PET-CT accurately predicts survival of follicular lymphoma patients

CHICAGO – For patients with follicular lymphoma, positron emission tomography–computed tomography performed at the end of induction therapy is strongly predictive of both progression-free and overall survival, a retrospective analysis showed.

The pooled analysis of data on 246 PET-CT scans performed following chemoimmunotherapy in three clinical trials showed that patients with 18-fluorodeoxyglucose (FDG) uptake of 4 or greater on a 5-point scale had a fourfold higher risk for disease progression, compared with patients who became PET negative after induction, reported Dr. Judith Trotman of the University of Sydney (Australia).

At 4.5 years of follow-up, median progression-free survival (PFS) was 16.9 months for patients with a PET uptake of 4 or greater on the 5-point Deauville scale for postinduction response assessment, vs. 74 months for PET-negative patients.

Overall survival at 4.5 years for patients with a higher uptake of FDG PET was 87%, compared with 97% for patients who were PET negative after induction, Dr. Trotman reported at the American Society of Clinical Oncology annual meeting.

"We argue that for the patients who remain PET positive, follicular lymphoma is no longer an indolent histology," Dr. Trotman said.

The study results also showed that conventional CT assessment provides only limited additional value, and that "PET-CT applying the 5-point scale should be the new gold standard for therapeutic response assessment in this lymphoma," she said.

Not so indolent

Although the natural history of follicular lymphoma is a generally indolent course, approximately 15% of patients will die within 5 years of diagnosis, and high-risk scores on the Follicular Lymphoma International Prognostic Index (FLIPI) or its revision (FLIPI2) are not sufficient for predicting which patients are at greatest risk for death, Dr. Trotman said.

Three recent clinical trials reported that positron emission tomography assessment after first-line rituximab-based chemotherapy has good predictive value in patients with high tumor burden follicular lymphoma. Dr. Trotman and his colleagues conducted a pooled analysis of data from the trials with independent review of PET-CT scans to come up with more precise survival estimates and identify the best cutoff for survival using the Deauville scale for response assessment of FDG-avid lymphoma.

The trials were the PRIMA (Primary Rituximab and Maintenance) study of 122 patients, the FOLL05 randomized trial of the Fondazione Italiana Linfomi in 202 patients, and the PET Folliculaire trial in 106 patients.

The Deauville 5-point scale for FDG-avid lymphoma uses the following criteria:

1. No uptake.

2. Uptake less than or equal to mediastinum.

3. Uptake greater than mediastinum but less than or equal to liver.

4. Uptake moderately higher than liver.

5. Uptake markedly higher than liver and/or new lesions.

Dr. Trotman and his colleagues looked at cutoffs of 3 and higher and 4 and higher to see whether they were predictive of prognosis. Reviews of concordance with the trial results, performed by three independent reviewers, showed that a cutoff of 3 or higher had moderate concordance, while a score of 4 or higher had substantial agreement with results.

They then evaluated PET results to see whether they could sharpen the prognostic ability, and found that both cutoffs predicted PFS, but because of the higher concordance score, they chose to focus on the 4+ cutoff.

They found that the hazard ratio (HR) for progression with a score of 4 or greater was 3.9 (P less than .0001), and the hazard ratio for death was 6.7 (P = .0002). Median overall survival in patients with scores of 4 or greater was 79 months, vs. not reached for PET-negative patients.

In multivariate analyses, factors associated with PFS included PET-positive scores of 4 or greater (HR, 3.1; P less than .0001), stable or progressive disease vs. complete responses or complete responses unconfirmed (CR/CRu; HR, 3.7; P = .0013), and partial responses (PRs) vs. CR/CRu (HR, 1.6; P = .04).

Factors associated with OS were PET score and stable/progressive disease vs. CR/CRu (HR, 5.3; P = .05).

"I hope that we can now move on: postinduction PET-CT is a platform for response–adapted therapy, because while achieving PET negativity can better reassure our patients, particularly those otherwise in CRu or PR, the inferior survival of those who remain PET positive compels us to study such PET-response–adapted approaches," Dr. Trotman said.

The invited discussant, Dr. Christopher Flowers of the department of hematology and medical oncology at Emory University, Atlanta, noted that in their analysis, Dr. Trotman and his colleagues included only those scans that were of sufficient quality for central review, and that slightly more than half of all patients had PET scans.

"I think it’s important to try and understand how the PET-available cohort compared to the other clinical trial characteristics of patients to understand whether or not this PET population is a unique population, and [whether] the behavior characteristics may be different from what you might expect from a broader population of patients," he said.

It will be important to see whether the findings will hold up in patients treated with emerging regimens, such as rituximab and bendamustine, and other combinations now in clinical trials, he said.

Dr. Trotman reported having no relevant relationships to disclose. Dr. Flowers disclosed uncompensated consultation from several companies, and receiving research funding from Gilead Sciences, Janssen Pharmaceuticals, Millennium, and Spectrum Pharmaceuticals.

