Absence of Aberrant Plasma Cells in the Apheresis Product Predicts for Minimal Residual Disease Negativity after Autologous Transplantation in Myeloma Patients Who Receive First Line Therapy

2019 ◽  
Vol 19 (10) ◽  
pp. e184-e185
Author(s):  
Evangelos Terpos ◽  
Ioannis V. Kostopoulos ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Aristea-Maria Papanota ◽  
Paraskevi Micheli ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Plasma Cells ◽  
Residual Disease ◽  
Autologous Transplantation ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual

Longitudinal Evaluation of Minimal Residual Disease in Patients with Multiple Myeloma who Achieve Complete Response After First Line Therapy

2019 ◽  
Vol 19 (10) ◽  
pp. e185-e186
Author(s):  
Ioannis V. Kostopoulos ◽  
Efstathios Kastritis ◽  
Aristea-Maria Papanota ◽  
Paraskevi Micheli ◽  
Panagiotis Malandrakis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Complete Response ◽  
First Line ◽  
Longitudinal Evaluation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual

Minimal Residual Disease Is a Predictor for Progression-Free and Overall Survival in Chronic Lymphocytic Leukemia (CLL) That Is Independent of the Type or Line of Therapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 540-540 ◽  
Author(s):  
Marwan Kwok ◽  
Andy C. Rawstron ◽  
Abraham Varghese ◽  
Peter Hillmen
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Line Of Therapy ◽  
Minimal Residual

Abstract Abstract 540 The depth of remission in CLL correlates with survival in a large number of trials regardless of the therapy used and the depletion of minimal residual disease (MRD), when reported, is usually associated with improved progression free and overall survival. However it is not clear whether this improved outcome is due to the attainment of MRD negativity or whether MRD eradication is a surrogate for other variables that predict for good response. In order to address the true impact of achieving MRD negativity we present data from 137 patients with CLL who were treated between 1996 and 2007, achieved a good clinical response and had bone marrow examined post-therapy to assess remission status including MRD. The MRD assessment was performed in a single laboratory (HMDS, Leeds, UK) using multicolor flow cytometry capable of detecting minimal residual disease (MRD) to a level of one CLL cell in 10000 leukocytes as recently recommended in the IWCLL Guidelines. Patients were followed for a median duration of 3.1 years (range 0.2 - 12.7) after treatment with chlorambucil (n=13), fludarabine (n=17), fludarabine and cyclophosphamide (n=58), fludarabine and cyclophosphamide with mitoxantrone and/or rituxumab (n=8), alemtuzumab (n=29), autologous stem cell transplantation (n=7) and various other treatments (n=5). Of these, 48 achieved a complete response (CR), 24 achieved a CR with incomplete marrow recovery (CRi), 27 achieved a nodular partial response (nPR) and 38 achieved a partial response (PR). Altogether 58 individuals (42.3%) were MRD negative at the end of treatment, including 28 CR, 20 CRi, 3 nPR and 7 PR patients. Results of the univariate and multivariate analyses are summarized below: Age, number of prior therapies and MRD negativity were independently correlated with overall survival. MRD negativity in the marrow at the end of therapy was independently significant in multi-variate analysis including when analysed against age, stage, prior therapy, IWCLL response assessment and cytopenia. One of the most striking findings was in patients having their first CLL treatment. Of the 58 patients in this series who had achieved a clinical response to first line therapy 24 patients (21 patients following FC, 1 FCR, 1 chlorambucil and 1 fludarabine à autologous SCT) achieved an MRD-negative remission and 34 were MRD-positive. With a median follow-up of 38 months (range 7-153) the 5 year PFS for MRD negative patients was 89% (95% CI 55-97%) compared to 0% for the MRD positive patient (95% CI <1%) and the 5 year OS was 95% (95% C.I. 61-99%) vs 53% (95% C.I. 15-74%) for MRD-negative vs. MRD-positive patients, respectively. Although achieving MRD-negativity with subsequent therapy is relatively beneficial, the greatest differences in outcome were seen in front-line treatment. This data suggests that achieving MRD-negativity after first-line therapy has a profound effect on overall survival. In conclusion, we demonstrate that achieving MRD negativity in CLL is an independent predictor of survival in multivariate even when a variety of different treatment approaches are considered and regardless of the line of therapy.. This is the strongest evidence yet that achieving MRD negativity is the most appropriate aim of therapy in CLL for patients who are fit enough for such an approach. Furthermore patients who achieve MRD negativity after their first therapy have a 5 year PFS of 89% and a 5 year overall survival of 95% suggesting that the optimal time to attempt to achieve MRD negativity is with first line therapy. Disclosures: Hillmen: Roche Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Efficacy of a bendamustine and rituximab combination in first-line therapy for chronic lymphocytic leukemia: Results of the BEN-001 study

