Pegylated Liposomal Doxorubicin (Doxil®), Dexamethasone and Low Dose Thalidomide (DDt) as Therapy for Newly Diagnosed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5164-5164 ◽  
Author(s):  
Delva Deauna-Limayo ◽  
Omar S. Aljitawi ◽  
Mathew Mayo ◽  
David C. Bodensteiner ◽  
Siddhartha Ganguly ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Pulmonary Embolism ◽  
Stem Cell ◽  
Induction Therapy ◽  
Low Dose ◽  
High Dose ◽  
Combination Regimen ◽  
Cell Transplant ◽  
Full Dose ◽  
Cell Harvest

Abstract Background: Thalidomide with dexamethasone is considered the current standard induction therapy for multiple myeloma. Previously, treatment consisted mainly of infusional vincristine, adrimaycin and dexamethasone (VAD). High dose thalidomide is associated with significant toxicity. We conducted a study to evaluate efficacy and toxicity of adding liposomal adriamycin (Doxil®) to dexamethasone and low dose thalidomide. Stem cell harvest yield was also assessed. Methods: Patients were treated with Doxil® 40mg/m2 IV d1, thalidomide 100 mg PO Q HS, and dexamethasone 40 mg PO d1–4 and 15–18 Q 28 days for 4 cycles. After 4 cycles, eligible patients underwent autologous stem cell transplant. Patients received prophylactic Amoxicillin 250 mg PO Q day and Acyclovir 200 mg PO BID. Erythropoietin and biphosphonates were administered. Aspirin was changed to full dose coumadin anticoagulation after one death from pulmonary embolism. Results: Between 3/03 and 5/05, 11 out of planned 25 patients were enrolled on the study; 1 patient excluded for wrong diagnosis. Median age 61.5 (51–81yrs); 7 males; 7 IgG, 2 IgA and 1λ-light chain subtypes; Stage IB-1, Stage IIA-4, Stage IIIA-5; median albumin 3.75 (range:1.6–5.1 g/dL), creatinine 0.95 (range: 0.7 – 2.7 mg/dL) and B2M 1.95 (range: 1.1–10.1 mg/L). Four patients completed 4 cycles; one is undergoing treatment; three patients taken off study-one after 2 cycles per patient’s request, one secondary to grade 4 toxicity after cycle 1, and another after greater than 3 weeks treatment delay after cycle 3 secondary to pneumonia. Three patients (30%) developed grade 3–4 toxicities- two due to pneumonia (after cycles 2 and 3, respectively); and one with dehydration and renal failure after cycle 1. There were 2 deaths-one secondary to pulmonary embolism after cycle 1; another due to myocardial infarction after cycle 2. Two patients developed VTE- one after cycle 1 while on low dose coumadin; another died of pulmonary embolism after cycle 1, while on aspirin, requiring amendment to full dose coumadin anticoagulation. No further thrombotic episodes were encountered. Five patients underwent stem cell harvest with cyclophosphamide mobilization. The median harvest yield was 9.76 x106 CD34/kg (range: 5.27 – 31.94) with a median of 1 day (range: 1–7) to achieve at least 5 x 106 CD34/kg. Of the ten patients who received at least one cycle and assessable for response, the ORR was 80% (near complete remission(nCR)-10%; PR-70%), 1 MR, 1 SD. The M-spike response after first cycle of therapy ranged from 8% to 71%, with six patients (60%) having greater than 50% reduction in M-protein level. One patient achieved nCR after 2 cycles. Responses after the 3rd and 4th cycles were minimal. Conclusions: Doxil®, dexamethasone and low dose thalidomide represents an active induction therapy for patients with untreated multiple myeloma. Major responses were achieved rapidly, arguing for early stem cell harvest and autologous transplant after two cycles of therapy. Treatment related complications occurred early in the course of treatment. Full dose anticoagulation to prevent deep venous thromboembolism is essential when using this combination regimen. No adverse impact on stem cell harvest is associated with this therapy.

The Prognosis of PR Patients after Induction Therapy Was Not Inferior to CR in ASCT-Eligible NDMM Patient.

