Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study.

UNLABELLED: We report a phase II study to evaluate the efficacy and toxicity of abbreviated immunochemotherapy followed by (90) Y Ibritumomab tiuxetan ((90) Y-IT) in patients with recurrent follicular lymphoma. Of the 52 patients enrolled, 50 were treated with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone), followed by (90) Y-IT regimen (15 MBq/kg, maximum 1200 MBq) preceded by two infusions of 250 mg/m(2) rituximab. The overall response rate was 98% with complete response (CR) 30% and partial response (PR) 68%. 18 patients with a PR following chemotherapy improved to a CR following (90) Y-IT: a conversion rate of 40%. Seven patients with PR following (90) Y-IT subsequently improved to a CR 12-18 months later, leading to an overall CR rate of 44%. With a median follow-up of 5 years, median progression-free survival was 23·1 months and overall survival was 77·5% at 5 years. High trough serum rituximab levels (median 112 µg/ml; range 52-241) were attained after four doses of rituximab, prior to (90) Y-IT; this was not found to influence response rates. The treatment was well tolerated with few (13·5%) grade 3 or 4 infective episodes and manageable haematological toxicity. Abbreviated immunochemotherapy followed by (90) Y-IT is an effective and well-tolerated treatment in recurrent follicular lymphoma patients previously exposed to rituximab. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00637832.

Fractionated 9°Y-ibritumomab tiuxetan radioimmunotherapy as an initial therapy of follicular lymphoma: an international phase II study in patients requiring treatment according to GELF/BNLI criteria.

PURPOSE: We report an international, multicenter phase II trial to evaluate the efficacy and toxicity of fractionated (90)Y-ibritumomab tiuxetan ((90)Y-IT) as initial therapy of follicular lymphoma (FL). PATIENTS AND METHODS: A total of 74 patients, with a median age of 61 years (range, 28 to 80 years), were recruited requiring initial therapy by Groupe d'Etude des Lymphomes Folliculaires (GELF)/British National Lymphoma Investigation (BNLI) criteria. Among them, 78% had stage III-IV disease, 32% intermediate, and 44% high-risk (according to FL International Prognostic Index). Treatment consisted of two doses of (90)Y-IT (11.1 MBq/kg) administered 8 to 12 weeks apart. Patients with more than 20% lymphoma infiltration of bone marrow (BM) received one infusion per week for 4 consecutive weeks of rituximab (375 mg/m(2)) and proceeded to fractionated radioimmunotherapy (RIT) only if a repeat BM biopsy demonstrated clearing of lymphoma to less than 20% involvement. The primary end point was end of treatment response of the intention-to-treat population. Secondary objectives were safety and progression-free survival (PFS). RESULTS: Initial overall response rate (ORR) was 94.4% (68 of 72 patients) with combined complete response (CR/CRu) of 58.3% (42 of 72 patients). Nine patients subsequently improved response making an ORR of 95.8% (69 of 72 patients) and CR/CRu of 69.4% (50 of 72 patients). At a median follow-up of 3.1 years (range, 0.2 to 5.2 years) estimated 3-year PFS is 58%, treatment-free survival 66%, and overall survival 95%. Median PFS is 40.2 months. Thirty patients have experienced disease progression and 24 have required further treatment. The treatment was well tolerated with few (2.8%) grade 3 or 4 infectious episodes or adverse events and manageable hematologic toxicity. CONCLUSION: Fractionated RIT using (90)Y-IT is an effective initial treatment for advanced-stage FL in patients with higher tumor burden requiring treatment.

Phase 1/2 study of fractionated (131)I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy.

The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of (131)I-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of (131)I-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of (131)I-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent (131)I-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of (131)I-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity.

Quality control of slope-intercept measurements of glomerular filtration rate using single-sample estimates.

OBJECTIVES: Measurement of glomerular filtration rate (GFR) using the slope-intercept technique determines the plasma clearance curve by fitting a straight line to the logarithm of sample count rate. When two samples are used there is no check on the validity of curve fitting. GFR may also be estimated from single-sample concentrations. This study describes a method of quality control for the two-sample technique using the agreement between the one-sample and two-sample estimates. METHODS: GFR measurements using Tc-DTPA were performed on 225 adults and 100 children using two samples taken between 2 h and 4 h post-injection. The two-sample values obtained using the British Nuclear Medicine Guidelines slope-intercept technique were compared to one-sample estimates obtained using a new general equation. Equations describing the variation of GFR error with GFR value were defined. These were used to determine action levels giving the limits of expected agreement between slope-intercept and single-sample values. The use of these action levels for quality control was demonstrated in a further 120 GFR measurements. RESULTS: The variation of single-sample error estimate with GFR depended both on the time of sample and body surface area. For specific sample groups, the error variation with GFR could be approximated using a truncated quadratic equation. Four studies were identified as failing quality control in the dataset used to define the error equations. Two studies failed in the test dataset. CONCLUSIONS: One-sample equations give reliable estimates of GFR, which may be used for quality control of slope-intercept GFR assessment.

A general equation for estimating glomerular filtration rate from a single plasma sample.

OBJECTIVES: Glomerular filtration rate (GFR) may be estimated from a single plasma sample measurement using empirical equations. This method forms the basis of international guidelines on GFR measurement. New guidelines have recently been recommended by the British Nuclear Medicine Society (BNMS). These use the slope-intercept technique in which several samples are obtained. Quality control of measurement may be achieved by comparison with the individual single-sample values. This paper compares international guideline single-sample estimates of GFR with the new BNMS method and derives an improved general single-sample equation. METHODS: GFR measurements using Tc-DTPA were performed on 180 adults and 100 children using samples at approximately 2 h and 3 h and a further 45 adults with samples at 2, 3 and 4 h. The two-sample values obtained using the BNMS guideline method were compared to one-sample estimates obtained using (1) international guidelines and (2) a new equation derived from the data. The new equation was evaluated in a further 145 subjects. RESULTS: The international guidelines technique had systematic differences between the one-sample and two-sample estimates of GFR. The new equation had minimal systematic error and reduced random error (standard error of the estimate 4.5 ml . min per 1.73 m). CONCLUSIONS: There were significant differences between GFR values obtained using the international guidelines single-sample method and the slope-intercept method described in the BNMS guidelines. The new equation described in this paper gave considerably improved agreement and is recommended if single-sample estimates are to be used as quality control for BNMS guideline measurements.

Guidelines for the measurement of glomerular filtration rate using plasma sampling.

These guidelines have been adopted by the British Nuclear Medicine Society.