Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

Follow up Analysis for MRC Myeloma VII Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 927-927
Author(s):  
Gareth J. Morgan ◽  
Faith E. Davies ◽  
Kim Hawkins ◽  
Susan E. Bell ◽  
Julia M. Brown ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Therapy Group ◽  
Intensive Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Conventional Dose

Abstract The results of the MRC Myeloma VII trial and overview analysis of comparable trials have suggested that VAD-like induction chemotherapy followed by high dose therapy (HDT) with autologous transplantation may be regarded as a new standard treatment for multiple myeloma. However, there is a need for data from the extended follow up of patients in such trials to provide confirmatory evidence of the benefit of treatment incorporating HDT compared with conventional dose treatment, in particular to determine the long term difference in survival and the impact of attaining a complete response (CR) following intensive treatment. We present an updated analysis of Myeloma VII with median follow up of 5.5 years. Myeloma VII is the largest trial of its type in which patients with previously untreated multiple myeloma, age <65 years, were randomized to receive either standard conventional-dose combination chemotherapy (ABCM) or a sequence of treatment, C-VAMP followed by high dose therapy (HDT), typically melphalan 200g/m2 with autologous stem cell transplant. The planned maintenance in both arms was interferon α-2a. The trial, initiated in 1993 and closed to entry in 2000 and was conducted to MRC guidelines for good clinical practice in clinical trials. In the 401 evaluable patients the CR rate was 44% in the intensive therapy group, 8% in the standard therapy group (p<0.001). Intention to treat analysis showed a survival benefit of 14.1 months in the intensive arm (Figure 1); median 56.3 months (95% CI 46.0–74.6) vs. 42.2 months (95% CI 33.1–48.9), p=0.004 (log rank test). Progression free survival was also improved in the intensive group, median 31.2 months (95% CI 27.1–37.5) compared with 19.5 months (95% CI 16.2–21.6) in the standard group (p=<0.001). This analysis provides confirmatory evidence that treatment including high dose therapy is superior to conventional dose chemotherapy. Long term follow up of this study shows that the benefits of intensive treatment are maintained long term and that an important therapeutic aim is the achievement of CR. For the patients receiving the full protocol, the differences are accentuated, implying that maximising numbers of patients getting to transplant is an important therapeutic aim. These results would also support the continuing development of peri-HDT strategies to further improve outcomes. Figure Figure

The Effect of Bortezomib Containing Induction On the Long Term Outcome of autologous Haemopoietic Stem Cell Transplantation in Multiple Myeloma Patients Outside Clinical Trials - a Single Center Experience

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5050-5050
Author(s):  
Miklos Udvardy ◽  
Remenyi Gyula ◽  
Attila Kiss ◽  
Peter Batar ◽  
Arpad Illes ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Median Survival ◽  
Induction Therapy ◽  
High Dose ◽  
High Dose Therapy ◽  
Long Term Outcome ◽  
Dose Therapy ◽  
Starting Point ◽  
The Mean

Abstract Abstract 5050 Introduction: We aimed to investigate the effect of bortezomib-based induction therapy for the treatment of transplant-eligible multiple myeloma (MM) patients, as compared to non-bortezomib-based treatments, in daily clinical practice. Patients and methods: All 122 transplant eligible MM patients treated at our center between 2003 and 2011 were reviewed retrospectively without selection. Patients had received induction with or without a bortezomib-based regimen, followed by high dose therapy (single Mel200+APSCT). The group consistend of 64 males and 58 females, mean age: 55, 2±8, 7 year. 45, 9% of the patients had IgGκ (56), 18% IgGλ (22), 10, 6% IgAκ (13), 7, 3% IgAλ (9), 0, 8% IgMκ (1), 3, 2% κ (4), 10, 6% λ (13), and 3, 2% had non secretory (4) MM. Bone marrow FISH analysis revealed del-13q in 2 cases, monosomy 13 in 14, t4:14 in 1, monosomy 13 + del 17p in 1. Plasma cell leukemia (primary and secondary) was found in 2 cases. Induction therapy was applied either in our center, or patients were referred to us to perform high dose therapy after induction therapy given in other regional hematology departments. Due to regulatory reasons, patients mainly received non-bortezomib containing induction (VAD, thal-dex 78%, bortezomib-based 22%) until 2008. Later predominantly bortezomib-based therapy was used (69%, mainly VTD or PAD), the remaining (mainly those referred to our center) cases had thal-dex, or CTD induction. Results: Patients without bortezomib in induction: The mean followup of the 22 patients who did not receive bortezomib as part of induction was 53. 2+21. 9 month, 14 of them died (66, 7%) during followup. Median survival reached at 38 month following induction, or if calculated after completion of high dose therapy median survival was 52 month. Patients with bortezomib based induction. The mean follow-up time of this 100 patients time was 44, 5+ 27, 6 months. 25 pts died (25%) and survival probability at 50 month from the initation of induction was 69. 8 % in these patients compared to the 40. 7% estimated survival for the patients without bortezomib (p<0. 01). Survival probabilty at 50 month after completion of high dose therapy (as a new starting point of followup) was 39, 7% without bortezomib-based induction and 74, 6%, in patients receiving bortezomib-based induction (p<0. 05). Median survival times has not reached following induction and high dose therapy. Conclusions: This retrospective survey clearly supports the important role of that bortezomib containing induction regimens achieving prolonged survival both after induction and following high dose therapy in multiple myeloma clinical practice settings, as compared to regimens without bortezomib. Disclosures: Off Label Use: Rituximab is not authorized for Mantle Cell Lymphoma in Hungary.

