Abnormal Serum IgA Kappa / IgA Lambda Ratios at Maximum Response Predict Poor Progression Free Survival in Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4879-4879 ◽  
Author(s):  
Heinz Ludwig ◽  
Stephen Harding ◽  
Caroline Bradley ◽  
Dejan Milosavljevich ◽  
Mark T Drayson ◽  
...  
Keyword(s):  
Serum Proteins ◽  
Progression Free Survival ◽  
Maximum Response ◽  
High Dose ◽  
Free Survival ◽  
Monoclonal Protein ◽  
Clinical Assessments ◽  
Stem Cell Rescue ◽  
Site Group ◽  
High Dose Melphalan

Abstract Abstract 4879 For some myeloma patients, co-migration of IgA monoclonal proteins with other proteins can make serum protein electrophoresis (SPE) densitometry inaccurate. Immunofixation (IFE) will identify the monoclonal immunoglobulins, however, it is not quantitative and requires skilful interpretation. Measurement of total IgA can also be used but has limited value when the monoclonal protein level is low. Antibodies which target the heavy and light chains of the immunoglobulin have now been developed, making it possible to quantify IgAk and IgA» in serum and to calculate the IgAk/IgA» ratio. Here we describe 2 patient groups where archived sera have been analysed to evaluate the utility of IgAk/IgA» ratios for monitoring response to treatment in myeloma patients. We also compared progression free survival (PFS) or overall survival (OS) for patients who did / did not achieve a normal IgAk/IgA» ratio at maximum response. Sequential, archived sera were analysed from 31 patients treated in the UK Myeloma VII trial (21 IgAk /10 IgA») and 27 patients treated at The Centre for Oncology and Haematology, Vienna (14 IgAκ /13 IgA»). Treatments utilised varied from combinations of cyclophosphamide, vincristine, doxorubicin and methylprednisolone with/without high-dose melphalan/stem cell rescue (UK) to VAD, Thalidomide-Dexamethasone, VMCP, DCEP with/without high dose melphalan/stem cell rescue (Vienna). Between 3 and 51 (median=6) sera were available for each patient. Serum IgAk and IgA» measurements were performed on a Siemens Dade-Behring BN™II nephelometer in UK and on a Roche Cobas Integra 800™ immunturbimeter in Vienna. IgAk/IgA» ratios were compared with a normal range derived from measurement of >100 blood donor sera. SPE and IFE were performed on a SEBIA Hydrasys™ electrophoresis system (UK) and on a SEBIA Kapillarys™ capillary electropheresis system and a Helena SPE 2000™(Vienna). IgAk/IgA» results were compared retrospectively to clinical assessment and outcome. Kaplan Meier curves and Cox regression analysis were performed using SPSS v14.0. For all 31 UK patients, changes in the IgAk/IgA» ratio were in accordance with the clinical assessments. With regard to the detection of residual disease, the IgAk/IgA» ratios remained abnormal beyond the time when SPE results had normalised and appeared approximately equal to IFE in sensitivity. The IgAk/IgA» ratio remained abnormal in all sera from the 13/31 patients who achieved a partial response (PR) or less. In 10/31 patients, SPE densitometry could not accurately quantify the monoclonal protein, either because there was no obvious monoclonal protein (5/10) or the monoclonal protein was obscured by other serum proteins (5/10). 18/31 patients achieved a complete response (CR) but 9/18 still had abnormal IgAk/IgA» ratios at this time and had a shorter progression free survival (PFS; 277 days v 912 days: p=0.01). Similarly, for the 27 Viennese patients, changes in the IgAκ/IgA» ratios were in accordance with overall clinical assessments. In 18/27 patients, where clinically determined maximum response was reached, an abnormal IgAk /IgA» was associated with a shorter overall survival (344 days v 2241 days: p=0.028). Monoclonal IgA proteins can be difficult to identify and measure using electrophoresis techniques because of their co-migration with other serum proteins. The results from this preliminary study indicate that the use of IgAk/IgA» ratios may offer an alternative technique for monitoring these myeloma patients. Furthermore, the IgAk/IgA» ratio may provide prognostic information at the point of maximum response. Disclosures Ludwig: Celgene: Honoraria; Mundipharma: Honoraria; AMGEN: Honoraria; Ortho-Biotech : Honoraria; Janssen-Cilag: Research Funding; Roche: Honoraria. Harding:The Binding Site Group Ltd: Employment. Bradwell:The Binding Site Group Ltd: Shareholder.

