scholarly journals Survival and Years of Life Lost in Different Age Cohorts of Patients With Multiple Myeloma

2010 ◽  
Vol 28 (9) ◽  
pp. 1599-1605 ◽  
Author(s):  
Heinz Ludwig ◽  
Vanessa Bolejack ◽  
John Crowley ◽  
Joan Bladé ◽  
Jesus San Miguel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Relative Survival ◽  
Staging System ◽  
High Dose ◽  
Years Of Life Lost ◽  
Survival Times ◽  
Entire Cohort ◽  
Age Cohorts ◽  
Risk Of Death ◽  
The Impact

Purpose To assess the impact of age on outcome and to analyze the projected years of life lost in patients with multiple myeloma. Patients and Methods Ten thousand five hundred forty-nine patients were evaluated; 6,996 patients were treated with conventional chemotherapy, and 3,553 patients were treated with high-dose therapy with autologous stem-cell transplantation. Results Mean observed and relative overall survival times in the entire cohort were 3.7 and 3.9 years, respectively. Observed survival decreased steadily from 6.4 years in patients younger than age 50 years to 2.5 years in patients ≥ age 80 years. A similar decrease was noted for relative survival. Higher age correlated significantly with higher International Staging System (ISS) stage. Relative excess risk of death differed significantly between 10-year age cohorts beginning from age 40 years (P < .001 for age 50 to 59 v age 40 to 49, P < .001 for age 60 to 69 v age 50 to 59, P < .001 for age 70 to 79 v age 60 to 69, and P = .009 for age ≥ 80 v 70 to 79). The average years of life lost per patient was 16.8 years in the entire patient cohort and decreased steadily from 36.1 years in patients younger than 40 years old to 4.6 years in patients ≥ age 80 years. Conclusion Age is associated with higher ISS stage and is an important risk factor for early mortality. Survival declined continuously by each decade from age 50 to age ≥ 80 from more than 6 to less than 3 years. The average of years of life lost in patients with myeloma is higher than in many other cancers and amounts to more than 30 years in patients younger than 40 years old but decreases to less than 5 years in patients age 80 years or older.

scholarly journals Efficacy of Modified Vrd-Lite for Transplant Ineligible Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Mizuki Ogura ◽  
Tadao Ishida ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Junichiro Nashimoto ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Multiple Myeloma ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Treatment Interruption ◽  
Cardiac Complications ◽  
High Dose ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
The Impact

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.

scholarly journals Autologous Stem Cell Transplantation in Multiple Myeloma in the Era of Novel Drug Induction: A Retrospective Single-Center Analysis

2017 ◽  
Vol 137 (3) ◽  
pp. 163-172 ◽  
Author(s):  
Gabriela B. Thoennissen ◽  
Dennis Görlich ◽  
Ulrike Bacher ◽  
Thomas Aufenberg ◽  
Anne-Christin Hüsken ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Staging System ◽  
High Dose ◽  
Single Center ◽  
The Impact

Within this retrospective single-center study, we analyzed the survival of 320 multiple myeloma (MM) patients receiving melphalan high-dose chemotherapy (HDCT) and either single (n = 286) or tandem (n = 34) autologous stem cell transplantation (ASCT) from 1996 to 2012. Additionally, the impact of novel induction regimens was assessed. Median follow-up was 67 months, median overall survival (OS) 62 months, median progression-free survival (PFS) 33 months (95% CI 27-39), and treatment-related death (TRD) 3%. Multivariate analysis revealed age ≥60 years (p = 0.03) and stage 3 according to the International Staging System (p = 0.006) as adverse risk factors regarding PFS. Median OS was significantly better in newly diagnosed MM patients receiving induction therapy with novel agents, e.g., bortezomib, thalidomide, or lenalidomide, compared with a traditional regimen (69 vs. 58 months; p = 0.01). More patients achieved at least a very good partial remission in the period from 2005 to 2012 than from 1996 to 2004 (65 vs. 30%; p < 0.001), with a longer median OS in the later period (71 vs. 52 months, p = 0.027). In conclusion, our analysis confirms HDCT-ASCT as an effective therapeutic strategy in an unselected large myeloma patient cohort with a low TRD rate and improved prognosis due to novel induction strategies.

