Progress and Promise in the Treatment of Indolent Lymphomas

Abstract

In the era of conventional alkylating agent-based chemotherapy, advanced stage indolent lymphoma has been considered incurable. The failure of our traditional therapies to cure these patients, coupled with the indolent course of the disease and the elderly population affected, has fostered a nihilistic attitude about the treatment of these diseases. Twenty years ago, in the absence of interesting alternatives to alkylating agents, judicious use and reuse of alkylators was perhaps the best we could do. There are now many reasons for optimism and excitement in the treatment of these diseases, including the availability of promising agents such as interferon-α, the nucleoside analogues, and rituximab. Radioimmunotherapy will also likely play a role in future therapy programs. Allogeneic stem cell transplantation is a high-risk approach that is not an option for all patients, but it has the potential to cure patients, even in the setting of relapse. Mini-allogeneic transplantation may permit an approach to allogeneic transplantation that is better tolerated than standard transplant strategies. In addition to these therapy options, biological insights have provided new options for monitoring patients. Molecular monitoring (polymerase chain reaction for bcl-2) is a stringent measure of short-term treatment efficacy, and one that correlates with durability of remission, i.e., it is a surrogate marker by which to judge treatment efficacy. There used to be a limited number of conventional treatment approaches, which consistently failed. The pendulum has swung. There are now many promising new options. It is time to plan and conduct trials that are geared for success. The

The Role of Mitoxantrone in the Treatment of Indolent Lymphomas

“…Cyclophosphamide, the most frequently used alkylating agent in the treatment of lymphomas, was first described as therapy for diffuse large-cell lymphoma in 1975 [29].The CHOP regimen subsequently became standard treatment for patients with aggressive lymphomas and is also frequently used by clinicians to treat indolent lymphomas [5]. However, the standard CHOP regimen has not been proven to be capable of eradicating MRD in patients with follicular lymphomas, as documented by the persistence of cells bearing the bcl-2 gene rearrangement in blood and marrow.…”

“…Besides its activity as a single agent in the treatment of patients with follicular lymphomas, investigators have reported responses with mitoxantrone in combination with fludarabine, with or without dexamethasone, that appear better than those obtained with single-agent fludarabine in similar patient populations [5,23]. Four clinical trials using combinations of mitoxantrone and fludarabine (FM) were reported recently (Table 2).…”

“…Most patients with indolent lymphomas appear to have diseases that progress so slowly that delayed treatment is a management option, justifying a "watch and wait" approach to the initial treatment. However, over time, clinical progression occurs in almost all patients, and median survival rates with standard regimens such as cyclophosphamide, doxorubicin (Adriamycin [1,2,5,6]. More recently, with the introduction of newer therapeutic approaches, improved 10-year survival rates (37%-60%) have been reported in some studies [7].…”

Effective Treatment of Indolent Non-Hodgkin’s Lymphomas with Mitoxantrone, Chlorambucil and Prednisone

“…In general, this disease is characterised by a slow clinical pace and by responsiveness to a variety of treatment approaches [2]. Although the initial treatment results are satisfactory (remission rates up to 85%), relapse after standard chemotherapy [3][4][5][6][7][8][9][10] is almost inevitable and therefore these lymphomas are virtually incurable with conventional treatment approaches [2]. New approaches with stem cell transplantation [11][12][13][14], monoclonal antibodies [15][16][17] or cancer vaccines [18,19] are currently under investigation.…”

Morphology and immunophenotyping issues in the integrated diagnosis of hematologic disorders of elderly patients

“…20 In parallel, the introduction of targeted immunotherapy has revolutionized the management of patients with B-cell lymphomas. 21 These advances have two consequences. The first is that treated patients live longer and reach an older age where the surveillance of their disease becomes complicated by the morphological and perhaps immunophenotypic alterations related to age.…”