Non-Hodgkin Lymphoma

follicular lymphoma

The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).

The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.

This is the third EC approval for obinutuzumab.

The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.

The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.

The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

follicular lymphoma

The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).

The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.

This is the third EC approval for obinutuzumab.

The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.

The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.

The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

follicular lymphoma

The European Commission (EC) has expanded the marketing authorization for obinutuzumab (Gazyvaro).

The drug is now approved for use in combination with chemotherapy to treat patients with previously untreated, advanced follicular lymphoma (FL). Patients who respond to this treatment can then receive obinutuzumab maintenance.

This is the third EC approval for obinutuzumab.

The drug was first approved by the EC in 2014 to be used in combination with chlorambucil to treat patients with previously untreated chronic lymphocytic leukemia and comorbidities that make them unsuitable for full-dose fludarabine-based therapy.

In 2016, the EC approved obinutuzumab in combination with bendamustine, followed by obinutuzumab maintenance, in FL patients who did not respond to, or who progressed during or up to 6 months after, treatment with rituximab or a rituximab-containing regimen.

The EC’s latest approval of obinutuzumab is based on results of the phase 3 GALLIUM trial, which were presented at the 2016 ASH Annual Meeting.

The study enrolled 1401 patients with previously untreated, indolent non-Hodgkin lymphoma, including 1202 with FL.

Half of the FL patients (n=601) were randomized to receive obinutuzumab plus chemotherapy (followed by obinutuzumab maintenance for up to 2 years), and half were randomized to rituximab plus chemotherapy (followed by rituximab maintenance for up to 2 years).

The different chemotherapies used were CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone), CVP (cyclophosphamide, vincristine, and prednisolone), and bendamustine.

Patients who received obinutuzumab had significantly better progression-free survival than patients who received rituximab. The 3-year progression-free survival rate was 73.3% in the rituximab arm and 80% in the obinutuzumab arm (hazard ratio [HR]=0.66, P=0.0012).

There was no significant difference between the treatment arms with regard to overall survival. The 3-year overall survival was 92.1% in the rituximab arm and 94% in the obinutuzumab arm (HR=0.75, P=0.21).

The overall incidence of adverse events (AEs) was 98.3% in the rituximab arm and 99.5% in the obinutuzumab arm. The incidence of serious AEs was 39.9% and 46.1%, respectively.

The incidence of grade 3 or higher AEs was higher among patients who received obinutuzumab.

Grade 3 or higher AEs occurring in at least 5% of patients in either arm (rituximab and obinutuzumab, respectively) included neutropenia (67.8% and 74.6%), leukopenia (37.9% and 43.9%), febrile neutropenia (4.9% and 6.9%), infections and infestations (3.7% and 6.7%), and thrombocytopenia (2.7% and 6.1%).

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Anderson Cancer Center

Researchers say they have created guidelines for managing the unique toxicities associated with chimeric antigen receptor (CAR) T-cell therapy.

The guidelines focus on cytokine release syndrome (CRS); neurological toxicity, which the researchers have dubbed “CAR-T-cell-related encephalopathy syndrome (CRES);” and adverse effects related to these syndromes.

“The toxicities are unique, and every member of the care team needs to be trained to recognize them and act accordingly,” said Sattva Neelapu, MD, of University of Texas MD Anderson Cancer Center in Houston.

Dr Neelapu and his colleagues described the toxicities and related recommendations in Nature Reviews Clinical Oncology.

The team’s guidelines include supportive-care considerations for patients receiving CAR T‑cell therapy. For example, they recommend:

• Baseline brain MRI to rule out central nervous system disease
• Cardiac monitoring starting on the day of CAR T‑cell infusion
• Assessing a patient’s vital signs every 4 hours after CAR T-cell infusion
• Assessing and grading CRS at least twice daily and whenever the patient’s status changes
• Assessing and grading CRES at least every 8 hours.

CRS

One section of the guidelines is dedicated to CRS, with subsections on pathophysiology, precautions and supportive care, the use of corticosteroids and IL‑6/IL‑6R antagonists, and grading CRS.

The researchers noted that CRS typically manifests with constitutional symptoms, such as fever, malaise, anorexia, and myalgias. However, CRS can affect any organ system in the body.

