LOW DOSE REGIMEN FOR EARLY HODGKIN LYMPHOMA

June 15, 2010 (Barcelona, Spain) – Early favorable Hodgkin's lymphoma can be treated less intensively with markedly reduced toxicity using 2 cycles of ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) followed by 20 Gy of involved-field radiotherapy (IFR). The German Hodgkin Study Group recommends this as the new standard of care.

Results from the HD10 trial were presented here at the 15th Congress of the European Hematology Association by Peter Borchmann, MD, from the University Hospital Cologne, Germany, on behalf of the German Hodgkin Study Group.

"In our study, we asked 2 questions. Regarding chemotherapy, do we need 4 cycles or 2 cycles of ABVD? Regarding radiotherapy, do we need 30 Gy or 20 Gy? This is the first of our studies to take a noninferiority approach," Dr. Borchmann told the conference.

Between 1998 and 2003, 1370 patients were randomized into 4 study groups: 4 cycles of ABVD (4 × ABVD) followed by 30 Gy of IFR; 4 × ABVD followed by 20 Gy of IFR; 2 × ABVD followed by 30 Gy of IFR; and 2 × ABVD followed by 20 Gy of IFR. More than 99% of cases were included in the final analysis.

With a median follow-up of 79 to 91 months, there was no significant difference between 4 × ABVD and 2 × ABVD in terms of overall survival at 5 years (97.1% and 96.6%, respectively), freedom from treatment failure (93.0% and 91.1%), or progression-free survival (93.5% and 91.2%).

"Most important, 2 cycles of ABVD are not inferior to 4 cycles if followed by radiotherapy," Dr. Borchmann reported.

In terms of radiotherapy, progression-free survival was 93.7% with 30 Gy and 93.2% with 20 Gy IFR. He added that 20 Gy was as effective as 30 Gy when added after chemotherapy.

Toxicity, a major drawback of both therapies, differed significantly among the 4 study groups, and between both 4 and 2 ABVD cycles and 20 and 30 Gy IFR.

"Regarding chemotherapy, we found that 2 cycles of ABVD, compared with 4, is less toxic, with 33% vs 54% for [World Health Organization] grade 3/4 toxicities," the German investigator reported. Toxicities with 4 × ABVD vs 2 × ABVD included leukopenia (24% vs 15%), and hair loss (28% vs 15%).

Overall toxic events were more frequent with 30 Gy IFR than with 20 Gy IFR (8.7% vs 2.9%, respectively), added Dr. Borchmann.

Toxicity was at a very low level for the study groups. "There is no significant reduction in late toxicities, although more time is needed to judge late toxicities. Ideally, we need 10 to 15 years at least," he told Medscape Hematology.

A note of caution was voiced by Patrice Carde, MD, Hodgkin's lymphoma specialist from Clinique Hartman, Neuilly sur Seine, France, who noted that the 2 × ABVD plus 20 Gy IFR might be more suitable for specialist clinics.

These findings are "true in the setting of a trial, with patients who are well studied and who have a complete work-up by experts. But it is unlikely to be as relevant with nonspecialized hematologists. I would therefore advise not to decrease treatment too much or [you might] risk incorrect evaluation of the patient. If this happens, then this less toxic treatment will cause relapse. So be aware that this result is obtained by expert hematologists and cannot be transposed to any setting," remarked Dr. Carde.

Dr. Carde explained that the EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte scientific boards advocate a slightly more flexible regimen of 3 cycles of ABVD and radiotherapy between 20 and 30 Gy as standard treatment for early favorable Hodgkin's lymphoma patients.

"I am confident there is no difference in toxicity between 2 and 3 cycles of ABVD, or even 4 cycles. We are therefore playing with subtle differences that put patients at risk of relapse if everything is not well followed," Dr. Carde said.

Dr. Borchmann and Dr. Carde have disclosed no relevant financial relationships.

15th Congress of the European Hematology Association (EHA): Abstract 1145. Presented June 13, 2010.