Rituximab purging and maintenance combined with auto-SCT: long-term molecular remissions and prolonged hypogammaglobulinemia in relapsed follicular lymphoma

Hicks, Lisa K.; Woods, Anthony; Buckstein, Rena; Mangel, Joy; Pennell, Nancy; Zhang, Libo; Imrie, Kevin; Spaner, David; Cheung, Matthew C.; Boudreau, Angela; Reis, Marciano D.; Crump, Michael; Berinstein, Neil L.

doi:10.1038/bmt.2008.382

Cited by 65 publications

(40 citation statements)

References 58 publications

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“…The safety findings in the present study did not differ from those previously reported (12), confirming the safety of rituximab in maintenance therapy. Treatment was delayed in only two patients due to rituximab toxicity.…”

Section: Discussionsupporting

confidence: 70%

“…The use of rituximab for the in vivo purging of hematopoetic stem cell products has yielded encouraging results in disease eradication (up to 79% of MRD rendered undetectable after in vivo purging with rituximab), resulting in five-year OS and PFS of up to 78% (16)(17)(18)(19)). An ongoing prospective study in patients with relapsed follicular lymphoma showed that the use of rituximab for in vivo graft purging and maintenance therapy following auto-STC resulted in undetectable MRD in a high proportion of patients (12). In this study, MRD was present in 56.5% of the patients (13/23) prior to treatment, but became undetectable in 77% of the patients after auto-SCT and in another two patients after subsequent rituximab maintenance therapy.…”

Section: Discussionmentioning

confidence: 77%

“…In this clinical setting, the application of rituximab for in vivo purging of stem cell grafts resulted in a high purging efficiency and improved response rates (10,11). Five-year interim results from an ongoing study have shown the efficacy of in vivo rituximab graft purging and post-transplant rituximab maintenance therapy in combination with auto-SCT in patients with relapsed follicular lymphoma (12). However, these results need to be confirmed in studies using additional patient cohorts, such as DLBCL patients.…”

Section: Introductionmentioning

confidence: 79%

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Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Jiao¹,

Zhou²,

Shen³

2010

Oncology Letters

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Abstract. The aim of this prospective, single-arm study was to test the efficacy and tolerability of autologous stem cell transplantation (auto-SCT) combined with in vivo rituximab purging and post-transplant rituximab maintenance therapy in patients with diffuse large B-cell lymphoma (DLBCL). This study included 12 DLBCL patients aged 18-65 years with an International Prognostic Index ≥2. The patients received 4-6 cycles of induction therapy consisting of rituximab plus cyclophosphamide, adriamycin, vincristine and prednisone followed by salvage therapy prior to stem cell mobilization. This regimen was followed by rituximab maintenance therapy (375 mg/m 2 every three months for two years). Prior to auto-SCT, six patients (50%) achieved complete remission (CR) and six (50%) achieved unconfirmed complete remission (CRu). Three months after transplantation, 11 patients (91.7%) achieved CR and one achieved CRu. After two cycles of rituximab maintenance therapy, all 12 patients achieved CR. Long-term CR was achieved by 10 patients, while two experienced relapse at 14 and 20 months after the end of rituximab maintenance therapy. The median follow-up period was 44 months (range 35-61). Disease-free survival was noted in 10 patients, while two experienced relapse. The three-year overall survival (OS) and progression-free survival (PFS) were 100 and 83%, respectively. Prolonged hypogammaglobulinemia occurred in two patients, although no increase in major infections was observed. Hepatitis B surface antigen was continuously negative in all 12 patients. Our results demonstrated that auto-SCT combined with in vivo rituximab purging and post-transplant rituximab maintenance is safe and effective, and may extend OS and PFS in younger high-risk DLBCL patients.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 79%

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Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Jiao¹,

Zhou²,

Shen³

2010

Oncology Letters

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“…Both groups of patients tend to develop low IgM, but not IgG and IgA. In contrast, some patients with refractory follicular lymphoma treated with rituximab and HSCT developed persistently low IgA and IgG with recovery of IgM levels 34, 37. Underlying disease can therefore influence the development of isotype‐specific hypogammaglobulinemia.…”

