Non-Hodgkin Lymphoma

Photo by Steve Fisch

Experiments in mice have shown that injecting immune-stimulating agents directly into a tumor can help the immune system eradicate tumors in other areas of the body.

The approach worked for several cancers, including lymphomas.

The researchers believe the local application of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse effects often seen with more widespread immune stimulation.

“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself,” said Ronald Levy, MD, of Stanford University Medical Center in California.

“In the mice, we saw amazing, body-wide effects, including the elimination of tumors all over the animal. This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

Dr Levy and his colleagues described this approach in Science Translational Medicine.

The method involves reactivating cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site.

One of the agents is an unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand. It works with nearby immune cells to amplify the expression of OX40 on the surface of T cells.

The other agent is an antibody that binds to OX40. It activates the T cells to lead the charge against the cancer cells.

Because the agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The researchers found this approach worked well in mice with A20 B-cell lymphoma tumors transplanted in two sites on their bodies.

Injecting one tumor site with the agents caused regression of the untreated tumor as well as the treated one. In this way, 87 of 90 mice were cured.

Although lymphoma recurred in 3 of the mice, the tumors again regressed after a second treatment with CpG and anti-OX40.

The researchers saw similar results in mice with melanoma as well as breast and colon cancer.

Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, the team explored the specificity of the T cells by transplanting two types of tumors into mice.

They transplanted A20 lymphoma cells in two locations and a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the colon cancer cells.

“This is a very targeted approach,” Dr Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

Dr Levy and his colleagues have launched a clinical trial (NCT03410901) to test this treatment approach. The researchers hope to determine the adverse effects and optimal dose of the TLR9 agonist SD-101, the anti-OX40 antibody BMS 986178, and radiation therapy in patients with low-grade B-cell non-Hodgkin lymphomas.

If the trial is successful, Dr Levy believes the treatment could be useful for many tumor types.

“I don’t think there’s a limit to the type of tumor we could potentially treat,” he said, “as long as it has been infiltrated by the immune system.”

Photo by Steve Fisch

Experiments in mice have shown that injecting immune-stimulating agents directly into a tumor can help the immune system eradicate tumors in other areas of the body.

The approach worked for several cancers, including lymphomas.

The researchers believe the local application of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse effects often seen with more widespread immune stimulation.

“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself,” said Ronald Levy, MD, of Stanford University Medical Center in California.

“In the mice, we saw amazing, body-wide effects, including the elimination of tumors all over the animal. This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

Dr Levy and his colleagues described this approach in Science Translational Medicine.

The method involves reactivating cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site.

One of the agents is an unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand. It works with nearby immune cells to amplify the expression of OX40 on the surface of T cells.

The other agent is an antibody that binds to OX40. It activates the T cells to lead the charge against the cancer cells.

Because the agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The researchers found this approach worked well in mice with A20 B-cell lymphoma tumors transplanted in two sites on their bodies.

Injecting one tumor site with the agents caused regression of the untreated tumor as well as the treated one. In this way, 87 of 90 mice were cured.

Although lymphoma recurred in 3 of the mice, the tumors again regressed after a second treatment with CpG and anti-OX40.

The researchers saw similar results in mice with melanoma as well as breast and colon cancer.

Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, the team explored the specificity of the T cells by transplanting two types of tumors into mice.

They transplanted A20 lymphoma cells in two locations and a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the colon cancer cells.

“This is a very targeted approach,” Dr Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

Dr Levy and his colleagues have launched a clinical trial (NCT03410901) to test this treatment approach. The researchers hope to determine the adverse effects and optimal dose of the TLR9 agonist SD-101, the anti-OX40 antibody BMS 986178, and radiation therapy in patients with low-grade B-cell non-Hodgkin lymphomas.

If the trial is successful, Dr Levy believes the treatment could be useful for many tumor types.

“I don’t think there’s a limit to the type of tumor we could potentially treat,” he said, “as long as it has been infiltrated by the immune system.”

