Marked Response to Chemoimmunotherapy in a Patient with Follicular Lymphoma of Huge Mesenteric Lymphadenopathy
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Abstract:
Follicular lymphoma (FL) is the most common subtype of indolent non-Hodgkin's lymphomas. We present the case of a 57-year-old woman who initially complained of abdominal fullness and unintentional weight loss. A computerized tomography scan disclosed a huge mesenteric mass and confluent lymphadenopathy in the paraaortic area, and the pathological diagnosis of a paraaortic lymph node biopsy showed histological Grade 1–2 FL. She received chemoimmunotherapy, including rituximab plus cyclophosphamide, vincristine, and prednisolone, for Ann Arbor Stage III FL disease accompanied by compression symptoms, and achieved a nearly complete remission after completing eight cycles of chemoimmunotherapy. She is currently receiving maintenance rituximab therapy.Keywords:
Chemoimmunotherapy
Follicular lymphoma
Paraaortic lymph nodes
Since its approval in 1997, the anti-CD20 monoclonal antibody rituximab has had a profound impact on the treatment and outcome of patients with follicular lymphoma. Overall survival for this incurable disease has dramatically improved over the past two decades, 1 and the routine incorporation of rituximab into chemotherapy regimens has demonstrated significant trends toward improved overall survival compared with chemotherapy alone. 2 Rituximab is now appropriately used ubiquitously in the treatment of follicular lymphoma, both as initial therapy and in the setting of relapsed disease. 3 It is therefore remarkable how little was known about the optimal schedule of singleagent therapy with this antibody in the setting of follicular lymphoma; however, numerous strategies have been employed in clinical trials without direct comparison. Fortunately, two recently published articles have largely closed this knowledge gap. The initial studies of single-agent rituximab in follicular lymphoma used a schedule of 375 mg/m 2 administered once per week for 4 weeks, derived empirically, with response rates of approximately 40% and progression-free survival (PFS) of 1 year in the setting of relapsed disease. 4 Given this promising activity, early studies then evaluated the outcomes of single-agent rituximab as initial therapy for low–tumor burden follicular lymphoma. 5,6 Response rates were expectedly better than in the setting of relapsed disease. Enthusiasm for an extended schedule or maintenance rituximab started with a study performed by the Swiss Group for Clinical Cancer Research (SAKK) in which both previously untreated and relapsed patients with follicular lymphoma were treated with rituximab once per week for 4 weeks. Responding patients were then randomly assigned to either observation or an extended schedule that consisted of an additional dose of rituximab administered once every 2 months for a total of four cycles. 7 At a median follow-up of 9 years, the median event-free survival was 13 months for the standard and 24 months for the maintenance arm, with a trend toward a survival benefit in the maintenance arm. Toxicity was not significantly exacerbated by prolonged rituximab exposure, and, importantly, rituximab re-treatment happened infrequently because of limited drug availability in Europe at that time. Other studies using alternative schedules of single-agent rituximab followed by maintenance have also demonstrated substantial impact on PFS or event-free survival with prolonged rituximab exposure. 8 On the basis of these promising studies, Ardeshna et al 9 conducted a randomized trial of patients with low–tumor burden, advanced-stage follicular lymphoma, and compared 187 patients who were initially approached with observation (watch and wait) with 192 patients who were treated with rituximab once per week for 4 weeks followed by 12 infusions of rituximab given once every other month for 2 years. Not surprisingly, there was a significant difference in the time to start of new treatment between the two arms, with a median follow-up of 46 months: 56% of patients in the watchful waiting group required new treatment compared with 17% of patients in the maintenance rituximab (MR) group. Importantly, only four patients in the observation group received rituximab as a subsequent management approach; the remainder were treated with chemotherapy. There was no difference in 3-year overall survival (94% for the watchful waiting and 97% for the MR group), and there was no significant difference in biopsy-proven histologic transformation rates between the two arms. Patient-reported outcomes in this trial suggested improvement in psychological well-being in the rituximab group, but otherwise, there were no significant differences in symptom burden or physical functioning domains. Interestingly, the original design of this trial included a third arm of single-agent rituximab alone, given once per week for 4 weeks (no maintenance), which was prematurely closed because of poor accrual. Eighty-four patients were enrolled in this arm before closure, and the outcomes in this group were similar to those of the MR group, without statistically significant differences in time to start of new treatment. These authors concluded that “rituximab monotherapy should be considered as an immediate treatment option for patients with asymptomatic, low-tumour-burden follicular lymphoma.” 9(p434 )
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Read the full review for this Faculty Opinions recommended article: Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi.
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Is rituximab maintenance therapy after first-line induction chemoimmunotherapy for follicular lymphoma associated with improved outcomes?Compared with observation, rituximab maintenance therapy prolongs progression-free survival without an improvement in overall survival or quality of life after first-line induction chemoimmunotherapy.
Chemoimmunotherapy
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Rituximab changed the treatment of patients with follicular lymphoma. When added to standard chemotherapy regimens, it increased the response rate and the complete remission rate.1,2 Rituximab has often been administered as maintenance therapy after a remission that was induced either by single-agent rituximab or by rituximab combined with standard chemotherapy drugs, and it has been shown to prolong the duration of remission.3,4 Since 2000, when rituximab became widely available, survival among patients with low-grade follicular lymphoma has increased from a median of approximately 10 years to a median of approximately 15 to 20 years.5,6 In this issue of the Journal, . . .
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Rituximab-induced acute thrombocytopenia (RIAT), a rare complication of rituximab administration, has not yet been described in follicular lymphoma (FL). A 65-year-old man received rituximab for the treatment of high tumor burden follicular lymphoma in the leukemic phase. The next day, his platelet count abruptly dropped from 85,000 to 5,000/μL, which spontaneously recovered in a few days without specific treatment. We speculate that the occurrence of infusion-related cytokine release syndrome in rituximab-sensitive high tumor burden FL contributed to the development of RIAT. Frequent monitoring of the platelet count is advisable for select patients considered to be at a high risk for RIAT.
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