2017 ◽  
Vol 89 (7) ◽  
pp. 57-64
Author(s):  
E A Stadnik ◽  
V V Strugov ◽  
T O Andreeva ◽  
Yu V Virts ◽  
A M Rumyantsev ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Survival Rates ◽  
Lymphocytic Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mutational Status ◽  
Minimal Residual

Aim. To evaluate the efficacy and safety of the BR regimen containing bendamustine in patients with chronic lymphocytic leukemia (CLL) who have not previously received specific therapy. Subjects and methods. The results of the Russian prospective observational multicenter study BEN-001 (2012—2015) covering 196 CLL patients from 34 centers of the Russian Federation were analyzed. The diagnosis was confirmed by the results of peripheral blood lymphocyte immunophenotyping. A centralized approach was employed to make IGHV gene mutational status analysis, FISH examination, and minimal residual disease according to standardized methods. Quality-of-life (QOL) indicators were estimated using the EQ-5D and FACT-Leu questionnaires. Survival rates were calculated applying by the Kaplan-Meier method. Results. The patients’ median age was 61 years. 41% of patients had a decline in estimated creatinine clearance less than 70 ml/min/1.73 m2. The combination of bendamustine and rituximab could achieve a common response in 83.2% of the patients, including complete remission in 59.7%. Eradication of minimal residual disease was achieved in 23 (27.4%) of 84 patients. Two-year progression-free survival rates were 85.9%. The QOL indicators were noted to be improved during the treatment. Conclusion. The investigation shows the good tolerability of bendamustine when it is used in clinical practice. Due to the high cost of new drugs (ibrutinib, obinutuzumab, ofatumumab, etc.) and toxicity of the FCR regimen, the combination including bendamustine can be the best first-line therapy option for all CLL patients, regardless of their age and comorbidity.

Cladribine Alone or in Combination with Cyclophosphamide or Cyclophosphamide and Mitoxantrone as First Line Treatment in Chronic Lymphocytic Leukemia: An Early Report of Prospective Randomized Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 337-337 ◽  
Author(s):  
Tadeusz Robak ◽  
Jerzy Z. Blonski ◽  
Joanna Gora-Tybor ◽  
Marek Kasznicki ◽  
Jadwiga Dwilewicz-Trojaczek ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Residual Disease ◽  
Early Report ◽  
Randomized Study ◽  
Lymphocytic Leukemia ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual

Abstract The aim of the study was to determine the efficacy and toxicity of cladribine alone (2-CdA) and in combination with cyclophosphamide - CY (CC) or CY and mitoxantrone - MIT (CMC) in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia in a randomized, multicenter study. 2-CdA was given at a dose of 0.12 mg/kg/d in 2 h I.V. infusion for 5 consecutive days in monotherapy and for 3 days in combination. In CC and CMC programmes cyclophosphamide was administered at a dose of 650 mg/m2 I.V. on day 1 and additionally mitoxantrone 10 mg/m2 I.V. on day 1 in CMC. Courses were repeated at 28 day intervals or longer if myelosuppression and/or infection developed, for a maximum of 6 courses. The response criteria were those recommended by NCI sponsored Working Group. Minimal residual disease (MRD) were evaluated by flow cytometry if CR was achieved. In conclusion, the results of our study indicate that 2-CdA combined with CY or CY+MIT as first line therapy give higher CR rate than 2-CdA alone. However, CMC is more toxic than 2-CdA or CC. We recommend CC combination for further studies. Treatment 2-CdA CC CMC p value Entered pts 167 169 163 Evaluated pts 143 152 139 CR 37 (25.9%) 43 (28.3%) 55 (39.6%) 0.03 OR 106 (74.1%) 125 (82.2%) 110 (79.1%) 0.2 MRD 15 (46.9%) 22 (82.2%) 25 (56.8%) 0.7 Median OR duration (years) 1.67 1.81 1.43 0.1 Relapse 48 (45.3%) 45 (29.6%) 43 (30.9%) 0.2 AIHA 10 (7.0%) 10 (6.6%) 5 (3.6%) 0.4 Thrombocytopenia grIII/IV 25 (17.5%) 25 (16.4%) 32 (23.0%) 0.3 Neutropenia grIII/IV 27 (18.9%) 43 (28.3%) 52 (37.4%) <0.001 Infections 39 (27.3%) 47 (30.9%) 53 (38.1%) 0.07 Died 39 (27.3%) 30 (19.7%) 37 (26.6%) 0.4

