CLL Therapy: Focus on comorbidities, not age

CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.

In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.

Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.

However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.

“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.

Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”

However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.

Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.

Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.

When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.

For this reason, comorbidities should be the determining factor in treatment selection, he said.

No standard criteria for assessing fitness exist, but there are a few tools that can help.

Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.

The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.

A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.

“But in general terms, this is a good way to be making these sorts of assessments,” he said.

Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

[email protected]

CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.

In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.

Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.

However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.

“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.

Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”

However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.

Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.

Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.

When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.

For this reason, comorbidities should be the determining factor in treatment selection, he said.

No standard criteria for assessing fitness exist, but there are a few tools that can help.

Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.

The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.

A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.

“But in general terms, this is a good way to be making these sorts of assessments,” he said.

Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

[email protected]

CHICAGO – The majority of patients with chronic lymphocytic leukemia (CLL) are elderly patients over age 65 years, which underscores the need for a careful assessment of fitness for therapy – not necessarily because of age, but because of comorbidity burden, according to Dr. John G. Gribben.

In fact, 68% of CLL patients are over age 65 years (median, 71 years), and 41% are over age 75 years. Perhaps more importantly, 89% of elderly CLL patients have one or more comorbidities, and 46% have at least one major comorbidity, said Dr. Gribben of Barts Cancer Institute, Queen Mary University of London.

Conventional wisdom has long suggested that CLL shortens the life span only in younger patients; older patients were thought to be more likely “to die with CLL rather than of CLL,” he said at the American Society of Hematology Meeting on Hematologic Malignancies.

However, recent findings suggest that CLL shortens the life span of elderly patients as well, he noted.

“I think we probably have been undertreating and underthinking about the impact that CLL can have on these more elderly patients, and I think it does represent an area of unmet need,” he said.

Treatment options in the elderly include FCR (fludarabine, cyclophosphamide, rituximab) in those deemed fit enough to tolerate the regimen, he said, adding, “if you are concerned about neutropenia associated with FCR, there are those who use rituximab-fludarabine [RF], and that’s certainly a good option.”

However, in those with an 11q abnormality, good data show that the addition of the alkylator does add benefit. “I do think that FCR is worthwhile pushing [in those cases],” he said.

Bendamustine-rituximab is also an attractive option, as demonstrated in the CLL10 trial, but it is important to remember that patients in that trial were “fit, healthy patients” based on Clinical Illness Rating Scale (CIRS) scores of less than 6; they were patients who were deemed fit to be randomized to receive FCR.

Chlorambucil-based therapies administered with anti-CD20 monoclonal antibodies are also an option, as are novel agents in those with 17p deletions or a P53 mutation, he said.

When it comes to assessing elderly patients’ fitness for therapy, comorbidities play a more important role than age, he said, explaining that many patients over age 65 are very fit and would do well with therapies such as FCR.

For this reason, comorbidities should be the determining factor in treatment selection, he said.

No standard criteria for assessing fitness exist, but there are a few tools that can help.

Eastern Cooperative Oncology Group performance status and organ function (for example, creatinine clearance) can be helpful and often are used in trial settings, as are criteria for excluding patients from participation, but CIRS, used by the German CLL study group, is a more formal tool for assessing comorbidity.

The German group is not the first to use the tool – CIRS is a widely validated test that provides an objective measurement of fitness for more aggressive chemotherapy regimens – but the group did demonstrate in CLL11 that it could be used to enroll more elderly patients with comorbidities into clinical trials, Dr. Gribben said.

A CIRS score of 6 or lower indicates fitness, whereas increasing scores indicate an increasing lack of fitness, he explained, noting that “like every scoring system there are some issues … somebody could easily have a score higher than 6 with comorbidities that really don’t impact on chemotherapy tolerability.

“But in general terms, this is a good way to be making these sorts of assessments,” he said.

Dr. Gribben has received research funding from the National Institutes of Health, Cancer Research UK, MRC, and Wellcome Trust. He has received honoraria from Roche/Genentech, Celgene, Janssen, Pharmacyclics, Gilead, Mundipharma, Infinity, TG Therapeutics, and Ascerta, and he has a patent or receives royalties from Celgene. He also has been the principal investigator on a clinical trial for Roche, Takeda, Pharmacyclics, Gilead, and Infinity.

[email protected]