Non-Hodgkin Lymphoma

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

and Drug Administration

The US Food and Drug Administration (FDA) has released new information on breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL).

The agency said it is now aware of 414 cases of BIA-ALCL, which includes 9 patients who died.

In addition, the medical literature suggests that patients with textured breast implants have a lifetime risk of developing BIA-ALCL that ranges from 1 in 3817 to 1 in 30,000.

“The FDA has been closely tracking the relationship between breast implants and a rare type of non-Hodgkin’s lymphoma since we first identified this possible association,” said Binita Ashar, MD, director of the division of surgical devices in the FDA’s Center for Devices and Radiological Health.

“We’ve been working to gather additional information to better characterize and quantify the risk so that patients and providers can have more informed discussions about breast implants. As part of that effort, we are working to update and enhance the information we have on this association, including updating the total number of known cases of BIA-ALCL and the lifetime risk of developing BIA-ALCL as reported in medical literature.”

Reports to FDA

Most of the BIA-ALCL cases reported to the FDA occurred in patients with textured implants (n=242), but 30 occurred in patients with smooth implants. In the remaining 173 cases, the implant surface was not specified.

There were more silicone implants (n=234) than saline implants (n=179), and there was 1 case in which the implant filling was not specified.

The patients’ median age was 53 (range, 24-90), and the median time from last implant to BIA-ALCL diagnosis was 8 years (range, 0-44).

Cases of BIA-ALCL were ALK-negative (n=124) or did not have ALK status specified (n=290). And they were CD30-positive (n=126) or did not have CD30 status specified (n=288).

The most common clinical presentation was seroma (n=203), followed by breast swelling/pain (n=101), peri-implant mass/lump (n=45), and capsular contracture (n=42). In some cases, more than one clinical presentation was listed, and there were 141 cases where clinical presentation was unspecified/uncertain.

Medical literature

The FDA said a “significant body of medical literature” on BIA-ALCL has been published since the agency’s 2011 report on this malignancy.

For the aforementioned lifetime risk estimates—1 case of BIA-ALCL in 3817 to 30,000 individuals with textured implants—the FDA cited 3 sources:

• BIA-ALCL Resources : By the numbers, and what they mean
• Breast Implant–Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk
• Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast.

Recommendations, more updates

The FDA said this updated information does not change its recommendations regarding breast implants. The agency said the decision to obtain breast implants should be made based on individual needs and with the most complete information about risks and benefits.

“We hope that this information prompts providers and patients to have important, informed conversations about breast implants and the risk of BIA-ALCL,” Dr Ashar said. “At the same time, we remain committed to working in partnership with all stakeholders to continue to study, understand, and provide updates about this important public health issue.”

The FDA is also updating the content and format of the webpage for the agency’s breast implant post-approval studies to make current information about these studies easier for patients to read and understand.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Photo courtesy of CDC

ORLANDO—Results of a retrospective study showed that survivors of lymphoma or breast cancer had a significantly greater risk of congestive heart failure (CHF) than patients who did not have cancer.

This increased risk was observed as early as a year after cancer diagnosis but was still present 20 years after diagnosis.

Overall, 1 in 10 cancer patients had CHF at the 20-year mark.

“The majority of patients do not develop heart failure, but our research helps us recognize the factors associated with it and the importance of appropriate heart care following cancer treatment,” said Carolyn Larsen, MD, of the Mayo Clinic in Rochester, Minnesota.

“Our research suggests that periodic cardiac imaging to monitor for heart damage may be needed for some cancer patients, even if they have no signs of heart damage initially after chemotherapy. Additionally, it emphasizes that working to live a heart-healthy lifestyle is important for cancer patients and survivors to reduce the overall risk of heart disease.”

Dr Larsen and her colleagues presented this research as a poster (abstract 1105-066) at the American College of Cardiology’s 67th Annual Scientific Session & Expo (ACC.18).

Patients

Using data from the Rochester Epidemiology Project, the researchers retrospectively tracked CHF cases in 900 cancer patients and 1550 non-cancer patients. Patients were treated in Olmsted County in Minnesota from 1985 to 2010.

For both patient groups, the median age at baseline was about 53, a little more than 90% of each group was white, and nearly 80% of each group was female.

Six to 7% of patients had diabetes, and about 30% of each group had hypertension. Thirty-eight percent of each group had hyperlipidemia, and 31% were obese.

Five percent of cancer patients and 2% of controls had coronary artery disease (P<0.001). This was the only significant difference in baseline characteristics.