scholarly journals Addition Of Bortezemib To High Dose Melphalan Does Not Improve Response Rate Or Progression-Free Survival

2010 ◽  
Vol 16 (2) ◽  
pp. S200-S201
Author(s):  
M. Sharma ◽  
M.H. Qazilbash ◽  
C.M. Hosing ◽  
P.F. Thall ◽  
F.L. Mendoza ◽  
...  
Keyword(s):  
Response Rate ◽  
Progression Free Survival ◽  
High Dose ◽  
Improve Response Rate ◽  
Free Survival ◽  
High Dose Melphalan

Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

1995 ◽  
Vol 13 (5) ◽  
pp. 1089-1095 ◽  
Author(s):  
W P Vaughan ◽  
E Kris ◽  
J Vose ◽  
P J Bierman ◽  
P Gwilt ◽  
...  
Keyword(s):  
Phase I ◽  
Continuous Infusion ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

Bortezomib-High Dose Melphalan Conditioning for the Treatment of MM Patients Undergoing ASCT

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2273-2273
Author(s):  
Victor Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Jason Tay ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Proteasome Inhibitor ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Melphalan

Abstract Introduction Recent data suggests that bortezomib, a proteasome inhibitor, in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the level of response for MM patients undergoing auto-SCT. In the present study, patients receiving induction followed by ASCT with Bor-HDM and HDM alone were evaluated. Methods All consecutive patients undergoing ASCT from 01/2004 to 03/2016 were evaluated. All patients received induction chemotherapy before undergoing auto-SCT. Patients received conditioning with either HDM at 200 mg/m2 (or adjusted as per renal failure) or HDM with Bortezomib (Bor-HDM). Most of patients received Bortezomib conditioning at 1.3 mg/m2. As per physician discretion, the dose of 1 mg/m2 was also employed in 30% of cases. Definitions of response and progression were used according to the EBMT modified criteria. MRD negativity was assessed by flow cytometry at day-100 post-ASCT. Results Clinical characteristics are shown in Table 1. Among 301 cases, 129 were treated with Bor-HDM while 172 patients went onto receive HDM alone as part of the conditioning regimen. Induction regimens are shown in Table 1. At the time of analysis, 83% and 58% of patients in the Bor-HDM and HDM group are still alive and 34% and 69.1% of patients have already progressed, respectively. At day-100 post ASCT, ORR of 97%, with CR/VGPR rate of 84.2% was seen in the Bor-HDM group compared to 94.2% and 68.6% in the HDM group (p=0.001). MRD negativity was higher in the Bor-HDM group (33.3%) compared to HDM (12.2%) (p=0.001). Median OS was similar for Bor-HDM and HDM (p=0.864) (Fig 1a). In addition, median PFS did not differ among patients receiving HDM or Bor-HDM (37.7months vs 29.3 months, p=0.2) (Fig1b) In conclusion,Bor-HDMis a conditioning regimen able to provide higher rates ofnCR/CR, as well as MRD negativity compared to HDM alone. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed. Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Overall Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1 Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Figure 1. Progression-Free Survival according to the conditioning regimen employed for patients with MM undergoing ASCT Disclosures Jimenez-Zepeda: Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene, Janssen, Amgen, Onyx: Honoraria. Neri:Celgene and Jannsen: Consultancy, Honoraria. Bahlis:Onyx: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; BMS: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel Expenses, Research Funding, Speakers Bureau.

scholarly journals Bortezomib and High Dose Melphalan (Bor-HDM) Compared to HDM Conditioning for the Treatment of Transplant Eligible Multiple Myeloma: Report from a Single Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3189-3189
Author(s):  
Victor H Jimenez-Zepeda ◽  
Peter Duggan ◽  
Paola Neri ◽  
Ahsan Chaudhry ◽  
Marcia Culham ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Overall Survival ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival ◽  
High Dose Melphalan ◽  
The Impact