Section: Discussionmentioning

confidence: 99%

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Reddy

Martinez

Isenberg

et al. 2017

Arthritis Care & Research

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ObjectiveB cell–depletion therapy based on rituximab is a therapeutic option for refractory disease in patients with systemic lupus erythematosus (SLE). The aim of this observational study was to document long‐term effects on B cell function by following serum immunoglobulin levels in patients with SLE treated with rituximab in routine clinical practice.MethodsWe included 57 consecutive patients with SLE treated with rituximab and concomitant/sequential immunosuppressants and measured serum total IgG, IgM, and IgA and IgG anti‐dsDNA antibodies, over a median of 48 months most recent followup. Flow cytometry was used prospectively to assess B cell phenotypes in 17 of 57 patients.ResultsTwelve patients (21%) had persistent IgM hypogammaglobulinemia (<0.4 gm/liter), and 4 of 57 (5%) had low IgG (<7 gm/liter) at the most recent followup (range 12–144 months). This was not associated with serious adverse events or high anti–double‐stranded DNA (anti‐dsDNA) antibodies (>1,000 IU/ml; normal <50 IU/ml). Factors predictive of low serum IgM included baseline serum IgM ≤0.8 gm/liter (receiver operator curve analysis) and subsequent therapy with mycophenolate mofetil (MMF; odds ratio 6.8, compared with other immunosuppressants). In patients maintaining normal IgM levels (9 of 17), the frequency of circulating IgD+CD27+ B cells was significantly higher (P = 0.05). At 12 months after rituximab, 7 of 30 SLE patients with baseline anti‐dsDNA ≤1,000 IU/ml had lost seropositivity.ConclusionLower baseline serum IgM levels and sequential therapy with MMF were predictive of IgM hypogammaglobulinemia after rituximab in SLE, but this was not associated with higher levels of anti‐dsDNA antibodies or an increased risk of infections. This provides useful directions for clinicians regarding rituximab and sequential immunosuppressive treatment for patients with SLE.

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“…Twenty-three patients with relapsed FL were enrolled in this prospective single-arm study. 39 Five-year OS and 5-year PFS are 78% (95% confidence interval [CI] 61% to 95%) and 59% (95% CI 38% to 80%), respectively. Time to progression with the rituximab-containing regimen was significantly improved compared with each patient's previous treatment (P  0.001).…”

Section: Dovepressmentioning

confidence: 99%

Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

Badin

Hayslip

2010

CEOR

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Rituximab is an important and well established component in the treatment of many patients with B-cell non-Hodgkin lymphoma. In this paper we review recent clinical trials investigating the addition of rituximab to standard chemotherapy regimens for treatment of patients with diffuse large B cell lymphoma and follicular lymphoma. This report focuses upon treatment efficacy, quality of life, and safety of rituximab or rituximab-containing regimens. More uniquely, we review economic aspects of lymphoma treatments, including the cost of standard chemotherapy regimens with or without rituximab, cost effectiveness of rituximab in both induction and maintenance treatment, and lymphoma’s impacts on patient’s productivity and their caregivers. We conclude that adding rituximab to standard chemotherapy treatment for patients with B-cell non-Hodgkin lymphoma is safe and cost-effective in numerous settings during both induction and maintenance therapies. Despite extensive review of the literature, many important questions have yet to be answered in the rituximab era and these represent important directions for future study.

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Rituximab purging and maintenance combined with auto-SCT: long-term molecular remissions and prolonged hypogammaglobulinemia in relapsed follicular lymphoma

Cited by 65 publications

References 58 publications

Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Rituximab purging and maintenance therapy combined with autologous stem cell transplantation in patients with diffuse large B-cell lymphoma

Pragmatic Treatment of Patients With Systemic Lupus Erythematosus With Rituximab: Long‐Term Effects on Serum Immunoglobulins

Rituximab in the treatment of B-cell non-Hodgkin lymphoma, focus on outcomes and comparative effectiveness

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