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

Reduced Intensity Stem Cell Transplantation and Donor Lymphocyte Infusion after Imatinib Induction To Eradicate Residual Disease in Chronic Myeloid Leukaemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1097-1097
Author(s):  
Nicholas Heaney ◽  
Mhairi Copland ◽  
Karen Stewart ◽  
Judith Godden ◽  
Anne Parker ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Control ◽  
Cell Transplantation ◽  
Residual Disease ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Reduced Intensity

Abstract Recommended first-line therapy for patients with chronic phase (CP) CML is imatinib mesylate (IM). Although IM induces complete cytogenetic responses (CCR) in the majority of patients, disease often remains detectable by Q-RT-PCR, likely reflecting stem cell persistence. Furthermore, primary and acquired resistance to IM have led to concerns about response durability. Allogeneic stem cell transplantation (SCT) remains the only curative option and with reduced intensity conditioning (RISCT) is less toxic and may be offered to a broader patient group. Our novel approach used IM to establish disease control (CCR) in patients with newly diagnosed CP CML prior to RISCT (fludarabine/melphalan/MabCampath). Prophylactic escalating DLI was given for residual disease. 18 patients (4 centres) were recruited between 2001 and 2006. Of these, 3 received myeloablative SCT, 2 for progression to blast crisis prior to SCT and the third for failing to reach a major cytogenetic response. 15 patients with a median age of 39y (21–56y) received sibling RISCT. Hasford scores were 38% low, 54% intermediate and 8% high risk. EBMT risk scores were 1–2 (13 patients) and 3–4 (2 patients). 5 patients required IM dose escalation to achieve CCR prior to RISCT. Follow-up data extends to a median of 31 (12–61) months (m) post RISCT. The RISCT procedure was well tolerated with rapid engraftment and short in-patient stays. 53% had infective episodes post RISCT, including CMV reactivation (86% patients at risk), EBV+ post transplant lymphoproliferative disease (2 patients) and PCP (1 patient). 1 patient developed aGvHD (grade III) and 8 cGvHD (6 limited, 2 extensive). DLI was given to 13 patients (87%), 6 for elevated Bcr-Abl, 4 for mixed chimerism and 2 for both. The median total dose was 0.65 × 107CD3+cells/kg (0.1–6.65 × 107cells/kg) in a median of 2 infusions. GvHD was seen in 6 of 12 patients receiving DLI (50%). IM was required in 4 patients with residual disease and all discontinued IM once disease control was re-established (4–13m of IM). 1 of 15 transplanted has died (at 12m with GvHD and infection). Of surviving patients median Bcr-Abl measurements fell as follow-up progressed. 8 patients currently have sustained undetectable Bcr-Abl. 7 of these 8 received DLI, the other had GvHD. The interval between last DLI and first proof of disease eradication was median 2m (range 1–28m). Only 2 of these 8 patients received IM post-transplant. In this study, the patients receiving RISCT were in early CP with a CCR to IM. It is likely that the majority would have maintained CCR if not offered transplantation. However the number of patients who achieved undetectable Bcr-Abl following RISCT and DLI compares favourably with the response expected with IM alone. The patients have tolerated the transplant procedure well and are currently off all treatment for CML. Regular monitoring remains necessary, however if relapse occurs it should be DLI responsive. Currently IM is the accepted first line therapy in the majority of patients however we would highlight the importance of RISCT in selected groups and believe our approach is effective and well tolerated.

