ONCAlert | Upfront Therapy for mRCC

Best Practices for Patients at High Risk for Progression

Targeted Oncology
Published Online:12:00 PM, Fri July 26, 2019

Timothy Fenske, MD, MS: When patients are initially diagnosed with follicular lymphoma, it’s possible to assess the risk of their disease. Some patients will have low-risk disease, some patients will have high-risk disease, and there are a number of ways to assess that. One is a tool called the FLIPI [Follicular Lymphoma International Prognosis Index] score. This has been well validated in a number of studies. There’s a refinement to the FLIPI score called the FLIPI2. There’s another refinement called the m7-FLIPI, which incorporates the expression levels of a number of different genes in the tumor tissue. And there are other tools that people have been looking at, like circulating tumor DNA and PET [positron emission tomography] scan results, at baseline and then as the patient goes through treatment. And while all these tools have some predictive value, the reality is that none of them is robust in predicting which patients are going to have early progression of disease. We don’t really have a way at the beginning to select certain patients for more aggressive treatment in order to reduce their risk of early progression.

When selecting a treatment regimen for patients with follicular lymphoma going through first-line therapy, there are a couple of choices that the oncologist needs to make. One, does that patient need chemotherapy or can they get by with just an anti-CD20 antibody? This is based primarily on disease burden and symptomatology that the patient may have. In most cases we’re using an antibody-chemotherapy combination at this time. That may change in the future, but currently that would still be the standard of care for most symptomatic patients with follicular lymphoma. Having made the decision that it’s going to be an antibody-chemotherapy combination, the oncologist has 2 choices: which chemotherapy regimen and which antibody.

The most commonly used chemotherapy regimens would be bendamustine and CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], and they’re both active regimens. They do have slightly different toxicity profiles. If you have somebody who has got cardiac concerns, bendamustine may be a preferred option there. If you’re concerned that there may be a focus of histological transformation, maybe the biopsy was under sampled potentially or you have areas on your PET scan that look particularly FDG [fluorodeoxyglucose] avid, you may have a concern that that patient actually has an undiagnosed transformed component. In that scenario, CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] would be a better option.

There is a decision to be made about the chemotherapy, and there’s also a decision to be made about which antibody. I think people are used to using rituximab. It’s been out for over 20 years. The newer antibodies have been obinutuzumab, and as we discussed earlier in the GALLIUM study, obinutuzumab-chemotherapy combinations did perform better in terms of progression-free survival. I think the difference is that there’s another exploratory analysis that they did in the GALLIUM study, and if they divided the patients page-wise, those who were under 60 versus over 60, the benefit of obinutuzumab was even more pronounced in the younger patients.

I think for me, in practice if I have a younger patient—say under 60, or someone in their early to mid-60s—who’s otherwise quite fit, this is a patient I would be more likely to use obinutuzumab for. It’s not to say you couldn’t use it in an older patient, but if you’re going to use it, it’s that younger group of patients who seemed to benefit the most.

During the maintenance phase, whether you’re using rituximab or obinutuzumab, there are some concerns that we need to watch for in terms of infection. This seems to be more of an issue after obinutuzumab was the original chemotherapy. Again, that’s really not specific to 1 of the antibodies. That seems to be more related to which chemotherapy the patient got during their induction.

Transcript edited for clarity.

Timothy Fenske, MD, MS: When patients are initially diagnosed with follicular lymphoma, it’s possible to assess the risk of their disease. Some patients will have low-risk disease, some patients will have high-risk disease, and there are a number of ways to assess that. One is a tool called the FLIPI [Follicular Lymphoma International Prognosis Index] score. This has been well validated in a number of studies. There’s a refinement to the FLIPI score called the FLIPI2. There’s another refinement called the m7-FLIPI, which incorporates the expression levels of a number of different genes in the tumor tissue. And there are other tools that people have been looking at, like circulating tumor DNA and PET [positron emission tomography] scan results, at baseline and then as the patient goes through treatment. And while all these tools have some predictive value, the reality is that none of them is robust in predicting which patients are going to have early progression of disease. We don’t really have a way at the beginning to select certain patients for more aggressive treatment in order to reduce their risk of early progression.

When selecting a treatment regimen for patients with follicular lymphoma going through first-line therapy, there are a couple of choices that the oncologist needs to make. One, does that patient need chemotherapy or can they get by with just an anti-CD20 antibody? This is based primarily on disease burden and symptomatology that the patient may have. In most cases we’re using an antibody-chemotherapy combination at this time. That may change in the future, but currently that would still be the standard of care for most symptomatic patients with follicular lymphoma. Having made the decision that it’s going to be an antibody-chemotherapy combination, the oncologist has 2 choices: which chemotherapy regimen and which antibody.

The most commonly used chemotherapy regimens would be bendamustine and CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], and they’re both active regimens. They do have slightly different toxicity profiles. If you have somebody who has got cardiac concerns, bendamustine may be a preferred option there. If you’re concerned that there may be a focus of histological transformation, maybe the biopsy was under sampled potentially or you have areas on your PET scan that look particularly FDG [fluorodeoxyglucose] avid, you may have a concern that that patient actually has an undiagnosed transformed component. In that scenario, CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone] would be a better option.

There is a decision to be made about the chemotherapy, and there’s also a decision to be made about which antibody. I think people are used to using rituximab. It’s been out for over 20 years. The newer antibodies have been obinutuzumab, and as we discussed earlier in the GALLIUM study, obinutuzumab-chemotherapy combinations did perform better in terms of progression-free survival. I think the difference is that there’s another exploratory analysis that they did in the GALLIUM study, and if they divided the patients page-wise, those who were under 60 versus over 60, the benefit of obinutuzumab was even more pronounced in the younger patients.

I think for me, in practice if I have a younger patient—say under 60, or someone in their early to mid-60s—who’s otherwise quite fit, this is a patient I would be more likely to use obinutuzumab for. It’s not to say you couldn’t use it in an older patient, but if you’re going to use it, it’s that younger group of patients who seemed to benefit the most.

During the maintenance phase, whether you’re using rituximab or obinutuzumab, there are some concerns that we need to watch for in terms of infection. This seems to be more of an issue after obinutuzumab was the original chemotherapy. Again, that’s really not specific to 1 of the antibodies. That seems to be more related to which chemotherapy the patient got during their induction.

Transcript edited for clarity.
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