The team recommends managing CRS according to grade. For example, patients with grade 1 CRS should typically receive supportive care. However, physicians should consider giving tocilizumab or siltuximab to grade 1 patients who have a refractory fever lasting more than 3 days.

The researchers also noted that CRS can evolve into fulminant hemophagocytic lymphohistiocytosis (HLH), also known as macrophage-activation syndrome (MAS).

The team said HLH/MAS encompasses a group of severe immunological disorders characterized by hyperactivation of macrophages and lymphocytes, proinflammatory cytokine production, lymphohistiocytic tissue infiltration, and immune-mediated multi-organ failure.

The guidelines include diagnostic criteria for CAR T‑cell-related HLH/MAS and recommendations for managing the condition.

CRES

One section of the guidelines is dedicated to the grading and treatment of CRES, which typically mani­fests as a toxic encephalopathy.

The researchers said the earliest signs of CRES are diminished attention, language disturbance, and impaired handwriting. Other symptoms include confusion, disorientation, agitation, apha­sia, somnolence, and tremors.

Patients with severe CRES (grade >2) may experience seizures, motor weakness, incontinence, mental obtundation, increased intracra­nial pressure, papilledema, and cerebral edema.

Therefore, the guidelines include recommendations for the management of status epilepticus and raised intracranial pressure after CAR T‑cell therapy.

The researchers also devised an algorithm, known as CARTOX-10, for identifying neurotoxicity. (An existing general method didn’t effectively quantify the neurological effects caused by CAR T-cell therapies.)

CARTOX-10 is a 10-point test in which patients are asked to do the following:

• Name the current month (1 point) and year (1 point)
• Name the city (1 point) and hospital they are in (1 point)
• Name the president/prime minister of their home country (1 point)
• Name 3 nearby objects (3 points)
• Write a standard sentence (1 point)
• Count backward from 100 by tens (1 point).

A perfect score indicates normal cognitive function. A patient has mild to severe impairment depending on the number of questions or activities missed.

Dr Neelapu and his colleagues believe their recommendations will be applicable to other types of cell-based immunotherapy as well, including CAR natural killer cells, T-cell receptor engineered T cells, and combination drugs that use an antibody to connect T cells to targets on cancer cells.

Researchers involved in this work have received funding from companies developing/marketing CAR T-cell therapies.

Photo from Genentech

Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).

One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.

The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).

The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.

The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.

The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).

The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.

However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.

Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.

In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.

According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.

Photo from Genentech

Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).

One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.

The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).

The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.

The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.

The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).

The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.

However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.

Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.

In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.

According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.

Photo from Genentech

Roche has announced a partial clinical hold on 2 trials of the anti-PD-L1 antibody atezolizumab (Tecentriq).

One is a phase 1b/2 study (NCT02631577) in which researchers are evaluating atezolizumab in combination with obinutuzumab plus lenalidomide in patients with relapsed or refractory follicular lymphoma.

The other is a phase 1b study (NCT02431208) of atezolizumab alone or in combination with an immunomodulatory drug and/or daratumumab in patients with multiple myeloma (MM).

The partial clinical hold on these trials means patients who are currently enrolled and are deriving clinical benefit may continue to receive treatment, but no additional patients will be enrolled.

The decision to place these trials on hold is related to risks identified in 2 trials of the anti-PD-1 agent pembrolizumab. Results from these trials showed that combining pembrolizumab with dexamethasone and an immunomodulatory agent (lenalidomide or pomalidomide) increases the risk of death in patients with MM.

The results led to clinical holds on these trials (and a third trial of pembrolizumab) as well as an investigation by the US Food and Drug Administration (FDA).

The FDA has stressed its belief that the benefits of taking pembrolizumab and other PD-1/PD-L1 inhibitors for their approved uses continue to outweigh the risks.

However, the agency also thinks there may be an unfavorable risk-benefit ratio for patients receiving PD-1/PD-L1 treatment alone or in other combinations in unapproved indications.

Therefore, the FDA is investigating trials of PD-1/PD-L1 inhibitors being studied in combination with immunomodulatory agents or other classes of drugs in patients with hematologic malignancies.

In the course of this investigation, the FDA has placed holds on trials of nivolumab and durvalumab as well as atezolizumab.

According to Roche, there is no evidence of an increased risk of death or serious events with the use of atezolizumab in combination with immunomodulatory agents.

PRNewsfoto/Bayer

The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.

The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.

Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.

Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.

According to Bayer, copanlisib is now available. The prescribing information is available for download here.

In addition, Bayer has created the Aliqopa™ Resource Connections (ARC^TM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.

The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.

Phase 2 results

The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.

The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.

The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.

The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).

The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).

There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.

PRNewsfoto/Bayer

The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.

The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.

Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.

Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.

According to Bayer, copanlisib is now available. The prescribing information is available for download here.

In addition, Bayer has created the Aliqopa™ Resource Connections (ARC^TM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.

The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.

Phase 2 results

The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.

The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.

The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.

The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).

The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).

There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.

PRNewsfoto/Bayer

The US Food and Drug Administration (FDA) has granted accelerated approval to copanlisib (Aliqopa), an intravenous PI3K inhibitor developed by Bayer.

The drug is now approved to treat adults with relapsed follicular lymphoma (FL) who have received at least 2 prior systemic therapies.

Copanlisib received accelerated approval from the FDA because it has not yet shown a clinical benefit in these patients.

The FDA’s accelerated approval program allows conditional approval of a drug that fills an unmet medical need for a serious condition.

Accelerated approval is based on a surrogate or intermediate endpoint—in this case, overall response rate—that is reasonably likely to predict clinical benefit.

Continued approval of copanlisib for the aforementioned indication may be contingent upon verification of clinical benefit in confirmatory trials.

The FDA previously granted copanlisib priority review, fast track designation, and orphan drug designation.

According to Bayer, copanlisib is now available. The prescribing information is available for download here.

In addition, Bayer has created the Aliqopa™ Resource Connections (ARC^TM) Program, which includes resources to help patients navigate the insurance process and identify sources of financial assistance.

The program offers free medication to patients who are uninsured or underinsured and meet the eligibility criteria. It includes a $0 co-pay program for covered patients.

Phase 2 results

The FDA’s approval of copanlisib is based on data from the phase 2 CHRONOS-1 trial. Data from this trial were presented at the AACR Annual Meeting 2017 and the 2017 ASCO Annual Meeting.

The trial included 104 patients with FL who had relapsed after at least 2 prior systemic therapies.

The median duration of treatment with copanlisib was 22 weeks (range, 1-105). Thirty-three patients (32%) were still on treatment at last follow-up.

The overall response rate was 59%, with 14% of patients achieving a complete response. The median duration of response was 12.2 months (range, 0+ to 22.6).

The most common treatment-emergent adverse events (in ≥25% of patients) were diarrhea (34% all grades, 5% ≥grade 3), reduced neutrophil count (30% all grades, 24% ≥grade 3), fatigue (30% all grades, 2% ≥grade 3), and fever (25% all grades, 4% ≥grade 3).

There were 6 deaths, and 3 of them were attributed to copanlisib. One patient died of lung infection, 1 died of respiratory failure, and 1 died of a thromboembolic event.

Micrograph showing DLBCL

MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.

The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.

Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.

An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.

Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).

“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”

“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”

Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:

• Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
• Four patients with pre-B acute lymphoblastic leukemia (ALL)
• Two patients with mantle cell lymphoma (MCL)
• Two patients with chronic lymphocytic leukemia (CLL)
• One patient with FL transformed from Burkitt lymphoma.

Eleven patients received preconditioning with cyclophosphamide (500 mg/m²) and fludarabine (3 doses at 25 mg/m²).

All patients received CAR T cells at 1 x 10⁸, 2 x 10⁷, or 2 x 10⁸ cells/m². These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.

The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.

Efficacy and safety

Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.

All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).

Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.

Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.

All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.

Immune status

An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.

Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.

High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.

“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.

“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”

Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.

This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.

Micrograph showing DLBCL

MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.

The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.

Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.

An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.

Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).

“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”

“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”

Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:

• Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
• Four patients with pre-B acute lymphoblastic leukemia (ALL)
• Two patients with mantle cell lymphoma (MCL)
• Two patients with chronic lymphocytic leukemia (CLL)
• One patient with FL transformed from Burkitt lymphoma.

Eleven patients received preconditioning with cyclophosphamide (500 mg/m²) and fludarabine (3 doses at 25 mg/m²).

All patients received CAR T cells at 1 x 10⁸, 2 x 10⁷, or 2 x 10⁸ cells/m². These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.

The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.

Efficacy and safety

Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.

All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).

Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.

Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.

All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.