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5682-5682
Author(s):  
Anna Takahashi ◽  
Yuko Mishima ◽  
Norihito Inoue ◽  
Yoshiharu Kusano ◽  
Hirofumi Yamauchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Induction Therapy ◽  
Research Funding ◽  
Residual Disease ◽  
High Dose ◽  
Myeloma Cells ◽  
Ecog Ps ◽  
Cell Harvest

Abstract Introduction: Autologous stem cell transplantation (ASCT) is standard therapy for newly diagnosed multiple myeloma (NDMM) patients who are younger than 70 years old. In the IFM 90 trial, 5-year OS was 52% in the ASCT group compared to 12% in the initial chemotherapy group (p=0.03). 5-year EFS was 28% in the ASCT group compared to 10% in the chemotherapy only group (p=0.01). MRC Ⅳ trial also showed a higher rate of OS (p=0.04) and PFS (p<0.001) in the ASCT group. However, there was no result about the differences of the prognosis between CR and PR before ASCT. In this study, we studied the response level before ASCT to understand if it is related to the prognosis after ASCT. Methods: We studied 25 NDMM patients who received ASCT in our hospital from 2005 to 2015. Induction therapies were VRD, VCD, VAD, VD, Rd or VTD-PACE. Stem cells were collected using G-CSF or cyclophosphamide plus G-CSF. After stem cell harvest, all patients underwent high dose melpharan (200mg/m2) before ASCT. The responses according to the IMWG guidelines were performed at the point of 4-6 weeks after ASCT. Statistical analyses were performed using a software, EZR version 1. Results: The total number of NDMM patients was 25. The median age was 55 years (range 33-62), the median follow-up period was 1,375 days (range 340-3,763). Male were 16 (64%), 11 patients (44%) were ISS Ⅱor more and 20 (80%) were D&S stageⅡor more. ECOG PS 2 was 4 patients (8%) and one (4%) is ECOG PS 3. Before ASCT, 21 patients (84%) received 1 regimen and 4 (16%) received 2 regimens. In the 1 regimen group, 9 patients (43%) were treated by VCD with 2-4 cycles, 9 received VD with 4-5 cycles and 5 (24%) were received VAD with 3 cycles before ASCT. In the 2 regimens group, details of induction therapy were VD with BCD, VCD with Rd, VCD with VRD and VCD with VTD-PACE. In all patients, 3-year OS was 91.6% (95% CI, 70-98%) and 3-year PFS was 56% (95% CI, 34-74%). After induction therapy, CR was achieved in 11 (44%), VGPR was 2 (8%), PR was 11 (44%) and MR was 1 (4%). After ASCT, CR was achieved in 18 (72%), VGPR was 2 (8%), PR was 4 (16%) and PD was 1 (4%). 4 patients (16%) died for progression of multiple myeloma. There were no statistical differences in 3-year OS and PFS between CR group and VGPR + PR group after induction therapy (3-year OS; 100% vs 92%, p=0.11, 3-year PFS; 70% vs 50%, p=0.26). There were also no differences between the two groups CR group and PR without VGPR group (3-year OS; 100% vs 90%, p=0.18a, 3-year PFS; 70% vs 60%, p=0.4). As sub-analysis, the achievement time until normalization of FLC and disappearance of serum or urine M-protein in IFE did not affect 3-year OS and PFS. Discussion and Conclusions: When MM patients having residual disease did the stem-cell harvest, it has been possible to contaminate of myeloma cells in their collected stem cells. Several literatures described the contamination of myeloma cells in the stem cells induced inferior prognosis after ASCT. However our limited data suggested that the prognosis of patients who had residual disease after induction therapy, if they had achieved better than PR, were not inferior to CR group. This is reasonable data for recommendation of ASCT to MM patients getting PR after induction therapy. Disclosures Mishima: Chugai: Consultancy. Nishimura:Chugai: Consultancy. Yokoyama:Chugai: Consultancy. Terui:Yanssen: Honoraria. Hatake:Chugai: Research Funding; Otsuka: Consultancy; Kyowa Kirin: Honoraria, Research Funding; Meiji-Seika: Consultancy.

