Minimal residual disease (MRD) status pre- and post- high-dose therapy/autologous stem (HDC/ASCT) cell transplantation for multiple myeloma (MM) in the era of novel agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8605-8605
Author(s):  
Adetola Kassim ◽  
Jeremy Scott McDuffie ◽  
Claudio A Mosse ◽  
Bipin N. Savani ◽  
John P. Greer ◽  
...  
Keyword(s):  
Residual Disease ◽  
Prognostic Significance ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Disease Stage ◽  
High Dose ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact

8605 Background: MRD assayed by multi-parameter flow cytometer (MFC), has prognostic significance after HDT/ASCT for MM (Paiva et. al. 2008). The frequency of MRD negativity (-) after induction therapy using novel agents such as immunomodulatory drugs like lenalidomide (IMiDs), and proteasome inhibitors like bortezomib, is unknown. The impact of HDT/ASCT on MRD status in this patient group has not been studied. Methods: We performed a retrospective study of all MM patients undergoing HDT/ASCT (January 2010 - December 2012) in our institution. No restrictions on inclusion were made based on the International Myeloma Working Group response criteria. All patients had novel agents as part of their initial induction regimen. Statistical analysis was by SPSS software (V 12.0). MRD status was determined by MFC on bone marrow samples pre- HDC/ASCT [M1] and post- HDC/ASCT (D100 [M2] and I year [M3]). MFC was done with antibodies against CD45, CD19, CD138, CD38, CD20, CD56, and anti-k and l cytoplasmic antibodies. Results: MRD status was available on 91 patients pre-transplant. Of these patients, 80 had MFC recorded at M2 and 17 patients had MFC recorded at M3. Fifty-eight percent were male and 76% were Caucasian. Forty percent received IMiDs, while 60% got proteasome based therapies. Of the 91 patients with MRD pre-HDC/ASCT, 58% (53/91) were MRD (-), and of these patients 89% (41/46) remained MRD (-) at M2. 48 patients were MRD positive (+) pre-HDC/ASCT, 58% (20/34) became MRD (-) at M2. Age, cytogenetic risk, disease stage, number of chemotherapy cycles or immunofixation status had no impact on MRD status. There were only 6 relapses in the cohort, thus the impact of MRD status on progression-free survival could not be studied. Conclusions: Novel agents improve depth of response pre-transplant. HDC/ASCT increases MRD negativity post-transplant. MRD status could aid better timing of HDC/ASCT or adoption of a risk-adapted strategy for high-risk patients. MRD status validation in a prospective cohort is underway at our center (NCT01215344). With future follow-up, the impact of MRD on progression-free survival in the era of novel agents will be determined.

scholarly journals Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials

2017 ◽  
Vol 35 (25) ◽  
pp. 2900-2910 ◽  
Author(s):  
Juan-Jose Lahuerta ◽  
Bruno Paiva ◽  
Maria-Belen Vidriales ◽  
Lourdes Cordón ◽  
Maria-Teresa Cedena ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Pooled Analysis ◽  
Disease Stage ◽  
Cox Models ◽  
Depth Of Response ◽  
The Impact

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P < .001) and OS (median not reached; P < .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients with MM and a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM.

The role of complete response in multiple myeloma

Blood ◽  
2009 ◽  
Vol 114 (15) ◽  
pp. 3139-3146 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Michel Attal ◽  
Herve Avet-Loiseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Prognostic Impact ◽  
Free Survival ◽  
Depth Of Response ◽  
The Impact ◽  
Good Partial Response

AbstractIn multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM. However the benefit of CR achievement depends on the type of treatment and is not identical for all patients. In elderly patients, treatments inducing more CR may be more toxic. Although CR achievement is necessary in patients with poor-risk disease, it might not be as critical for long survival in more indolent MM. CR achievement is not the only objective of treatment because it is possible to further improve the depth of response and the outcome by continuing treatment after CR achievement. Finally, there are several levels of CR and in the future it will be necessary to confirm the prognostic impact of immunophenotypic or molecular CR or of CR defined by imaging procedures.

Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8029-8029
Author(s):  
Binod Dhakal ◽  
Shruti Sharma ◽  
Svetlana Shchegrova ◽  
Minu Maninder ◽  
Meenakshi Malhotra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Residual Disease ◽  
Prognostic Significance ◽  
Unmet Need ◽  
Progression Free Survival ◽  
Multiparameter Flow Cytometry ◽  
High Dose ◽  
Blood Samples ◽  
Ctdna Analysis

8029 Background: Despite treatment with high-dose chemotherapy followed by autologous stem cell transplantation (AHCT), MM patients invariably relapse. MRD-negativity post-AHCT has emerged as the most important prognostic marker. Currently, MRD in MM is monitored via bone marrow aspirate sampling. Marrow MRD assays are limited by the spatial heterogeneity of marrow MM localization; extramedullary disease and sampling variability of marrow aspiration. Sensitive, non-invasive blood-based MRD assay is an unmet need. ctDNA as a noninvasive biomarker can be utilized to predict relapse in MM. Here we attempt to evaluate MRD using ctDNA in AHCT recipients with MM. Methods: In this retrospective, single-center study, we analyzed ctDNA MRD in blood samples collected from 28 patients with MM after upfront AHCT. A total of 80 plasma timepoints were available pre and post AHCT with a median follow-up of 92.4 months. Multiparameter flow cytometry (MFC) at 10-4 level was used to assess the MRD from the BM biopsy. Individual bone marrow aspirates or FFPE slides from the time of MM diagnosis and matched normal blood were whole-exome sequenced, and somatic mutations were identified. MRD assessment at 3 months post-AHCT was performed by ctDNA analysis using a personalized, tumor-informed (SignateraTM, bespoke mPCR NGS assay). The prognostic value of ctDNA was evaluated by correlating MRD status with clinical outcomes. Results: Table provides the baseline disease characteristics. Median age was 67 [41-75] years and 16 [57.1%] were males. ctDNA was detectable in 70.8% (17/24) of pre-AHCT, 53.6% (15/28) of ̃3 months post-AHCT, and 39.2% (11/28) of patients during the surveillance phase post-AHCT. Of the 15 ctDNA MRD positive patients, 93.3% (n=14) experienced relapse on follow-up (hazard ratio: 5.64; 95% CI: 1.8-17; p=0.0003). Patients negative for ctDNA at 3 months post-AHCT had significantly superior progression-free survival (PFS) compared to positive (median PFS, 84 months vs. 31 months; p=0.003) The positive predictive value (PPV) for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, and significantly higher than marrow MFC of 68.4%. Conclusions: Our study shows the feasibility that a tumor-informed assay on archival blood samples is predictive of relapse post-AHCT. Future prospective studies with real-time marrow NGS and ctDNA samples are needed to define the role of ctDNA in MM and its prognostic significance.[Table: see text]

Changes in shedding of soluble tumor necrosis factor receptors (sR1/R2) and in dynamic MRI as early predictors of outcome with NGR-hTNF.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22145-e22145
Author(s):  
Paolo A. Zucali ◽  
Matteo Simonelli ◽  
Fabio De Vincenzo ◽  
Armando Santoro ◽  
Antonio Lambiase ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Dynamic Mri ◽  
High Dose ◽  
Vascular Effects ◽  
Free Survival ◽  
Early Predictors ◽  
Receptor Shedding ◽  
Early Effects ◽  
The Impact ◽  
Necrosis Factor

