Repeat Rituximab Dosing Effective in Low-Grade NHL

BETHESDA, Md—Low-grade lymphomas usually respond to initial chemotherapy but almost inevitably relapse. Each subsequent chemotherapy regimen produces a shorter response. Research presented at the American Society of Hematology meeting suggests that this may not be the case with the anti-CD20 antibody rituximab (Rituxan).

Thomas Davis, MD, of the NCI, and his colleagues reported that about 40% of patients with low-grade or follicular non-Hodgkin’s lymphoma who had initially responded to rituximab also responded to a second round of treatment, and that re-treatment produced response durations as good as those of initial rituximab therapy.

A Case Study

As an example of the efficacy of rituximab re-treatment, Dr. Davis presented a case study of a 44-year-old female diagnosed with low-grade NHL, IWF type B, in November 1990. Prior treatments included PROMACE-MOPP, radiotherapy, interferon-alfa, 5-FAMP, and FND.

The patient received three courses of rituximab, with times to progression of 8.1 months, 9.8 months, and 10.6 months, respectively. The third course produced shrinkage (the sum of the perpendicular diameters of lesions) from 15.63 cm at baseline to 4.08 cm 2 months after treatment and 1.75 cm 2 months after that, a shrinkage of 89% in the tumor burden.

A fourth course of rituximab has produced an ongoing partial remission.

“Rituximab has good efficacy in about half of patients in whom the real question becomes, how long can you continue to treat with the antibody and avoid alternate therapies?” Dr. Davis said in an interview. “For patients who have low-grade or follicular lymphoma, survival may ultimately depend on how many different treatments you can give.”

This open-label, single-arm study enrolled 58 patients. All were treated with one additional course of rituximab (375 mg/m² intravenously once weekly for 4 weeks), and two patients also received a third course.

All patients were relapsed or refractory to prior chemotherapy but had previously responded to rituximab. All had relapsed after rituximab and required further treatment. In addition to chemotherapy, 18 patients had received bioimmunotherapy other than rituximab, and 18 had received radiotherapy.

Dr. Davis reported data from 57 patients who were evaluable for efficacy. The overall response rate to the second round of rituximab was 40%. This included complete responses in six patients (11%) and partial responses in 17 patients (30%). This is in contrast to patients treated with chemotherapy who typically do not respond to repeated administration of a regimen once their disease has progressed.

Response Duration

At the time of this report, the median duration of response was 15+ months (range, 2.5 to 25.1 months), and the median time to progression was 16.7+ months (range, 4.6 to 26.6 months).

“There is evidence that for patients who respond to a first course of rituximab, the duration of response will be longer than the duration of their response to prior chemotherapy. From this study, we see that they also respond at least as well to rituximab the second time around,” Dr. Davis said.

The safety profile was similar to that reported for initial treatment with rituximab, consisting primarily of infusion-related adverse events usually occurring within the first few hours of the first infusion. None of the patients developed human antichimeric antibodies (HACA).

“The side effects of this treatment are more tolerable than those of radiotherapy or chemotherapy, so if we can use rituximab repeatedly, patients should have a better quality of life,” Dr. Davis said.

He advised that patients who have responded to rituximab and relapsed “should definitely be retreated. You may want to consider doing another fine-needle aspiration biopsy to make sure the tumor still has CD20 expression and thus has a chance of responding to the antibody.”

Experience to date suggests that rituximab does not induce resistance to subsequent chemotherapy or reduce its efficacy. “The benefits of multiple courses of rituximab include deferring toxic alternative treatments and preserving marrow function,” he said.