Abstract Introduction Preclinical and clinical data suggest that bortezomib in combination with high-dose melphalan (Bor-HDM) provides with a synergistic effect able to improve the quality of response for MM patients undergoing auto-SCT. In the present study, we aimed to assess the impact of Bor-HDM conditioning on ORR, and MRD negativity for MM patients undergoing single auto-SCT at our Institution. Methods All consecutive patients who underwent single auto-SCT at Tom Baker Cancer Center (TBCC) from 01/2004 to 06/2015 using Bor-HDM or HDM as conditioning regimen were evaluated. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. MRD negativity was assessed by multiparameter flow cytometry. All patients received induction chemotherapy before undergoing auto-SCT. Bortezomib was administered intravenously at 1-1.3 mg/m2 on days −5, −2, 1, and 4, while melphalan was given at 200 mg/m2 on day −1. A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Results Two-hundred and fifty-eight consecutive patients receiving Bor-HDM or HDM alone were evaluated. A total of 85 patients received Bor-HDM conditioning and 173 received HDM. Clinical characteristics and chemotherapy induction regimens are listed in Table 1. At day-100 post auto-SCT a ³VGPR was seen in 83.3% in the Bor-HDM group compared to 67.6% for HDM patients. The CR/nCR rate was higher in the Bor-HDM group (47.6% vs 23.6%) as well as MRD negativity assessed by flow cytometry (30.9% vs 9.7%, p=0.0001). Median OS in the Bor-HDM group was NR compared to 95 months for HDM alone (p=0.572), while median PFS was 39.3 months for Bor-HDM compared to 27 months for HDM (p=0.1). Median OS was shorter in the HR cytogenetic group regardless of the type of conditioning regimen employed (39 months vs NR for SR cytogenetics). In addition, patients who achieved MRD negativity, exhibited a longer OS (NR vs 78 months, p=0.007). Transplant-related mortality (TRM) was similar between both groups (p0.5). In conclusion, Bor-HDM is a safe and efficacious conditioning regimen able to increase the nCR/CR and MRD negativity rates compared to HDM. Further studies are warranted to explore this regimen, especially when other upfront therapies are employed, with special view on the high-risk MM patients where response rates are good but sustainability remains an issue. Table 1. Clinical Characteristics Characteristic Bor/HDM, N=85 HDM alone, N=173 Age (median) 58 59 GenderMaleFemale 51 (60%)34 (40%) 113 (65.3%)60 (34.7%) Hb (g/L) 112 117 Calcium (µmol/L) 2.25 2.29 Creatinine (µmol/L) 85 80 B2microglobulin (µmol/L) 3.3 2.79 Albumin (g/L) 31 35 Stage IStage IIStage III 154723 617333 M-spike (g/L) 34 30 LDH (IU/L) 194 180 BMPC (%) 40 33 Heavy chain:IgGIgAIgDFLC onlyBiclonalIgM 491811511 1142403210 Light chain:KappaLambdaBiclonal 50351 124471 High riskStandard risk 2263 36135 InductionCyBorDVDDexamethasoneRVD 4524016 16544315 Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 1. Overall Survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 2. Progression-Free survival for patients with MM undergoing single auto-SCT according to the type of conditioning regimen Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Figure 3. Overall Survival for patients with MM undergoing single auto-SCT according to MRD negativity assessed by flow cytometry Disclosures Jimenez-Zepeda: Celgene: Honoraria; J&J: Honoraria; Amgen: Honoraria. Duggan:Jansen: Honoraria; Celgene: Honoraria. Neri:Celgene: Research Funding. Bahlis:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Johnson & Johnson: Speakers Bureau; Johnson & Johnson: Consultancy; Amgen: Consultancy; Johnson & Johnson: Research Funding.