Cancer patients had been diagnosed with non-Hodgkin lymphoma (28%), Hodgkin lymphoma (9%), or breast cancer (64%). Forty-seven percent had received radiation, including right chest (21%), left chest (23%), and mediastinal (4%).

Eighty-four percent of patients had received anthracycline therapy. The median doxorubicin isotoxic dose was 240 mg/m².

At baseline, 12% of cancer patients were on beta-blockers, 8% were on angiotensin converting enzyme inhibitors, 4% were on angiotensin receptor blockers, and 11% were on statins.

Results

Cancer patients were more than 3 times as likely as controls to develop CHF. The hazard ratio (HR) was 3.6 (P<0.01) in an analysis adjusted for age, gender, diabetes, hypertension, coronary artery disease, dyslipidemia, and obesity at baseline.

The increased CHF risk among cancer patients was evident after the first year from cancer diagnosis and persisted at 20 years of follow-up.

“The risk of heart failure doesn’t go away after a couple of years,” Dr Larsen said. “It’s a long-term issue that patients need to discuss with their doctors and use as motivation to stay heart healthy.”

The incidence of CHF—in cancer patients and controls, respectively—was as follows:

• 1 year—1.5% vs 0.1%
• 5 years—3.1% vs 0.9%
• 10 years—5.0% vs 2%
• 20 years—10.1% vs 5.8%.

A multivariable analysis in the cancer patients revealed a few independent risk factors for CHF, including:

• Doxorubicin isotoxic dose ≥ 300 mg/m² (HR=2.34, P=0.003)
• Age at diagnosis (HR=3.06 for age ≥ 80 vs 60-69, P=0.01)
• Coronary artery disease at diagnosis (HR=2.27, P=0.04)
• Diabetes mellitus at diagnosis (HR=2.39, P<0.01).

Dr Larsen said additional research is needed to determine why diabetes carries a greater risk than other traditional risk factors, such as high blood pressure, in this group.

Mitigating risk

These findings raise important questions about what the appropriate surveillance should be for heart problems post-cancer treatment, Dr Larsen said. She believes more frequent cardiac imaging may be warranted in some patients to detect signs of CHF earlier.

“It’s an area that needs to be better defined,” Dr Larsen said. “An echocardiogram is usually done 6 to 12 months after cancer treatment with an anthracycline, but how often should it be done after that? We need to be more vigilant in making sure we try to prevent or control heart issues post-cancer care, especially in light of the growing appreciation of the connection between some cancer treatments and heart disease.”

Dr Larsen also noted that patients themselves can play a role in decreasing their risk of CHF, even if they are starting at a disadvantage.

A heart-healthy lifestyle—maintaining a normal body weight, regular exercise, and controlling other risk factors such as high blood pressure, diabetes, and high cholesterol—can help lower the risk of heart disease and CHF.

“If patients know they have received a drug treatment that might increase their risk of heart failure, it’s even more important to take care of the aspects of their life that they can control to reduce their risk as much as possible and to work with their medical care team to detect issues as early as possible,” Dr Larsen said.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Amandeep Godara, MD

SALT LAKE CITY—Results of a large, retrospective analysis support the notion that patients who receive cord blood (CB) transplants have a higher risk of infection than other hematopoietic stem cell transplant (HSCT) recipients.

Investigators found that CB recipients had a significantly higher risk of bacterial, viral, and fungal infections in the early post-transplant period than patients who received peripheral blood (PB) or bone marrow (BM) transplants.

In addition, CB recipients had longer hospital stays, higher inpatient costs, and greater inpatient mortality than PB and BM recipients.

Amandeep Godara, MD, of Tufts Medical Center in Boston, Massachusetts, presented these results at the 2018 BMT Tandem Meetings (abstract 30*).

“Infections are considered more common in cord blood transplant recipients based on some prior retrospective analyses,” Dr Godara noted. “But there is limited data comparing these infectious complications between cord blood transplant and peripheral blood/bone marrow stem cell transplants during the inpatient stay for the stem cell transplant.”

With this in mind, Dr Godara and his colleagues analyzed data from the Healthcare Cost and Utilization Project National Inpatient Sample. This database covers 46 US states and contains data from more than 7 million hospital stays each year.

The investigators searched the database for hospital admissions for HSCT from 2002 to 2014. They identified 2979 CB transplants and 56,845 PB or BM transplants.

The CB recipients had a median age of 48, and 55% were male. Fifty-nine percent were white, 18% Hispanic, 13% black, 5% Asian, and 5% “other.” Sixty-six percent of patients had acute leukemia, 18% non-Hodgkin lymphoma, 5% Hodgkin lymphoma, and 11% “other” diseases.

