my personal edition > lymphomas > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Induces High Response Rates in Previously Treated Patients With Diffuse Large B-Cell Lymphoma: Presented at ICML

By Chris Berrie

LUGANO, SWITZERLAND -- June 14, 2005 -- Radioimmunotherapy with ⁹⁰Y-ibritumomab tiuxetan is well tolerated with no unexpected toxicities, and induces high and durable response rates in previously treated patients with diffuse large B-cell lymphoma (DLBCL), according to researchers.

Franck Morschhauser, MD, senior consultant in haematology and head, lymphoma unit, department of haematology, Regional University Hospital, Lille, France, discussed the multicentre, nonrandomised, open-label, phase 2 trial here on June 10^th at the 9^th International Conference on Malignant Lymphoma (ICML).

"⁹⁰Y-ibritumomab tiuxetan has been shown to be highly active in patients with follicular lymphoma, and we wanted to evaluate its efficacy and safety in elderly patients with relapsed/refractory DLBCL who were not appropriate [candidates] for autologous stem cell transplantation," Dr. Morschhauser said.

Patients fell into 2 main groups according to previous treatment: chemotherapy alone (Chemo; n = 76), and chemotherapy plus immunotherapy (rituximab; R-Chemo; n = 28). The Chemo patients were further stratified into primary refractory disease (A1; n = 33), relapsed < 1 year from first diagnosis (A2; n = 10), and > 1 year from first diagnosis (A3; n = 33).

Inclusion criteria were: age 60 years or greater, not eligible for myeloablative therapy, histologically confirmed CD20+ first-relapse or primary DLBCL, 1 prior CHOP or CHOP-like chemotherapy (cyclophosphamide, doxorubicin, prednisolone, vincristine) with or without rituximab, less than 25% bone marrow involvement; World Health Organization performance status (PS) 2 or less, and a life expectancy of 3 months or greater.

To avoid large toxicity, Dr Morschhauser said, "We decided to exclude patients with impaired bone marrow, patients who had prior bone marrow transplantation, and patients who had more than 1 prior chemotherapy treatment and those who had >25% irradiation to the active bone marrow."

The treatment schedule included a 250-mg/m² predose of rituximab on day 1, which was repeated on day 8. The schedule also included optional dosimetry trials of low-dose ⁹⁰Y-ibritumomab tiuxetan on days 1, 2, 4, 5, and 7. A single 14.8 MBq/kg (0.4 mCi/kg) therapeutic dose of ⁹⁰Y-ibritumomab tiuxetan immediately followed the second rituximab predose on day 8, to a maximum dose of 1184 MBq (32 mCi).

Dr. Morschhauser noted that following the prior first-line therapy in the refractory chemotherapy-alone patients (Chemo-A1), two thirds (67%) had shown a partial response, but no complete response, and 24% had displayed progressive disease. In comparison, while the R-Chemo patients showed a rate of complete response or unconfirmed complete response (CR/Cru) of 50%, they also showed the highest rate of progressive disease with the prior treatment, at 36%.

With 100 patients receiving the entire treatment, after a 22-month follow-up, the overall response rate (ORR) ranged from 20% in the optimal R-Chemo group to 58% in the Chemo-A3 group. Dr Morschhauser also emphasised the very good ORR of 53% in the Chemo-A1 refractory patients that included 25% in CR/CRu, and the 40% ORR of the Chemo-A2 group.

For progression-free survival across the Chemo groups, around 40% of the patients had a durable response, which fell to around 10% for the R-Chemo patients.

A general 40% to 50% Common Toxicity Criteria (CTC) grade 3/4 thrombocytopaenia and neutropaenia was seen, with the timing of the rapid fall in platelet counts seen at week 4.

There were 4 deaths that were unrelated to disease progression -- 2 from probable cerebral haemorrhage during CTC grade 4 thrombocytopaenia, 1 from duodenal ulcer bleeding, and 1 from a gastric adenocarcinoma that was not related to treatment. Infections and pyrexia were not a serious problem with this treatment, Dr. Morschhauser said.

Levels of lactic dehydrogenase (normal vs elevated; P =.013) and bulk disease (maximum lesion diameter; 5 cm; P =.008) were the only significant predictors found for a good response to ⁹⁰Y-ibritumomab tiuxetan therapy.

Dr. Morschhauser stressed that these high rates of durable response with good tolerability now justify the use of ⁹⁰Y-ibritumomab tiuxetan as part of first-line therapy in patients with DLBCL.


[Presentation title: Yttrium-90 Ibritumomab Tiuxetan (Zevalin) Induces High Response Rates in Previously Treated Patients With Diffuse Large B-Cell Lymphoma (DLBCL). Abstract 065]

E-Mail this DGDispatch to a colleague

To print, use this version