Photo by Steve Fisch

Experiments in mice have shown that injecting immune-stimulating agents directly into a tumor can help the immune system eradicate tumors in other areas of the body.

The approach worked for several cancers, including lymphomas.

The researchers believe the local application of the agents could serve as a rapid and relatively inexpensive cancer therapy that is unlikely to cause the adverse effects often seen with more widespread immune stimulation.

“Our approach uses a one-time application of very small amounts of two agents to stimulate the immune cells only within the tumor itself,” said Ronald Levy, MD, of Stanford University Medical Center in California.

“In the mice, we saw amazing, body-wide effects, including the elimination of tumors all over the animal. This approach bypasses the need to identify tumor-specific immune targets and doesn’t require wholesale activation of the immune system or customization of a patient’s immune cells.”

Dr Levy and his colleagues described this approach in Science Translational Medicine.

The method involves reactivating cancer-specific T cells by injecting microgram amounts of two agents directly into the tumor site.

One of the agents is an unmethylated CG–enriched oligodeoxynucleotide (CpG)—a Toll-like receptor 9 (TLR9) ligand. It works with nearby immune cells to amplify the expression of OX40 on the surface of T cells.

The other agent is an antibody that binds to OX40. It activates the T cells to lead the charge against the cancer cells.

Because the agents are injected directly into the tumor, only T cells that have infiltrated it are activated. In effect, these T cells are “prescreened” by the body to recognize only cancer-specific proteins.

Some of these tumor-specific, activated T cells then leave the original tumor to find and destroy other identical tumors throughout the body.

The researchers found this approach worked well in mice with A20 B-cell lymphoma tumors transplanted in two sites on their bodies.

Injecting one tumor site with the agents caused regression of the untreated tumor as well as the treated one. In this way, 87 of 90 mice were cured.

Although lymphoma recurred in 3 of the mice, the tumors again regressed after a second treatment with CpG and anti-OX40.

The researchers saw similar results in mice with melanoma as well as breast and colon cancer.

Mice genetically engineered to spontaneously develop breast cancers in all 10 of their mammary pads also responded to the treatment. Treating the first tumor that arose often prevented the occurrence of future tumors and significantly increased the animals’ life span, the researchers found.

Finally, the team explored the specificity of the T cells by transplanting two types of tumors into mice.

They transplanted A20 lymphoma cells in two locations and a colon cancer cell line in a third location. Treatment of one of the lymphoma sites caused the regression of both lymphoma tumors but did not affect the colon cancer cells.

“This is a very targeted approach,” Dr Levy said. “Only the tumor that shares the protein targets displayed by the treated site is affected. We’re attacking specific targets without having to identify exactly what proteins the T cells are recognizing.”

Dr Levy and his colleagues have launched a clinical trial (NCT03410901) to test this treatment approach. The researchers hope to determine the adverse effects and optimal dose of the TLR9 agonist SD-101, the anti-OX40 antibody BMS 986178, and radiation therapy in patients with low-grade B-cell non-Hodgkin lymphomas.

If the trial is successful, Dr Levy believes the treatment could be useful for many tumor types.

“I don’t think there’s a limit to the type of tumor we could potentially treat,” he said, “as long as it has been infiltrated by the immune system.”

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

Photo by Aaron Logan

Existing drugs could be combined to treat double-hit lymphoma (DHL), according to preclinical research published in Science Translational Medicine.

The drugs are tigecycline, an antibiotic, and venetoclax, a BCL2 inhibitor.

Researchers observed promising activity with these drugs in combination, both in cell lines and mouse models of DHL.

The team therefore believes the drugs could be repurposed to treat DHL, which currently has a dismal prognosis.

Study author Micol Ravà, PhD, of the European Institute of Oncology in Milan, Italy, and her colleagues noted that DHL is driven by the abnormal activation of MYC and BCL2. However, selective BCL2 inhibitors like venetoclax have failed to halt disease progression in DHL patients.

