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LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.
At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.
BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).
Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).
ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.
CD30 expression
One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.
For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.
“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.
“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”
“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”
Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.
“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”
Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.
PTCL subtypes
Meeting attendees also discussed the value of BV in different PTCL subtypes.
At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.
As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).
Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
CHOP vs. CHOEP
The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.
A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).
Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.
Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.
However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.
Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.
ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.
Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.
At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.
BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).
Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).
ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.
CD30 expression
One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.
For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.
“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.
“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”
“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”
Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.
“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”
Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.
PTCL subtypes
Meeting attendees also discussed the value of BV in different PTCL subtypes.
At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.
As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).
Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
CHOP vs. CHOEP
The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.
A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).
Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.
Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.
However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.
Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.
ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.
Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Results from the ECHELON-2 trial led to the U.S. approval of brentuximab vedotin (BV) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP), but there are still questions about how to apply the trial results to practice.
At the annual T-cell Lymphoma Forum, trial investigators and other physicians debated the best use of this combination.
BV-CHP is approved to treat patients with previously untreated systemic anaplastic large-cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS).
Patients who received BV-CHP in ECHELON-2 had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results were initially presented at the 2018 annual meeting of the American Society of Hematology and simultaneously published in The Lancet (2019 Jan 19;393[10168]:229-40).
ECHELON-2 investigator Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, also presented details on the trial at the T-cell Lymphoma Forum. His presentation was followed by a discussion with meeting attendees about applying the trial results to clinical practice.
CD30 expression
One of the issues discussed was the importance of CD30 expression in deciding which patients should receive BV.
For a patient to be eligible for ECHELON-2, the diagnostic biopsy had to show at least 10% of the neoplastic cells were CD30-positive. However, the Food and Drug Administration (FDA) has not made a similar requirement for prescribing BV. PTCL patients with any level of CD30 expression are eligible for treatment with BV-CHP, according to the FDA.
“[I]t’s still a matter of great debate and controversy as to whether we have good enough data to suggest that there’s a threshold effect with regard to the expression of CD30 and responsiveness or sensitivity to brentuximab vedotin,” Dr. O’Connor said.
“This has been an issue from the very first day with this drug, which is, ‘Just how much CD30 do you need to get a response?’ I can’t speak on behalf of the FDA, but I think they are not absolutely convinced that there’s a threshold. They take [CD30-] positive as ‘good enough’ across the board.”
“The FDA has said, ‘The data we’ve seen says there’s a lot of heterogeneity [with biopsies].’ You may do a biopsy and find 30% [of cells are CD30-positive], and you may do another biopsy [in the same patient] and find less than 10%. I don’t think the regulatory agencies are convinced that a single biopsy looking at CD30 ... is representative of the entire tumor burden.”
Andrei Shustov, MD, an ECHELON-2 investigator from the University of Washington in Seattle, questioned whether CD30 expression should be considered when deciding on the use of BV in PTCL.
“Is CD30 staining relevant at all, or should we default back to studies, say, in colon cancer where we didn’t even care about EGFR because we might be missing it by current techniques?” Dr. Shustov asked. “Should we even worry about CD30 expression ... because we cannot reliably detect low levels of CD30?”
Some attendees echoed this sentiment, questioning the utility of assessing CD30 expression. Other attendees said they would defer to the trial data and only treat patients with BV-CHP if they had at least 10% CD30.
PTCL subtypes
Meeting attendees also discussed the value of BV in different PTCL subtypes.
At the request of European regulatory agencies, ECHELON-2 was largely focused on patients with sALCL. They made up 70% of the total trial population, while 16% of patients had PTCL-NOS, 12% had AITL, and a small number of patients had other subtypes. These numbers meant ECHELON-2 was not powered to determine differences in OS or PFS in non-sALCL subtypes.
As a result, some attendees expressed concerns about using BV-CHP to treat PTCL-NOS or AITL. They argued that it wasn’t clear whether patients with these subtypes would derive more benefit from BV-CHP, CHOP, or CHOP plus etoposide (CHOEP).
Other attendees said they would feel comfortable using BV-CHP in patients with PTCL-NOS or AITL based on ECHELON-2 results.
CHOP vs. CHOEP
The use of CHOP in ECHELON-2 was another point of discussion. Some attendees said CHOEP should have been used as the comparator instead.
A few individuals mentioned retrospective data suggesting CHOEP may confer a benefit over CHOP in PTCL (Blood. 2010 Nov 4;116[18]:3418-25).
Marek Trneny, MD, of Charles University General Hospital in Prague, referenced new data from the Czech National Lymphoma Registry, which showed that patients newly diagnosed with PTCL had superior PFS and OS when they received CHOEP rather than CHOP.
Based on these findings, Dr. Trneny said he would consider treating CD30-positive PTCL patients with CHOEP plus BV rather than BV-CHP.
However, most other attendees said they would not consider adding BV to CHOEP due to the absence of clinical trial data supporting this approach.
Some attendees did say they would use CHOEP instead of BV-CHP, particularly in patients with PTCL-NOS or AITL and in patients with CD30 expression below 10%.
ECHELON-2 was funded by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical Company.
Dr. O’Connor and Dr. Shustov were investigators on ECHELON-2. Dr. O’Connor is a cochair of the T-cell Lymphoma Forum. The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
EXPERT ANALYSIS FROM TCLF 2019