scholarly journals Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial

2010 ◽  
Vol 28 (13) ◽  
pp. 2259-2266 ◽  
Author(s):  
Maria-Victoria Mateos ◽  
Paul G. Richardson ◽  
Rudolf Schlag ◽  
Nuriet K. Khuageva ◽  
Meletios A. Dimopoulos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Response Rates ◽  
Phase Iii ◽  
High Dose ◽  
First Line ◽  
Agent Based ◽  
Risk Of Death ◽  
Clinical Benefits ◽  
The Impact

PurposeThe purpose of this study was to confirm overall survival (OS) and other clinical benefits with bortezomib, melphalan, and prednisone (VMP) versus melphalan and prednisone (MP) in the phase III VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial after prolonged follow-up, and evaluate the impact of subsequent therapies.Patients and MethodsPreviously untreated symptomatic patients with myeloma ineligible for high-dose therapy received up to nine 6-week cycles of VMP (n = 344) or MP (n = 338).ResultsWith a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide- (41% v 53%) and lenalidomide-based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%. Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months.ConclusionVMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent antimyeloma therapy. First-line bortezomib use does not induce more resistant relapse. VMP used upfront appears more beneficial than first treating with conventional agents and saving bortezomib- and other novel agent–based treatment until relapse.

Comorbidities Influence Survival in Patients with Multiple Myeloma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3142-3142 ◽  
Author(s):  
Tanya Wildes ◽  
Ravi Vij ◽  
Graham A Colditz
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Age Group ◽  
Entire Cohort ◽  
Risk Of Death ◽  
Increased Risk ◽  
Comorbidity Index ◽  
The Impact

Abstract Abstract 3142 Introduction: Advancing age is associated with poorer prognosis in patients with multiple myeloma (MM). Comorbidities increase in prevalence with age, but the impact of comorbidities on survival in patients with MM is not known. The purpose of this study was to examine the impact of comorbidities on survival in multiple myeloma. Methods: All patients (pts) with MM diagnosed and treated at Washington University School of Medicine in St. Louis, Missouri from 1999–2010 were identified from the Barnes-Jewish Hospital Oncology Data Services Database. The institution's cancer registrars retrospectively collect clinical, demographic and survival data in accordance with the American College of Surgeons Commission on Cancer guidelines. Comorbidities are graded as None, Mild, Moderate or Severe using the ACE-27 comorbidity index [Piccirillo et al. J Reg Mgmt 1999]. Patients without data on comorbidities were excluded from the study. The primary endpoint was overall survival (OS), calculated from the date of diagnosis and censored at the time of last follow-up. OS was estimated using the Kaplan-Meier method, and compared between comorbidity groups using the Log-Rank test. The independent effects of age and comorbidities were evaluated using Cox Proportional Hazards Modeling. Results: 569 patients were identified in the database. Median age of patients was 59 years (range 33–91 years); 54.8% were male, 45.2% were female; 74.9% were white, 23.2% were black, and 1.9% were other races/ethnicities. Based on the ACE-27 comorbidity index, 181 pts (31.8%) had no comorbid medical conditions, 226 (39.7%) had mild comorbidities, 115 (20.2%) had moderate comorbidities, 47 (8.3%) had severe comorbidities. In the entire cohort, the median OS was 49.2 months [95% confidence intervals (CI) 42.9 – 55.6 months]. Survival by comorbidity category and age group are shown in table 1. The differences in survival between comorbidity groups in each age group and the entire cohort were statistically significant (log-rank p<0.001). Severe comorbidities were associated with a significantly increased risk of death after controlling for age (HR 1.97, P=0.002). Conclusion: The presence and severity of comorbidities confer a poorer prognosis in patients with MM. Further study is needed to determine to what extent comorbidities directly impact survival versus impacting therapeutic decision-making and tolerance of therapy. Disclosures: Vij: Celgene: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau.

Global Approaches in Myeloma: Critical Trials That May Change Practice

2018 ◽  
pp. 656-661 ◽  
Author(s):  
Philippe Moreau ◽  
Cyrille Touzeau
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Therapeutic Strategies ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
The Past ◽  
Induced Changes ◽  
The Impact ◽  
Specific Section

The treatment of multiple myeloma (MM) has changed dramatically in the past decade with the introduction of new drugs into therapeutic strategies both in the frontline and relapse settings. With the availability of at least six different classes of agents that can be combined in doublet, triplet, or even quadruplet regimens and used together with high-dose therapy and autologous stem cell transplantation, the choice of the optimal strategy at diagnosis and at relapse represents a challenge for physicians. Also problematic is the lack of trials addressing questions, such as sequencing or the duration of maintenance. This review will focus on the results of recent clinical trials both in the frontline and relapse settings that have induced changes in clinical practice and will discuss the impact of important ongoing trials. A specific section will discuss therapeutic strategies when new drugs are not available.