scholarly journals Utilization of Autologous Stem Cell Transplantation in Older Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5701-5701
Author(s):  
Justin King ◽  
Mark A. Fiala ◽  
Scott R. Goldsmith ◽  
Keith E. Stockerl-Goldstein ◽  
Mark A. Schroeder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Older Patients ◽  
Research Funding ◽  
Small Sample ◽  
Poor Performance Status ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Equity Ownership

Historically, high-dose therapy in combination with autologous stem cell transplants (ASCT) for multiple myeloma (MM) was reserved for younger patients. In more recent years, the use of ASCT has expanded in the older population. However, there is still limited data on the utilization and efficacy of ASCT in older patients, particularly those over the age of 75. To further evaluate this issue, we retrospectively analyzed all patients with newly diagnosed MM between the ages of 75-78, the institutional cutoff for ASCT eligibility, that were referred to the stem cell transplant unit at our institution for consultation from the years 2012-2018. Baseline characteristics, anti-myeloma treatments, and patient outcomes were abstracted through chart review. Seventy-five patients were referred to our institution. 71% were male, 29% female. 39% patients were considered ineligible for ASCT by the consulting transplant physician. Most patients were considered transplant ineligible due to comorbidities or poor performance status. Of the 46 patients eligible for ASCT, 52% underwent the procedure during their first-line therapy. The majority of those patients received reduced intensity melphalan (140 mg/m2) while 2 patients received conventional dosing (200 mg/m2). The other 22 patients eligible for ASCT declined or elected to defer the procedure and to be treated with conventional therapy. The characteristics of these three groups were similar and are detailed in Table 1. After a median follow-up of 30 months, 25% of the patients had expired. Estimated median overall survival (OS) was 71.3 months (unable to quantitate 95% CI) for all patients. Compared to transplant eligible patients, regardless of transplant receipt, those who were transplant ineligible had a 186% increase risk for death (HR 2.86; 95% CI 1.12-7.35; p = 0.029). There was also a notable trend for longer OS in those who underwent ASCT compared to those who were eligible but declined the procedure, but it was not statistically significant (HR 0.36; 95% CI 0.10-1.28; p = 0.114). At a transplant center, two-thirds of patients referred for newly diagnosed MM between the ages 75-78 were considered eligible for ASCT and one-third underwent the procedure. Outcomes were better for patients eligible for ASCT, regardless of whether they underwent the procedure. There was also a trend for better OS in patients who underwent the procedure compared to those who declined. While small sample sizes and the retrospective nature of the study limit our ability to draw conclusions, it appears that ASCT has an OS benefit among patients age 75-78. Disclosures Fiala: Incyte: Research Funding. Stockerl-Goldstein:AbbVie: Equity Ownership; Abbott: Equity Ownership. Vij:Genentech: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Wildes:Janssen: Research Funding; Carevive: Consultancy.

Bortezomib-Thalidomide-Dexamethasone as Primary Induction Therapy for Newly Diagnosed Multiple Myeloma Significantly Decreases Bone Resorption While Sparing Bone Formation as Compared to Thalidomide-Dexamethasone

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5117-5117 ◽  
Author(s):  
Patrizia Tosi ◽  
Elena Zamagni ◽  
Paola Tacchetti ◽  
Giulia Perrone ◽  
Michela Ceccolini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Bone Resorption ◽  
Bone Formation ◽  
Induction Therapy ◽  
Phase Iii ◽  
High Dose ◽  
Newly Diagnosed ◽  
Bone Formation Markers