e22145 Background: Dose-response curve of NGR-hTNF, a selective antivascular agent, is typically biphasic with activity shown either at low dose (LD) or high dose (HD). Receptor shedding may block drug activity. Vascular effects at LD are characterized by early vessel stabilization and late vessel damage, while at HD by rapid vessel disruption. Methods: 60 pts (median age: 61; M/F: 44/16; PS 0/≥1: 25/35; median prior lines: 3) received in 2 ph I trials NGR-hTNF at LD (0.2-1.6 µg/m2; n=14) or HD (60-325 µg/m2; n=46) every 3 weeks. We tested the impact of early changes (post 1st dose) in baseline-normalized plasma receptor levels (n=60) and in DCE-MRI-assessed Ktrans (n=49) on treatment effect, including disease control (DC, rate of pts progression free at 6 weeks by RECIST criteria) and progression free survival (PFS). Results: Baseline receptor levels were not related to outcome. Post-dosing levels of sR1 (median, 4.6 ng/mL; interquartile range, 2.8-5.7) and sR2 (8.6; 4.5-10.7) increased with dose (p<.0001 for both), with median values of sR1 (0.3) and sR2 (0.5) at LD being significantly lower than those of sR1 (4.9) and sR2 (9.6) at HD (p<.0001 for both). Using as cutoff the 1st quartile, low sR1 levels (≤2.8 ng/mL) correlated with improved DC (OR=4.9; p=0.01) and PFS (HR=0.30; p=.003). In low vs high groups, median DC duration was 7.4 vs 2.9 months and 6-month PFS was 29% vs 0%, respectively. By adjusting for baseline covariates (age, sex, PS and prior lines), low sR1 levels remained independently associated with better DC (p=.02) and PFS (p=.008). Similar effects were noted for sR2. Levels of sR1 (r=-0.35; p=.01) and sR2 (r=-0.27; p=.07) inversely correlated with early fractional decreases in Ktrans, which resulted in median values unchanged after LD (4%; p=.73) and reduced after HD (-32%; p=.009). However, Ktrans significantly declined over time after both LD (-24%; p=.04) and HD (-44%; p=.001). Early changes in Ktrans did not relate with DC as defined by RECIST, but smaller decreases in Ktrans were associated with longer PFS (HR=0.56; p=.04). Conclusions: NGR-hTNF at LD is associated with better outcome than at HD likely due to early effects that involve minimal receptor shedding and vessel stabilization. Clinical trial information: NCT00878111-NCT00914628.

scholarly journals Prognostic Value of the Novel Mucosal Associated Lymphoid Tissue Prognostic Index (MALT-IPI) in Marginal Zone Lymphoma (MZL) Cases

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2885-2885
Author(s):  
Hian Li Esther Chan ◽  
Liang Piu Koh ◽  
Vanessa CL Chong ◽  
Xin Liu ◽  
Sanjay De Mel ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Marginal Zone ◽  
Prognostic Significance ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Large Cohort ◽  
Disease Stage ◽  
Free Survival ◽  
Patient Cohort ◽  
Asian Patients