The Impact of Different Mobilization Strategies in the Setting of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3254-3254
Author(s):  
Francesco Mazziotta ◽  
Gabriele Buda ◽  
Nadia Cecconi ◽  
Giulia Cervetti ◽  
Lorenzo Iovino ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Peripheral Blood ◽  
High Dose ◽  
Roc Curve Analysis ◽  
Cd34 Cells ◽  
Significant Difference ◽  
The Impact

INTRODUCTION Multiple myeloma (MM) is considered an incurable disease. Despite the introduction of novel agents allowed deeper response, high-dose chemotherapy and autologous stem cell transplantation (ASCT) remain the standard of care for patients (pts) in good clinical conditions. The most used strategies to mobilize stem cells from bone marrow (BM) into peripheral blood are high-dose cyclophosphamide (HD-CTX) plus G-CSF and G-CSF plus plerixafor (G-CSF+P). The goal of this retrospective study is to investigate whether the two different mobilization strategies have an impact on the clearance of monoclonal PCs in the apheresis products and on pts' outcome. PATIENTS AND METHODS We analyzed 62 pts (median age 61, range 41-75, 37 males and 25 women) diagnosed with MM and treated with ASCT between Mar 2014 and Mar 2018 at our Hematology Division (Pisa, Italy). All pts received induction therapy with at least 4 cycles of bortezomib, thalidomide and dexamethasone (VTD). 9/62 pts obtained a less than partial response (PR) and received lenalidomide-based regimens. After induction, 8 (12,9%) pts achieved complete remission (CR), 26 (41,9%) were in PR, 28 (45,2%) obtained a very good partial response (VGPR). 43/62 fit pts received HD-CTX (2-3 g/sqm) on day 1 followed by G-CSF (30 MU/day) started on day 4 until day 7, increased to 60 MU/day from day 8 until the end of apheresis. In 19/62 pts, after 4 days of G-CSF (60 MU/day) administration and not sufficient mobilization, we added plerixafor (0,24 mg/kgbw) for up to 4 consecutive days. In 43/62 pts we collected apheresis samples (10μl) analyzed through flow citometry to enumerate clonal residual PCs. The panel used to asses clonality included: CD138 Per-Cp, CD38 APC, CD19 PE-Cy7, CD45 APC-Cy7, cytoplasmic immunoglobulin K chain and L chain. RESULTS At the end of the peripheral blood stem cell (PBSC) collection, pts treated with HD-CTX presented a higher CD34+ absolute count (p=0.0489) and achieved the threshold of 5x106 CD34+ cells/kgbw in a significantly (p=0.006) higher percentage. We found a nearly significant (p=0.0517) lower count of CD34+ PBSCs in pts who received lenalidomide-based regimens before the mobilization. Performing flow citometry on apheresis samples, we observed that the number of the harvested clonal PCs showed a significant correlation (p=0.0115) with the occurrence of post-ASCT relapse. ROC curve analysis investigating the predictive effect of the number of pathological PCs on disease relapse showed an area under the curve of 0,6978 (95% CI 0.5392-0.8564; p=0.0267). Neither BM residual PCs detectable on BM biopsies performed before apheresis (r=-0.1323; p=0.609) nor the type of mobilization scheme (p=0.707) had an impact on the proportion of clonal PCs in the graft. Additionally, we did not observe any statistically significant difference in progression free- (PFS) (p=0.8276) and overall survival (OS) (p=0.2475) between the HD-CTX and G-CSF+P groups. DISCUSSION PBSC mobilization has a succession rate > 85%. Despite the use of HD-CTX to increase PBSC yields and decrease tumor burden, there is not clear evidence of a superior mobilization strategy. Additionally, HD-CTX has a not negligible toxicity and approximately 10% of the pts require hospitalization. Conversely, G-CSF+P is a safe and effective approach also in poor mobilizers. In our study, we observed a significative difference in the apheresis yields (p=0.0489) and in the percentage of pts who achieved the threshold of 5x106 CD34+ cells/kgbw (p=0.006) in favor of HD-CTX. Additionally, the detection of harvested residual clonal PCs could be a promising strategy to recognise pts more likely to relapse after ASCT. Nonetheless, we failed to demonstrate a superior effect of HD-CTX in the clearance of harvested clonal PCs, in agreement with the absence of a different pts' outcome amongst the two mobilization strategies. In conclusion, the choice between the two regimens is challenging and requires careful consideration of multiple factors. Overall, young fit pts, especially in the high-risk setting, should be treated with all appropriate modalities including chemiomobilization followed by double-ASCT. Conversely, in pts candidate to a single-ASCT it is reasonable to use G-CSF+P, since HD-CTX does not improve PFS and OS and add toxicity. The absence of an in-vivo purging effect on apheresis products of chemiomobilization further strengthens a chemotherapy-free mobilization. Disclosures Galimberti: Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau.