Seeking a way to sensitize DHL to BCL2 inhibitors, the researchers turned to tigecycline, which interferes with mitochondria to trigger a MYC-dependent cell death pathway.

The team found that tigecycline and venetoclax demonstrated synergy in 5 DHL cell lines. The drugs were synergistic in 3 cell lines—Karpas-422, SU-DHL-6, and DOHH-2—in which neither drug alone showed significant pro-apoptotic activity.

In 2 other cell lines—SU-DHL-4 and OCI-LY8—venetoclax was active when given alone, but its activity was enhanced by the addition of tigecycline.

In mouse models of DHL (using the human cell lines SU-DHL-6, DOHH-2, and OCI-LY8), each of the drugs alone were able to slow tumor progression somewhat.

However, combination tigecycline and venetoclax exhibited “strong antitumoral activity,” according to the researchers. In fact, the combination caused full disease regression in all 8 SU-DHL-6 mice and 3 of 9 OCI-LY8 mice.

Dr Ravà and her colleagues also found the combination produced “rapid and marked tumor regression” in mice with a patient-derived xenograft.

The researchers observed no toxicity when tigecycline and venetoclax were given at low doses. However, mice receiving more aggressive treatment had some inflammation in the liver and spleen. And some mice treated with high doses of tigecycline and venetoclax died within 1 week of treatment initiation.

Finally, Dr Ravà and her colleagues found that tigecycline and venetoclax each synergized with rituximab. The team therefore concluded that tigecycline and venetoclax “have the potential to reinforce rituximab-containing therapies in the clinic.”

of Western Australia

Researchers say they have developed a new technique for assessing chromosomal abnormalities in chronic lymphocytic leukemia (CLL).

The team believes their method, called immuno-flowFISH, could be used at the time of CLL diagnosis for disease stratification and after treatment to assess residual disease.

Kathryn A. Fuller, PhD, of The University of Western Australia in Crawley, Australia, and her colleagues described immuno-flowFISH in the journal Methods.

The name “immuno-flowFISH” acknowledges what has been incorporated into this technology.

“Immuno” recognizes that immunology testing is used to identify the CLL cells. “Flow” is used because the machine is an imaging flow cytometer. And “FISH” is the test that identifies the chromosomes inside the cells.

The researchers said they found that immuno-flowFISH could detect trisomic chromosomal abnormalities in cells with the phenotype of CLL.

And immuno-flowFISH provided greater specificity and sensitivity than standard FISH.

In particular, the researchers were able to analyze 10,000 to 20,000 cells in each sample, which is 100 to 200 times greater than traditional FISH methods.

“The imaging cytometer can analyze samples at a rate of up to 2000 cells per second, which means we can investigate a large number of cells in a relatively short amount of time, giving us greater sensitivity,” Dr Fuller said.

“This immuno-flowFISH method is an exciting development in personalizing pathology testing for leukemia,” added study author Wendy N. Erber, MD, DPhil, PhD, of The University of Western Australia.

Dr Erber and her colleagues are now expanding immuno-flowFISH so it can be applied to other malignancies as well.

of Western Australia

Researchers say they have developed a new technique for assessing chromosomal abnormalities in chronic lymphocytic leukemia (CLL).

The team believes their method, called immuno-flowFISH, could be used at the time of CLL diagnosis for disease stratification and after treatment to assess residual disease.

Kathryn A. Fuller, PhD, of The University of Western Australia in Crawley, Australia, and her colleagues described immuno-flowFISH in the journal Methods.

The name “immuno-flowFISH” acknowledges what has been incorporated into this technology.

“Immuno” recognizes that immunology testing is used to identify the CLL cells. “Flow” is used because the machine is an imaging flow cytometer. And “FISH” is the test that identifies the chromosomes inside the cells.