Abstract Background/Objective: Marginal zone B-cell lymphomas (MZL) represent a heterogeneous group of indolent lymphomas, comprising of MALT lymphomas, nodal MZL and splenic MZL. Currently, there has been no widely accepted prognostic indices for these lymphomas. Recently, the International Extranodal Lymphoma Study Group (IELSG) developed a novel simplified MALT prognostic index (MALT-IPI)1, which was subsequently validated by a western cohort of MALT cases. To date, there has not been an assessment of the applicability of this score in other subtypes of MZL or in the Asian population, where geographic and ethnical differences may influence disease epidemiology and outcomes. Our study aimed to 1) Evaluate clinical characteristics and survival outcomes for a large cohort of Southeast Asian patients with MZL who were diagnosed between 1993 - 2018 and ii) Assess the prognostic significance of the MALT-IPI for this patient cohort. Patients and Methods: We retrospectively studied 286 consecutive patients with newly diagnosed MZL treated between 1993 to 2016 at 2 tertiary cancer centres in Singapore. Data on clinical parameters, treatments, response, and survival were evaluated. In addition, all patients with available data were classified according to the MALT-IPI (N =236, including MALT lymphomas N= 190 and nodal/splenic MZL, N= 46) and the prognostic significance of this score was evaluated. Results: Among 286 patients with MZL, 230 patients (80%) had MALT lymphomas, 35 (12%) had nodal MZL and 21 (7%) had splenic MZL. The median age was 60 years (range 15- 94), 49% of the patients were male and 183 patients (64%) had Stage I-II disease. The majority of the patients were managed by either radiotherapy (N= 77, 27%), chemo and/or immunotherapy (N= 76, 27%), watchful waiting (N-= 46, 16%) or antibiotics (N= 33, 11.5%).With a median follow-up of 46 mths (range 1 - 266 mths) for all patients, the 5 yr-PFS for the cohort was 59.8 %. Progression free survival was significantly better for the MALT subgroups compared to the nodal and splenic MZL subgroups ( 5 yr PFS of 63.6 vs 49.7 % vs 30.5 % respectively, p=0.002). The 5-yr OS was excellent at 86.7% and there were no differences between the MALT, nodal MZL and splenic MZL cohorts (5-yr PFS 87.1 vs 85.3% vs 86.4, p=0.667). Age, ECOG status and elevated LDH were prognostic for PFS on univariate analysis but none has significant impact on multivariate analysis. No other baseline clinical characteristic (including gender and disease stage) was significantly associated with PFS. Age and ECOG was significantly associated with OS on both univariate and multivariate analysis. In our cohort, the MALT-IPI was a significant prognostic marker with ability to discriminate different prognostic groups with respect to PFS and OS. The 5-year progression-free survival rate for patients who had MALT-IPI scores of 0, 1 or 2-3 were 78%, 58% and 42%, respectively (p<0.001). The 5-year OS rates for patients who had MALT-IPI scores of 0, 1 or 2-3 were 98% , 89% and 68% respectively (p <0.001). Table 1 and Figure 1A and B summarises the survival endpoints (PFS and OS) according to the MALT-IPI in our patient cohort. Conclusion We demonstrated the prognostic applicability of the MALT-IPI to identify patients at risks of progression or death, in a large cohort of Asian patients with MZL. Patients with high risk MALT-IPI appear to be associated with poor outcomes and may be candidates for novel treatment approaches. Disclosures Jeyasekharan: AstraZeneca: Other: Collaboration; Merck Sharp & Dohme: Honoraria; PerkinElmer: Other: Collaboration; Janssen: Research Funding. Goh:Johnson & Johnson: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Sanofi-Aventis: Consultancy, Honoraria; Bristol-Myers-Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria.

scholarly journals Differential Impact of ALK Mutations in Neuroblastoma

2021 ◽  
pp. 492-500
Author(s):  
Tara O'Donohue ◽  
Nitya Gulati ◽  
Audrey Mauguen ◽  
Brian H. Kushner ◽  
Neerav Shukla ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Risk Groups ◽  
Tyrosine Kinase Receptor ◽  
Differential Impact ◽  
Mutation Site ◽  
Free Survival ◽  
Anaplastic Lymphoma ◽  
The Impact

