Trofosfamide in the treatment of elderly or frail patients with diffuse large B-cell lymphoma
The introduction of immunochemotherapy has led to a significant improvement in treatment results and prognosis of diffuse large B-cell non-Hodgkins lymphoma (DLBCL) both at initial diagnosis and in relapse. Trofosfamide, an oxazaphosphorine derivative, has been utilized as alternative treatment option for patients with lymphoproliferative diseases unsuitable for conventional chemotherapy agents and protocols because of age, comorbidity, or poor performance score. While data on the activity and safety of single-agent trofosfamide have been published, the potential value of this agent in immunochemotherapy in combination with anti-CD20 antibodies such as rituximab has not been investigated to our knowledge.
Safety and therapeutic effectiveness of trofosfamide given orally at a dose of 50 mg twice daily alone, or in combination with standard-dose rituximab, was investigated in a cohort of elderly and/or highly comorbid patients with histologically confirmed primary or secondary DLBCL.
Treatment with trofosfamide in this combination setting was generally well tolerated with no treatment-related deaths and manageable side effects, most of which were WHO class I–II; the most clinically relevant toxicity was cytopenia. 19 of 21 examined patients responded to therapy with 11 of 21 (52.4%) achieving a complete remission (CR). Median overall and progression-free survival (OS and PFS) in the CR-group was 14 and 9 months, respectively. In the subgroup with trofosfamide-based first-line therapy, 7 of 10 (70%) achieved CR and median PFS was not reached.
Immunochemotherapy with rituximab and trofosfamide (RT) is safe and effective in elderly and poor-performance patients with DLBCL. Response rates are comparable to most commonly used primary and salvage treatment protocols. The potential value of TR regimen in both first-line and relapsed/refractory DLCBL merits further investigation and is probably underestimated.
KeywordsTrofosfamide Diffuse large B-cell lymphoma Elderly Prognosis
The authors would like to thank Svenja Kopelke and Rudina Marx for their administrative support.
Study design and drafting of manuscript: NG, HW, HB and DR. Data collection and analysis, revision of manuscript: HW, NG, HL, HM and SF. Revision and final approval of manuscript: all authors.
The authors declare no funding source for this study.
Compliance with ethical standards
This study was approved by the ethics committee of the University of Luebeck (Reference no: 17-266) and was conducted in accordance with the Declaration of Helsinki and internationally accepted ethical guidelines.
Upon hospital admission, all participants gave their written informed consent for the storage of personal data and the use of data for research purposes.
Availability of data and materials
Data supporting the conclusions of this article are included in the article.
Conflict of interest
The authors declare that they have no conflict of interest.
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