Immune status

An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.

Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.

High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.

“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.

“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”

Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.

This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.

Micrograph showing DLBCL

MAINZ/FRANKFURT, GERMANY—Outcomes of treatment with a third-generation chimeric antigen receptor (CAR) T-cell therapy are associated with a patient’s immune status, according to a phase 1/2a trial.

The CD19-specific CAR T-cell therapy produced a complete response (CR) in 6 of 15 patients with relapsed/refractory CD19-positive leukemia or lymphoma.

Though all responders eventually relapsed, 4 patients—including 2 with stable disease (SD) after treatment—responded to subsequent therapy and are still alive, 1 of them beyond 36 months.

An analysis of blood samples taken throughout the study revealed that a patient’s immune status was associated with treatment failure and overall survival.

Tanja Lövgren, PhD, of Uppsala University in Sweden, and her colleagues presented these findings at the Third CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival (abstract B156).

“CD19-specific CAR T-cell therapy has yielded remarkable response rates for patients who have B-cell acute lymphoblastic leukemia,” Dr Lövgren said. “However, many patients relapse.”

“In addition, response rates are more variable for patients who have other CD19-positive B-cell malignancies, and many patients experience serious adverse events. We set out to investigate the safety and effectiveness of a third-generation CD19-specific CAR T-cell therapy and to identify potential biomarkers of treatment outcome.”

Dr Lövgren and her colleagues studied 15 patients (ages 24-72) who had relapsed or refractory CD19-positive B-cell malignancies:

• Six patients with diffuse large B-cell lymphoma (DLBCL), including 3 cases that were transformed from follicular lymphoma (FL)
• Four patients with pre-B acute lymphoblastic leukemia (ALL)
• Two patients with mantle cell lymphoma (MCL)
• Two patients with chronic lymphocytic leukemia (CLL)
• One patient with FL transformed from Burkitt lymphoma.

Eleven patients received preconditioning with cyclophosphamide (500 mg/m²) and fludarabine (3 doses at 25 mg/m²).

All patients received CAR T cells at 1 x 10⁸, 2 x 10⁷, or 2 x 10⁸ cells/m². These were autologous, CD19-targeting CAR T cells with 3 intracellular signaling domains derived from CD3 zeta, CD28, and 4-1BB.

The researchers assessed tumor responses via bone marrow/blood analysis and/or radiology, depending on the type of malignancy. The team also collected blood samples before CAR T-cell infusion and at multiple times after infusion.

Efficacy and safety

Six patients achieved a CR to treatment—3 with DLBCL (1 transformed), 2 with ALL, and 1 with CLL. Two patients had SD—1 with MCL and 1 with CLL. The remaining patients progressed.

All patients with a CR eventually relapsed. The median duration of CR was 5 months (range, 3-24 months).

Four patients—2 complete responders and 2 with SD—responded well to subsequent therapy and are still alive with 27 to 36 months of follow-up. This includes 1 patient with DLBCL, 1 with MCL, and 2 with CLL.

Four patients had serious adverse events. Three had cytokine-release syndrome, and 2 had neurological toxicity.

All cases of cytokine-release syndrome resolved after treatment with corticosteroids/anti-IL6R therapy. The neurological toxicity resolved spontaneously.

Immune status

An analysis of the blood samples taken throughout the study showed that high levels of monocytic myeloid-derived suppressor cells (MDSCs) prior to treatment was associated with decreased overall survival. In addition, increased levels of MDSCs after treatment preceded treatment failure.

Furthermore, high plasma levels of immunosuppressive factors—such as PD-L1 and PD-L2—after treatment were associated with decreased overall survival.

High plasma levels of biomarkers of an immunostimulatory environment—including IL-12, DC-LAMP, TRAIL, and FasL—before the administration of CAR T-cell therapy was associated with increased overall survival.

“[A]n immunostimulatory environment was associated with improved overall survival, while immunosuppressive cells and factors were associated with treatment failure and decreased overall survival,” Dr Lövgren said.

“We are hoping to follow up this study with another clinical trial that will combine CAR T-cell therapy with chemotherapy known to decrease the number of monocytic myeloid-derived suppressive cells. We are also looking to further optimize the CAR T-cell therapy.”

Dr Lövgren said the main limitations of this study are that it only included 15 patients, the patients had several different malignancies, and some patients may have been too sick to respond to any treatment.