PURPOSE The tyrosine kinase receptor anaplastic lymphoma kinase (ALK) can be abnormally activated in neuroblastoma, and somatic ALK mutations occur in 6%-10% of patients. The differential clinical impact of these mutations has not been clearly elucidated. METHODS Data on patients with neuroblastoma harboring ALK mutations were retrospectively analyzed. ALK sequencing was performed by whole-genome sequencing, hybrid-based capture of targeted exomes, or hotspot ALK mutation profiling. The differential impact of ALK mutation site on clinical characteristics, response to treatment, and survival was analyzed. In a subgroup of patients with locoregional neuroblastoma diagnosed after 2014, the impact of all ALK mutations was compared with wild-type ALK. RESULTS Of 641 patients with neuroblastoma with ALK status analyzed on at least one tumor sample, 103 (16%) had tumors harboring ALK mutations. Mutations existed across all ages (birth to 67.8 years), stages (30% locoregional and 70% metastatic), and risk groups (20%, 11%, and 69% with low-, intermediate-, and high-risk disease, respectively). Mutation sites included F1174 (51%), R1275 (29%), R1245 (10%), and others (10%). Mutation site was not prognostic for progression-free survival or overall survival in the entire cohort, high-risk subgroup, or locoregional subgroup. Locoregional tumors with any ALK mutation were generally invasive: L2 by International Neuroblastoma Research Group staging in 30/31 patients with a 2-year progression-free survival (59%, 95% CI, 37.4 to 80.5) that was inferior to historical controls. This observation was corroborated in the post-2014 subgroup in which gross total resection was less likely for ALK-mutated tumors. CONCLUSION Somatic ALK mutations are present across all stages and risk groups of neuroblastoma. No specific mutation carries differential prognostic significance. Locoregional neuroblastoma has an invasive phenotype when harboring somatic ALK mutations in this population.

Survival and long-term toxicities of biochemotherapy for metastatic melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8553-8553
Author(s):  
D. R. Minor ◽  
J. Miller ◽  
M. Kashani-Sabet
Keyword(s):  
Residual Disease ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
High Dose ◽  
Consecutive Series ◽  
Term Survival ◽  
Free Survival ◽  
Long Term Survivors ◽  
Disease Free

8553 Purpose: Because long-term survival after therapy for advanced stage IV melanoma is rare, we thought it would be useful to examine our series of survivors treated with biochemotherapy for melanoma to analyze the characteristics of survivors and their chronic toxicities. Patients and Methods: We reviewed our previously reported (J Clin Oncol. 2005:23:16s suppl, abstract 7547) consecutive series of 38 patients treated between 9/02 and 7/04. They received 6 cycles of inpatient temozolomide, cisplatin, vinblastine, decrescendo high- dose iv IL-2 , and interferon followed by maintenance immunotherapy using IL-2 and sargramostim using the O’Day regimen (Clinical Cancer Res. 2002:8:2775).Two of the ten long-term survivors received surgery for resection of residual disease after achieving a partial response with biochemotherapy. Maintenance immunotherapy was given for 6 to 24 months after biochemotherapy. Results: The median progression- free survival was 7.3 months. No patient developed progression later than 17 months after the start of therapy with the progression-free survival curve level at 24%. Median overall survival was 16.2 months. 10 of the 38 patients are alive and disease-free off therapy after an average of 3.3 years follow-up. Durable complete responses were seen in visceral sites including lung, bone, and pericardium, with 8 of 10 long- term survivors having M1B or M1C disease. 3 patients have significant lymphedema related to prior surgery, radiation therapy, or both. 2 patients, one with pre-existing diabetes, have significant persisting neuropathy. 5 of the 10 patients are hypothyroid. Menstrual function returned in the three women under age 45 in this study. Conclusion: This series supports the findings from other series that biochemotherapy, like high-dose IL-2, can give prolonged disease-free survival. Survivors have a high incidence of hypothyroidism but neuropathy and lymphedema, which affected a minority of patients, were the most bothersome long-term toxicities. No significant financial relationships to disclose.

Differential response to carfilzomib based on initial therapy with bortezomib in multiple myeloma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19515-e19515
Author(s):  
Sarvari Yellapragada ◽  
Chizoba Ifeorah ◽  
Luke Fletcher ◽  
Gustavo Rivero ◽  
Zahida Yasin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Medical Center ◽  
Proteasome Inhibitors ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Resistance Mechanisms ◽  
Cross Resistance ◽  
Primary Resistance ◽  
Free Survival ◽  
Depth Of Response