Poorer Survival in Multiple Myeloma Correlates with Patients’ Age and Is Linked to a Higher Stage at Presentation but Prognostic Parameters Reflecting the Biology of the Myeloma Clone Are Not Associated with Age.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1491-1491 ◽  
Author(s):  
Heinz Ludwig ◽  
Brian G.M. Durie ◽  
Erik Rasmussen ◽  
John Crowley
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Serum Albumin ◽  
Prognostic Parameters ◽  
Age Cohorts ◽  
Number Of Patients ◽  
Age Cohort ◽  
The Impact ◽  
Tumor Clone ◽  
Low Serum

Abstract Up to now no systematic analysis on the impact of different age categories on survival in patients with multiple myeloma has been reported. Information on possible correlations of host and tumor related prognostic factors with different age categories are lacking. We studied these parameters in a large cohort of patients with multiple myeloma (n=10.750) submitted by participating institutions and groups in the international staging system (ISS) project. Prognostic factors were recorded and age was calculated at start of initial chemotherapy. Patients were grouped into 6 age cohorts (<40, 40−<50, 50−<60, 60−<70, 70−<80 and ≥80 years). P values were calculated with the Jonckheere-Terpstra test and Spearman’s correlation coefficient was used where appropriate. The sequential median survivals constantly decreased by decade from 61 months to 60, 53, 40, 32 and 24 months in the 6 patient cohorts from age < 40 years to age >80 years examined, respectively, with a median value of 44 months (p<0.0001). The distribution of prognostic factors by age revealed a highly significant correlation between high serum ß2 microglobulin ( Sß2M, ≥3.5mg/dl) and age, ranging from 45% in patients in the youngest to 75% of patients in the oldest age cohort (r=0.17 (0.15–0.19), p<0.0001). A similar correlation was seen between low serum albumin (<3.5g/dl) and age: The proportion of patients with low serum albumin levels increased from 32% in patients at age < 40 years to 54% in patients > 80 years (r= −0.11(−0.13, −0.09), p<0.0001). Consequently, as Sß2M and serum albumin constitute the prognostic parameters of the ISS, a close correlation between ISS stage and age was found (p< 0.0001). The proportion of patients with ISS stage I (Sß2M < 3.5mg/dl and serum albumin ≥ 3.5 mg/dL) was 40% in patients aged <40 years and only 12% in those aged ≥80 years. In contrast, 44% of patients of the oldest and 31% of the youngest age cohort presented with ISS stage III. In addition, a similar, albeit lesser trend was noted for decreasing hemoglobin with age (r=−0.08 (−0.10, −0.07, p<0.0001) and increasing serum creatinine with age (r=0.08 (0.06, 0.10), p <0.0001). The parameters reflecting the biology of the myeloma clone did not vary between different age cohorts. Bone marrow plasma cell infiltration (BMPC) ≥33%, CRP levels ≥0.8 (mg/dL) and normal LDH was seen in similar frequencies in the different age categories. Similarly, no age dependent variation in cytogenetically defined prognostic variables was seen. The proportion of patients with Del 13 and of those with t (11; 14), t (4; 14) did not differ between the different age categories; these data were obtained in a limited number of patients only (616, 544 and 418 patients, respectively). In conclusion, age was identified as important prognostic factor in the six different age cohorts examined. Poorer survival with higher age is closely linked to higher ISS stage. In addition, creatinine and low hemoglobin correlate, albeit to a lesser degree, with increasing age, but not parameters reflecting adverse biologic features of the tumor clone (LDH, BMPC, CRP, del 13, t(11;14) t(4;14). Hence, an ailing host and not a more aggressive tumor clone seems to account for the inverse correlation between survival and age.

Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3090-3090 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima M. Saliba ◽  
Marilyn S. Davis ◽  
Floralyn L. Mendoza ◽  
Chitra Hosing ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Cell Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Significant Difference ◽  
Preparative Regimen ◽  
The Impact

Abstract Backround: Arsenic trioxide (ATO) has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a phase I/II trial to determine the safety and efficacy of a combination of arsenic trioxide, melphalan and ascorbic acid (AA) as preparative regimen in patients undergoing high-dose therapy (HDT) and autologous hematopoietic progenitor cell transplantation for multiple myeloma (MM). We also assessed the impact ATO levels on melphalan pharmacokinetics (PK), engraftment and toxicity. Methods: Forty-eight patients with secretory myeloma (23 females, 25 males; median age: 54, range: 3570) were treated between 4/04 and 8/05. All patient received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days -9 to -3. Patients were randomized to 3 arms; no ATO (arm 1), ATO 0.15 mg/kg IV on days -9 to -3 (arm 2) and ATO 0.25 mg/kg IV on days -9 to -3 (arm 3). Twelve patients had disease progression or relapse after a prior autograft. Median CD34 cells dose infused was 4.5 x 106/kg (range 2.3–10.9). Results: Patients in all 3 arms were evenly matched. With a median F/U of 14.0 months (range 6–25) post autograft, no dose-limiting toxicity or non-relapse mortality was seen. Toxicity was limited to grade I or II nausea, vomiting and diarrhea. Median ATO levels on day 0 in arms 1, 2 and 3 were 0.2, 26.3 and 46.2 ng/ml, respectively. Melphalan PK was not altered by ATO pretreatment. Median time to neutrophil engraftment (ANC >500/ dl) was 9 days. There were no engraftment failures or delays in the ATO arms. CR rate for the entire group was 23%, and total response rate (CR + PR) was 75%. 1-year Progression-free survival (PFS) and overall survival (OS) were 75% and 95%, respectively. There was no significant difference in CR, RR, PFS or OS between the 3 arms (p = 0.9, 0.9, 0.4 and 0.6, respectively). A prior autologous transplant (p = 0.02) and abnormal cytogenetics at transplant (p = 0.04) were associated with a significantly shorter remission. Conclusions: ATO + melphalan + ascorbic acid is a safe, effective and well tolerated preparative regimen for patients with multiple myeloma undergoing an autotransplant. A longer follow up is needed to assess the impact of ATO on progression-free and overall survival.

Improved Overall Survival in Myeloma Patients Treated with Regimens Including Thalidomide/Revlimid/Velcade Vs Melphalan/Prednisone; a Retrospective Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4961-4961
Author(s):  
Pandora Ashley ◽  
Mark Holguin ◽  
Juhee Song
Keyword(s):  
Retrospective Analysis ◽  
Conflicts Of Interest ◽  
High Dose Chemotherapy ◽  
Rank Test ◽  
P Value ◽  
High Dose ◽  
Survival Times ◽  
Entire Cohort ◽  
Stem Cell Rescue ◽  
Kaplan Meier

Abstract Abstract 4961 A retrospective study was conducted to ascertain if the use of thalidomide, revlimid and or velcade was associated with improved survival compared to melphalan and prednisone or vincristine, adriamycin and dexamethasone (VAD). To avoid possible confounding issues of treatment with high dose chemotherapy and stem cell rescue, those patients were excluded from this analysis. From 1997 to 2003, 98 patients diagnosed with myeloma and treated at Scott & White Memorial Hospital using non-transplant containing regimens were identified through the Scott & White Tumor Registry. Patients were divided into two groups based on treatment received. One group was treated with melphalan and prednisone or VAD chemotherapy (59 patients) and the second group was treated with regimens that included thalidomide, revlimid, or velcade (39 patients). Median survival times were estimated for the entire cohort and each treatment group. Kaplan-Meier estimates of the survival by treatment received were estimated and log-rank test was performed to compare the survival distributions of the two treatment groups. Five year survivals of the 2 groups were compared using the Z test. Median follow-up time for the entire cohort is 32.6 months (95% CI: 24.4-37.6) Median survivals are 38.7 months (95% CI 32.7-58.5) for the thalidomide/revlimid/velcade group and 24.4 months (95% CI: 14.4-35.7) for the melphalan and prednisone or VAD group. Five year Kaplan-Meier survival estimates are 0.3452 (95% CI: 0.2007-0.4945) for the thalidomide/revlimid/velcade group and 0.1325 (95% CI: 0.0593-0.2354) for the melphalan and prednisone or VAD group. The difference in survival between the two groups is statistically significant with p value of 0.0179. In this retrospective analysis, treatment with newer agents such as thalidomide, revlimid or velcade is associated with a significant improvement in survival compared to melphalan and prednisone or VAD. Disclosures No relevant conflicts of interest to declare.

