Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?
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ABSTRACT:
SUBMITTER: Ferrero S
PROVIDER: S-EPMC5566011 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
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Minimal residual disease in mantle cell lymphoma: are we ready for a personalized treatment approach?
Ferrero Simone S Dreyling Martin M
Haematologica 20170701 7
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Project description:Background: Minimal residual disease (MRD) has shown the prognostic value in mantle cell lymphoma (MCL). To quantify the relationships between progression free survival (PFS) and overall survival (OS) with MRD status in MCL, we conducted this meta-analysis. Methods: We searched databases including Pubmed, Embase, Web of Science and the Cochrane Library up to July 15th, 2020. Data of patients' characteristics, MRD assessment and survival outcomes were extracted and analyzed. Results: Ten articles were included. For the impact of post-induction MRD status on survival outcomes, MRD positive status was associated with worse PFS (HR=1.44; 95%CI 1.27-1.62; P<0.00001) and OS (HR=1.30; 95%CI 1.03-1.64; P=0.03) compared with MRD negative status. Regarding the impact of post-consolidation MRD status on survival outcomes, MRD positivity predicted shorter PFS (HR=1.84; 95%CI 1.49-2.26; P<0.00001) and OS (HR=2.38; 95%CI 1.85-3.06; P<0.00001) than MRD negativity. Conclusions: This study indicated that MRD positivity after induction and consolidation treatments was associated with worse PFS and OS for MCL. MRD-based treatment strategies should be further explored in clinical trials and real-world practice.
| S-EPMC7738989 | biostudies-literature
Project description:BackgroundIn the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial.Design and methodsPeripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression.ResultsThirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis.ConclusionsDetection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma.
| S-EPMC3347669 | biostudies-literature
Project description:High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival. Using next-generation sequencing, we explore whether the diagnostic MCL clonotype is present within the infused SCP. MRD was detected in 4/17 of the SCPs, ranging 4-568 clonal cells/100,000 cells. With a median survival of 17 months, 3/4 of patients with MRD+ graft succumbed from MCL relapse versus 2/13 in the MRD- fraction. Patients receiving MRD+ grafts had increased risk of mortality, and thus screening of SCPs may be important for clinical decision-making.
| S-EPMC9418493 | biostudies-literature
Project description:Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in of 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, P < .001) and inferior overall survival (52% vs 68%, P = .05). The sensitivity and specificity of ASC MRD positivity for progression and death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in multivariable analysis (hazard ratio [HR], 3.7; P < .001). Post-ASCT surveillance MRD testing of plasma, but not PBMC samples, reliably identified patients with an impending relapse. A positive plasma MRD result was associated with inferior PFS (HR, 3.0; P = .016) in a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range, 0-518 days). In conclusion, the detection of MRD in ASC samples is associated with a very high risk of relapse, justifying alternative treatment strategies or trials of novel consolidation options in these patients. Furthermore, post-ASCT MRD monitoring may facilitate the evaluation of the early initiation of treatment at molecular relapse. This trial has been registered at www.clinicaltrials.gov as #NCT02362997.
| S-EPMC10468363 | biostudies-literature
Project description:Classic hairy cell leukemia (HCL) is a rare indolent B-cell lymphoproliferative disorder characterized by profound pancytopenia and frequent infectious complications due to progressive infiltration of the bone marrow and spleen. Lacking effective treatment options, affected patients were confronted with a dismal survival prognosis of less than 5 years when the disease was first described in 1958. Tremendous therapeutic advances were accomplished with the introduction of purine analogues such as cladribine in the 1990s, facilitating a near-normal life expectancy in most HCL patients. Nevertheless, nearly all patients eventually relapse and require successive retreatments, while drug-associated myelotoxicity may accumulate and secondary malignancies may evolve. Detection of minimal residual disease (MRD) in a substantial portion of treated patients has become a surrogate for this still limited treatment efficacy. In the last decade, novel biologic insights such as identification of the driver mutation BRAF V600E have initiated the development and clinical investigation of new, chemotherapy-free, targeted drugs in HCL treatment, with encouraging efficacy in early clinical trials aimed at boosting eradication of MRD while optimizing drug tolerability. This review summarizes current clinical trials investigating treatment strategies beyond purine analogues in HCL and discusses clinically relevant obstacles still to overcome.
| S-EPMC8869886 | biostudies-literature
Project description:Lymphoma is a highly heterogeneous lymphohematopoietic tumor. As our understanding of the biological and pathological characteristics of lymphoma improves, we are identifying an increasing number of lymphoma subtypes. Genotyping has enhanced our ability to diagnose, treat, and monitor the prognosis of lymphoma. Despite significant improvements in treatment effectiveness, traditional methods for assessing disease response and monitoring prognosis are imperfect, and there is no significant improvement in overall remission rates for lymphoma patients. Minimal Residual Disease (MRD) is often indicative of refractory disease or early relapse. For lymphoma patients, personalized MRD monitoring techniques offer an efficient means to estimate disease remission levels, predict early relapse risk, and assess the effectiveness of new drug regimens. In this review, we delve into the MRD procedures in lymphoma, including sample selection and requirements, detection methods and their limitations and advantages, result interpretation. Besides, we also introduce the clinical applications of MRD detection in lymphoma.