This study was supported by funds from AFA Insurance AB, the Swedish Cancer Society, the Swedish Research Council, the Lions Fund at Uppsala University Hospital, and the Swedish State Support for Clinical Research. Dr Lövgren declared no conflicts of interest.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Rhoda Baer

Deaths from cancer are on the decline in the US, but new cases of cancer are on the rise, according to the 7th annual American Association for Cancer Research (AACR) Cancer Progress Report.

The data suggest the cancer death rate declined by 35% from 1991 to 2014 for children and by 25% for adults, a reduction that translates to 2.1 million cancer deaths avoided.

However, 600,920 people in the US are projected to die from cancer in 2017.

And the number of new cancer cases is predicted to rise from 1.7 million in 2017 to 2.3 million in 2030.

The report also estimates there will be 62,130 new cases of leukemia in 2017 and 24,500 leukemia deaths this year.

This includes:

• 5970 cases of acute lymphocytic leukemia and 1440 deaths
• 20,110 cases of chronic lymphocytic leukemia and 4660 deaths
• 21,380 cases of acute myeloid leukemia (AML) and 10,590 deaths
• 8950 cases of chronic myeloid leukemia and 1080 deaths.

The estimate for lymphomas is 80,500 new cases and 21,210 deaths.

This includes:

• 8260 cases of Hodgkin lymphoma (HL) and 1070 deaths
• 72,240 cases of non-Hodgkin lymphoma and 20,140 deaths.

The estimate for myeloma is 30,280 new cases and 12,590 deaths.

The report says the estimated new cases of cancer are based on cancer incidence rates from 49 states and the District of Columbia from 1995 through 2013, as reported by the North American Association of Central Cancer Registries. This represents about 98% of the US population.

The estimated deaths are based on US mortality data from 1997 through 2013, taken from the National Center for Health Statistics of the Centers for Disease Control and Prevention.

Drug approvals

The AACR report notes that, between August 1, 2016, and July 31, 2017, the US Food and Drug Administration (FDA) approved new uses for 15 anticancer agents, 9 of which had no previous FDA approval.

Five of the agents are immunotherapies, which the report dubs “revolutionary treatments that are increasing survival and improving quality of life for patients.”

Among the recently approved therapies are 3 used for hematology indications:

• Ibrutinib (Imbruvica), approved to treat patients with relapsed/refractory marginal zone lymphoma who require systemic therapy and have received at least 1 prior anti-CD20-based therapy
• Midostaurin (Rydapt), approved as monotherapy for adults with advanced systemic mastocytosis and for use in combination with standard cytarabine and daunorubicin induction, followed by cytarabine consolidation, in adults with newly diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test.
• Pembrolizumab (Keytruda), approved to treat adult and pediatric patients with refractory classical HL or those with classical HL who have relapsed after 3 or more prior lines of therapy.

Disparities and costs

The AACR report points out that advances against cancer have not benefited everyone equally, and cancer health disparities are some of the most pressing challenges.

Among the disparities listed is the fact that adolescents and young adults (ages 15 to 39) with AML have a 5-year relative survival rate that is 22% lower than that of children (ages 1 to 14) with AML.

And Hispanic children are 24% more likely to develop leukemia than non-Hispanic children.

Another concern mentioned in the report is the cost of cancer care. The direct medical costs of cancer care in 2014 were estimated to be nearly $87.6 billion. This number does not include the indirect costs of lost productivity due to cancer-related morbidity and mortality.

With this in mind, the AACR is calling for a $2 billion increase in funding for the National Institutes of Health in fiscal year 2018, for a total funding level of $36.2 billion.

The AACR also recommends an $80 million increase in the FDA budget, bringing it to $2.8 billion for fiscal year 2018.

Photo by Bill Branson

MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.

Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.

Survival rates were also similar between the treatment arms, as were adverse events (AEs).

Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).

The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.

Patients and treatment

The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.

The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.

Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)

Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.

Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.

Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.

ORR and survival

The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.

The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).

The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.

The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).

The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).

Safety

During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).

There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.

Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.

During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).

There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.

Photo by Bill Branson

MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.

Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.

Survival rates were also similar between the treatment arms, as were adverse events (AEs).

Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).

The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.

Patients and treatment

The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.

The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.

Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)

Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.

Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.

Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.

ORR and survival

The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.

