Dr. Younes: So although the watch-and-wait policy has been implemented for many years for patients with advanced-stage follicular lymphoma who are asymptomatic, I think this strategy is fading away based on the LymphoCare analysis, which showed the vast majority of patients are treated.1 In lieu of watch and wait, I think many oncologists now are electing to treat patients with either rituximab alone or even with combination of rituximab and other agents.1
However, if one, let's say, has a patient who [was] observed for, let's say, two to three years with no therapy and the patient was not symptomatic, and now the patient is developing symptoms or signs requiring therapy, there are now two widely used approaches for such a patient. One is the use of bendamustine plus rituximab [R]2,3 and the other one is to use standard R-CHOP [cyclophosphamide-doxorubicin-vincristine-prednisone] chemotherapy.4-6 There is an advantage and a disadvantage for using either one alone. There are data now to suggest that bendamustine plus rituximab can produce longer progression-free survival [PFS], which means longer disease control. But there's not much data about the impact on survival yet.
Narrator: Bendamustine plus rituximab was compared with standard R-CHOP for six cycles in a randomized, phase 3 trial of patients with advanced indolent or mantle-cell lymphomas.2 The bendamustine arm showed superior median progression-free survival (69.5 versus 31.2 months) for all histologic subtypes except marginal zone lymphoma. Less toxicity was observed as well, including lower rates of grade 3 and 4 neutropenia and leukocytopenia, fewer infectious episodes, less paresthesia and stomatitis, and no alopecia. There was no difference in overall survival (OS) at a median follow-up of 45 months. The long-term toxicity profile and impact on future treatments are unknown at this time.
Standard R-CHOP was compared with R-CVP (cyclophosphamide-vincristine-prednisone) and R-FM (fludarabine-mitoxantrone) in a randomized trial of 534 patients with advanced-stage follicular lymphoma.5 The R-CHOP and R-FM arms were associated with superior rates of three-year PFS and time to treatment failure, versus R-CVP; a survival analysis was not performed. R-FM had higher rates of severe neutropenia and second malignancies.
Dr. Younes: For the average patient who becomes symptomatic and, let's say, has a borderline heart function or has some signs of potential histologic transformation—and this is usually indicated by areas in the PET scan that show a high SUV value—one would probably attempt to then select either/or [approach]. So with a borderline left ventricular ejection fraction, I would stay away from anthracycline-based regimen, and I would use a bendamustine-based regimen. If there's an early indication of histologic transformation, then my preference is to use R-CHOP chemotherapy instead of R-bendamustine.
Narrator: Support for this approach is provided by retrospective analyses of patients with histologic transformation and extrapolation of data from patients with de novo diffuse large B-cell lymphoma (DLBCL). Retrospective studies suggest that some patients who have received little prior therapy treated with chemoimmunotherapy alone have five-year survival rates of approximately 60%.7-9
Dr. Younes: Outside these two scenarios, I think it's patient-physician preference and one can use either one of these regimens, knowing that if one starts with R-bendamustine and the patient has relapsed disease or progression after a few years, you can treat with R-CHOP and vice versa.
For patients who achieve a remission after R-CHOP or R-bendamustine, would you do a maintenance rituximab? There are data for the R-CHOP regimen.10 There are not much data about R-bendamustine, but one thinks that the principle should hold for either one; although, this needs to be tested in a clinical trial. But it is also an option to then follow up with maintenance rituximab, especially for those who have positive PET residual lesions at the end of R-CHOP chemotherapy. There may be some benefit for prolonging the time to next therapy and the time to progression.