The PB/BM recipients had a median age of 45, and 58% were male. Seventy-nine percent were white, 8% Hispanic, 6% black, 3% Asian, and 4% “other.” Sixty-one percent of patients had acute leukemia, 16% non-Hodgkin lymphoma, 4% Hodgkin lymphoma, and 19% “other” diseases.

Results

Dr Godara and his colleagues compared the rates and types of infection from the time of HSCT to hospital discharge in CB and PB/BM recipients. The team also compared early inpatient mortality, the cost of hospitalization, and the length of hospital stay.

“[W]e observed a higher risk for infections in cord blood transplant patients compared to peripheral blood and bone marrow stem cell transplant patients, and this risk for infection extended through a wide spectrum of pathogens,” Dr Godara said.

“We also observed a higher all-cause inpatient mortality in cord blood transplant compared to peripheral blood and bone marrow transplant, especially in patients who had bacterial sepsis or invasive fungal infection.”

The rate of bacterial sepsis was 34.87% in CB recipients and 20.20% in PB/BM recipients (P<0.0001). Rates of viral infection were 20.05% and 8.19%, respectively (P<0.0001). And rates of invasive fungal infection were 12.87% and 7.89% (P<0.0001).

There was a similar distribution of bacterial infections in CB and PB/BM recipients. The most common was pneumonia (47% and 41%, respectively), followed by abdominal infections (29% and 31%, respectively), urinary tract infections (17% and 21%, respectively), central line-associated bloodstream infections (4% and 6%, respectively), and acute sinusitis (3% and 1%, respectively).

The rate of Clostridium difficile infection was significantly higher in CB recipients than PB/BM recipients—11.75% and 8.90%, respectively (P=0.02). However, there was no significant difference in mortality related to C. difficile—14% and 10%, respectively (P=0.3).

On the other hand, all-cause inpatient mortality was significantly higher in CB recipients than PB/BM recipients—16% and 7%, respectively (P<0.0001).

Inpatient mortality rates were significantly higher for CB recipients with bacterial sepsis (33% vs 23%, P=0.001) and invasive fungal infections (29% vs 16%, P=0.0045) but not viral infections (19% vs 17%, P=0.5).

The median length of hospital stay was 36 days for CB recipients and 25 days for PB/BM recipients. The mean inpatient charges were $448,892 and $250,437 respectively.

*Data in the abstract differ from the presentation.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Gilead Sciences, Inc.

Gilead Sciences International Ltd. recently withdrew its application for European approval of idelalisib (Zydelig) in combination with rituximab and bendamustine for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL).

Idelalisib is currently approved in the European Union for use in combination with an anti-CD20 monoclonal antibody (rituximab or ofatumumab) to treat adults with CLL who have received at least 1 prior therapy or as first-line treatment of CLL in the presence of 17p deletion or TP53 mutation in patients who are not eligible for any other therapies.

Idelalisib is also approved as monotherapy for adults with follicular lymphoma that is refractory to 2 prior lines of treatment.

In seeking expanded approval for idelalisib, Gilead submitted data from a study (NCT01569295) comparing idelalisib plus bendamustine and rituximab to placebo plus bendamustine and rituximab.

Interim results from this study were published in The Lancet Oncology in March 2017.

Gilead withdrew the application for idelalisib after the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) had evaluated documentation provided by the company and formulated lists of questions.

Gilead had not responded to the last round of questions at the time of the withdrawal.

At that point, the CHMP was of the provisional opinion that idelalisib should not be approved for use in combination with rituximab and bendamustine in patients with relapsed/refractory CLL.

The CHMP said additional, longer-term data are needed to show the benefits of idelalisib plus rituximab and bendamustine outweigh the risks.

Gilead said its withdrawal of the application was based on the CHMP’s opinion that there was insufficient evidence of a favorable benefit-risk profile.

The company also said the withdrawal does not impact ongoing trials of idelalisib.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—An antibody targeting KIR3DL2 has “very promising activity” in relapsed/refractory cutaneous T-cell lymphoma (CTCL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

The antibody, IPH4102, produced an overall response rate (ORR) of 44% in a phase 1 trial of CTCL patients, with an ORR of 50% in patients with Sézary syndrome (SS).

There were 2 serious adverse events (AEs) that were considered possibly related to IPH4102, and 1 of these was fatal.

Youn H. Kim, MD, of Stanford Cancer Institute in Palo Alto, California, presented these results at this year’s T-cell Lymphoma Forum. The research was sponsored by Innate Pharma, the company developing IPH4102.

