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Background: Rituximab has revolutionized the treatment of lymphomas and has been shown to improve clinical outcomes in patients with follicular lymphoma. Our study evaluated the ...progression free survival (PFS) and overall survival (OS) in patients with grades I and II follicular lymphoma when rituximab was used as initial therapy, as salvage or if no rituximab was used. Methods: Patients with grades I and II follicular lymphoma treated between June 1981 and January 2010 were included. Disease and treatment related variables were compared based on type of treatment (No rituximab-Group I, rituximab as salvage-Group II, Rituximab as initial treatment-Group III) using the Kruswal Wallis or chi-square tests. Univariate probabilities of PFS and OS were estimated using the Kaplan Meier method. Multivariate analyses were performed using Cox proportional hazards regression analysis to evaluate differences in risk of treatment failure and mortality in the three groups while adjusting for covariates. Results: There were 226 patients in group I, 84 in group II and 110 in group III. Significant differences were found in some of the disease and treatment related variables. Univariate analysis is shown in the Table. The relative risk of treatment failure for group II was 0.82 (p=0.26) and 2.63 (p=0.0001) respectively in the first 10 years and after 10 years while it was 0.52 (p=0.0003) and 3.97 (p=0.001) respectively for group III in the first 10 years and after 10 years. The relative risk of mortality in group II was 0.63 (p=0.008) and group III was 0.32 (p<0.0001). Conclusions: Overall survival for patients with low grade follicular lymphoma is significantly improved when rituximab is used as initial treatment or as salvage when compared with no rituximab. Table: see text
While approved for treatment of cancer-related hypercalcemia, gallium nitrate (Ganite®; GN) has displayed broad antitumor activity as a single agent in Phase 2 trials, particularly in patients (pts) ...with bladder disease, Hodgkin's disease, and NHL who received GN by bolus or continuous IV infusion (CIVI). To establish the safety profile and clincial activity in a large cohort of patients with a wide variety of histologies, we conducted a Phase 2 study in pts with both T- and B-cell lymphoma who had relapsed from standard anti-lymphoma therapy.
Eligibility criteria included: relapsed NHL; ECOG PS ≤ 2; measurable disease; adequate renal and hepatic function. GN was administered by CIVI daily via ambulatory infusion pump x 7 days every 3 wks at 1 of 2 daily dose levels, 200 or 300 mg/m2/d. Evaluation for efficacy required treatment with ≥ 2 cycles; all treated pts were considered evaluable for safety. A total of 88 pts were accrued to the trial, 44 pts at each dose level. Pt characteristics included: median age, 61 yrs (range 19–83); median prior regimens, 5 (range 1–13); median prior drugs, 9 (range, 1–15); median prior rituximab regimens, 2 (range, 1–6); no. of pts with prior stem cell transplant, 25 (28%); no. of pts with prior radiation therapy, 29 (33%).
At the 300 mg/m2 dose level, 30 pts are evaluable for response. The ORR in this dose level was 30% (7% CR or uCR), including 3/12 pts with diffuse LCL (DLCL) (2 post-BMT), 3/11 with follicular lymphomas (1 post-BMT), 2/3 pts with mantle cell NHL (1 CR), 0/2 pts with SLL, and 1/2 pts with peripheral T-cell NHL (1 uCR). The results in the 200 mg/m2 dose level are preliminary and currently under evaluation.
Most frequent (> 10%) grade 3/4 adverse reactions (through July 2004) included: anemia (32%); hypocalcemia (19%) (occasionally requiring parenteral replacement with Ca++ and Mg++); dyspnea (15%); and hypotension (11%). Optic neuritis or visual disturbance occurred in 4 pts: 3 pts at the 300 mg/m2 dose level (after 2, 3 and 6 cycles, respectively) and 1 pt at the 200 mg/m2 dose level (after 7 cycles). All patients discontinued therapy as a consequence of this adverse event; two pts were treated with high-dose corticosteroids. All patients improved after discontinuation.
These results demonstrate that gallium nitrate is an active and well tolerated agent in a heavily pretreated population of patients with NHL and suggest that it may be particularly useful in patients who cannot tolerate myelosuppressive regimens.
Abstract A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell ...transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days −11, −8, −5, and −2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m2 ) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day −11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m2 but it was later decreased to 1 mg/m2 because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial.
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