For best results, Dr. Avram advises “appropriate overlap with the laser” to get an even and uniform improvement in the redness, with about a 15% overlap. Spacing laser spots too far apart can result in “foot printing,” the appearance of clearance in the areas of the laser pulse, but not in areas immediately around it “so it looks almost polka dotted.” After treatments, all patients should avoid the sun, he added.

What’s ahead for acne treatment

Until now, laser and light-based treatments for acne, “have provided inconsistent benefits for patients and all too often disappointing results,” Dr. Avram said in the interview. But several developments on the horizon may offer more effective therapies based on completely different technologies than are currently available. “Each of these therapies will be targeting the sebaceous glands in order to provide improved treatment for acne.”

One is a cryolysis device that uses cooling to selectively target lipids in the sebaceous glands. (Cryolysis is similar to cryolipolysis, which uses cooling to target fat cells.) The lipid-filled adipocytes are more sensitive to cold than is the water-rich dermis, thereby preserving the surrounding structures. There are also laser wavelengths that are absorbed by lipids, one of which is at about 1720 nm. In this case, heating rather than cooling targets the lipids.

Another technology in development is the use of nanoparticles coated with elements such as gold that are massaged through the skin into the sebaceous glands. Laser treatment with multiple different wavelengths targets the nanoparticles, heating them within the sebaceous glands, resulting in improvements in acne. In this case, treatment does not depend on the absorption spectrum of lipids. Clinical trials of this approach are now underway.

It is too early to tell which of these technologies is going to be effective or what potential side effects may occur. “However, the exciting news is that there will be multiple different technologies” designed to improve acne by targeting the sebaceous gland, and there is “the promise of potentially more effective noninvasive treatments that don’t require topical medications or oral medications,” Dr. Avram said.

For these potential new treatments, some objective outcome measure is needed to judge their efficacy. Right now, all that can be said is that they target the sebaceous gland, and clinical work still needs to be done to determine whether they will be effective, the degree of effectiveness, and how to optimize treatment, he noted.

Dr. Avram reported financial relationships with Cytrellis Biosystems, Invasix, Kythera, Masters of Aesthetics, Sciton, Zalea, and Zeltiq Aesthetics.

BOSTON – Patients with rosacea, particularly the erythrotelangiectatic form, are considered good candidates for treatment with lasers and light therapies, but for acne, treatments with these therapies are still in the development stage.

For acne, treatments that are being studied include those that target the sebaceous glands, according to Mathew M. Avram, MD, who spoke about laser and light therapies for acne and rosacea at the American Academy of Dermatology summer meeting.

Light therapies for rosacea

Oxyhemoglobin in the blood absorbs light from lasers at wavelengths of about 595 nm (pulsed dye laser) and 532 nm (KTP laser), creating heat that helps destroy capillaries that contribute to the appearance of rosacea. Over a period of 3-4 weeks, the vessels are resorbed, and facial redness diminishes.

Patients with rosacea that are expected to do best with laser therapy are those with telangiectasia. Laser therapy is also effective for background redness but will be less effective for people with the papules associated with rosacea and “almost not effective at all for preventing flushing,” Dr. Avram said in an interview at the meeting.

Intense pulsed light (IPL) is another modality for treating rosacea. As with lasers, the mode of action is heating of certain structures and chromophores, causing their destruction and resorption, but unlike lasers, IPL output is broad spectrum and can be modified using filters.

With IPL, “basically, the endpoint that you want to see is transient purpural change, just a fleeting period of some black and blue, or if you’re treating vessels, you want to see vessel clearance when you’re firing the laser or the intense pulsed light,” said Dr. Avram, director of the Massachusetts General Hospital Dermatology Laser & Cosmetic Center, Boston.

On-screen settings of laser or IPL devices are essential, “but ultimately, if you want to have an effective treatment you really have to see what’s happening to your target … you need to pay attention to clinical endpoints, which is seeing that black and blue or that vessel clearance, not just paying attention to what’s on the screen.”

With IPL, too much pressure can compress vessels and blanch the skin, resulting in a less effective treatment, he added. He noted that tissue graying, whitening, or contraction indicates overly aggressive treatment, with the risk of scarring.