“KIR3DL2 is a target that’s a member of the killer immunoglobulin-like receptor [KIR] family, and it’s also very specifically expressed in CTCL,” Dr Kim explained. “The antibody [IPH4102] is Fc-modified to enhance the antibody-dependent cell cytotoxicity and also works by antibody-dependent cell phagocytosis. It binds and, with the immunologic effect, kills the cancer cells.”

“[IPH4102] is specific for cancer cells because [KIR3DL2] is only minimally expressed in normal T cells as well as natural killer [NK] cells. About a third of NK cells that do express [KIR3DL2] don’t get affected [by IPH4102]. So it looks like the killer cells don’t kill each other, and they specifically target the neoplastic cells.”

Patients

Dr Kim and her colleagues have tested IPH4102 in 25 patients with relapsed/refractory CTCL—20 with SS, 4 with mycosis fungoides (MF), and 1 with CD4+ CTCL not otherwise specified. At baseline, patients had a median age of 71 (range, 42-90).

The patients had received a median of 4 prior systemic regimens (range, 2-10). Among the MF and SS patients, 1 patient had stage IB disease, 3 had stage IIB, and 20 had stage IVA disease.

Treatment

This study has a dose-escalation portion (accelerated 3+3 design) and an expansion portion. Dr Kim presented results for the 25 patients in the dose-escalation portion, which was completed in May 2017.

Patients received IPH4102 at 10 dose levels, ranging from 0.0001 mg/kg to 10 mg/kg. They received the drug once weekly for 4 doses, every 2 weeks for 10 doses, and every 4 weeks thereafter. They were treated until progression or unacceptable toxicity.

The expansion cohorts (which include SS and transformed MF patients) started enrolling in July 2017, with patients receiving IPH4102 at the recommended phase 2 dose—750 mg.

Safety

There were no dose-limiting toxicities with IPH4102. So the equivalent of 10 mg/kg—a 750 mg flat dose—was deemed the recommended phase 2 (and expansion) dose.

The incidence of AEs was 92% (n=23), and the incidence of treatment-related AEs was 52% (n=13).

Treatment-related AEs included lymphopenia (16%, n=4), asthenia (12%, n=3), nausea (8%, n=2), chills (8%, n=2), pyrexia (8%, n=2), arthralgia (8%, n=2), and muscle spasms (8%, n=2).

Eight patients had serious AEs, and 2 had serious AEs that were considered possibly related to treatment.

One patient had grade 2 atrial flutter diagnosed 1 hour after the first dose of IPH4102. The patient had a history of cardiac arrhythmia. She was hospitalized after the atrial flutter, received amiodarone, and the arrhythmia resolved. She went on to receive 15 more doses of IPH4102 without recurrence.

The other patient with a serious AE considered possibly related to treatment had hepatitis that occurred 6 weeks after the last dose of IPH4102. The patient had discontinued treatment due to progression after receiving IPH4102 for a year and achieving a partial response (PR).

This patient ultimately died of the hepatitis. Another fatal AE, considered unrelated to treatment, was Staphylococcus aureus sepsis.

“The safety looks very solid,” Dr Kim said, “[with] very low numbers of any significant severe adverse effects.”

Efficacy

The best global ORR was 44%, with 10 PRs and 1 complete response (CR). Twelve patients had stable disease, and 2 progressed.

In patients with SS, the best global ORR was 50%. One patient had a CR, 9 had PRs, and 8 had stable disease. The ORR was 60% in the skin and a 65% in the blood compartment for patients with SS.

Four responses were ongoing at last follow-up. The median follow-up was 15 months.

The median duration of response for the entire cohort was 8.2 months (range, 64 days to 519+ days). For SS patients, the median duration of response was 9.9 months (range, 64 days to 519+ days).

The median progression-free survival was 9.8 months overall (range, 28 days to 610+ days). For SS patients, the median progression-free survival was 10.8 months (range, 28 days to 610+ days).

“So with the efficacy and the safety profile, we are really hoping to get this drug to the phase 2 level and are excited to move forward,” Dr Kim concluded.

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Fluorodeoxyglucose positron emission tomography (FDG PET) cannot replace bone marrow (BM) biopsy in T-cell lymphomas, according to a speaker at the 10th Annual T-cell Lymphoma Forum.

Researchers found that FDG PET results did not exactly correlate with BM biopsy results relating to tumor involvement in patients with T-cell lymphomas.

However, results from FDG PET were found to be an independent prognostic factor for progression-free survival (PFS) and overall survival (OS).