The researchers said they found that immuno-flowFISH could detect trisomic chromosomal abnormalities in cells with the phenotype of CLL.

And immuno-flowFISH provided greater specificity and sensitivity than standard FISH.

In particular, the researchers were able to analyze 10,000 to 20,000 cells in each sample, which is 100 to 200 times greater than traditional FISH methods.

“The imaging cytometer can analyze samples at a rate of up to 2000 cells per second, which means we can investigate a large number of cells in a relatively short amount of time, giving us greater sensitivity,” Dr Fuller said.

“This immuno-flowFISH method is an exciting development in personalizing pathology testing for leukemia,” added study author Wendy N. Erber, MD, DPhil, PhD, of The University of Western Australia.

Dr Erber and her colleagues are now expanding immuno-flowFISH so it can be applied to other malignancies as well.

of Western Australia

Researchers say they have developed a new technique for assessing chromosomal abnormalities in chronic lymphocytic leukemia (CLL).

The team believes their method, called immuno-flowFISH, could be used at the time of CLL diagnosis for disease stratification and after treatment to assess residual disease.

Kathryn A. Fuller, PhD, of The University of Western Australia in Crawley, Australia, and her colleagues described immuno-flowFISH in the journal Methods.

The name “immuno-flowFISH” acknowledges what has been incorporated into this technology.

“Immuno” recognizes that immunology testing is used to identify the CLL cells. “Flow” is used because the machine is an imaging flow cytometer. And “FISH” is the test that identifies the chromosomes inside the cells.

The researchers said they found that immuno-flowFISH could detect trisomic chromosomal abnormalities in cells with the phenotype of CLL.

And immuno-flowFISH provided greater specificity and sensitivity than standard FISH.

In particular, the researchers were able to analyze 10,000 to 20,000 cells in each sample, which is 100 to 200 times greater than traditional FISH methods.

“The imaging cytometer can analyze samples at a rate of up to 2000 cells per second, which means we can investigate a large number of cells in a relatively short amount of time, giving us greater sensitivity,” Dr Fuller said.

“This immuno-flowFISH method is an exciting development in personalizing pathology testing for leukemia,” added study author Wendy N. Erber, MD, DPhil, PhD, of The University of Western Australia.

Dr Erber and her colleagues are now expanding immuno-flowFISH so it can be applied to other malignancies as well.

Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Malignant plasma cells

A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.

The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.

Patients with MGUS also had a significantly shorter median survival than controls.

Researchers reported these findings in NEJM.

“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”

With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.

The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.

During that time, 147 patients progressed to another disorder, including:

• 97 to multiple myeloma
• 19 to non-Hodgkin lymphoma
• 14 to AL amyloidosis
• 13 to Waldenstrom’s macroglobulinemia
• 3 to chronic lymphocytic leukemia
• 1 to plasmacytoma.

The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.

The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.

“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.

The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).

Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.

Malignant plasma cells

A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.

The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.

Patients with MGUS also had a significantly shorter median survival than controls.

Researchers reported these findings in NEJM.

“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”

With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.

The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.

During that time, 147 patients progressed to another disorder, including:

• 97 to multiple myeloma
• 19 to non-Hodgkin lymphoma
• 14 to AL amyloidosis
• 13 to Waldenstrom’s macroglobulinemia
• 3 to chronic lymphocytic leukemia
• 1 to plasmacytoma.

The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.

The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.

“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.

The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).

Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.

Malignant plasma cells

A long-term study showed that patients with monoclonal gammopathy of undetermined significance (MGUS) were still at risk of progressing to other plasma-cell or lymphoid disorders after more than 30 years of follow-up.

The risk of developing such disorders was nearly 7 times higher in MGUS patients than in matched control subjects.

Patients with MGUS also had a significantly shorter median survival than controls.

Researchers reported these findings in NEJM.

“Monoclonal gammopathy of undetermined significance is present in more than 3% of the general population age 50 and older,” said study author S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minnesota.