Abstract Bone disease occurs in approximately 80% of patients with newly diagnosed multiple myeloma (MM) and is caused by the interaction of the neoplastic clone with bone marrow microenvironment, ultimately resulting in an altered balance between bone resorption and bone formation. It has been previously reported that therapies aimed at eradicating the myeloma clone could contribute to decrease bone resorption, even though bone formation remains impaired even in responding patients, due to the use of high-dose steroids. It has been recently demonstrated, both in vitro and in animal models, that Bortezomib improves bone formation by stimulating osteoblasts. In order to test whether this activity was retained also in vivo, we evaluated markers of bone resorption (serum crosslaps) and bone formation (serum osteocalcin-OC and bone alkaline phosphatase - BAP) in a series of patients who were enrolled in the “Bologna 2005” phase III clinical trial at our Center. By study design, after registration patients were randomized to receive three 21-days courses of induction therapy with either VTD (Bortezomib, 1.3 mg/sqm on d 1, 4, 8, and 11, plus Dexamethasone, 40 mg on each day of and after Bortezomib administration plus Thalidomide 200 mg/d from d 1 to 63.) or TD (Thalidomide as in VTD and Dexamethasone 40 mg/d on d 1–4 and 9–12 of every 21-d cycle), prior to stem cell collection and double autologous stem cell transplantation. As of January 2008, 27 patients (19 male and 8 female, median age = 57.5 yrs) entered the sub-study; of these, 15 and 12 patients were randomized in the VTD and TD arm, respectively. At diagnosis, both groups of patients showed a marked increase in serum crosslaps as compared to upper baseline limit (7321±1445pmol/L in the VTD arm and 11140±2576pmol/L in the TD arm) while both OC and BAP were reduced as compared to lower baseline limits. After completion of the induction therapy, serum crosslaps were significantly decreased in both treatment groups (2747±319pmol/L in VTD arm, p=0.007; 3686±1084pmol/L in the TD arm, p=0.0015). In the TD group a significant further reduction in bone formation markers was also observed (42% reduction in serum OC and 30% in BAP, p=0.03 and 0.04 as compared to pre-treatment values); on the contrary, in the VTD arm both OC and BAP were not significantly decreased as compared to baseline values (15% and 11% for OC and BAP, respectively). These data suggest that incorporation of Bortezomib into induction therapy counteracts the inhibitory effects of high-dose steroids on osteoblastogenesis, thus sparing bone formation.

Efficacy of Novel Agents in Multiple Myeloma in Comparison to Autologous Stem Cell Transplant: A Retrospective Study in a Single Inner City Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5118-5118
Author(s):  
Tareq Braik ◽  
Dayra Avila ◽  
Shivi Jain ◽  
Manila Gaddh ◽  
Barabara Yim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Survival ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy ◽  
Novel Therapy

Abstract Abstract 5118 Introduction: Since the mid 1990s, high dose chemotherapy with hematopoietic stem cell rescue has been considered the standard of care for front-line treatment in younger patients with multiple myeloma. This standard of care has been based on randomized controlled trials that compared autologus stem cell transplant (ASCT) with conventional chemotherapy. During the past decade, novel agents (NA), thalidomide, bortezomib and lenalinomide, have replaced conventional chemotherapy in the treatment of myeloma. These agents, used frontline, have shown promise in improving the outcome of myeloma patients without increasing toxicity. There are no studies to date comparing NA therapy to ASCT to determine whether there is a survival difference or whether NA therapy may reduce the need for transplantation. Many of our patients have no health insurance coverage and transplant is not a therapeutic option for them. We have attempted to compare the outcome of such patients receiving NA therapy with those in the literature who received conventional chemotherapy followed by ASCT. Methods: Ninety nine patients with multiple myeloma were treated at John H Stroger Hospital of Cook County between 2001 and 2011. All patients received novel agents (thalidomide, bortezomib and lenalinomide) as part of their therapy. Only 18/99 (18.2%) went for high-dose chemotherapy with ASCT and the remaining 81/99 (81.8%) received novel therapy without ASCT. We compared the outcome of patients who received novel therapy alone to a historical control group from the literature who received ASCT with conventional therapy (N Engl J Med 2003;348:1875–83). Overall survival was determined by Kaplan-Meier estimates. Results: We evaluated 99 consecutive myeloma patients (38% males and 61% female) of which 65% were African Americans, 19% Hispanics and 7% whites. All 3 stages (international staging system) of myeloma were equally represented. The median age at diagnosis was 60 years (40–85yr). Median follow up was 48 months (12–120). During the ten year follow up period, 60 patients (60.4%) have died. Twenty four out of 99 patients (24.2%) received only one line of therapy. 75 patients received more than one line of therapy. 75% received thalidomide-based therapy, 13% received bortezomib-based therapy and 12% received lenalinomide-based therapy. The median survival of patients who received novel therapy without ASCT (n=81) was 60 months, which is higher than the median survival of the historical controls who received ASCT reported by Child et al, N Engl J Med 2003;348:1875–83, (median survival = 54.1 months), the difference was statistically significant (P=0.0329). There was no statistically significant difference between the two groups by sex (p=0.927) and race (p=0.421). The 5-year survival of patients who received novel therapy without ASCT (n=81) was 48.2%. For those who were younger than 65 years (n=54), the median survival was 72 months and the 5-year survival was 58.1% in comparison to those who were 65 years and older (n=27), the median survival was 46 months and the 5-year survival was 29.2% (P=0.029). Conclusion: Novel agents are effective frontline therapy for multiple myeloma, especially in patients younger than 65. Our cohort had remarkable results in comparison to a historical population of patients who had ASCT with conventional chemotherapy. Since there is no curative therapy to date, a prospective randomized trial comparing NA with ASCT will be essential to clarify the role of ASCT in the era of novel therapy. Disclosures: No relevant conflicts of interest to declare.

