Patients with relapsed or refractory B- or T-cell aggressive non-Hodgkin lymphomas (NHL) pose a great challenge as they represent failure of the standard frontline therapy, mostly due to chemoresistant disease. The standard of care in these cases is to try and obtain at least a partial response with salvage therapy and, if possible, to consolidate with high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) [1]. Otherwise, results are generally poor and even in the case of consolidation with ASCT, long-term survival is still disappointing in more than half of the patients.
Thus, we need something more and the future will probably include the addition of new drugs to the traditional standard salvage therapy in order to improve results for specific subtypes of lymphoma. However, while we wait for these new trials to guide our clinical practice, we may summarize what we have learned with standard immune-chemotherapy during recent years. First, in the case of aggressive B-cell lymphomas, rituximab improves outcomes when combined with most standard salvage therapies. Second, there is a lack of phase 3 clinical trials to compare standard salvage therapy for aggressive B- or T-cell NHL (DHAP, ESHAP, ICE, MINE, EPOCH, or CEPP). Furthermore, new schemes based on gemcitabine or bendamustine may obtain acceptable results with a better toxic profile, even in the case of older patients and those who are not candidates for intensive treatment [2, 3]. Third, in some of these trials or retrospective data, outcomes were better when patients received consolidation or maintenance after an initial response. Fourth, late relapses fare generally better than refractory or early relapsing cases. Fifth, as an important issue in the salvage setting, patients who tolerate full dose fare better than those requiring dose intensity reductions (DIR).
In the last issue of Acta Haematologica, a retrospective single-center study by Zlotnick et al. [4] presents real-life data, illustrating most of these conclusions derived from their experience with gemcitabine-based protocols. The authors report better results in the case of chemosensitivity, in relapse versus chemorefractory disease, in first or second relapse versus further treatment lines, as well as those receiving full dose versus requiring DIR. However, they present a slightly inferior overall response rate (37%) or complete response rate (24%) as well as a worse progression-free survival (PFS) that could be related to the special characteristics of the cohort – a heterogeneous sample of B- and T-cell NHL, two thirds not candidates for intensive chemotherapy and a little bit more overtreated than previous reported series – which may highlight some of the limitations of gemcitabine-based and other current salvage schemes.
Unfortunately, the study was not powered enough or designed to address the value of consolidation of patients achieving a response. However, our experience, as well as that of others, points to considering consolidation as a major factor influencing PFS in aggressive NHL [1, 3]. For this reason, we support obtaining a good response with more specific or low-toxicity yet effective drugs that will not preclude further consolidation or maintenance therapy as an approach to improve the duration of response and PFS in aggressive NHL [5]. Another future alternative currently being tested is using gemcitabine-based schemes as a potential basis to analyze the inclusion of new specific drugs or targeted therapy. Ongoing trials with combinations such as R-GemOx-ibrutinib or R-GDP-lenalidomide are designed to test this hypothesis and will eventually improve results in aggressive NHL by using precision medicine.
Disclosure Statement
The author has no conflicts of interest.
