Hodgkin Lymphoma: Doing More with Less

Hodgkin lymphoma is one of the success stories in the history of cancer treatment. Cure rates approach 90 percent in limited stage disease and range from 50-80 percent in advanced stage, depending upon the prognostic score. Most patients are diagnosed at a relatively young age, and there is increasing recognition of iatrogenic late complications, which increase morbidity and mortality in Hodgkin survivors.

In an effort to improve cure rates while minimizing late complications of therapy, investigators at Stanford University have developed the Stanford V regimen. For patients with stage III, IV, and bulky stage II, this is a 12-week chemotherapy program followed by IFRT (36 Gy) to nodal masses greater than 5 cm or to macroscopic splenic disease. For patients with non-bulky stage I or IIA disease, this is an eight-week chemotherapy program followed by IFRT (30 Gy). At this year’s ASH meeting, Dr. Sandra Horning combined the data from the two different protocols for the purpose of reporting toxicity and any long-term complications of therapy. The most frequent acute toxicities are expected myelosuppression and constipation. Notably, there have been no cases of bleomycin lung toxicity, radiation pneumonitis, therapy-related MDS, or acute leukemia. Second cancers have been rare and in the cases reported, a significant association with prior radiotherapy is not seen. Twenty- five percent of individuals have successfully conceived after therapy. This updated outcome data, combined with the toxicity data, provide additional rationale for the ongoing support of E2496, an intergroup study comparing Stanford V to ABVD for bulky stage II and stage III/IV disease.

The German Hodgkin Lymphoma Study Group presented data from an interim analysis of their ongoing HD10 Trial. In this study, 1131 patients with favorable limited stage Hodgkin lymphoma were randomized to ABVD x 4 plus 30 Gy IFRT, ABVD x 4 plus 20 Gy IFRT, ABVD x 2 plus 30 Gy IFRT, or ABVD x 2 plus 20 Gy IFRT. With a median follow-up of two years, the overall survival for the entire cohort is 98.5 percent, and the freedom from treatment failure is 96.6 percent. To date, no differences in freedom from treatment failure or overall survival have been demonstrated when comparing ABVD x 4 vs. ABVD x 2, or for the comparison of 30 Gy IFRT vs. 20 Gy IFRT. The suggestion is that less therapy may produce comparable outcomes for this subgroup of limited stage patients. However, very few events have been observed to date, and it would be prudent to await mature results before making any alterations in the routine management of these patients.

The German Hodgkin Lymphoma Study Group also presented interim data from their HD 11 trial. This trial is designed for patients with clinical stage I or IIA with adverse risk factors, or stage IIB patients with elevated ESR and/or 3 nodal areas. Between 1998 and 2002, 1363 patients were randomized to ABVD x 4 plus 30 Gy IFRT, ABVD x 4 plus 20 Gy IFRT, BEACOPP x 4 plus 30 Gy IFRT, or BEACOPP x 4 plus 20 Gy IFRT. With a median observation time of two years, the overall survival for the entire group is 97 percent and the freedom from treatment failure is 90 percent. For both OS and FFTF, there is no difference to date between the ABVD and BEACOPP arms or the 30 Gy IFRT and the 20 Gy IFRT arms. More time is needed to see if intensifying the chemotherapy or de-intensifying the radiotherapy has any effect on the outcome of these patients.