The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).

The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.

The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).

The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).

Safety

During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).

There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.

Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.

During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).

There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.

Photo by Bill Branson

MADRID—The biosimilar GP2013 has demonstrated equivalence to its reference drug rituximab in patients with previously untreated, advanced-stage follicular lymphoma (FL), according to researchers.

Treatment with GP2013 plus cyclophosphamide, vincristine, and prednisone (CVP) produced a similar overall response rate (ORR) as rituximab plus CVP in the phase 3 ASSIST-FL trial.

Survival rates were also similar between the treatment arms, as were adverse events (AEs).

Results from this study were published in The Lancet Haematology and presented at ESMO 2017 Congress (abstract 994O).

The study was funded by Hexal AG, a Sandoz company (part of the Novartis group), which is marketing GP2013 as Rixathon in Europe.

Patients and treatment

The trial included 629 patients with previously untreated, advanced-stage FL. They were randomized to receive 8 cycles of GP2013-CVP (n=314) or rituximab-CVP (n=315). Responders in either arm could receive monotherapy maintenance for up to 2 years.

The mean age was 57.5 in the GP2013 arm and 56.4 in the rituximab arm. Fifty-eight percent and 54% of patients, respectively, were female.

Fifty-seven percent of patients in the GP2013 arm and 56% in the rituximab arm had an ECOG performance status of 0. Forty percent and 39%, respectively, had a status of 1. Two percent and 4%, respectively, had a status of 2. (For the remaining 1% of patients in each arm, data on performance status were missing.)

Patients had an Ann Arbor stage of III—46% in the GP2013 arm and 43% in the GP2013 arm—or IV—54% in the GP2013 arm and 57% in the rituximab arm.

Fifty-six percent of patients in each arm were high-risk according to FLIPI. Thirty-four percent in the GP2013 arm and 33% in the rituximab arm were intermediate-risk. Ten percent and 11%, respectively, were low-risk.

Fourteen percent of patients in the GP2013 arm and 18% in the rituximab arm had bulky disease. Fifteen percent and 13%, respectively, had splenic involvement.

ORR and survival

The patients had a median follow-up of 23.8 months. The primary efficacy endpoint was equivalence in ORR, defined by a 95% confidence interval (CI) with a margin of ± 12% standard deviation.

The primary endpoint was met, as the ORR was 87% in the GP2013 arm and 88% in the rituximab arm, with a difference of –0.40% (95% CI –5.94%, 5.14%).

The complete response rate was 15% in the GP2013 arm and 13% in the rituximab arm. The partial response rates were 72% and 74%, respectively.

The median progression-free survival and overall survival have not been reached. However, the progression-free survival rate was 70% in the GP2013 arm and 76% in the rituximab arm (hazard ratio [HR]=1.31; 95% CI 1.02, 1.69).

The overall survival rate was 93% in the GP2013 arm and 91% in the rituximab arm (HR=0.77; 95% CI 0.49, 1.22).

Safety

During the combination phase, the incidence of AEs was 93% in the GP2013 arm and 91% in the rituximab arm. The incidence of serious AEs was 23% and 20%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were neutropenia (26% and 30%), constipation (22% and 20%), and nausea (16% and 13%). The most common grade 3/4 AE was neutropenia (18% and 21%).

There were 11 deaths reported during the combination phase—4 in the GP2013 arm and 7 in the rituximab arm.

Three deaths in the GP2013 arm (sudden death, septic shock, and respiratory failure) and 2 deaths in the rituximab arm (multiple organ dysfunction syndrome and sepsis) were suspected to be related to study treatment.

During the maintenance phase, the incidence of AEs was 63% in the GP2013 arm and 57% in the rituximab arm. The incidence of serious AEs was 6% and 4%, respectively.

The most frequent AEs (in the GP2013 and rituximab arms, respectively) were infections and infestations (20% and 27%), neutropenia (10% and 6%), cough (9% and 6%), and upper respiratory tract infection (3% and 6%). The most common grade 3/4 AE was neutropenia (7% and 4%).

There were 4 deaths reported during the maintenance phase, 2 in each treatment arm.

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo courtesy of NIH

Adult survivors of childhood cancer have a greater cumulative burden of chronic health conditions than the general public, according to research published in The Lancet.