e19515 Background: Proteasome inhibitors (PIs) are efficacious in multiple myeloma (MM). In randomized phase 3 studies Carfilzomib doubled the progression free survival (PFS) compared to Bortezomib from 9.4 mo to 18.7 mo (ENDEAVOR study) in relapsed and refractory MM. However concern for suboptimal Carfilzomib based therapy (CBT) response in patients (pt) progressing on Bortezomib based therapy (BBT) suggests “cross-resistance”. Methods: AfterIRB approval, all pt with symptomatic MM over the last 10 years at the Michael E. DeBakey VA Medical Center with initial BBT followed by salvage CBT at progression were included. The primary aim was to evaluate ORR (PR + VGPR+CR) and and PFS by the IMWG criteria, among relapsed/refractory pt treated with salvage CBT whether or not they had an initial BBT response (i.e., primary refractory+stable vs CR+PR+VGPR). Results: In this cohort, the median overall survival was 45 mo. Pt initially treated with BBT had an ORR of 17/19 (89.4%) and median PFS of 7.7 mo. For 12 pt attaining PR, PFS was 4.3 mo, whereas for those achieving CR/VGPR was 9.1 mo, p= 0.03. Two pt were primary refractory to BBT and also to CBT. For initially treated BBT responders the ORR with CBT was 68.4% (13/19), median PFS was 5.26 mo. 6/19 pt (32%) were CBT refractory. PFS during BBT for CBT responders versus CBT refractory patients was not statistically different. Among those who responded to both CBT and BBT there was no significant correlation between the PFS or depth of response (CR vs VGPR vs PR) with initial BBT and PFS with CBT. Conclusions: In our retrospective analysis, pt who exhibited primary resistance to initial BBT did not benefit from salvage therapy with CBT, raising the possibility that hard-wired PI-resistance mechanisms exist. Among BBT responders, CBT ORR was 68%. However the PFS with CBT was significantly shorter than the published literature of CBT in RRMM naïve to PI leading us to hypothesize that uncharacterized resistance mechanisms from “priming” bortezomib leads to inferior outcome with salvage CBT. We conclude that CBT can be attempted in those who respond to BBT independent of depth of response or PFS duration. However, alternative therapies should be considered in pt with primary refractoriness to BBT.

Pretransplant hemoglobin and serum creatinine levels correlate with progression free survival in myeloma patients undergoing autologous stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Taner Demirer ◽  
Guldane Cengiz Seval ◽  
Selami Kocak Toprak ◽  
Sinem Civriz Bozdag ◽  
Meltem Kurt Yuksel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Serum Creatinine ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
The Impact

e19532 Background: High dose melphalan and autologous stem cell transplantation (ASCT) significantly prolong survival for patients with multiple myeloma (MM). The purpose of this study is to assess the effects of hemoglobin (Hgb) and serum creatinine (Crea) values at the time of transplantation on the overall outcome of patients with multiple myeloma treated at our transplant center. Material & Methods: This analysis included 247 consecutive patients who underwent ASCT for MM between 2010-2016. Hemoglobin was grouped as low or high relative to their sample median. Patients were also stratified according to serum Crea value at the time of transplantation ( < 2 or ³2 mg/dl). Results: The median age was 57 (29-75) years and most patients were male (n = 151, 61.1%), IgG subtype (n = 124, 50.2%), and ISS stage 3 (n = 122, 49.4%). The interval from the time of diagnosis to ASCT was median 7 months and median follow-up from ASCT was 49 months (range, 3-198 months). The most commonly induction regimens included VAD (vincristine, doxorubicin and dexamethasone) and VCD (bortezomib, cyclophosphamide, dexamethasone), respectively. Since maintenance was not an approved treatment in myeloma most patients did not receive any. For the entire cohort, the median Hgb and Crea were 11.5 g/dL and 0.9 mg/dL respectively. No difference in progression free survival (PFS) was observed between a lower and higher Hgb (82 vs. 81 months, p = 0.96). However, the median PFS was significantly longer in patients with a lower Crea compared to those with a higher Crea (83 vs. 48 months, p = 0.01). Patients with both a lower hemoglobin and higher Crea experienced shorter PFS compared to those with a higher hemoglobin and lower Crea (45 vs. 82 months, p < 0.001). We failed to demonstrate the impact of creatinin levels on time to neutrophil and platelet engraftment. There were no differences in OS according to lower vs. higher Hgb (58 vs. 52 months; p = 0.29, respectively) but in higher crea cohort worse OS was observed (41 months vs. 57 months; p = 0.02, respectively). Conclusions: We demonstrate that hemoglobin and creatinine represent important determinants of clinical outcomes after ASCT. A lower hemoglobin and higher creatinine, individually and when combined, were associated with shorter PFS. Therefore, further studies of larger randomized cohorts are required to clarify the impact of pre-transplant Hgb and Crea levels on ASCT outcomes.