Characteristics Of Multiple Myeloma Patients With 6-Year Or Longer Progression-Free Survival After a Single Autologous Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3366-3366 ◽  
Author(s):  
Kehinde U.A. Adekola ◽  
Qaiser Bashir ◽  
Nina Shah ◽  
Sai Ravi Pingali ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Autologous Transplant ◽  
Preparative Regimen

Background High dose chemotherapy followed by an autologous stem cell transplant (auto-HCT) is considered standard of care in patients with newly diagnosed multiple myeloma (MM). In a recent randomized trial, median progression free survival (PFS) after auto-HCT, with or without maintenance therapy was 46 and 27 months, respectively (McCarthy P et al. NEJM 2012). However, about 15% of patients are reported to have much longer PFS (Pineda-Roman M et al. Cancer 2008). Here we tried to identify the factors that may predict a long PFS after auto-HCT. Methods We performed a retrospective chart review of patients who received an auto-HCT for MM between January 2000 and March 2007. A total of 1135 patients underwent an auto-HCT during this period, and 194 patients (17%) had a minimum PFS of 72 months or longer after a single auto-HCT. The primary objective was to determine the variables associated with a long PFS and overall survival (OS). Results Patient characteristics and outcomes are shown in the attached Table. The median age at auto-HCT was 56 years, and the median time from diagnosis to auto-HCT was 7.5 months. Twenty-three (13%) patients had ≥ 10% plasma cells in the bone marrow at auto-HCT and only 9 patients (4.8%) had high-risk cytogenetic abnormalities. One-hundred and fifty (77%) patients received induction therapy containing either an immunomodulatory (IMiD) agent or a proteasome inhibitor (PI). At the time of the auto-HSCT, only 13 (6.7%) patients were in CR and 38 (19.6%) were CR or VGPR after induction therapy (Table). One-hundred and sixty three (84%) patients received mephalan alone as conditioning regimen. Eighty-one (42%) patients received post auto-HCT maintenance. Eighty (41%) patients achieved a CR, while 104 (54%) achieved CR + VGPR after auto-HCT. Six patients (3.1%) developed a second primary malignancy post- autologous transplant. After a median follow-up of 95.4 months, median PFS was 97.3 months and median OS has not been reached. The 10-year PFS and OS were 41% and 73% respectively. Use of melphalan alone as preparative regimen was associated with a longer PFS and OS (p=0.004 and 0.004, respectively). Achievement of CR after auto-HCT was associated with a longer PFS only (p=0.001), and the use of IMiD or a PI as induction was associated with a longer OS (p=0.01). Conclusion Approximately 17% patients achieved a median PFS of 6 years or longer after a single auto-HCT. The long PFS in this cohort may be associated with younger age, low incidence of HR cytogenetics, use of an IMiD or PI as induction therapy, relatively low disease burden at auto-HCT, transplant from the year 2000 onwards, achievement of CR in >40% and the use of melphalan alone as preparative regimen. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees.

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