Youngil Koh, MD, of Seoul National University Hospital in Seoul, South Korea, presented this research in a poster and oral presentation at this year’s T-cell Lymphoma Forum.

He and his colleagues set out to investigate the clinical value of FDG PET for evaluating BM tumor involvement and prognosis in T-cell lymphoma patients.

The team analyzed 109 patients who underwent staging with FDG PET and BM biopsy. Most patients had extranodal natural killer/T-cell lymphoma, nasal type (NKTCL, n=46), or angioimmunoblastic T-cell lymphoma (AITL, n=41).

Patients also had peripheral T-cell lymphoma not otherwise specified (n=12), anaplastic large-cell lymphoma (n=4), enteropathy-associated T-cell lymphoma (n=4), and subcutaneous panniculitis-like T-cell lymphoma (n=2).

Most patients (87.2%) received chemotherapy as first-line treatment. Fifty percent were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, 48.1% were IMEP (ifosphamide, methotrexate, etoposide, and prednisolone) or IMEP-like regimens, and 1.9% were “other” regimens.

Other first-line treatments included radiotherapy followed by chemotherapy (10.1%), excision (0.9%), and no treatment (1.8%).

The patients’ median OS was 60.03 months, and the median PFS was 15.7 months.

BM involvement

The researchers analyzed PET BM uptake both visually and quantitatively using the marrow-to-liver ratio (MLR), and they compared these results to BM biopsy results.

According to BM biopsy, 35.8% of patients had tumor involvement.

By visual analysis, the sensitivity of PET for diagnosing positive BM biopsy was 58.5%, and the specificity was 77.9%. By MLR, the sensitivity was 64.1%, and the specificity was 72.9%.

The diagnostic performance of PET for BM involvement was not different across the lymphoma subtypes, Dr Koh said.

Prognosis

“Although FDG PET did not correlate very well with bone marrow biopsy, it had prognostic value, especially MLR,” Dr Koh noted. “And most importantly, in bone marrow biopsy-negative patients, it [MLR] had prognostic value.”

MLR was a significant prognostic factor for PFS (P=0.005) and OS (P<0.001). The same was true for BM biopsy (P=0.009 for PFS and P<0.001 for OS), while visual PET analysis was a significant prognostic factor for OS (P=0.015) but not PFS (P=0.476).

In patients negative by BM biopsy, MLR was a significant prognostic factor for PFS (P=0.001) and OS (P=0.005).

Dr Koh and his colleagues also analyzed the prognostic value of PET and BM biopsy specifically in patients with NKTCL and AITL.

In AITL patients, BM biopsy was a significant prognostic factor for OS (P=0.002) but not PFS (P=0.246). Visual PET analysis was not significant for PFS (P=0.910) or OS (P=0.581), and neither was MLR (P=0.053 for PFS and P=0.156 for OS).

In patients with NKTCL, BM biopsy was a significant prognostic factor for PFS (P=0.008) and OS (P<0.001). Visual PET analysis was not significant for PFS (P=0.469) or OS (P=0.092). And MLR was significant for PFS (P=0.004) and OS (P=0.012).

“Bone marrow findings of FDG PET are an independent prognostic factor in these tumors,” Dr Koh said, “suggesting the biologic relevance of FDG PET findings for aggressiveness or covert bone marrow involvement of tumor cells.”

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

Photo by Larry Young

LA JOLLA, CA—Results of a phase 1 trial suggest MRG-106 can provide clinical improvement in patients with mycosis fungoides (MF), whether the drug is given alone or in conjunction with other therapies.

MRG-106 is an inhibitor of microRNA-155, which is upregulated in MF.

In this ongoing trial, 90% of patients who received MRG-106 have experienced an improvement in mSWAT score, and 59% of patients who received the drug for at least 1 month had a partial response.

The most common adverse events (AEs) attributed to MRG-106 were neutropenia, injection site pain, and fatigue.

Christiane Querfeld, MD, PhD, of the City of Hope in Duarte, California, presented these results at the 10th Annual T-cell Lymphoma Forum. The research is sponsored by miRagen Therapeutics, Inc., the company developing MRG-106.

The trial has enrolled 36 MF patients, 69% of whom are male. Their median age at enrollment was 63 (range, 21-85).

Patients had received a median of 4 prior systemic therapies (range, 1-13) and a median of 3 prior skin-directed therapies (range, 1-8).

At baseline, patients had a median mSWAT score of 43 (range, 2-180). The modified Severity Weighted Assessment Tool (mSWAT) measures the severity of skin disease over a patient’s body.

