Radioimmunotherapy as Initial Therapy for Lymphoma

Zosia Chustecka

January 22, 2013

Radioimmunotherapy might be useful as an initial and standalone treatment for follicular non-Hodgkin's lymphoma, according to a phase 2 study.

The study, by Christian Scholz, MD, and colleagues from the Charité-Universitatsmedizin Berlin, Germany, working with teams in Austria, Germany, Italy, and Sweden, was published in the January 20 issue of the Journal of Clinical Oncology.

Around 35% of the 59 patients had long-lasting responses, the researchers report, although not all patients benefit equally.

"In our opinion, radioimmunotherapy is a particularly attractive therapy for older patients, patients with significant comorbidity, or patients who refuse chemotherapy," they write.

Radioimmunotherapy involves treatment with an antibody carrying high-energy short-lived radionucleotides. The product used in this trial was 90yttrium ibritumomab tiuxetan (90YIT), which is marketed as Zevalin (Spectrum Pharmaceuticals). 90YIT is currently approved in the United States and Europe for use, in combination with rituximab (MabThera, Genentech/Roche), in the treatment of relapse follicular lymphoma. It is also approved for use as a consolidation therapy after first-line chemotherapy, and has shown dramatic results in this setting.

"Given the excellent results with 90YIT as consolidation therapy, we asked whether an induction chemotherapy is needed at all," Dr. Scholz and colleagues write.

They therefore investigated its use as a standalone initial treatment. They report an overall response rate (ORR) at 6 months of 86%, with 41% of patients achieving a complete response (CR), 15% achieving an unconfirmed complete response, and 31% achieving a partial response. Median progression-free survival was 25.9 months (95% confidence interval, 18.2 - 33.7 months).

Might Prevent Overtreatment

A previous trial using this approach with a different product, iodine-131 (131I)-tositumomab (Bexxar, GlaxoSmithKline), also showed long-lasting responses (N Engl J Med. 2005;352:441-449). In that trial, 75% of patients achieved a complete response and progression-free survival at 5 years was achieved by 59%, Dr. Scholz and colleagues report.

There is speculation that the different results are related to differences in the 2 radioimmunotherapy products, but there could also have been differences in the patient populations (there is a suggestion that some of the patients in the 131I-tositumomab trial had more indolent disease), they note.

The 90YIT results build on the 131I-tositumomab results and "provide further evidence that approximately 30% to 40% of patients with follicular lymphoma might achieve long-lasting remissions with first-line radioimmunotherapy alone," Dr. Scholz and colleagues conclude.

"This might delay or even avoid the need for chemotherapy for a considerable number of patients," they explain.

It might also provide a "step toward designing strategies that intensify treatment only for relapsing patients," they add. Current strategies of trying to maximize responses for all patients with aggressive first-line regimens might result in overtreatment in a significant portion of individuals, they point out.

This is a lingering question, writes Thomas Witzig, MD, professor of medicine at the Mayo Clinic in Rochester, Minnesota, in an accompanying editorial. Dr. Witzig was the first author of a consensus report on the use of radioimmunotherapy in follicular lymphoma (Leuk Lymphoma. 2011;52:1188-1199).

"Follicular lymphoma is unique among cancers because it is often diagnosed at a time when the patient is in an advanced stage of disease but asymptomatic," he writes.

Administering early chemotherapy has not been shown to confer a survival advantage, so a "watch and wait" approach has been adopted, he explains. Although it was fairly easy to watch and wait when the only alternative was chemotherapy, it has become more difficult in the current era, when there are now 2 less toxic treatments that can be offered — upfront radioimmunotherapy and upfront rituximab.

Reviewing studies of both these approaches, Dr. Witzig notes that radioimmunotherapy appears to be more active. Upfront single-agent rituximab achieved an ORR in the low 70% range and a CR rate in the 30% range, whereas upfront single-agent radioimmunotherapy produced an ORR in the 80% to 95% range and a CR rate in the 30% range.

An appropriate study for the future would be a head-to-head comparison of these 2 approaches, he notes.

In the meantime, Dr. Witzig concludes that "it is reasonable" to treat patients who are in an early asymptomatic state with single-agent radioimmunotherapy to induce a CR, a long progression-free survival, and a potential cure.

He points out that in both of the upfront radioimmunotherapy studies, only patients who achieved a CR had a durable response, which makes this a "key goal" of single-agent upfront treatment with this modality.

"In the end, perhaps the optimal use of radioimmunotherapy upfront will be in patients with favorable clinical features in whom CR is likely," he writes.

Dr. Scholz and several coauthors report receiving honoraria and research funding from and/or acting as consultants for Bayer Schering Pharma. Dr. Witzig reports receiving research funding from Celgene, Novartis, Millenium, and Spectrum; and acting as a consultant for Celgene, Spectrum, Hospira, and Avila.

J Clin Oncol .2013;31:294-296, 308-313. Editorial, Abstract