“In some cases, people with monoclonal gammopathy of undetermined significance go on to develop multiple myeloma.”

With this in mind, Dr Rajkumar and his colleagues studied 1384 patients—210 with IgM MGUS and 1129 with non-IgM MGUS. Patients were diagnosed with MGUS from 1960 through 1994, and their median age at diagnosis was 72.

The median follow-up was 34.1 years (range, 0.0 to 43.6), so there were 14,130 person-years of follow-up.

During that time, 147 patients progressed to another disorder, including:

• 97 to multiple myeloma
• 19 to non-Hodgkin lymphoma
• 14 to AL amyloidosis
• 13 to Waldenstrom’s macroglobulinemia
• 3 to chronic lymphocytic leukemia
• 1 to plasmacytoma.

The rate of progression in MGUS patients—11%—represented a risk of these disorders that was 6.5 times higher than the risk observed in an age- and sex-matched control population.

The risk of progression also increased over time for MGUS patients. Without accounting for death due to competing causes, the risk of progression was 10% at 10 years, 18% at 20 years, 28% at 30 years, and 36% at both 35 and 40 years.

“We also found that patients with monoclonal gammopathy of undetermined significance had shorter survival than comparable people without the condition, which raises the possibility there may be other disorders associated with monoclonal gammopathy of undetermined significance that still need further study,” Dr Rajkumar said.

The median survival was 8.1 years in MGUS patients and 12.4 years in controls (P<0.001).

Overall, 1300 MGUS patients (94%) had died at last follow-up. Of the 84 patients who were still alive, 5 had progressed.

Photo from Novartis

The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).

Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.

If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.

Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.

Supporting data

The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.

Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.

Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.

About priority review, accelerated assessment

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

Photo from Novartis

The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).

Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.

If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.

Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.

Supporting data

The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.

Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.

Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.

About priority review, accelerated assessment

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

Photo from Novartis

The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel (Kymriah, formerly CTL019) is getting fast-tracked in the United States (US) and European Union (EU).

The US Food and Drug Administration (FDA) has accepted for priority review the supplemental biologics license application (sBLA) for tisagenlecleucel for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who are ineligible for, or relapse after, autologous hematopoietic stem cell transplant (auto-HSCT).

Meanwhile, the European Medicines Agency (EMA) has granted accelerated assessment to the marketing authorization application (MAA) for tisagenlecleucel for the treatment of children and young adults with R/R B-cell acute lymphoblastic leukemia (ALL) and for adults with R/R DLBCL who are ineligible for auto-HSCT.

If the sBLA and MAA are approved, tisagenlecleucel will be the first CAR T-cell therapy available for 2 distinct indications in non-Hodgkin lymphoma and B-cell ALL.

Tisagenlecleucel became the first CAR T-cell therapy to receive regulatory approval when it was approved by the FDA in August 2017 for use in patients up to 25 years of age who have B-cell precursor ALL that is refractory or in second or later relapse.

Supporting data

The regulatory applications for tisagenlecleucel in the US and EU are supported by data from the Novartis-sponsored global clinical trial program in children and young adults with R/R B-cell ALL and adults with R/R DLBCL.

Results from the phase 2 JULIET trial served as the basis of the sBLA and MAA for tisagenlecleucel in adults with R/R DLCBL. Data from this trial were presented at the 2017 ASH Annual Meeting in December.

Results from the phase 2 ELIANA study were submitted as part of the MAA for tisagenlecleucel in children and young adults with R/R B-cell ALL. Data from this trial were presented at the 2017 EHA Congress last June.

About priority review, accelerated assessment

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The FDA’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.

The EMA grants accelerated assessment when a product is expected to be of major public health interest, particularly from the point of view of therapeutic innovation.

Accelerated assessment shortens the review period from 210 days to 150 days.

Photo from Business Wire

Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.

This is the first intravenous alternative to Velcade available in the US.

Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.

The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.

For details, see the prescribing information for Bortezomib for Injection.

Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.

Photo from Business Wire

Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.

This is the first intravenous alternative to Velcade available in the US.

Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.

The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.

For details, see the prescribing information for Bortezomib for Injection.

Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.

Photo from Business Wire

Fresenius Kabi has introduced its generic version of Velcade, Bortezomib for Injection, to the US market.

This is the first intravenous alternative to Velcade available in the US.

Bortezomib for Injection is available as a single dose vial containing 3.5 mg of lyophilized powder.

The product is approved to treat patients with multiple myeloma and patients with mantle cell lymphoma who have received at least 1 prior therapy.

For details, see the prescribing information for Bortezomib for Injection.

Velcade is a registered trademark of Millennium Pharmaceuticals, Inc.

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Photo by Rhoda Baer

A new report has revealed differences in survival among adolescents and young adults (AYAs) with hematologic malignancies.

The report includes information on AYAs—ages 15 to 39—living in Los Angeles County who were diagnosed with common cancers between 1988 and 2014.

The data showed differences in 5-year survival rates according to sex, race, age, and socioeconomic status (SES).

For example, lymphoma survival rates were lower for males, African Americans (AAs), older AYAs, and patients with low socioeconomic status (SES).

For AYAs with leukemias, there was no survival difference according to sex, but AAs had worse survival than patients of other races. And the impact of age and SES varied according to leukemia type.

“Cancer survival data are poorly understood for 15- to 39-year-olds,” noted Amie Hwang, PhD, of the University of Southern California Keck School of Medicine in Los Angeles.

That is why she and her colleagues created the report, “Cancer in Los Angeles County: Survival Among Adolescents and Young Adults 1988-2014.”

According to the authors, this is the first report to break down cancer survival rates for AYAs into segments on race/ethnicity, sex, age group, SES, and cancer stage.

Survival data for patients with hematologic malignancies were as follows.

Acute lymphoblastic leukemia

There were 1137 cases of acute lymphoblastic leukemia in the AYA population in Los Angeles County during the period studied. This included 752 males and 385 females.

Five-year survival was similar between males (43%) and females (41%).

Younger AYAs had better survival than older AYAs (48% for ages 15-24, 35% for ages 25-34, and 32% for ages 35-39).

Survival was highest among non-Latino whites (NLWs, 56%), followed by Asian/Pacific Islanders (APIs, 52%), patients of other/unknown races (51%), Latino whites (LWs, 38%), and AAs (29%).

Survival declined with SES (55% for high, 42% for middle, and 36% for low SES).

Acute myeloid leukemia

There were 1195 cases of acute myeloid leukemia—641 males and 554 females.

Five-year survival was similar for males (40%) and females (43%) as well as for the different age groups (45% for ages 15-24 vs 40% for the older age groups).

Survival was highest among NLWs (44%), followed by LWs (43%), APIs (40%), other/unknown (33%), and AAs (25%).

Survival declined somewhat with SES (49% for high, 39% for middle, and 41% for low SES).

Chronic myeloid leukemia

There were 655 cases of chronic myeloid leukemia—408 males and 247 females.

Five-year survival was similar for males (70%) and females (71%), but it was slightly higher for older AYAs (69% for ages 15-24, 68% for ages 25-34, and 76% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (76%), followed by LWs (73%), NLWs/APIs (both 72%), and AAs (57%).

Survival declined somewhat with SES (76% for high, 67% for middle, and 68% for low SES).

Hodgkin lymphoma

There were 2993 AYAs diagnosed with Hodgkin lymphoma—1553 males and 1440 females.

The 5-year survival rate was higher in females (93%) than males (86%) and in younger AYAs (93% for ages 15-24, 89% for ages 25-34, and 85% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (96%), followed by APIs/NLWs (both 91%), LWs (88%), and AAs (83%).