Thalidomide and Dexamethasone Induction Therapy Is Associated with Superior Progression-Free Survival after Autotransplant for Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1171-1171
Author(s):  
Dan T. Vogl ◽  
Selina Luger ◽  
David L. Porter ◽  
Elise A. Chong ◽  
Stephen J. Schuster ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Initial Treatment ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
High Dose ◽  
Free Survival ◽  
Autologous Transplant ◽  
High Dose Melphalan

Abstract BACKGROUND: High-dose melphalan with autologous stem cell support improves survival when incorporated in the initial treatment of multiple myeloma. Published data show that induction thalidomide and dexamethasone (Thal/Dex) has a higher response rate than dexamethasone alone (Dex) or anthracycline induction (VAD or DVD), but the effect of initial induction therapy on outcomes after autologous transplant remains unclear. PATIENTS: We reviewed the records of 164 patients who received high-dose melphalan with autologous stem cell support as part of initial therapy for multiple myeloma at the University of Pennsylvania. Median age was 55 years (range 25 – 72). Durie-Salmon stage at diagnosis was II in 27% and III in 70% of patients. Induction regimens included VAD (62%), DVD (12%), Thal/Dex (11%), Dex (5%), and more than one regimen (10%). Post-transplant therapies for consolidation or maintenance included thalidomide (7%), interferon (23%), tandem autologous transplant (4%), non-myeloablative allogeneic transplant (7%), autologous co-stimulated T-cell infusion (14%), or observation until progression (45%). Patients who received Thal/Dex initial therapy were not significantly different than those receiving anthracycline-containing induction regimens (VAD/DVD), except for lower serum creatinine (median 0.9 vs 1.1 mg/dl; p=0.01), with a trend toward lower beta-2 microglobulin (B2M) and correspondingly lower ISS stage. RESULTS: Median overall follow-up is 29 months (range 7–120). Thal/Dex induction trended towards a higher Very Good Partial Response (VGPR) rate than anthracycline induction (29% vs 14%, p=NS) and a higher overall response rate (76% vs 68%, p=NS). All of the patients who received Thal/Dex as induction therapy are alive, with a median follow-up of 23 months (range 13 – 34), while overall survival in the anthracycline induction group is 85% at 2 years. Progression-free survival at 2 years is 93% for Thal/Dex induction and 58% for VAD/DVD (HR 0.12, p=0.039). The improvement in progression-free survival persists in Cox regression models that include creatinine and either B2M or ISS stage. CONCLUSION: In myeloma patients who undergo autologous stem cell transplant, thalidomide and dexamethasone induction may result in improved progression-free survival compared with VAD or DVD. Further studies of initial therapies for myeloma should assess long-term outcomes after autologous transplant. Progression Free Survival, By Initial Treatment Progression Free Survival, By Initial Treatment

scholarly journals High-Dose Melphalan in 1 Day Versus over 2 Days Followed By Autologous Stem Cell Transplantation As Consolidation Treatment in Patients with Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3944-3944
Author(s):  
Mesire Aydin ◽  
Man Wai Tang ◽  
Marielle Wondergem ◽  
David C. de Leeuw ◽  
Jurgen J. Wegman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
High Dose ◽  
Advisory Committees ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Cell Counts ◽  
High Dose Melphalan