Part A

In part A of the study, 6 patients received MRG-106 via intralesional injection. A 75 mg dose of the drug was found to be well-tolerated, producing generally minor injection site reactions.

In addition, intralesional injection of MRG-106 produced improvements in CAILS score. The Composite Assessment of Index Lesion Severity (CAILS) score is obtained by adding the severity score of erythema, scaling, plaque elevation, and surface area for up to 5 index lesions.

Part B

In part B, 30 patients received MRG-106 via subcutaneous (SQ) injection, intravenous (IV) infusion, or IV bolus injection.

Patients who received SQ injection or IV infusion received doses of 300 mg, 600 mg, or 900 mg. Those who received an IV bolus only received the 300 mg dose.

Twenty-nine of the 30 patients in part B were evaluable for efficacy. Twenty-six of these patients—90%—had an improvement in mSWAT score from baseline.

“Twenty-six patients had at least stable disease to partial response,” Dr Querfeld noted. “No complete responses yet, but we’re close.”

Twelve patients were still receiving MRG-106 at last follow-up.

Ten of the 17 patients (59%) who had received MRG-106 for more than 1 month had at least a 50% improvement in mSWAT score, or a partial response. Once this was achieved, responses were durable.

One patient was still in response at roughly 470 days of follow-up.

Concomitant therapies

Dr Querfeld and her colleagues looked at patient outcomes in the context of concomitant therapies as well. They analyzed data from 26 patients who had received at least 6 doses of MRG-106.

Half of these patients were receiving MRG-106 alone, and the other half were receiving concomitant therapies, including bexarotene (n=7), interferon-alfa (n=2), methotrexate (n=1), vorinostat (n=1), and “other” treatments (n=2). Patients had been receiving these therapies for anywhere from 4 months to 45 months.

Outcomes were similar in the monotherapy and combination treatment groups. Seven patients in each group had at least a 50% improvement in mSWAT score.

Dosing and administration

“It appears the infusion is superior to the subcutaneous administration,” Dr Querfeld said.

She noted that durable partial responses have been achieved at all dose levels, but the 300 mg and 600 mg IV infusions had the best efficacy and tolerability profiles.

With the 300 mg IV bolus, fewer patients remained on treatment for more than 1 cycle, as compared to the other dosing cohorts. Dr Querfeld said this may be a result of lower total exposure or tolerability due to higher plasma C_max.

She also noted that patients who received MRG-106 SQ at 600 mg or higher had a higher incidence of injection site reactions.

Safety

AEs of any grade that were attributed to MRG-106 include neutropenia (16%), injection site pain (16%), fatigue (14%), nausea (5%), pruritus (5%), and headache (5%).

Grade 3/4 AEs attributed to MRG-106 were neutropenia (5%) and pruritus (5%).

There were no serious AEs attributed to MRG-106, but there were 2 dose-limiting toxicities. One was a grade 3 tumor flare in a patient receiving the 300 mg IV bolus.

The other dose-limiting toxicity was grade 3 worsening pruritus and possible tumor flare, which occurred twice in 1 patient—with the 900 mg SQ dose and with the 300 mg IV infusion.

The 300 mg IV infusion is the anticipated phase 2 dose.

Photo by Larry Young

LA JOLLA, CA—The EZH1/2 inhibitor DS-3201b could be a novel therapeutic option for non-Hodgkin lymphoma (NHL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

DS-3201b was considered well tolerated in a phase 1 study of Japanese patients with relapsed/refractory NHL.

In addition, DS-3201b demonstrated activity against B- and T-cell lymphomas, producing an overall response rate of 59%.

Kunihiro Tsukasaki, MD, PhD, of Saitama Medical University in Moroyama, Saitama, Japan, presented these results at the meeting.

The trial was sponsored by Daiichi Sankyo Co., Ltd.

Dr Tsukasaki presented data on 18 patients with relapsed/refractory NHL.

The 12 B-cell lymphoma patients had follicular lymphoma (n=5), diffuse large B-cell lymphoma (n=3), MALT lymphoma (n=2), nodal marginal zone lymphoma (n=1), and lymphoplasmacytic lymphoma (n=1).

The 6 patients with T-cell lymphoma had peripheral T-cell lymphoma not otherwise specified (n=2), angioimmunoblastic T-cell lymphoma (n=2), and adult T-cell leukemia/lymphoma (n=2).

The patients’ median age was 67 (range, 44-75), and 10 were female. All patients had an ECOG performance status of 0 (72%) or 1 (28%).