Certain factors can reduce the efficacy of IPL treatments of rosacea. Dr. Avram recommended against treating tanned skin and pointed out that anemic patients may benefit less from this approach since less hemoglobin presents a less-absorptive target for the treatments. He also advised particular caution when treating darker skin phototypes. But the most common factor that may make these treatments less effective is when a patient is on any type of anticoagulant, including NSAIDs or warfarin (Coumadin), because the mechanism of action is immediate microvascular hemorrhage, thrombosis, and eventual resorption.

For best results, Dr. Avram advises “appropriate overlap with the laser” to get an even and uniform improvement in the redness, with about a 15% overlap. Spacing laser spots too far apart can result in “foot printing,” the appearance of clearance in the areas of the laser pulse, but not in areas immediately around it “so it looks almost polka dotted.” After treatments, all patients should avoid the sun, he added.

What’s ahead for acne treatment

Until now, laser and light-based treatments for acne, “have provided inconsistent benefits for patients and all too often disappointing results,” Dr. Avram said in the interview. But several developments on the horizon may offer more effective therapies based on completely different technologies than are currently available. “Each of these therapies will be targeting the sebaceous glands in order to provide improved treatment for acne.”

One is a cryolysis device that uses cooling to selectively target lipids in the sebaceous glands. (Cryolysis is similar to cryolipolysis, which uses cooling to target fat cells.) The lipid-filled adipocytes are more sensitive to cold than is the water-rich dermis, thereby preserving the surrounding structures. There are also laser wavelengths that are absorbed by lipids, one of which is at about 1720 nm. In this case, heating rather than cooling targets the lipids.

Another technology in development is the use of nanoparticles coated with elements such as gold that are massaged through the skin into the sebaceous glands. Laser treatment with multiple different wavelengths targets the nanoparticles, heating them within the sebaceous glands, resulting in improvements in acne. In this case, treatment does not depend on the absorption spectrum of lipids. Clinical trials of this approach are now underway.

It is too early to tell which of these technologies is going to be effective or what potential side effects may occur. “However, the exciting news is that there will be multiple different technologies” designed to improve acne by targeting the sebaceous gland, and there is “the promise of potentially more effective noninvasive treatments that don’t require topical medications or oral medications,” Dr. Avram said.

For these potential new treatments, some objective outcome measure is needed to judge their efficacy. Right now, all that can be said is that they target the sebaceous gland, and clinical work still needs to be done to determine whether they will be effective, the degree of effectiveness, and how to optimize treatment, he noted.

Dr. Avram reported financial relationships with Cytrellis Biosystems, Invasix, Kythera, Masters of Aesthetics, Sciton, Zalea, and Zeltiq Aesthetics.

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura

The Food and Drug Administration has granted accelerated approval to pembrolizumab for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Approval was based on an objective response rate of 16% for 174 patients with recurrent or metastatic HNSCC who had disease progression on or after platinum-containing chemotherapy. These patients, a subgroup of patients in an international, multicenter, nonrandomized, open-label, multicohort study, received intravenous pembrolizumab (Keytruda) 10 mg/kg every 2 weeks or 200 mg every 3 weeks, the FDA said in a written statement.

The median response duration for patients receiving pembrolizumab, a checkpoint inhibitor targeting the PD-1/PD-L1 pathway, had not been reached at the time of analysis. The range for duration of response was 2.4 months to 27.7 months (response ongoing). Among the 28 responding patients, 23 (82%) had responses of 6 months or longer, the FDA said.

The most common adverse reactions observed in 192 patients with HNSCC who received at least one dose of pembrolizumab were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were similar to those occurring in patients with melanoma or NSCLC, with the exception of an increased incidence of facial edema (10% all grades, 2.1% grades 3-4) and new or worsening hypothyroidism (14.6% all grades). The most frequent serious adverse reactions were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. Clinically significant immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, adrenal insufficiency, diabetes mellitus, skin toxicity, myositis, and thyroid disorders, the FDA noted.

Merck Sharp & Dohme Corp., maker of pembrolizumab, is required to conduct a multicenter, randomized trial establishing the superiority of pembrolizumab over standard therapy as a condition for accelerated approval and is doing so with the ongoing KEYNOTE 040 study, with a primary endpoint of overall survival.

The FDA-recommended dose and schedule of pembrolizumab for patients with HNSCC and disease progression on or after platinum-containing chemotherapy is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks.