Abstract Background High-dose melphalan (HDM) at 200 mg/m2 is a myeloablative consolidation treatment prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) and is administered in 1-day or divided over 2-days. Although the 1-day regimen (lower AUC) has been shown to result in significantly less gastro-intestinal toxicity, it is not completely clear whether this administration strategy has any deleterious effects on efficacy, compared to the 2-day regimen. In this retrospective cohort study, we aimed to evaluate the effects of 1- or 2-day dosing of HDM on disease remission, progression-free survival (PFS) and overall survival (OS) in patients with MM. Methods Data from two academic centers in Amsterdam that have recently merged were used for the analysis, with one of the centers using the 1-day regimen and the other the 2-days regimen. A total of 265 patients with MM divided over the 1-day group (n=174) and 2-day group (n=91) treated between July 2017 and February 2020, were included in the study. The primary endpoint was the proportion of patients with at least very good partial remission (≥VGPR) at day ±90 post-ASCT. Secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of hospitalization post-ASCT, engraftment period of neutrophils and platelets, and complications (other than mucositis) during hospitalization. Results Patient characteristics are summarized in Table 1. Remission status of ≥VGPR was comparable between the 1-day and 2-day groups (84% vs. 80% respectively). After a median follow-up of 21 months, OS (92% vs. 91%) and PFS (80% vs. 81%) were comparable in the 1-day and 2-day group respectively. There were no differences in the incidence of hematologic adverse events between the 1-day and 2-day groups (neutropenia; 98% vs. 100%, thrombocytopenia; 90% vs. 96% respectively). Median time to neutrophil engraftment (ANC &gt;0.5 x10 9 L -1) was significantly shorter in the 2-day group than in the 1-day group (14 days vs. 18 days, p = 0.002). Median time to platelet engraftment (platelets &gt;20 x10 9 L -1) was comparable between the groups. Lower CD34+ cell counts were administered in the 1-day group compared to the 2-day group (2.6 vs. 3.4 x10 6/kg, p &lt;0.0001). A significant negative correlation between the reinfused CD34+ cell counts and time to neutrophil engraftment was found (R= - 0.244). Table 2 shows the number of hospitalization days after ASCT. The median number was 18 days in the 1-day group and 15 days in the 2-day group (OR 1.22, 95% C.I. (1.10-1.35), p &lt;0.0001). Incidences of infectious complications, febrile neutropenia and intensive care unit (ICU) admissions were not different between the groups. Conclusion The use of 1-day HDM as consolidation treatment in MM patients resulted in equal disease response, progression-free survival and overall survival as compared to 2-day HDM. Based on the results of this study showing comparable efficacy and earlier findings of reduced toxicity with the 1-day HDM administration, we recommend the 1-day protocol for HDM. Interestingly, our results also confirmed that patients might benefit from higher counts of reinfused CD34+/enucleated cells. Figure 1 Figure 1. Disclosures Wondergem: Novartis: Honoraria. de Leeuw: Takeda: Membership on an entity's Board of Directors or advisory committees. Biemond: Sanquin: Research Funding; Celgene: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Novartis: Honoraria, Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding, Speakers Bureau. van de Donk: Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Cellectis: Research Funding. Zweegman: Sanofi: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nur: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

scholarly journals Comparison of Patient Outcomes with Two Different Formulations of Melphalan As Conditioning Chemotherapy for Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Filiz Yucebay ◽  
Ashleigh Keiter ◽  
Qiuhong Zhao ◽  
Alison Neal ◽  
Nita Williams ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Propylene Glycol ◽  
Research Funding ◽  
Transfusion Requirement ◽  
Progression Free Survival ◽  
High Dose ◽  
Advisory Committees ◽  
Free Survival ◽  
High Dose Melphalan

Introduction: High-dose melphalan is the standard conditioning chemotherapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM). However, patients experience several side effects and toxicities from high-dose melphalan. In 2016, United States Food and Drug Administration approved Evomela, a propylene glycol-free formulation of melphalan, as conditioning chemotherapy for ASCT in MM. This was based on its bioequivalence to the standard propylene-glycol solubilized melphalan formulation (Alkeran) in a phase 2 study. Evomela has the advantages of improved solubility, stability, bioavailability and being free of propylene glycol that is associated with organ dysfunction. Methods: We conducted a retrospective study of patients who received ASCT with high dose chemotherapy using alkeran (n=255) or evomela (n=259) at our institution to compare their outcomes such as side effects, duration of cytopenias, transfusion requirements, length of hospital stay, readmission within 30 days and progression-free survival (PFS) post-SCT. Clinical and demographic characteristics were compared between two treatment regimens using the Chi-square test for categorical variables and the Wilcoxon rank sum test for the continuous variables. Overall survival (OS) was calculated from the date of transplant to death, censoring the alive patients at their last follow up date. Progression-free survival (PFS) was calculated from the date of transplant to date of relapse or death, whichever occurred first, censoring at the last follow-up if no relapse or death. OS and PFS estimates were calculated using the Kaplan-Meier method and compared using the log-rank test. Results: The baseline patient characteristics such as age, ISS stage, comorbidity index and number of prior lines of therapy prior to ASCT were similar between the two groups. (See table 1). Mucositis was seen in 77.2% of the patients who received Alkeran compared to 69.5% who received Evomela (p=&lt;0.001). Incidence of febrile neutropenia was 65.9% in the Alkeran group and 49.4% in the Evomela group (p=0.0002). Chemotherapy-induced nausea and vomiting were reported in 98.8% and 93.4% of the patients in the Alkeran and Evomela groups respectively (p=0.001). Rates of diarrhea and clostridium difficile infection were similar with the two drugs. Time to neutrophil engraftment was the same in both the groups while duration of thrombocytopenia (platelets &lt;20k) was slightly longer in the Evomela group (6 days in alkeran and 8 days in evomela group, p=&lt;0.001). Red cell transfusion requirement was higher with the use of Alkeran compared to Evomela (42.3% vs 21.8%, p=0.001) while platelet transfusion was the same. There was no difference in the duration of hospital stay between the two groups. However, rate of readmission within 30 days of discharge was higher in patients who got Evomela compared to Alkeran (9.4% versus 17.4%, p=0.008). Day +100 serological response (very good partial response or better), PFS post-SCT and OS were similar in both groups. (Figure 1). Conclusion: We conclude that use of Evomela is associated with a better side-effect profile and transfusion requirement while having similar outcomes as Alkeran. Disclosures Yucebay: Janssen: Membership on an entity's Board of Directors or advisory committees; BioXCell: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Membership on an entity's Board of Directors or advisory committees. Chaudhry:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment. Bumma:Amgen: Speakers Bureau; Sanofi: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy.

