Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie

Troch, Marlene; Kiesewetter, Barbara; Willenbacher, Wolfgang; Willenbacher, Ella; Zebisch, Armin; Linkesch, Werner; Fridrik, Michael A.; Müllauer, Leonhard; Greil, Richard; Raderer, Markus

doi:10.3324/haematol.2012.072587

Cited by 35 publications

(28 citation statements)

References 21 publications

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“…Our data clearly illustrated that the combination of rituximab and cladribine in advanced BALT lymphoma is highly effective, resulting in an ORR of 100% with 2 CR and 6 PR. However, despite the high ORR, the complete response rate is slightly inferior to that reported in previous study by Troch et al, in which the CR was 36.8% (7/19) in the non-gastric subgroup and much lower than that of gastric subgroup (CR 80%, 16/20) (24), and lower than the CR (ranging from 45 to 100%) reported in a review of BALT lymphoma by Zinzani et al (15). The difference in disease nature and pathogenic mechanism, for instance, autoimmune disorders in non-gastric MALT lymphoma versus HP infection in gastric subtype, might partially explain the inferior CR in BALT lymphoma when comparing with other non-gastric subtype and gastric subtype.…”

Section: Discussioncontrasting

confidence: 76%

“…Although one patient recovered fully without any severe complications and the thrombocytopenia occurred in the second patient was asymptomatic and did not require platelet transfusion, we still suggested the necessity for well-monitoring of the myelotoxicity of cladribine in a prolonged observation time. As every patient received anti-viral prophylaxis, no event of herpes zoster reactivation was recorded in our study, which was not a rare event in the series of Troch et al (24).…”

Section: Discussionmentioning

confidence: 55%

“…Monotherapy of cladribine is now considered the standard first-line treatment for hairy cell lymphoma (37,38). In addition, cladribine had shown satisfying effects in other indolent type of B-cell neoplasms, including marginal zone lymphoma, both as a single agent and in combination with other agents (22,24,25,34). Prolonged efficacy and longterm safety had been reported for cladribine in several publications (23,26).…”

Section: Discussionmentioning

confidence: 99%

“…Data of a total 16 patients with MALT lymphoma was analyzed in this study, whereas no BALT lymphoma was included. In 2013, Troch et al published the first prospective non-randomized trial assessing the efficacy of the combination of rituximab and subcutaneous cladribine in MALT lymphoma (24). In this study of a 43-patient cohort, which contained 21 cases of gastric MALT lymphoma and 19 non-gastric cases (a total of 6 pulmonary MALT included), an CR of 58% and an ORR of 81% were reported; in particular, the response rate is significantly higher in patients with gastric MALT lymphoma versus non-gastric MALT (90% ORR with 16 CR and 2 PR versus 74% ORR with 7 CR and 7 PR), as also seen in a trial of cladribine alone (22).…”

Section: Discussionmentioning

confidence: 99%

“…Both the anti-CD20 monoclonal antibody rituximab (R) and the nucleoside analogue 2-chlorodeoxyadenosine (cladribine, 2-CdA) have demonstrated high efficacy and minimal side effects in the treatment of MALT lymphoma (21)(22)(23). The combination of rituximab and cladribine (R-2-CdA) has also been tested and showed promising results in both non-gastric MALT lymphoma and refractory/relapsed indolent B-NHL (24)(25)(26). Nonetheless, the effect and safety of R-2-CdA therapy in untreated BALT lymphoma with unresectable advanced lesions had not been assessed.…”

Section: Introductionmentioning

confidence: 99%

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A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma

Wei

Cheng

et al. 2017

J. Thorac. Dis.

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Background: Bronchial-associated lymphoid tissue (BALT) lymphoma is a relatively rare form of B-cell non-Hodgkin lymphoma (B-NHL). To date, the standard systemic treatment for this disease is still under debate, and few data are accessible for newly diagnosed unresectable BALT lymphoma presented with advanced disease. The combination of rituximab (R) and cladribine (2-CdA) has shown some activity in indolent B-NHL, but its usage has not been tested in disseminated BALT lymphoma so far.Methods: An observational retrospective study was performed on homogeneous data of 8 patients with biopsy-proven stage IV BALT lymphoma to assess the efficacy and the safety of R-2-CdA therapy. All but one of the patients received six courses of R-2-CdA regimen consisted of rituximab 375 mg/m 2 IV day 1 and cladribine 0.1 mg/kg IV days 1-4 every 21 days; one patient completed 4 cycles and received additional R maintenance.Results: A high overall response rate (ORR) was observed (100%), with 2 patients (25%) achieved a complete remission (CR), the remaining (75%) a partial response. Improvement of pulmonary function was observed in all tested patients. Grade 3 and 4 toxicities were leukocytopenia and neutropenia in 3 patients (37.5%), diarrhea in one (12.5%). Estimated two-year progression-free survival (PFS) and 2-yr overall survival (OS) were 80.0% (95% CI, 20.3-96.7%) and 100%, respectively.Conclusions: R-2-CdA therapy demonstrated high activity and tolerable toxicity in chemotherapy-naïve patients with unresectable BALT lymphoma of advanced stage. Although further large-scale study is needed for consolidation, R-2-CdA regimen could be a good first-line therapy option for patients with unresectable BALT lymphoma. chronic antigen stimulation related to autoimmune process, persistent infection or toxic exposure (4). Additional genetic alterations, for instance, t(11;18)(q21;q21), contribute to the transformation of this reactive extranodal lymphoid tissue to lymphoma (5).In most cases, patients with BALT lymphoma are asymptomatic and pulmonary lesions are discovered via a routine chest radiographic study incidentally. In symptomatic patients, non-specific pulmonary symptoms (such as cough, sputum, chest pain and dyspnea) are the most common (6). Radiographic findings are usually nonspecific, including nodules, air space consolidation with or without bronchogram, patchy opacities and pleural effusion (6,7). The clinical role of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET-CT) in BALT lymphoma remains unclear, but several studies have reported high detection rate in BALT lymphoma suggesting PET-CT might be a promising tool in initial evaluation and response assessment of BALT lymphoma (8-10). Accurate diagnosis of BALT lymphoma depends upon histopathologic studies including morphological observation and immunohistochemical staining on biopsy specimen obtained by bronchoscopies, percutaneous lung biopsies or surgical resection (11). Benefiting from current findings revealing the pathogenesis of MALT lymphom...