[email protected]

On Twitter @NikolaidesLaura

Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

Six months of stable international normalized ratio values [INRs] while on warfarin therapy doesn’t predict continued INR stability, according to a Research Letter to the Editor published August 9 in JAMA.

Whether or not to switch patients with atrial fibrillation from warfarin to non–vitamin K anticoagulants remains controversial. “A common belief has been that patients with stable INRs while taking warfarin would continue to be stable and derive less benefit from switching to non–vitamin K oral anticoagulants,” said Sean D. Pokorney, MD, of the division of cardiology, Duke University Medical Center, Durham, N.C., and his associates.

But the results of their observational study of 3,749 patients enrolled in an atrial fibrillation registry show that such stability cannot be predicted, and “challenge the notion that patients who have done well taking warfarin should maintain taking warfarin,” the investigators said (JAMA. 2016;316:661-3).

They assessed INRs over the course of 3 years of follow-up using data from patients enrolled in the registry through 176 clinics. INR stability was defined as having 80% or more of INRs in the therapeutic range (2-3). The mean patient age was 75 years, and 43% were women.

A total of 968 patients showed such INR stability throughout the first 6 months of the study. However, 36% of them went on to have at least one “well out of range” INR during the following year. Even in the subgroup of 376 patients who had 100% of their INRs within the therapeutic range during the first 6 months, 33% went on to have at least one “well out of range” INR during the following year, according to Dr. Pokorney and his associates.

No sponsor was cited for this study. Dr. Pokorney reported ties to AstraZeneca, Boston Scientific, Gilead, Janssen, and Medtronic; his associates reported ties to numerous industry sources.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

According to a report published by AmericanEHR Partners, 61% of respondents in 2010 said they were “satisfied” or “very satisfied” with their electronic health records (EHRs), compared with just 34% in 2014. Additionally, close to half of all respondents reported a negative response to questions related to costs, efficiency, and productivity. SHM’s IT Committee would like to obtain your insight on the EHR within your institution. The findings from the survey will be released in a white paper on how the current state of EHRs affects the quality of patient care and the professional satisfaction of hospitalists.

Please take a few minutes to offer your feedback at www.hospitalmedicine.org/ITEHR.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

• Chicago: Aug. 27
• St. Louis: September
• Philadelphia: October
• Atlanta: Oct. 13
• Denver: Oct. 18
• San Francisco: Oct. 20
• New York City: Nov. 3
• Chicago: December

Visit www.futureofhospitalmedicine.org/events to learn more and see updated schedule details.

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Hydroxyurea

Photo by Zak Hubbard

Researchers say they have uncovered hydroxyurea’s main mechanism of action in sickle cell disease (SCD).

The drug’s mechanism has been a topic of debate, with some researchers claiming hydroxyurea works by reactivating fetal hemoglobin and others saying it increases the volume of red blood cells (RBCs), thereby reducing the concentration of sickle hemoglobin.

Now, research published in PNAS suggests the latter mechanism is the dominant one.

“Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community,” said study author Ming Dao, PhD, of the Massachusetts Institute of Technology in Cambridge.

“It’s exciting to see that, using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease.”

For this study, the researchers analyzed blood samples from patients with SCD.

The team used common-path interferometric microscopy to assess the biophysical properties (shape, surface area, and volume) and biomechanical properties (flexibility and stickiness) of RBCs.

The researchers separated RBCs into 4 groups based on their density. Normal, disc-shaped cells were the least dense, while severely sickled cells were the densest.

The team then compares samples from patients who were taking hydroxyurea and those who were not.

The RBCs of patients receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels.

Improvement in the physical properties of RBCs from patients treated with hydroxyurea correlated more with an increase in RBC volume than with levels of fetal hemoglobin.

The researchers hope these biophysical markers can be combined with biochemical and molecular-level markers to assess the severity of a patient’s disease, determine whether or not a patient will respond to hydroxyurea, and monitor the effectiveness of that treatment.

“There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease,” said study author Subra Suresh, ScD, of Carnegie Mellon University in Pittsburgh, Pennsylvania.

“This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies.”

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Micrograph showing MM

Health Canada has approved ixazomib (Ninlaro) for use in combination with lenalidomide and dexamethasone to treat adults with multiple myeloma (MM) who have received at least 1 prior therapy.

Ixazomib is the first oral proteasome inhibitor approved for this indication.

The approval was primarily based on results from the phase 3 trial TOURMALINE-MM1, which were presented at the 2015 ASH Annual Meeting.