The Influence of PET/Gallium (PET/Gal) Status and High-Dose Rituximab (HDR) in Patients with Aggressive, Large, B-Cell Lymphoma (LBCL) Receiving Autologous Stem Cell Transplants (ASCT).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3058-3058 ◽  
Author(s):  
Amin M. Alousi ◽  
Rima M. Saliba ◽  
Grace-Julia Okoroji ◽  
Chitra Hosing ◽  
Barry I. Samuels ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
De Novo ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Disease Status ◽  
High Dose ◽  
Free Survival ◽  
The Impact

Abstract Background: PET/Gal status has been reported to be an important predictor of outcome in patients with LBCL who receive an ASCT. Newer conditioning regimens which include high-dose rituximab (HDR) have been shown to improve results (Khouri, JCO, 2005). The impact of HDR on the outcome of patients based on PET/Gal status has not been determined. Methods: A retrospective review of patients with chemo-sensitive, LBCL who received an ASCT on a research protocol at MD Anderson between 1995 and 2005 was performed. Factors that were considered for outcome included: Age, IPI, # of prior chemotherapies, B2-microglobulin, disease status at transplant, HDR and PET/Gal status. In patients who received HDR, it was given with stem cell mobilization and then again on days +1 and +8 following transplant. Results: A total of 188 patients were identified. Median age was 49 years with 108 (57%) male patients. 147 patients (78%) had de novo LBCL and 41 (22%) had a LBCL of follicular origin (LBCL-F). 83 (39%) patients received HDR. At transplantation, 95 patients (50%) were in PR, 71 (38%) in CRU and 22 (12%) in CR. 142 (76%) patients were PET/Gal negative, 37 (20%) PET/Gal positive and 9 (4%) were unknown. Median follow-up was 47 months. On multivariate analysis, for patients with de novo LBCL, PET/Gal status and HDR were the only predictors for progression and progression free survival (PFS). Patients who were PET/Gal negative and those that received HDR had a hazard ratio (HR) of 0.3 (p<0.001) and 0.5 (p=0.02) for progression, respectively (see the table below for the cumulative incidence (CI) for progression and PFS at 54 months according to HDR and PET/Gal status for de novo LBCL undergoing ASCT). PET/Gal Status and HDR were also found to be predictive for patients with LBCL- F on univariate analysis, however due to the small numbers in this subset; multivariate analysis could not be performed. PFS at 54 months for patients with LBCL-F who were PET/Gal negative was 40% versus 17% in the PET/Gal positive group, (p=0.006). PFS for those LBCL-F patients who received HDR was 81% as compared to 23% for those who did not receive HDR, (p=0.007). Conclusions: The two most important predictors of outcome following ASCT are PET/Gal status and whether HDR was given with the transplant regimen. The addition of HDR to the transplant regimen decreases the risk for progression irrespective of PET/Gal status; however the improvement is more significant in patients with a negative PET/Gal scan. C.I. for progression and PFS at 54 months for de novo DLBCL PET/Gal Status HDR CI of Progression (%) Progression Free Survival Positive No 83 17 Positive Yes 54 45 Negative No 35 55 Negative Yes 22 75

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