Predictors and Treatment for Transformed Lymphoma: Current Paradigms

A Conversation with Richard I. Fisher, MD

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At the recent Pan Pacific Lymphoma Conference, held in Maui, Hawaii, Richard I. Fisher, MD, Chairman of the SWOG Lymphoma Committee and Vice-President for Strategic and Program Development at the University of Rochester Medical Center in New York, gave a presentation on the characteristics and treatment of transformed lymphoma. The ASCO Post subsequently spoke with Dr. Fisher about some of the topics he had addressed.

Transformation Predictors

What factors are predictive of lymphoma transformation?

I will define lymphoma transformation as the change in histology from a low-grade or indolent lymphoma to a more aggressive lymphoma, usually diffuse large B-cell lymphoma or Burkitt’s lymphoma. The diagnosis should always be made by a repeat biopsy. In that regard, there are certain clinical variables that have been shown to be predictive of transformation. They include advanced stage, high International Prognostic Index (IPI) or Follicular Lymphoma International Prognostic Index (FLIPI), and high β2 microglobulin, all at diagnosis.

After initial treatment, patients not achieving a complete remission are more likely to have a transformation. To date, it is unclear whether early treatment vs a “watch and wait” strategy has any impact on the risk of transformation. Most studies suggest there is no change in risk. Some data suggest that initial treatment with rituximab (Rituxan) does lower the risk of transformation, although this has not been proven. Finally, overall transformation does increase with time from diagnosis, approaching 30% of all cases in most series.

Outcome Predictors

What factors are predictive of outcome of transformed lymphoma?

The outcome for patients with transformed lymphoma historically has been very poor. Multiple series suggest the median survival ranges from only 1 to 2 years. However, certain series have suggested that some patients will have a better outcome after transformation—these include patients who had limited-stage disease at diagnosis, have not been treated with chemotherapy, and have achieved a complete remission from their initial treatment. Patients who have transformed in a single site, as opposed to having disseminated disease, have an improved survival in almost all series.

Treatment Options

What are the best available treatments for transformed lymphoma, and what new options may become available in the near future?

For many years, the standard of care has been to attempt to reinduce the patient into a very good response (either complete or partial remission) and then proceed to autologous stem cell transplantation. Results in selected series of patients treated in this manner have shown 5-year progression-free survival in the range of 30% to 45%. Treatment with allogeneic transplantation and radioimmunotherapy has also been reported in selected series.

Treatment Recommendations

How do you currently treat transformed lymphoma?

If patients have not received chemotherapy prior to their transformation, I traditionally treat them with a course of R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone]. Among patients achieving a complete response that is verified as being PET-negative, some may not need to have additional therapy—although this has not been proven convincingly. Other patients should be offered consolidation with autologous stem cell transplantation or radioimmunotherapy (Fig. 1).

Patients who achieve only a partial response to R-CHOP should receive an autologous transplant or radioimmunotherapy. Patients who have not had a partial response may be considered for treatment with another salvage therapy followed by autologous transplantation or radioimmunotherapy.

For patients who have a localized transformation, a course of R-CHOP followed by involved-field radiation seems reasonable. For patients who have had prior chemotherapy, I would consider a salvage therapy followed by autologous stem cell transplantation or radioimmunotherapy. It is hoped that new targeted therapies will also be able to impact disease at this stage, but this needs to be proven in future studies. ■

Disclosure: Dr. Fisher reported no potential conflicts of interest.