CHICAGO – For patients with follicular lymphoma, positron emission tomography–computed tomography performed at the end of induction therapy is strongly predictive of both progression-free and overall survival, a retrospective analysis showed.

The pooled analysis of data on 246 PET-CT scans performed following chemoimmunotherapy in three clinical trials showed that patients with 18-fluorodeoxyglucose (FDG) uptake of 4 or greater on a 5-point scale had a fourfold higher risk for disease progression, compared with patients who became PET negative after induction, reported Dr. Judith Trotman of the University of Sydney (Australia).

At 4.5 years of follow-up, median progression-free survival (PFS) was 16.9 months for patients with a PET uptake of 4 or greater on the 5-point Deauville scale for postinduction response assessment, vs. 74 months for PET-negative patients.

Overall survival at 4.5 years for patients with a higher uptake of FDG PET was 87%, compared with 97% for patients who were PET negative after induction, Dr. Trotman reported at the American Society of Clinical Oncology annual meeting.

"We argue that for the patients who remain PET positive, follicular lymphoma is no longer an indolent histology," Dr. Trotman said.

The study results also showed that conventional CT assessment provides only limited additional value, and that "PET-CT applying the 5-point scale should be the new gold standard for therapeutic response assessment in this lymphoma," she said.

Not so indolent

Although the natural history of follicular lymphoma is a generally indolent course, approximately 15% of patients will die within 5 years of diagnosis, and high-risk scores on the Follicular Lymphoma International Prognostic Index (FLIPI) or its revision (FLIPI2) are not sufficient for predicting which patients are at greatest risk for death, Dr. Trotman said.

Three recent clinical trials reported that positron emission tomography assessment after first-line rituximab-based chemotherapy has good predictive value in patients with high tumor burden follicular lymphoma. Dr. Trotman and his colleagues conducted a pooled analysis of data from the trials with independent review of PET-CT scans to come up with more precise survival estimates and identify the best cutoff for survival using the Deauville scale for response assessment of FDG-avid lymphoma.

The trials were the PRIMA (Primary Rituximab and Maintenance) study of 122 patients, the FOLL05 randomized trial of the Fondazione Italiana Linfomi in 202 patients, and the PET Folliculaire trial in 106 patients.

The Deauville 5-point scale for FDG-avid lymphoma uses the following criteria:

1. No uptake.

2. Uptake less than or equal to mediastinum.

3. Uptake greater than mediastinum but less than or equal to liver.

4. Uptake moderately higher than liver.

5. Uptake markedly higher than liver and/or new lesions.

Dr. Trotman and his colleagues looked at cutoffs of 3 and higher and 4 and higher to see whether they were predictive of prognosis. Reviews of concordance with the trial results, performed by three independent reviewers, showed that a cutoff of 3 or higher had moderate concordance, while a score of 4 or higher had substantial agreement with results.

They then evaluated PET results to see whether they could sharpen the prognostic ability, and found that both cutoffs predicted PFS, but because of the higher concordance score, they chose to focus on the 4+ cutoff.

They found that the hazard ratio (HR) for progression with a score of 4 or greater was 3.9 (P less than .0001), and the hazard ratio for death was 6.7 (P = .0002). Median overall survival in patients with scores of 4 or greater was 79 months, vs. not reached for PET-negative patients.

In multivariate analyses, factors associated with PFS included PET-positive scores of 4 or greater (HR, 3.1; P less than .0001), stable or progressive disease vs. complete responses or complete responses unconfirmed (CR/CRu; HR, 3.7; P = .0013), and partial responses (PRs) vs. CR/CRu (HR, 1.6; P = .04).

Factors associated with OS were PET score and stable/progressive disease vs. CR/CRu (HR, 5.3; P = .05).

"I hope that we can now move on: postinduction PET-CT is a platform for response–adapted therapy, because while achieving PET negativity can better reassure our patients, particularly those otherwise in CRu or PR, the inferior survival of those who remain PET positive compels us to study such PET-response–adapted approaches," Dr. Trotman said.

The invited discussant, Dr. Christopher Flowers of the department of hematology and medical oncology at Emory University, Atlanta, noted that in their analysis, Dr. Trotman and his colleagues included only those scans that were of sufficient quality for central review, and that slightly more than half of all patients had PET scans.

"I think it’s important to try and understand how the PET-available cohort compared to the other clinical trial characteristics of patients to understand whether or not this PET population is a unique population, and [whether] the behavior characteristics may be different from what you might expect from a broader population of patients," he said.

It will be important to see whether the findings will hold up in patients treated with emerging regimens, such as rituximab and bendamustine, and other combinations now in clinical trials, he said.

Dr. Trotman reported having no relevant relationships to disclose. Dr. Flowers disclosed uncompensated consultation from several companies, and receiving research funding from Gilead Sciences, Janssen Pharmaceuticals, Millennium, and Spectrum Pharmaceuticals.

