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Real-world data can guide decisions about which patients should receive immunotherapy

NEW YORK — The pool of patients eligible to receive immunotherapy likely should include many individuals who were excluded from early immunotherapy trials, according to a presenter at HemOnc Today New York.

“We need data from the real world,” Philip Bonomi, MD, professor of medical oncology at Rush University Medical Center, said during a presentation. “With the electronic medical record, we need to try to extract it and analyze it. This is going to give us a lot of useful information.”

Immunotherapy induces durable responses in subsets of patients with a variety of cancers.

Due to trial results and considerable marketing, patient demand for this modality also is high.

However, several groups were excluded from immuno-oncology trials, so questions remain about whether therapy is effective and safe in the excluded groups.

Common clinical trial exclusion criteria include organ dysfunction, ECOG performance status of 2 or higher, presence of brain metastases and prior cancer history.

Specific exclusion criteria for immunotherapy trials include autoimmune disorders (eg, rheumatologic, gastrointestinal or neurologic), chronic viral infections (eg, HIV, hepatis B virus or hepatitis C virus) and chronic immunosuppressive therapy.

Bonomi reviewed several studies in the literature that offer real-world insights into how some of these patient subsets fare with immunotherapy.

One analysis included 30 patients with melanoma and a pre-existing autoimmune disorder. All patients received the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol-Myers Squibb).

Eight patients (27%) experienced exacerbation of their autoimmune disorder, and all cases resolved after prednisone treatment. Ten patients (33%) experienced immune-related adverse events, and one patient died of colitis. Six patients (20%) responded to treatment.

Another analysis examined outcomes of 52 patients with melanoma and pre-existing autoimmune disorders who received anti-PD-1 monoclonal antibodies. Six patients (12%) discontinued therapy, but no immunotherapy-related deaths occurred and 52% of evaluable patients achieved tumor response.

Authors of those reports concluded ipilimumab alone and anti-PD-1 monoclonal antibodies are feasible for patients with autoimmune disorders.

“However, we have to keep in mind this is a small amount of data, which is why this is a work in progress,” Bonomi said. “And there certainly could have been selection bias.”

Additional studies show:

Ipilimumab appears to be feasible for patients with progressive hematologic malignancies after allogeneic transplant. There is minimal data for use of anti-PD-1 or anti-PD-L1 monoclonal antibodies for solid organ transplant recipients.

Early evidence suggests immune checkpoint inhibitors could help with viral clearance among patients with hepatitis B, hepatitis C or HIV infections. HIV and hepatitis C should not be viewed as a contraindication to anti-PD-1 treatment, Bonomi said.

Response rates to immune checkpoint inhibitors may be lower among patients on immunosuppression.

Bonomi also addressed the question of whether elderly patients can mount an immune response.

He summarized a paper published in 2016 that examined outcomes of 5,265 patients with cancer who received anti-CTLA-4 or anti-PD-1 treatment in randomized controlled trials. Age cutoffs were 65 years and 70 years

A meta-analysis that compared younger patients with older patients treated with immune checkpoint inhibitors showed both age groups derived benefits in terms of OS (HR for younger = 0.75; HR for older = 0.73) and PFS (HR for younger = 0.58; HR for older = 0.77).

Consequently, older age should not be a contraindication to treatment with immune checkpoint inhibitors, Bonomi said. Instead, functional status is a more relevant factor. However, additional data are needed regarding efficacy and toxicity of immune checkpoint inhibitors in the elderly.

An effort is underway within ASCO to try to relax eligibility criteria for clinical trials to try to make them more like the real world. Suggested strategies include excluding patients with brain metastases only if there is a compelling rationale; including low-risk patients with HIV; liberalizing creatinine clearance exclusions; and including most patients with prior cancer.

Efforts like this may produce new insights into certain patient subsets that may derive benefit from certain treatments, including immunotherapy.

“We need to increase the inclusiveness of trial eligibility criteria so when we get the results, they’ll look much more like what we are going to see when we treat real-world patients,” Bonomi said.

 

Reference:

Bonomi P. Who is eligible to receive immunotherapy? Presented at: HemOnc Today New York; March 8-10, 2018; New York.

 

Disclosure: Bonomi reports honoraria for participation in advisory boards and data monitoring committees with AstraZeneca, Biodesix, Bristol-Myers Squibb, Clovis, Helsinn, Imedex, Merck, Pfizer, Roche/Genentech, Spectrum and Trovagene.