The study showed that, by age 50, childhood cancer survivors (CCSs) had experienced, on average, 17.1 chronic health conditions, and matched control subjects had experienced 9.2.

“The cumulative burden of chronic disease revealed in this analysis, along with the complexity and severity of chronic conditions some survivors experience, found childhood cancer survivors to be a vulnerable, medically complex population,” said study author Nickhill Bhakta, MD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

For this study, Dr Bhakta and his colleagues assessed the lifelong impact of 168 chronic health conditions—such as hepatic, thyroid, ocular, and reproductive disorders—on CCSs and control subjects.

The 3010 evaluable CCSs had survived 10 years or longer from their initial cancer diagnosis and were 18 years or older as of June 30, 2015. The 272 controls had no history of pediatric cancer and were matched to CCSs by age and sex.

At age 50, the cumulative incidence of chronic health conditions (of any grade) was 99.9% in CCSs and 96.0% in controls (P<0.0001). The cumulative incidence of grade 3 to 5 chronic health conditions was 96.0% and 84.9%, respectively (P<0.0001).

The cumulative burden for CCSs was 17.1 chronic health conditions, including 4.7 that were grade 3 to 5. For controls, the cumulative burden was 9.2 chronic health conditions, including 2.3 that were grade 3 to 5 (P<0.0001 for both comparisons).

The researchers said second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden observed in CCSs. However, there was “notable heterogeneity” in burden according to the patients’ primary cancer diagnosis.

For instance, growth hormone deficiency was in the top 10th percentile of chronic health conditions for survivors of acute lymphoblastic leukemia but not for controls.

And pulmonary function deficits were in the top 10th percentile for survivors of acute myeloid leukemia and Hodgkin lymphoma but not for controls or survivors of acute lymphoblastic leukemia or non-Hodgkin lymphoma.

“This study found that the average childhood cancer survivor has a cumulative burden of chronic disease that requires a significant time investment by healthcare providers to disentangle and manage—time that community providers are unlikely to have,” Dr Bhakta said.

“The results suggest that childhood cancer survivors may benefit from the integrated, specialized healthcare delivery that is being tried for individuals infected with HIV or those with other complex, chronic health problems.”

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).

In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.

At present, no new patients can be enrolled in any of the 6 trials.

Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.

Patients enrolled in the trial on full clinical hold will discontinue the study treatment.

The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.

Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.

MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.

The FDA also placed the following trials on partial clinical hold:

• MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
• MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
• MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
• MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
• MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.

The trials that will continue to enroll are:

• MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
• CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.

Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.

The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.

Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).

In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.

At present, no new patients can be enrolled in any of the 6 trials.

Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.

Patients enrolled in the trial on full clinical hold will discontinue the study treatment.

The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.

Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.

MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.

The FDA also placed the following trials on partial clinical hold:

• MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
• MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
• MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
• MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
• MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.

The trials that will continue to enroll are:

• MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
• CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.

Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.

The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.

Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.

Photo from AstraZeneca

The US Food and Drug Administration (FDA) has placed a partial clinical hold on 5 trials and a full clinical hold on 1 trial of the anti-PD-L1 antibody durvalumab (Imfinzi™).

In these trials, researchers are testing durvalumab in combination with immunomodulatory and chemotherapy agents in patients with multiple myeloma (MM) and lymphomas.

At present, no new patients can be enrolled in any of the 6 trials.

Patients enrolled in the trials on partial clinical hold can remain on treatment if they are receiving clinical benefit.

Patients enrolled in the trial on full clinical hold will discontinue the study treatment.

The FDA’s decision to place these trials on hold is related to risks identified in trials studying another anti-PD-1 agent, pembrolizumab, in MM patients.

Data from the pembrolizumab trials indicate the risks outweigh the benefits when PD-1/PD-L1 treatment is given to MM patients in combination with dexamethasone and pomalidomide or lenalidomide.

In addition, there may be an unfavorable risk-benefit ratio for MM patients receiving PD-1/PD-L1 treatments alone or in other combinations.

With this in mind, the FDA placed the MEDI4736-MM-002 trial on full clinical hold.

MEDI4736-MM-002 is a phase 1b study designed to determine the recommended dose and regimen of durvalumab in combination with lenalidomide, with and without low-dose dexamethasone, in patients with newly diagnosed MM.

