Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna; Linker, Charles; Cheson, Bruce D.; Stock, Wendy

doi:10.3324/haematol.2011.050203

Cited by 70 publications

(66 citation statements)

References 26 publications

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“…Limited data exist regarding the use of polymerase chain reaction (PCR) amplification of immunoglobulin heavy chain rearrangements or flow-cytometry-based minimal residual disease (MRD) measures and outcome in MCL(21-23). These studies only included patients in prospective clinical trials using patient-specific PCR assays, and few data exist regarding the application of this strategy to an unselected population of MCL patients undergoing ASCT when routine clinical testing is employed.…”

Section: Introductionmentioning

confidence: 99%

Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission

Cowan

Stevenson

Cassaday

et al. 2016

Biology of Blood and Marrow Transplantation

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Autologous stem cell transplantation (ASCT) is standard therapy for mantle cell lymphoma (MCL) in remission following induction chemotherapy with the best results for patients in complete remission (CR). We hypothesized that evaluation of MRD prior to ASCT could further stratify outcomes for these patients. Patients with MCL who underwent ASCT in clinical CR between 1996 and 2011, with pretransplant MRD testing were eligible. Presence of a clonal IgH rearrangement, t(11;14) by PCR, or positive flow cytometry from blood or bone marrow was considered positive. An adjusted proportional hazards model for associations with progression-free (PFS) and overall survival (OS) was performed. Of 75 MCL patients in CR, 8 (11%) were MRD positive. MRD positivity was associated with shorter OS and PFS. The median OS for MRD-negative patients was not reached with 82% survival at 5 years, while for the MRD-positive patients was 3.01 years (hazard ratio [HR] 4.04, p = 0.009), with a median follow-up of 5.1 years. The median PFS for MRD-negative patients was not reached with 75 % PFS at 5 years, while for MRD-positive patients was 2.38 years (HR 3.69, p = 0.002). MRD positivity is independently associated with poor outcome following ASCT for MCL patients in CR.

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Section: Introductionmentioning

confidence: 99%

Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission

Cowan

Stevenson

Cassaday

et al. 2016

Biology of Blood and Marrow Transplantation

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“…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%

“…28 Several smaller studies have also shown the prognostic value of MRD status after various induction immunochemotherapies and before high-dose consolidation. [29][30][31][32] As far as ASCT is concerned, the question arises whether the presence of MRD in the stem cell product re-transfused is associated with inferior PFS. 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.…”

Section: Prognostic Value Of Mrd Before High-dose Consolidationmentioning

confidence: 99%

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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“…Several studies have confirmed, not surprisingly, that the achievement of molecular remission (MR; i.e., molecular CR) in peripheral blood and/or bone marrow following induction immunochemotherapy is significantly associated with a better outcome, independently of other prognostic variables in both elderly and younger patients (34,63), and should become the goal in upcoming or ongoing immunochemotherapy trials (64).…”

Section: Assessment Of Quality Of Response To Predict Outcomes: Mrd Amentioning

confidence: 99%

Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice

Avivi¹,

Goy

2015

Clinical Cancer Research

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Although mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma, proactive research efforts fueled by challenges in the management of MCL have led to an increase in median overall survival (OS) of 2.5 years in the mid 1990s to beyond 5 years nowadays. This improvement is due mostly to the use of dose-intensive strategies, particularly cytarabinecontaining regimens [with or without high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) consolidation], which are associated with deeper remission (and higher molecular complete response rate), as well as better salvage therapies. Along this line, MCL became the first lymphoma for which four novel agents have been approved in the relapsed/refractory setting: temsirolimus, lenalidomide, ibrutinib, and bortezomib (the last agent approved both in relapsed/ refractory disease and in first-line combination therapy). In addition, the use of rituximab maintenance has helped reduce relapse rates and improve outcome. However, in routine practice (i.e., outside clinical trials), the outcome of MCL remains overall unchanged with standard immunochemotherapy, and even after HDT-ASCT, most patients still relapse and frequently develop chemoresistance. The persistent lack of consensus for the treatment of MCL explains the rather impressive variability in management of these patients. The integration of newer therapies, either in combination with immunochemotherapy or as consolidation/maintenance postinduction, offers new opportunities for patients with MCL. This review highlights how such developments can help refine the current MCL paradigm.

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Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

Cited by 70 publications

References 26 publications

Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission

Pretransplantation Minimal Residual Disease Predicts Survival in Patients with Mantle Cell Lymphoma Undergoing Autologous Stem Cell Transplantation in Complete Remission

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

Refining the Mantle Cell Lymphoma Paradigm: Impact of Novel Therapies on Current Practice

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