The trial included 722 patients with relapsed or refractory MM. The patients were randomized to receive ixazomib, lenalidomide, and dexamethasone (IRd, n=360) or placebo, lenalidomide, and dexamethasone (Rd, n=362).

Baseline patient characteristics were similar between the treatment arms. Fifty-nine percent of patients in both arms had received 1 prior line of therapy, and 41% in both arms had 2 or 3 prior lines of therapy.

Seventy-eight percent of patients responded to IRd, and 72% responded to Rd (P=0.035). The rates of complete response were 12% and 7%, respectively (P=0.019).

At a median follow-up of about 15 months, the median progression-free survival was 20.6 months in the IRd arm and 14.7 months in the Rd arm. The hazard ratio was 0.742 (P=0.012).

At a median follow-up of about 23 months, the median overall survival had not been reached in either treatment arm.

The incidence of adverse events (AEs) was 98% in the IRd arm and 99% in the Rd arm. The incidence of grade 3 or higher AEs was 74% and 69%, respectively. And the incidence of serious AEs was 47% and 49%, respectively.

Common AEs in the IRd and Rd arms, respectively, were diarrhea (45% vs 39%), constipation (35% vs 26%), nausea (29% vs 22%), vomiting (23% vs 12%), rash (36% vs 23%), back pain (24% vs 17%), upper respiratory tract infection (23% vs 19%), thrombocytopenia (31% vs 16%), peripheral neuropathy (27% vs 22%), peripheral edema (28% vs 20%), thromboembolism (8% vs 11%), and neutropenia (33% vs 31%).

Ixazomib is currently under investigation in 3 other phase 3 trials of MM patients:

• TOURMALINE-MM2, investigating ixazomib vs placebo, both in combination with lenalidomide and dexamethasone in patients with newly diagnosed MM
• TOURMALINE-MM3, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM following induction therapy and autologous stem cell transplant
• TOURMALINE-MM4, investigating ixazomib vs placebo as maintenance therapy in patients with newly diagnosed MM who have not undergone autologous stem cell transplant.

Ixazomib is marketed by Takeda Pharmaceutical Company Limited.

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”

Study authors Jianan Gong,

David Segal, and Yuan Yao

Photo from the Walter

and Eliza Hall Institute

A new class of inhibitors may be effective in treating a majority of patients with multiple myeloma (MM), according to research published in Blood.

Experiments in multiple MM cell lines suggested the majority of myelomas rely on the protein MCL1 to stay alive.

And targeting MCL1 inhibited disease progression in mouse models of MM.

Therefore, researchers believe drugs designed to inhibit MCL1 may be a promising treatment option for MM.

“Our research shows that switching off MCL1 has the potential to be an effective new treatment approach for the majority of patients with myeloma,” said Jianan Gong, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, Victoria, Australia.

For this study, Dr Gong and her colleagues investigated the survival proteins that keep MM cells alive.

The team found that a majority of MM cell lines—about 70%—died when MCL1 was switched off. This included well-established, immortalized MM cell lines (17/25) and low-passage MM cell lines (5/7).

“In contrast, only around one quarter [of the cell lines] were susceptible to inhibiting BCL2,” Dr Gong said. “This finding is in keeping with earlier research at the Walter and Eliza Hall Institute that pinpointed MCL1 as the likely protein that keeps myeloma cells alive.”

The researchers also found that targeting MCL1 hindered MM growth in vivo.

The team targeted MCL1 by expressing the MCL1-selective ligand BIM2A in mice inoculated with 1 of 2 MM cell lines—AMO1 and H929. In both models, targeting MCL1 resulted in delayed disease progression and reduced disease burden.

Finally, the researchers identified a subtype of MM that is highly dependent upon BCLXL, so they’ve theorized that targeting both MCL1 and BCLXL could prove useful.

The team concluded that MCL1 is pivotal for maintaining the survival of most myelomas, so targeting the protein should be prioritized once validated inhibitors become available.

“As yet, these inhibitors are still in preclinical development,” said study author Andrew Roberts, MBBS, PhD, of The Walter and Eliza Hall Institute of Medical Research.

“Our results suggest that, once necessary laboratory testing for safety is completed, clinical trials of their effectiveness in treating patients with multiple myeloma that is no longer responding to current therapies would be well justified.”