CHICAGO – For patients with follicular lymphoma, positron emission tomography–computed tomography performed at the end of induction therapy is strongly predictive of both progression-free and overall survival, a retrospective analysis showed.

The pooled analysis of data on 246 PET-CT scans performed following chemoimmunotherapy in three clinical trials showed that patients with 18-fluorodeoxyglucose (FDG) uptake of 4 or greater on a 5-point scale had a fourfold higher risk for disease progression, compared with patients who became PET negative after induction, reported Dr. Judith Trotman of the University of Sydney (Australia).

At 4.5 years of follow-up, median progression-free survival (PFS) was 16.9 months for patients with a PET uptake of 4 or greater on the 5-point Deauville scale for postinduction response assessment, vs. 74 months for PET-negative patients.

Overall survival at 4.5 years for patients with a higher uptake of FDG PET was 87%, compared with 97% for patients who were PET negative after induction, Dr. Trotman reported at the American Society of Clinical Oncology annual meeting.

"We argue that for the patients who remain PET positive, follicular lymphoma is no longer an indolent histology," Dr. Trotman said.

The study results also showed that conventional CT assessment provides only limited additional value, and that "PET-CT applying the 5-point scale should be the new gold standard for therapeutic response assessment in this lymphoma," she said.

Not so indolent

Although the natural history of follicular lymphoma is a generally indolent course, approximately 15% of patients will die within 5 years of diagnosis, and high-risk scores on the Follicular Lymphoma International Prognostic Index (FLIPI) or its revision (FLIPI2) are not sufficient for predicting which patients are at greatest risk for death, Dr. Trotman said.

Three recent clinical trials reported that positron emission tomography assessment after first-line rituximab-based chemotherapy has good predictive value in patients with high tumor burden follicular lymphoma. Dr. Trotman and his colleagues conducted a pooled analysis of data from the trials with independent review of PET-CT scans to come up with more precise survival estimates and identify the best cutoff for survival using the Deauville scale for response assessment of FDG-avid lymphoma.

The trials were the PRIMA (Primary Rituximab and Maintenance) study of 122 patients, the FOLL05 randomized trial of the Fondazione Italiana Linfomi in 202 patients, and the PET Folliculaire trial in 106 patients.

The Deauville 5-point scale for FDG-avid lymphoma uses the following criteria:

1. No uptake.

2. Uptake less than or equal to mediastinum.

3. Uptake greater than mediastinum but less than or equal to liver.

4. Uptake moderately higher than liver.

5. Uptake markedly higher than liver and/or new lesions.

Dr. Trotman and his colleagues looked at cutoffs of 3 and higher and 4 and higher to see whether they were predictive of prognosis. Reviews of concordance with the trial results, performed by three independent reviewers, showed that a cutoff of 3 or higher had moderate concordance, while a score of 4 or higher had substantial agreement with results.

They then evaluated PET results to see whether they could sharpen the prognostic ability, and found that both cutoffs predicted PFS, but because of the higher concordance score, they chose to focus on the 4+ cutoff.

They found that the hazard ratio (HR) for progression with a score of 4 or greater was 3.9 (P less than .0001), and the hazard ratio for death was 6.7 (P = .0002). Median overall survival in patients with scores of 4 or greater was 79 months, vs. not reached for PET-negative patients.

In multivariate analyses, factors associated with PFS included PET-positive scores of 4 or greater (HR, 3.1; P less than .0001), stable or progressive disease vs. complete responses or complete responses unconfirmed (CR/CRu; HR, 3.7; P = .0013), and partial responses (PRs) vs. CR/CRu (HR, 1.6; P = .04).

Factors associated with OS were PET score and stable/progressive disease vs. CR/CRu (HR, 5.3; P = .05).

"I hope that we can now move on: postinduction PET-CT is a platform for response–adapted therapy, because while achieving PET negativity can better reassure our patients, particularly those otherwise in CRu or PR, the inferior survival of those who remain PET positive compels us to study such PET-response–adapted approaches," Dr. Trotman said.

The invited discussant, Dr. Christopher Flowers of the department of hematology and medical oncology at Emory University, Atlanta, noted that in their analysis, Dr. Trotman and his colleagues included only those scans that were of sufficient quality for central review, and that slightly more than half of all patients had PET scans.

"I think it’s important to try and understand how the PET-available cohort compared to the other clinical trial characteristics of patients to understand whether or not this PET population is a unique population, and [whether] the behavior characteristics may be different from what you might expect from a broader population of patients," he said.

It will be important to see whether the findings will hold up in patients treated with emerging regimens, such as rituximab and bendamustine, and other combinations now in clinical trials, he said.

Dr. Trotman reported having no relevant relationships to disclose. Dr. Flowers disclosed uncompensated consultation from several companies, and receiving research funding from Gilead Sciences, Janssen Pharmaceuticals, Millennium, and Spectrum Pharmaceuticals.