Lenalidomide with Low-Dose Dexamethasone (Rd) Continuously Versus Rd Induction, Tandem MEL140 with Autologous Transplantation and Lenalidomide Maintenance: Planned Interim Analysis of a Prospective Randomized Trial in Patients 60-75 Years of Age with Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3969-3969 ◽  
Author(s):  
Christian Straka ◽  
Kerstin Schaefer-Eckart ◽  
Florian Bassermann ◽  
Hansen Timon ◽  
Bernd Hertenstein ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Low Dose ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Stage I ◽  
High Dose ◽  
Free Survival ◽  
Cell Mobilization ◽  
High Dose Melphalan

Abstract Background: Lenalidomide with low-dose dexamethasone (Rd) is an emerging treatment option for newly diagnosed multiple myeloma patients with higher age. However, many older patients also remain candidates for autologous transplantation especially with age-adjustment of high-dose melphalan. Potentially, high-dose therapy could add to the benefit of Rd, alternatively the effect of high-dose therapy could be more or less redundant in this setting. The DSMM XIII trial is a multicenter, open-label, phase III trial comparing the safety and efficacy of continuous Rd versus Rd induction followed by age-adjusted tandem high-dose melphalan with autologous transplantation and lenalidomide maintenance. Methods: Patients with newly diagnosed multiple myeloma with symptomatic and measurable disease of age 60-75 years were randomly assigned to either (A1) lenalidomide (25 mg po d1-21/28d) with low-dose dexamethasone (Rd) (40 mg po d1, d8, d15, d22/d28) for 3 cycles followed by stem cell mobilization and continued Rd until progression or (A2) 3 cycles of Rd, followed by stem cell mobilization, tandem high-dose melphalan 140 mg2 (MEL140) with autologous blood stem cell transplantation and lenalidomide maintenance 10 mg daily until progression. At randomization, patients were stratified according to age (≤70 years vs >70 years) and ISS stage (I, II vs III). Antithrombotic prophylaxis with low molecular weight (LMW) heparin or aspirin was recommended. The primary endpoint was progression-free survival (PFS), and secondary endpoints included safety, responses, overall survival and others. We report the results of the planned first interim analysis after occurrence of one third of events as pre-specified. Results: Since March 2010, 253 patients have been randomized and data of 251 patients were available for analysis. The median age was 68 years (range 59-75), 30% were older than 70 years, 34% had ISS stage I, 37% ISS stage II, and 29% ISS stage III. The median PFS for the whole study population (A1 and A2) was 37.3 months. The comparison of PFS by randomization arm did not meet the formal criteria for early termination of the trial. The overall response rate after 3 cycles of Rd (A1 and A2) was 75%, with 2% demonstrating complete response (CR), 21% very good partial response (VGPR) and 52% partial response (PR). A further 20% of patients had stable disease and 6% of patients progressive disease. The 3-year-survival rate is 75% (95% confidence interval, 68-84) for all patients and with respect to ISS stage amounted to 90% (CI: 81-99, ISS stage I), 78% (CI: 66-91, ISS stage II) and 51% (CI: 35-74, ISS stage III). For the two age groups, the 3-year-survival was 73% (CI: 64-84) in patients with age ≤70 years and 80% (CI: 68-94) in patients with age >70 years. So far, 8 (3%) second primary malignancies (SPM) were observed, 4 skin tumors and 4 other solid tumors, but no hematological SPM was documented. Conclusion: In our trial, lenalidomide with low-dose dexamethasone (Rd) was found to be associated with a favorable median progression-free survival at 3 years. The survival in patients >70 years was not inferior compared to younger patients. The potential advantages and disadvantages of combining lenalidomide with high-dose melphalan and autologous transplantation in comparison to continous Rd are addressed by this ongoing trial and further data will be presented at the meeting. Disclosures Straka: Celgene: Consultancy, Honoraria, Research Funding. Off Label Use: Lenalidomide for first-line treatment.