Survival declined with SES (95% for high, 89% for middle, and 83% for low SES).

And survival was lower for patients with advanced-stage disease (93% localized, 94% regional, and 83% distant).

Non-Hodkgin lymphoma

There were 4485 AYAs diagnosed with non-Hodgkin lymphoma during the study period­—3064 males and 1421 females.

The 5-year survival rate was higher in females (75%) than males (46%) and in younger AYAs (69% for ages 15-24, 51% for ages 25-34, and 52% for ages 35-39).

Survival was highest among patients in the “other/unknown” race category (88%), followed by APIs (68%), LWs/NLWs (both 53%), and AAs (50%).

Survival declined with SES (68% for high, 54% for middle, and 45% for low SES).

And survival was lower for patients with advanced-stage disease (61% localized, 66% regional, and 46% distant).

“Adolescents and young adults go to the doctor less often because they have this superhero mentality, like they’re invincible,” said author Dennis Deapen, DrPH, of the University of Southern California Keck School of Medicine.

“Once they do go to a health professional, their cancer diagnosis can be delayed because cancer isn’t the first concern doctors have for this age group. It comes as no surprise that patients diagnosed with late-stage cancer have reduced survival rates.”

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.

Image by Joshua Stokes

Researchers have looked to deep-sea creatures with the goal of creating a better cytotoxicity assay.

The team harnessed the power of enzymes responsible for marine animal bioluminescence to create the “Matador assay,” which can be used to determine whether cellular and immune-therapeutic agents are actually killing target cells.

The researchers said the Matador assay is quick and simple as well as “highly sensitive,” with the ability to detect cytotoxicity induced by several types of therapies.

Preet M. Chaudhary, MD, PhD, of the University of Southern California Keck School of Medicine in Los Angeles, and his colleagues described the assay in Scientific Reports.

“One of the most promising areas in cancer research is immunotherapy. . .,” Dr Chaudhary said. “It is also one of the most difficult because the methods for testing immunotherapies are not ideal.”

“Radioactive chromium release assay is the gold standard for testing whether an immunotherapy kills cancer cells. This method is expensive, complicated, and requires special disposal practices. Other available methods also suffer from limitations and don’t allow scientists to rapidly screen immunotherapeutic agents to find the best candidates.”

Dr Chaudhary and his colleagues set out to develop a simple, precise, and inexpensive cytotoxicity assay based on marine animal luciferases, the enzymes responsible for bioluminescence.

The team used a group of small crustaceans and deep-sea shrimp, which were selected for their bright bioluminescence. Their luciferases became the basis of the Matador assay.

Engineered to get trapped inside cells, the luciferases leak out of cells when they die, causing a visible glow. The level of luminescence can then be measured with a luminometer.

To test the Matador assay’s effectiveness at measuring cell death, the researchers used several types of cancer cells, including chronic myelogenous leukemia, acute myelogenous leukemia, Burkitt lymphoma, and solid tumor cells.

The team treated these cells with a variety of therapies, including chimeric antigen receptor (CAR) T cells, bispecific T-cell engagers, monoclonal antibodies, and natural killer cells.

Results showed the Matador assay could detect the death of a single cell, a level of sensitivity superior to that of existing cytotoxicity assays.

The researchers also pointed out that the Matador assay is fast, inexpensive, and can be performed in a 384-well plate format, saving time and reagents.

“In our hands, the Matador assay can detect cell death in as little as 30 minutes, which can ultimately translate to more expedient treatments for patients getting cellular immunotherapies such as CAR T cells,” Dr Chaudhary said.

In fact, Dr Chaudhary’s lab has developed more than 75 cancer cell lines expressing the marine luciferases and used them with the Matador assay to develop next-generation CAR T cells.

Dr Chaudhary believes the Matador assay has many potential applications in biomedical research and cellular therapy manufacturing.

“It could potentially play a role in screening other types of anticancer agents or even measuring environmental toxins,” he said.