A Pilot Study of Lenalidomide and Dexamethasone as First Line Therapy in Patients with Primary Plasma Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4951-4951
Author(s):  
Pellegrino Musto ◽  
Maria Teresa Petrucci ◽  
Fortunato Morabito ◽  
Francesco Nobile ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Early Response ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 4951 Background Primary Plasma Cell Leukemia (PPCL) is an aggressive, rare variant of multiple myeloma, with clinical, molecular and phenotypic peculiarities, which accounts approximately for 2% to 4% of all myeloma diagnoses. The prognosis of PPCL patients is usually poor, with less than half of patients responding to conventional chemotherapy and a median survival of 7 months. Even by using autologous or allogeneic transplant procedures, survival generally does not exceed three years. Bortezomib has recently provided some promising results in this setting, but, given all the above, new treatments for PPCL are greatly awaited. Lenalidomide is a new immunomodulating agent with great efficacy in multiple myeloma, especially when associated with dexamethasone or other drugs. There are, indeed, some sporadic case reports of PPCL patients treated with lenalidomide as salvage therapy, but no data are currently available on the use of this drug as first line therapy in this disease. Patients and Methods On March, 2009, we started an open label, prospective, multicenter, exploratory, single arm, two-stage study aiming to evaluate safety and antitumor activity of the lenalidomide/low dose dexamethasone combination (Rd), as first line therapy in patients with PPCL. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were TTP, PFS, OS, percentage of eligible PPCL patients able to collect peripheral blood stem cells and to undergo autologous or allogeneic stem cells transplantation after Rd, serious and severe adverse event rate. According to this study protocol, all eligible, newly diagnosed adult patients with PPCL receive Lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Oral dexamethasone is administered at a dose of 40 mg daily on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, patients who achieve at least PR and not eligible for autologous or allogeneic stem cell transplantation, continue with Rd until clinically appropriate (disease progression, unacceptable toxicity, patient's decision to leave the protocol). In these patients, a maintenance dose of lenalidomide alone equal to 10 mg/die days 1-21 every month is considered after at least 8 full dose Rd cycles. Patients responding after 4 Rd cycles and eligible for transplant procedures, proceed according to single Centre transplant policy. Patients not responding after 4 cycles or progressing under Rd treatment are considered off-study. Appropriate contraception methods and anti-thrombotic prophylaxis are planned. Results Four enrolled patients (1 male, 3 female, mean age 65 years, range 58-69) are currently evaluable for early response. All had unfavourable cytogenetics, including del13, t(4;14), t (14;16), or a complex karyotype. Circulating plasma cells ranged from 4.4 to 9.2 ×10e9/l. One patient had at baseline a moderate degree of renal failure (serum creatinine levels 2 mg/dl). After at least 2 Rd cycles (range 2-4), two PR and two VGPR were achieved (overall response rate 100%), with disappearance or near complete reduction of circulating plasma cells in all cases. The most relevant toxicities were grade 3 neutropenia and pneumonia, occurring in one patient and resolved by appropriate lenalidomide dose reduction, introduction of G-CSF and antibiotic therapy. One patient died in PR, due to causes unrelated to PPCL or treatment. As, according to the Simon, two-stage design adopted, more than two responses occurred within the first ten patients enrolled (stage 1), a total of 22 PPCL subjects will be accrued to complete the stage 2 of the trial. Conclusions These findings, though very preliminary, suggest that the combination of lenalidomide and dexamethasone may be a safe and promising initial therapy for PPCL patients, which can rapidly control the disease and could permit to perform following single patient-adapted therapeutic strategies. An update of this study, including molecular data, a larger number of patients and a longer follow-up, will be presented at the Meeting. Disclosures Musto: Janssen-Cilag: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide is approved in Italy for advanced multiple myeloma, not for plasma cell leukemia. This is a clinical trial registered at AIFA (Italian regulatory Agency for Drugs), EudraCT No. 2008-003246 28. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Morabito:Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria; Janssen-Cilag: Honoraria.

Risk-adapted maintenance therapy (MaintRx) after ASCT in first-line therapy for multiple myeloma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8607-8607
Author(s):  
Jonathan L. Kaufman ◽  
Joanne Willey ◽  
Michael E. Williams ◽  
Brynn Tiscione ◽  
Arden Buettner ◽  
...  
Keyword(s):  
Induction Therapy ◽  
Plasma Cells ◽  
Autologous Stem Cell Transplant ◽  
Phase Iii ◽  
Cell Transplant ◽  
First Line ◽  
Case Scenario ◽  
First Line Therapy ◽  
Line Therapy ◽  
Best Response

8607 Background: Maintenance lenalidomide improves survival in patients who have undergone induction therapy and then autologous stem cell transplant (ASCT) as first line management for MM. We studied how the extent of cytoreduction after induction therapy à ASCT (as measured by CR, VGPR, or PR as best response) influences MAINTRX prescribing preferences among American Hematology-Oncology physicians (AHOP). Methods: We studied 284 individual AHOPs using a proprietary, live, case-based market research tool to assess prescribing preferences. A core case scenario and variations based on extent of response to induction à ASCT was constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of respondent selections. All sources of research support were double blinded. The core scenario involved a 59-year-old patient (42% plasma cells in BM, no cytogenetic abnormalities, CrCl 65ml/min, B2M 5.8, PS 1) treated with induction therapy of choice à ASCT. The same query was then posed in each of 3 settings: Following CR (or following VGPR or following PR) as best response, what, if any, further therapy would you recommend now? Results: See Table. Conclusions: Among patients with myeloma getting first-line therapy, MaintRx is almost uniformly preferred by AHOPs. Specific single or doublet therapy preferences are dependent upon best response to induction à ASCT treatment. Compared to the CR setting, preferences for 2 drug MaintRx are significantly increased in patients with VGPR (p <.0.001) or with PR (p < 0.001)] as best overall response. The potential for benefit from intensified MaintRx in these response subsets needs prospective phase III testing. [Table: see text]

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