Patients had a median of 2 prior chemotherapy regimens (range, 1-8).

For this study, they received DS-3201b at 150 mg (n=7), 200 mg (n=9), or 300 mg (n=2). They received the drug once daily in 28-day cycles until they progressed or experienced unacceptable toxicity.

DLTs and AEs

Dose-limiting toxicities (DLTs) were evaluated in cycle 1. All 18 patients were evaluable for DLT assessment.

There were 4 treatment-emergent adverse events (AEs) that met the definition of DLTs:

• 3 cases of grade 4 platelet count decrease (n=1 at 200 mg, n=2 at 300 mg)
• 1 case of grade 3 anemia requiring blood transfusion (at 300 mg).

All 4 DLTs led to treatment interruption.

There were 5 serious AEs reported in 3 patients. Only one of these—pneumocystis jiroveci pneumonia—was considered related to DS-3201b.

Hematologic AEs included decreases in platelets (grade 1-4), lymphocytes (grade 1-4), neutrophils (grade 2-4), and white blood cells (grade 2-3), as well as anemia (grade 1-3).

Other AEs (all grade 1/2) included dysgeusia, alopecia, diarrhea, decreased appetite, alanine aminotransferase increase, aspartate aminotransferase increase, nasopharyngitis, rash, and dry skin.

No deaths had been reported as of the data cutoff last November.

Responses

Seventeen patients were evaluable for response.

The overall response rate was 59%, with 1 patient achieving a complete response (CR) and 9 achieving a partial response (PR). Four patients had stable disease (SD), and 3 progressed.

Among the T-cell lymphoma patients, 1 had a CR, 4 had PRs, and 1 progressed. The complete responder had angioimmunoblastic T-cell lymphoma, and the patient who progressed had adult T-cell leukemia/lymphoma.

Among the B-cell lymphoma patients, 5 had PRs, 4 had SD, and 2 progressed.

Dr Tsukasaki said DS-3201b has demonstrated early clinical activity and therefore has the potential to be a novel therapeutic option for B-cell and T-cell lymphomas. However, further evaluation is warranted to determine the optimal dosing regimen and target diseases.

Photo by Larry Young

LA JOLLA, CA—The EZH1/2 inhibitor DS-3201b could be a novel therapeutic option for non-Hodgkin lymphoma (NHL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

DS-3201b was considered well tolerated in a phase 1 study of Japanese patients with relapsed/refractory NHL.

In addition, DS-3201b demonstrated activity against B- and T-cell lymphomas, producing an overall response rate of 59%.

Kunihiro Tsukasaki, MD, PhD, of Saitama Medical University in Moroyama, Saitama, Japan, presented these results at the meeting.

The trial was sponsored by Daiichi Sankyo Co., Ltd.

Dr Tsukasaki presented data on 18 patients with relapsed/refractory NHL.

The 12 B-cell lymphoma patients had follicular lymphoma (n=5), diffuse large B-cell lymphoma (n=3), MALT lymphoma (n=2), nodal marginal zone lymphoma (n=1), and lymphoplasmacytic lymphoma (n=1).

The 6 patients with T-cell lymphoma had peripheral T-cell lymphoma not otherwise specified (n=2), angioimmunoblastic T-cell lymphoma (n=2), and adult T-cell leukemia/lymphoma (n=2).

The patients’ median age was 67 (range, 44-75), and 10 were female. All patients had an ECOG performance status of 0 (72%) or 1 (28%).

Patients had a median of 2 prior chemotherapy regimens (range, 1-8).

For this study, they received DS-3201b at 150 mg (n=7), 200 mg (n=9), or 300 mg (n=2). They received the drug once daily in 28-day cycles until they progressed or experienced unacceptable toxicity.

DLTs and AEs

Dose-limiting toxicities (DLTs) were evaluated in cycle 1. All 18 patients were evaluable for DLT assessment.

There were 4 treatment-emergent adverse events (AEs) that met the definition of DLTs:

• 3 cases of grade 4 platelet count decrease (n=1 at 200 mg, n=2 at 300 mg)
• 1 case of grade 3 anemia requiring blood transfusion (at 300 mg).

All 4 DLTs led to treatment interruption.

There were 5 serious AEs reported in 3 patients. Only one of these—pneumocystis jiroveci pneumonia—was considered related to DS-3201b.

Hematologic AEs included decreases in platelets (grade 1-4), lymphocytes (grade 1-4), neutrophils (grade 2-4), and white blood cells (grade 2-3), as well as anemia (grade 1-3).