Lebanese experience in treating multiple myeloma: A multicenter retrospective study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20526-e20526
Author(s):  
Fadi Nasr ◽  
Lewis Nasr ◽  
Ahmad Ghoche ◽  
Saada Diab
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Progression Free Survival ◽  
Autologous Bone Marrow ◽  
Marrow Transplant ◽  
High Dose ◽  
Free Survival ◽  
Bony Lesions ◽  
Diagnostic Modalities ◽  
High Dose Melphalan

e20526 Background: Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly more than 10% of hematologic cancers. Novel agents and stem-cell transplantation are changing disease prognosis and patient’s survival. Our objective was to do a multicenter retrospective analysis in order to look at the effect of autologous bone marrow transplant on progression free survival (PFS) of multiple myeloma. Methods: 134 myeloma patients from different Lebanese centers were included in a retrospective, observational study. We reviewed disease characteristics of patients that were diagnosed with multiple myeloma between July 2002 and January 2018. Results: 62.7% were males and 33.7% females with a median age of 65.5 years at diagnosis. 37 patients had a Karyotype on diagnosis, of which 21.6% were normal and 78.4% had abnormal cytogenetics including loss of chromosome Y, hypoploidy and tetraploidy. Regarding the M component, we had 52.2% IgG, 17.9% IgA, 1.4% IgM, 11.2% Kappa, 5.2% lambda, and 0.7% had 2 spikes M and G. 53.7% patients had bony lesions on diagnosis, 16.4% didn’t and 29.9% patients were unknown. According to ISS staging, 11.9% patients had an ISS of 1, 11.2% an ISS of 2, and 23.9% an ISS of 3. The majority (40.3%) were transplanted, 24.6% were not and 6.7% were still on induction therapy at the time of data cutoff [31/12/2018]. 28.4% had an unknown transplant status. 6.7% patients were diagnosed based on atypical plasmacytosis, 22.4% had monoclonal spike and 67.8% had multiple diagnostic modalities including immunofixation and urine studies. 29.1% of patients had plasmocytes between 10 and 60% and 9% had more than 60% plasmocytes on bone marrow at diagnosis. VCD was the main induction protocol used (38.8%) followed by VTD (14.2%) and VRD (9%). For the transplant group, 11.7% were in CR, 23.5% in VGPR and 19.6% were in PR before high dose melphalan. No death occurred during induction. 126 patients were still alive and taking treatment at the time of data cutoff. Mean PFS was 49.69 months (± 32.83) and 22.28 months (± 16.36) in the transplant and non-transplant group respectively (p = 0.001). Conclusions: Few previous reports described transplant data in Lebanese myeloma patients. As in the international data, we found a significant progression free survival in the transplanted group compared to the non-transplanted one.

Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.

1996 ◽  
Vol 14 (11) ◽  
pp. 2984-2992 ◽  
Author(s):  
L J Ayash ◽  
A Elias ◽  
G Schwartz ◽  
C Wheeler ◽  
J Ibrahim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liver Toxicity ◽  
Autologous Bone Marrow Transplantation ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
High Dose Melphalan

PURPOSE Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.

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