We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in ...patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM P = 0.002; HR 0.548 (95% CI 0.38-0.80). Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.
Treatment of chronic lymphocytic leukemia (CLL) has advanced with the introduction of chemoimmunotherapy (CIT) agents that have improved the outcomes of frontline therapy. However, most treated ...patients will relapse and require subsequent therapy. This review focuses on recent advances in the treatment of relapsed or refractory CLL. Until recently, treatment options for relapsed CLL were of limited efficacy. Retreatment with fludarabine, cyclophosphamide, and rituximab (FCR) was recommended for patients with a durable response to first-line FCR, although acquired genetic aberrations, impaired marrow reserve, and comorbidities often made this suboptimal therapy for many patients. New options include two agents targeting B cell receptor (BCR) signaling pathways (ibrutinib and idelalisib) and a B cell lymphoma-2 (BCL-2) inhibitor (venetoclax). Allogeneic hematopoietic stem cell transplantation (HSCT) remains a potentially curative option for younger patients with a suitable donor.
Background; Monoclonal antibodies are being utilized for treatment of patients with low-grade non-Hodgkin's lymphoma as well as other cancers. Results from phase I and II clinical studies has shown ...that the chimeric monoclonal antibody Rituximab has minimal toxicity and significant therapeutic activity in low grade non-Hodgkin's lymphoma. Patients and methods; We have recently reported on a multi-centre pivotal phase III clinical trial involving 166 patients with recurrent low-grade lymphoma who were treated with four infusions of Rituximab. Eighty patients (48%) achieved objective responses including 10 patients (6%) with complete responses. Overall, 126 patients (76%) had a ≥ 20% reduction in overall tumor size. The median response duration and time to progression are 11.6 and 13.2 months, respectively. The infu-sional and long term toxicities were limited. Results: In this report we describe the pharmacokinetic data obtained on these patients. Measurable concentrations of Rituximab were detected in all patients after the first infusion and increased throughout the treatment course. The half-life of the monoclonal antibody increased from 76.3 hours after the first infusion to 205.8 hours after the fourth infusion and was concomitant with a four-fold decrease in the antibody clearance. At three months and six months post-treatment, the median Rituximab serum levels were 20.3 μg/ml (range 0.0 to 96.8 μg/ml in 104 patients) and 1.3 μg/ml (range 0.0-28.7 μg/ml in 13 patients), respectively. A statistically significant correlation was found between the median antibody concentration and response for multiple time points during the treatment and followup. The mean serum antibody concentration was also inversely correlated with measurements of tumor bulk and with the number of circulating B cells at baseline. Conclusions; We conclude that Rituximab is therapeuti-cally effective against B-cell lymphoma. Pharmacokinetic data suggests that certain subsets of patients may possibly benefit from increased dosing and studies to address this are currently underway.
Salivary gland lymphoproliferative disorders (SGLD) are very rare tumors and clinicopathological data is sparse. In a Canadian series of 30 cases, extracted from the surgical pathology files of The ...Ottawa Hospital between 1990 and 2010, a clinical, histopathological, and immunophenotypic analysis was conducted. Tumors were staged using the Ann Arbor staging and classified using the World Health Organization 2008 classification. There were 15 salivary gland (SG) primary lymphomas with localized disease, predominantly mucosa associated lymphoid tissue type marginal zone lymphoma (MALT-L), but with a significant incidence of low grade follicular lymphoma (FL) and diffuse large B cell phenotype as well. There were 7 systemic SG lymphomas and 5 patients were diagnosed with lymphoproliferative disorders originating from intra-parotid lymph nodes. Finally, the remaining 3 cases represented reactive sialadenitis. A literature review was conducted and our primary lymphoma group was compared to those from other countries. SGLDs are predominantly B cell lymphomas that develop in older adults. Primary tumors, which have MALT-L and low grade FL characteristics, have a favorable survival, however MALT-L have a high rate of relapse. A minority of SG lesions are excised secondary to lymphomas that definitely arose from intra-parotid lymph nodes.
The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively ...mediates host effector functions and is itself less immunogenic than are murine antibodies.
This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses.
From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient.
The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
This retrospective single-center study compared the incidence, spectrum and effect of infections in 1045 consecutive allogeneic (allo) and autologous (auto) hematopoietic SCT (HSCT) performed between ...1995 and 2006 in the inpatient (IP) or outpatient (OP) setting. We analyzed 374 allo-HSCT (196 IP and 178 OP) and 671 auto-HSCT (163 IP and 508 OP). The incidence of infection was lower both in auto-OP (25% OP vs 33% IP, P=0.042) and allo-OP cohorts (42.7% OP vs 55.6% IP, P=0.012). The mean number of infections per transplant was lower in both auto-OP (0.39 OP vs 0.57 IP, P=0.05) and in allo-OP cohorts (0.78 OP vs 1.09 IP, P=0.018). The 100-day non-relapse mortality (NRM) for OP auto-HSCT was 4.72% and for IP 3.95% (P=0.68). The 100-day NRM for OP allo-HSCT was lower at 14.1% than it was for IP at 22.6% (P=0.041). Time to onset of first infection and spectrum of infections was similar in all groups. We conclude that performing allo- and auto-HSCT in the OP setting results in short-term outcomes, including infections complications that are comparable to the standard IP setting.
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