Other AEs (all grade 1/2) included dysgeusia, alopecia, diarrhea, decreased appetite, alanine aminotransferase increase, aspartate aminotransferase increase, nasopharyngitis, rash, and dry skin.

No deaths had been reported as of the data cutoff last November.

Responses

Seventeen patients were evaluable for response.

The overall response rate was 59%, with 1 patient achieving a complete response (CR) and 9 achieving a partial response (PR). Four patients had stable disease (SD), and 3 progressed.

Among the T-cell lymphoma patients, 1 had a CR, 4 had PRs, and 1 progressed. The complete responder had angioimmunoblastic T-cell lymphoma, and the patient who progressed had adult T-cell leukemia/lymphoma.

Among the B-cell lymphoma patients, 5 had PRs, 4 had SD, and 2 progressed.

Dr Tsukasaki said DS-3201b has demonstrated early clinical activity and therefore has the potential to be a novel therapeutic option for B-cell and T-cell lymphomas. However, further evaluation is warranted to determine the optimal dosing regimen and target diseases.

Photo by Larry Young

LA JOLLA, CA—The EZH1/2 inhibitor DS-3201b could be a novel therapeutic option for non-Hodgkin lymphoma (NHL), according to a speaker at the 10th Annual T-cell Lymphoma Forum.

DS-3201b was considered well tolerated in a phase 1 study of Japanese patients with relapsed/refractory NHL.

In addition, DS-3201b demonstrated activity against B- and T-cell lymphomas, producing an overall response rate of 59%.

Kunihiro Tsukasaki, MD, PhD, of Saitama Medical University in Moroyama, Saitama, Japan, presented these results at the meeting.

The trial was sponsored by Daiichi Sankyo Co., Ltd.

Dr Tsukasaki presented data on 18 patients with relapsed/refractory NHL.

The 12 B-cell lymphoma patients had follicular lymphoma (n=5), diffuse large B-cell lymphoma (n=3), MALT lymphoma (n=2), nodal marginal zone lymphoma (n=1), and lymphoplasmacytic lymphoma (n=1).

The 6 patients with T-cell lymphoma had peripheral T-cell lymphoma not otherwise specified (n=2), angioimmunoblastic T-cell lymphoma (n=2), and adult T-cell leukemia/lymphoma (n=2).

The patients’ median age was 67 (range, 44-75), and 10 were female. All patients had an ECOG performance status of 0 (72%) or 1 (28%).

Patients had a median of 2 prior chemotherapy regimens (range, 1-8).

For this study, they received DS-3201b at 150 mg (n=7), 200 mg (n=9), or 300 mg (n=2). They received the drug once daily in 28-day cycles until they progressed or experienced unacceptable toxicity.

DLTs and AEs

Dose-limiting toxicities (DLTs) were evaluated in cycle 1. All 18 patients were evaluable for DLT assessment.

There were 4 treatment-emergent adverse events (AEs) that met the definition of DLTs:

• 3 cases of grade 4 platelet count decrease (n=1 at 200 mg, n=2 at 300 mg)
• 1 case of grade 3 anemia requiring blood transfusion (at 300 mg).

All 4 DLTs led to treatment interruption.

There were 5 serious AEs reported in 3 patients. Only one of these—pneumocystis jiroveci pneumonia—was considered related to DS-3201b.

Hematologic AEs included decreases in platelets (grade 1-4), lymphocytes (grade 1-4), neutrophils (grade 2-4), and white blood cells (grade 2-3), as well as anemia (grade 1-3).

Other AEs (all grade 1/2) included dysgeusia, alopecia, diarrhea, decreased appetite, alanine aminotransferase increase, aspartate aminotransferase increase, nasopharyngitis, rash, and dry skin.

No deaths had been reported as of the data cutoff last November.

Responses

Seventeen patients were evaluable for response.

The overall response rate was 59%, with 1 patient achieving a complete response (CR) and 9 achieving a partial response (PR). Four patients had stable disease (SD), and 3 progressed.

Among the T-cell lymphoma patients, 1 had a CR, 4 had PRs, and 1 progressed. The complete responder had angioimmunoblastic T-cell lymphoma, and the patient who progressed had adult T-cell leukemia/lymphoma.

Among the B-cell lymphoma patients, 5 had PRs, 4 had SD, and 2 progressed.

Dr Tsukasaki said DS-3201b has demonstrated early clinical activity and therefore has the potential to be a novel therapeutic option for B-cell and T-cell lymphomas. However, further evaluation is warranted to determine the optimal dosing regimen and target diseases.