High-Dose Cyclophosphamide: An Effective Non-Transplant Salvage Option in Relapsed/Refractory Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4947-4947
Author(s):  
Sikander Ailawadhi ◽  
Michael Keng ◽  
Eddie Thara ◽  
Andrew Hendifar ◽  
Tanya Price ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Median Time ◽  
Clinical Benefit ◽  
Single Agent ◽  
Staging System ◽  
Median Number ◽  
High Dose ◽  
Advanced Stage ◽  
Stage Disease

Abstract Abstract 4947 Background Recent advances in the treatment of multiple myeloma (MM) have significantly improved overall survival. With MM patients living longer, there is a constant need to find better therapeutic options, especially when patients are refractory to conventional agents, and are not eligible for experimental therapeutics in clinical trials. We evaluated treatment with single-agent high-dose cyclophosphamide (HDCy) in a cohort of heavily pre-treated patients with relapsed/refractory MM. Methods All the patients were previously treated for active MM at the University of Southern California (USC), Los Angeles, CA. Cyclophosphamide was administered at 1.2 gm/m2 in D5W intravenous (IV) over 1 hour every 3 hours for a total of 4 doses. Mesna was given to prevent urinary adverse events from cyclophosphamide as 4 gm/m2 in 1000 ml D5W IV to run at 50 ml/hr for 20 hours, starting 15 minutes prior to the first dose of cyclophosphamide. Patients were given pre-medications with 5HT3 antagonists an steroids. Treatment was administered in the in-patient setting and patients were discharged after the last dose of cyclophosphamide. Treatment was repeated every 4 weeks, if well-tolerated and continued response. Growth factor support was provided to the patients, as needed. Response to treatment was assessed after each 4-week cycle according to the International Uniform Response Criteria for MM. Results Seven patients (4 females, 3 males) were treated on this regimen with a median age of 53 years (range 34-61 yrs). These patients included 3 Hispanics (43%), 2 Asians (29%), 1 Caucasian (14%) and 1 African-American (14%). MM subtype was IgG disease in 3, IgA in 2, and light-chain only in 2 patients. Advanced stage disease (>stage 1) at the time of diagnosis as per the Durie Salmon (DS) staging system was present in 71% of the patients, while 3 patients (43%) had advanced stage disease as per the International Staging System (ISS). Four patients (57%) had lytic bone disease at the time of diagnosis, while only 1 patient was a non-secretor. Five of these patients (71%) never received an autologous stem cell transplant (ASCT) as a part of their MM treatment. Median number of therapies in these patients was 5 (range 4-8), while median number of therapies prior to high-dose cyclophosphamide (HDCy) were 3 (range 2-7). Median number of cycles of HDCy administered to the patients was 2 (range 1-5). Overall Response Rate (ORR = CR+PR) was 29% (n=2) with 1 patient achieving CR and 1 patient achieving VGPR. Four patients (57%) had stable disease (SD) and 1 patient had progressive disease (PD). Thus, the overall clinical benefit (CR+PR+SD) was seen in 6 out of the 7 patients (86%). Median time to best response was 5 weeks (range 4-10 weeks). Median time to progression was 16 weeks (range 8-24 weeks). Most common adverse events were cytopenias and fatigue, but were easily manageable with supportive care on an out-patient basis. Conclusions Despite improvement in therapeutic regimens for MM, it remains an incurable disorder. There is a constant need to develop regimens for treatment of relapsed/refractory MM patients that are efficacious and well-tolerated. We report the use of single-agent HDCy in heavily pre-treated MM patients. Despite the small number of patients studied, we have noted meaningful clinical benefit with a manageable toxicity profile. This warrants further investigation into developing therapeutic regimens with high-dose cyclophosphamide. Disclosures No relevant conflicts of interest to declare.

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