The FDA also placed the following trials on partial clinical hold:

• MEDI4736-MM-001: A phase 1b study to determine the recommended dose and regimen of durvalumab either as monotherapy or in combination with pomalidomide, with or without low-dose dexamethasone, in patients with relapsed and refractory MM
• MEDI4736-MM-003: A phase 2 study to determine the safety and efficacy of the combination of durvalumab and daratumumab in patients with relapsed and refractory MM
• MEDI4736-MM-005: A phase 2 study to determine the efficacy of the combination of durvalumab plus daratumumab in patients with relapsed and refractory MM who have progressed while on a current treatment regimen containing daratumumab
• MEDI4736-NHL-001: A phase 1/2 study to assess the safety and tolerability of durvalumab as monotherapy and in combination therapy in patients with lymphomas, including chronic lymphocytic leukemia. The only arm in this trial for which enrollment is suspended is the arm with the durvalumab, lenalidomide, and rituximab combination.
• MEDI4736-DLBCL-001: A phase 2 study to evaluate the safety and clinical activity of durvalumab in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or with lenalidomide plus R-CHOP in patients with previously untreated, high-risk diffuse large B-cell lymphoma.

The trials that will continue to enroll are:

• MEDI4736-MDS-001: A phase 2 study evaluating the efficacy and safety of subcutaneous azacitidine in combination with durvalumab in previously untreated patients with higher-risk myelodysplastic syndromes or in elderly (≥65 years) acute myeloid leukemia patients not eligible for hematopoietic stem cell transplant
• CC-486-MDS-006: A phase 2 study to evaluate the efficacy and safety of CC-486 alone or in combination with durvalumab in patients with myelodysplastic syndromes who fail to achieve an objective response to treatment with azacitidine for injection or decitabine.

Durvalumab is being developed by Celgene Corporation and MedImmune, the global biologics research and development arm of AstraZeneca.

The use of durvalumab in combination with other agents for the treatment of patients with hematologic malignancies is not approved by the FDA, and the safety and efficacy of those combinations has not been established.

Durvalumab has accelerated approval from the FDA to treat patients with locally advanced or metastatic urothelial carcinoma.

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”

Micrograph showing DLBCL

Researchers have reported the first known case of central nervous system (CNS) lymphoma responding to chimeric antigen receptor (CAR) T-cell therapy.

The investigational CAR T-cell therapy JCAR017 induced complete remission of brain metastasis in a patient with refractory diffuse large B-cell lymphoma (DLBCL).

When a subcutaneous tumor began to recur 2 months after the patient received JCAR017 and a surgical biopsy was performed, the CAR T cells spontaneously re-expanded and the tumor again went into remission.

While the patient eventually relapsed and died more than a year after receiving JCAR017, the brain tumor never recurred.

“Brain involvement in DLBCL carries a grave prognosis, and the ability to induce a complete and durable response with conventional therapies is rare,” said Jeremy Abramson, MD, of Massachusetts General Hospital in Boston.

“In addition, all available CAR T-cell trials have excluded patients with central nervous system involvement. This result has implications not only for secondary DLBCL like this case but also for primary central nervous system lymphoma, for which treatment options are similarly limited after relapse and few patents are cured.”

Dr Abramson and his colleagues described this case in a letter to NEJM. The patient was involved in a trial of JCAR017, which was sponsored by Juno Therapeutics.

The patient was a 68-year-old woman with germinal center B-cell-like DLBCL with a BCL2 rearrangement and multiple copies of MYC and BCL6.

The patients’ disease was refractory to conventional chemotherapy and an 8/8 HLA-matched stem cell transplant. After she enrolled in a phase 1 trial of JCAR017, the patient was found to have a new lesion in the right temporal lobe of her brain.

One month after the patient received JCAR017—given after lymphodepletion with fludarabine and cyclophosphamide—imaging showed complete remission of the brain lesion.

The subcutaneous lesion that recurred 2 months later disappeared after the biopsy with no further treatment. Blood testing showed an expansion of CAR T cells that coincided with the tumor’s regression.

While re-expansion of CAR T cells has been reported in response to other immunotherapy drugs, this is the first report of such a response to a biopsy.

“Typically, the drugs we use to fight cancer and other diseases wear off over time,” Dr Abramson said. “This spontaneous re-expansion after biopsy highlights this therapy as something entirely different, a ‘living drug’ that can re-expand and proliferate in response to biologic stimuli.”