NEW YORK — The pool of patients eligible to receive immunotherapy likely should include many individuals who were excluded from early immunotherapy trials, according to a presenter at HemOnc Today New York.

“We need data from the real world,” Philip Bonomi, MD, professor of medical oncology at Rush University Medical Center, said during a presentation. “With the electronic medical record, we need to try to extract it and analyze it. This is going to give us a lot of useful information.”

Immunotherapy induces durable responses in subsets of patients with a variety of cancers.

Due to trial results and considerable marketing, patient demand for this modality also is high.

However, several groups were excluded from immuno-oncology trials, so questions remain about whether therapy is effective and safe in the excluded groups.

Common clinical trial exclusion criteria include organ dysfunction, ECOG performance status of 2 or higher, presence of brain metastases and prior cancer history.

Specific exclusion criteria for immunotherapy trials include autoimmune disorders (eg, rheumatologic, gastrointestinal or neurologic), chronic viral infections (eg, HIV, hepatis B virus or hepatitis C virus) and chronic immunosuppressive therapy.

Bonomi reviewed several studies in the literature that offer real-world insights into how some of these patient subsets fare with immunotherapy.

One analysis included 30 patients with melanoma and a pre-existing autoimmune disorder. All patients received the anti-CTLA-4 antibody ipilimumab (Yervoy, Bristol-Myers Squibb).

Eight patients (27%) experienced exacerbation of their autoimmune disorder, and all cases resolved after prednisone treatment. Ten patients (33%) experienced immune-related adverse events, and one patient died of colitis. Six patients (20%) responded to treatment.

Another analysis examined outcomes of 52 patients with melanoma and pre-existing autoimmune disorders who received anti-PD-1 monoclonal antibodies. Six patients (12%) discontinued therapy, but no immunotherapy-related deaths occurred and 52% of evaluable patients achieved tumor response.

Authors of those reports concluded ipilimumab alone and anti-PD-1 monoclonal antibodies are feasible for patients with autoimmune disorders.

“However, we have to keep in mind this is a small amount of data, which is why this is a work in progress,” Bonomi said. “And there certainly could have been selection bias.”

Additional studies show:

Ipilimumab appears to be feasible for patients with progressive hematologic malignancies after allogeneic transplant. There is minimal data for use of anti-PD-1 or anti-PD-L1 monoclonal antibodies for solid organ transplant recipients.

Early evidence suggests immune checkpoint inhibitors could help with viral clearance among patients with hepatitis B, hepatitis C or HIV infections. HIV and hepatitis C should not be viewed as a contraindication to anti-PD-1 treatment, Bonomi said.

Response rates to immune checkpoint inhibitors may be lower among patients on immunosuppression.

Bonomi also addressed the question of whether elderly patients can mount an immune response.

He summarized a paper published in 2016 that examined outcomes of 5,265 patients with cancer who received anti-CTLA-4 or anti-PD-1 treatment in randomized controlled trials. Age cutoffs were 65 years and 70 years

A meta-analysis that compared younger patients with older patients treated with immune checkpoint inhibitors showed both age groups derived benefits in terms of OS (HR for younger = 0.75; HR for older = 0.73) and PFS (HR for younger = 0.58; HR for older = 0.77).

Consequently, older age should not be a contraindication to treatment with immune checkpoint inhibitors, Bonomi said. Instead, functional status is a more relevant factor. However, additional data are needed regarding efficacy and toxicity of immune checkpoint inhibitors in the elderly.

An effort is underway within ASCO to try to relax eligibility criteria for clinical trials to try to make them more like the real world. Suggested strategies include excluding patients with brain metastases only if there is a compelling rationale; including low-risk patients with HIV; liberalizing creatinine clearance exclusions; and including most patients with prior cancer.

Efforts like this may produce new insights into certain patient subsets that may derive benefit from certain treatments, including immunotherapy.

“We need to increase the inclusiveness of trial eligibility criteria so when we get the results, they’ll look much more like what we are going to see when we treat real-world patients,” Bonomi said.

 

Reference:

Bonomi P. Who is eligible to receive immunotherapy? Presented at: HemOnc Today New York; March 8-10, 2018; New York.

 

Disclosure: Bonomi reports honoraria for participation in advisory boards and data monitoring committees with AstraZeneca, Biodesix, Bristol-Myers Squibb, Clovis, Helsinn, Imedex, Merck, Pfizer, Roche/Genentech, Spectrum and Trovagene.

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