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Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma

Wei

Cheng

et al. 2017

J. Thorac. Dis.

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Treatment of gastric marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue with rituximab, cyclophosphamide, vincristine and prednisone

Aguiar-Bujanda

Llorca-Martínez

Rivero-Vera

et al. 2013

Hematological Oncology

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There is no standard treatment for patients with gastric marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who are resistant to, or ineligible for, anti-Helicobacter pylori (anti-HP) therapy. In this study, we investigated the activity of the rituximab, cyclophosphamide, vincristine and prednisone (R-CVP) regimen in patients with gastric MALT lymphoma. Patients were included provided they had untreated gastric MALT lymphoma (except for anti-HP therapy) and were resistant to, or ineligible for, anti-HP therapy. Treatment plan consisted of six to eight 21-day cycles of the R-CVP chemotherapy regimen. Toxicity, response, relapse and survival were evaluated. Twenty patients (12 women and 8 men) were included in the analyses with median age of 59 years. Thirteen patients (65%) had stage I tumours, and seven patients (35%) had stages II-IV tumours. The overall response rate was 100%, with 19 (95%) complete responses and one (5%) partial response. Regimen toxicity was mild and mainly hematological, and no cases of gastric bleeding or perforation occurred. After a median follow-up of 56.3 months, three patients had relapsed, and 19 patients remained alive (specific lymphoma survival 100%), of whom 17 had no evidence of disease. In our experience, the R-CVP regimen is a well-tolerated and effective treatment for patients with gastric MALT lymphoma who are resistant to, or ineligible for, anti-HP therapy.

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Fludarabine–Mitoxantrone–Rituximab regimen in untreated indolent non‐follicular non‐Hodgkin's lymphoma: experience on 143 patients

Zinzani

Pellegrini

Gandolfi

et al. 2014

Hematological Oncology

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Indolent non-follicular lymphomas (inFLs) are generally regarded as incurable, apart from extranodal mucosa-associated lymphatic tissue lymphomas, which can be partially cured by surgery, local radiotherapy, or antibiotic treatment. The aim of the present study was to test the degree of effectiveness and the safety of the regimen containing fludarabine, mitoxantrone, and rituximab (FMR) in inFL patients considering all the different entities belonging to this group. An observational retrospective study was conducted on 143 inFL patients providing that their first chemoimmunotherapy performed was FMR regimen and diagnosis from September 2000 to March 2011. There were 32 small lymphocytic lymphomas and 111 marginal zone lymphomas. At the end of treatment, overall response rate was 96.5% with 88% of complete responses (CR) and 8.5% of partial responses. With a median follow-up of 48 months, 10 out of 125 (8%) CR patients had disease relapse, yielding an estimated 9-year disease-free survival (DFS) of 74.9% and an estimated 10-year overall survival of 92.8%. The estimated 9-year progression free survival was 70.5%. The 10 relapsed patients showed lymphoma recurrence within 52 months: after this time, the DFS curve presented a plateau configuration. Only two (1.4%) patients developed a secondary hematological neoplasia. This study showed promising findings for the use of a fludarabine-based regimen in combination with rituximab in the front-line treatment of symptomatic inFL with a noteworthy high percentage of CR associated to an interesting long-term DFS and favorable acute and long-term safety profile.

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Rituximab plus subcutaneous cladribine in patients with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue: a phase II study by the Arbeitsgemeinschaft Medikamentose Tumortherapie

Cited by 35 publications

References 21 publications

A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma

A single center experience: rituximab plus cladribine is an effective and safe first-line therapy for unresectable bronchial-associated lymphoid tissue lymphoma

Treatment of gastric marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue with rituximab, cyclophosphamide, vincristine and prednisone

Fludarabine–Mitoxantrone–Rituximab regimen in untreated indolent non‐follicular non‐Hodgkin's lymphoma: experience on 143 patients

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