| S-EPMC11345172 | biostudies-literature
Project description:Multiple myeloma (MM) is a neoplasm of plasma cells that secrete patient specific monoclonal immunoglobulins. A recognized problem in MM treatment is the early recognition of minimal residual disease (MRD), the major cause of relapse. Current MRD detection methods (multiparameter flow cytometry and next generation sequencing) are based on the analysis of bone marrow plasma cells. Both methods cannot detect extramedullary disease and are unsuitable for serial measurements. We describe the methodology to generate high affinity DNA aptamers that are specific to a patient's monoclonal Fab region. Such aptamers are 2000-fold more sensitive than immunofixation electrophoresis and enabled detection and quantification of MRD in serum when conventional MRD methods assessed complete remission. The aptamer isolation process that requires small volumes of serum is automatable, and Fab specific aptamers are adaptable to multiple diagnostic formats including point-of-care devices.
| S-EPMC7747622 | biostudies-literature
Project description:Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with historically poor long-term survival compared with other B-cell malignancies. Treatment strategies for this disease are variable and dependent on symptoms and patient fitness. Despite recent advances, MCL remains incurable and patients with high-risk disease have particularly poor outcomes. This review focuses on recent developments that enhance our understanding of the biology of MCL and new treatment approaches that have led to substantial improvements in clinical outcomes. We will outline induction immuno-chemotherapy and maintenance strategies in transplant-eligible patients. In addition, effective strategies for patients unfit for intensive induction will be discussed, with a particular focus on novel molecular therapies with activity in MCL. Lastly, a number of ongoing clinical trials will be presented; the data from these trials are anticipated to redefine standards of care in the near future.
| S-EPMC6069726 | biostudies-literature
Project description:BackgroundOfatumumab is a humanized type 1 anti-CD20 monoclonal antibody. Preclinical studies show improved complement-mediated cytotoxicity (CMC) compared to rituximab in mantle cell lymphoma (MCL). This study evaluates the safety and efficacy of combining ofatumumab with HyperCVAD/MA (O-HyperCVAD) in newly diagnosed MCL.MethodsIn this single-arm phase 2 study, 37 patients were treated with the combination of O-HyperCVAD for 4 or 6 cycles, followed by high dose chemotherapy and autologous stem cell transplant. Primary objectives were overall response rate (ORR) and complete response (CR) rate at the end of therapy. Secondary objectives included minimal residual disease (MRD) negativity, progression-free survival (PFS), and overall survival (OS).ResultsMedian age was 60 years; ORR was 86% and 73% achieved a CR by modified Cheson criteria. The MRD negativity rate was 78% after 2 cycles of therapy, increasing to 96% at the end of induction; median PFS and OS were 45.5 months and 56 months, respectively. Achieving a post-induction CR by both imaging and flow cytometry was associated with improved PFS and OS. Early MRD negativity (post-2 cycles) was also associated with an improved PFS but not OS. There were 3 deaths while on therapy, and grades 3 and 4 adverse events (AEs) were observed in 22% and 68% of the patients.ConclusionThe addition of ofatumumab to HyperCVAD/HD-MA led to high rates of MRD negativity by flow cytometry in patients with newly diagnosed MCL. Achieving a CR post-induction by both imaging and flow cytometry is associated with improved overall survival.
| S-EPMC10086838 | biostudies-literature
Project description:Minimal residual disease (MRD) is usually defined as the small number of cancer cells that remain in the body after treatment. The clinical significance of MRD kinetics is well recognized in treatment of hematologic malignancies, particularly acute lymphoblastic leukemia (ALL). Real time quantitative PCR targeting immunoglobulin (Ig) or T-cell receptor (TCR) rearrangement (PCR-MRD), as well as multiparametric flow cytometric analysis targeting antigen expression, are widely used in MRD detection. In this study, we devised an alternative method to detect MRD using droplet digital PCR (ddPCR), targeting somatic single nucleotide variants (SNVs). This ddPCR-based method (ddPCR-MRD) had sensitivity up to 1E-4. We assessed ddPCR-MRD at 26 time points from eight T-ALL patients, and compared it to the results of PCR-MRD. Almost all results were concordant between the two methods, but ddPCR-MRD detected micro-residual disease that was missed by PCR-MRD in one patient. We also measured MRD in stored ovarian tissue of four pediatric cancer patients, and detected 1E-2 of submicroscopic infiltration. Considering the universality of ddPCR-MRD, the methods can be used as a complement for not only ALL, but also other malignant diseases regardless of tumor-specific Ig/TCR or surface antigen patterns.
| S-EPMC10225364 | biostudies-literature