Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma

Pott, Christiane; Schrader, Carsten; Gesk, Stefan; Harder, Lana; Tiemann, Markus; Raff, Thorsten; Brüggemann, Monika; Ritgen, Matthias; Gahn, B.; Unterhalt, Michael; Dreyling, Martin; Hiddemann, Wolfgang; Siebert, Reiner; Dreger, Peter; Kneba, Michael

doi:10.1182/blood-2005-07-2845

Cited by 150 publications

(117 citation statements)

References 33 publications

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“…These clinical results are in agreement with recent data demonstrating the importance of good quality remissions in MCL as a crucial factor for sustained disease control. 34 A favorable outcome for patients in complete remission after treatment with single-agent bortezomib was also reported in the PINNACLE-trial. 16,18 Consolidation treatment with rituximab may have contributed to these favorable results, although we did not observe a clinically detectable improvement in the remission status during rituximab consolidation.…”

Section: Discussionmentioning

confidence: 59%

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Lamm¹,

Kaufmann²,

Raderer³

et al. 2011

Haematologica

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BackgroundBortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations. Design and MethodsThe activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m 2 on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m 2 , day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled. ResultsThe overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy. ConclusionsBortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.Key words: bortezomib, rituximab, mantle cell lymphoma, relapse. Haematologica 2011;96(7):1008-1014. doi:10.3324/haematol.2011 Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma Citation: Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, and Drach J. Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma.

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Section: Discussionmentioning

confidence: 59%

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Lamm¹,

Kaufmann²,

Raderer³

et al. 2011

Haematologica

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“…Chemotherapy using cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) does not seem to result in a relevant reduction of tumor load in PB, BM, or PB stem cell products, even among patients who achieve a clinical remission, as reported in the Nordic MCL1 study 5 and a single-center series of homogeneously treated patients (Table 2). 16 Immunochemotherapy with rituximab plus CHOP (R-CHOP) in the MCL Younger and MCL Elderly trials showed (for the first time) relevant rates of molecular remission (MRD negativity) of 40%, with 21% of patients MRD negative already at midterm induction. 4,23 Further intensification of induction treatment with HA in the arm of the MCL Younger trial, which used alternating R-CHOP and rituximab plus dexamethasone, HA, and cisplatin (R-DHAP), was associated with 66% molecular remissions, with 39% of patients MRD negative already at midterm induction.…”

Section: Mrd During and After Induction Treatmentmentioning

confidence: 99%

“…Four studies consistently reported that the presence of or the relative content of tumor cells in the stem cell product did not affect further clinical outcome. 5,16,29,31 This could indicate that tumor cells contaminating the reinfused stem cells might not be able to cause or promote clinical progression, and that cytoreduction in the involved tissues by induction and consolidation treatment has the strongest impact on tumor control.…”

Section: Prognostic Value Of Mrd Before High-dose Consolidationmentioning

confidence: 99%

“…In the 2 series of patients with MCL who were treated with CHOPlike chemotherapy by which virtually no molecular remissions were achieved, molecular remission rates of 38% 5 and 52% 16 were observed after high-dose consolidation and ASCT. In the MCL Younger trial, high-dose consolidation increased molecular remission rates after R-CHOP from 47% to 68% in PB and from 26% to 59% in BM; after R-CHOP/R-DHAP, rates increased from 79% to 85% in PB and from 61% to 79% in BM.…”

Section: Mrd After High-dose Consolidationmentioning

confidence: 99%

“…In the single-center report 16 of 27 patients treated with myeloablative radiochemotherapy after CHOP-like induction, MRD positivity in PB or BM during the first year after ASCT was highly predictive for clinical progression, with median PFS of 21 months in patients who were MRD positive compared with 92 months in patients who were MRD negative. MRD positivity after ASCT was also prognostic for shorter OS, and the prognostic relevance of MRD positivity for PFS and OS was independent of baseline variables and clinical complete remission (CR).…”

Section: Predictive Value Of Mrd In Clinical Remission After Treatmentmentioning

confidence: 99%

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Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Hoster

Pott

2016

Hematology

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Despite the recent substantial improvement of clinical outcome in mantle cell lymphoma (MCL), resistance to immunochemotherapy and common relapses are challenges for long-term tumor control. The assessment of minimal residual disease (MRD) by real-time quantitative polymerase chain reaction has emerged as a widely feasible and standardized tool for direct assessment of therapy-induced reduction of tumor burden and regrowth after cytotoxic treatment in MCL, with much improved sensitivity compared with conventional staging procedures. Several studies have shown that intensification of initial treatment, which has resulted in improved clinical outcome, is immediately reflected in higher molecular remission rates; they have also shown that high-dose consolidation might not be able to compensate for less intensive induction regimens. Persistence or reappearance of MRD in clinical remission proved to be highly predictive for imminent clinical relapse associated with shorter overall survival. Therefore, the investigation of novel MRD-guided treatment strategies aimed at early eradication of MRD and pre-emptive treatment of molecular relapse seems warranted. Furthermore, the integration of MRD assessment into clinical response criteria could result in a more specific and potentially earlier end point for treatment efficacy. New technical developments such as high-throughput sequencing will further enhance the wide applicability of MRD detection in MCL.Learning Objectives

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Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma

Dietrich

Tielesch

Rieger

et al. 2010

Cancer

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In this article, the design and measurement of a 77‐GHz Marchand balun matched to 50 Ω single‐ended and 100 Ω differential‐ends using multiple metal layers in silicon technology is discussed. The balun is measured with an insertion loss of 1.8 dB at 77 GHz, an amplitude imbalance of ±1.8 dB, and phase imbalance of ±1.5°. Also, this article presents the effect of parasitic reactance in the load terminations and dummy metal fills on balun's performance. It was found that the interlevel dummy metal fills and increase the insertion and also cause significant amplitude imbalance in the balun especially at frequencies above 50 GHz. © 2011 Wiley Periodicals, Inc. Microwave Opt Technol Lett 53:664–666, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.25756

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Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma

Cited by 150 publications

References 33 publications

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment

Patterns and outcome of relapse after autologous stem cell transplantation for mantle cell lymphoma

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