Induction Therapy in Multiple Myeloma

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 306-312 ◽  
Author(s):  
Jean-Luc Harousseau
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
Hematologic Malignancies ◽  
Tumor Burden ◽  
Prolonged Treatment ◽  
Induction Treatment ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
High Dose Melphalan

Abstract In most hematologic malignancies the role of induction treatment is to achieve complete remission (CR). In multiple myeloma this has been possible only with the introduction of high-dose therapy plus autologous stem-cell transplantation (ASCT). In the context of ASCT there is a statistical relationship between CR or very good partial remission (VGPR) achievement and progression-free survival or overall survival. High-dose therapy consists of 3 to 6 courses of a dexamethasone alone or combined with vincristine-adriamycin (VAD) to reduce the tumor burden and the plasma cell infiltration followed by 1 or 2 courses of high-dose melphalan plus ASCT. This treatment induces 20% to 40% CR and 40% to 55% CR/VGPR. The introduction of novel agents in the induction treatment is changing this scenario. The combinations of dexamethasone with thalidomide, bortezomib or lenalidomide increase the CR/VGPR rates compared to dexamethasone or VAD. Triple combinations are currently being evaluated, but preliminary results with not more than 3 or 4 cycles show post-ASCT CR/VGPR rates of 60% to 75% In elderly patients who are not candidates for ASCT, combinations of melphalan-prednisone with a novel agent (thalidomide, bortezomib or lenalidomide) yield CR/VGPR rates that are quite comparable to those achieved in younger patients with ASCT. Prolonged treatment with the combination of lenalidomide plus dexamethasone can be administered safely and appears to induce very high (up to 70%) CR/VGPR rates as well.

scholarly journals Adverse Cytogenetics, with or without Trisomies, in Patients Undergoing High Dose Therapy for Multiple Myeloma and Impact of Post-Transplant Maintenance Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3456-3456
Author(s):  
Gregory P Kaufman ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Single Agent ◽  
Prognostic Significance ◽  
Common Mechanism ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Abstract Background FISH abnormalities including t(14;16), t(14;20), t(4;14) and the loss of P53 remain a common mechanism for classifying patients (pts) with newly diagnosed multiple myeloma (MM) as adverse risk. In contrast, trisomies in MM are associated with superior outcomes and may ameliorate the negative prognostic significance conferred by adverse FISH abnormalities. High dose therapy (HDT) consisting of high dose melphalan and autologous stem cell transplantation with consideration of maintenance therapy is a common treatment strategy for transplant eligible MM pts. However, there is limited information regarding the impact of various cytogenetic abnormalities, alone or in combination with trisomies, in the context of HDT, and the efficacy of maintenance approaches in the novel agent era. Aim To determine the clinical significance of FISH abnormalities in MM pts undergoing HDT and subsequent consideration of maintenance therapy in recent years. Methods We retrospectively examined a cohort of all pts with MM who underwent first HDT at Mayo Clinic Rochester between 2008 and 2012. Medical records were reviewed under IRB approval in accordance with the principals of the Helsinki declaration. FISH results were obtained from within 6 months of diagnosis (Dx), and if unavailable pts were excluded. Pts were considered for maintenance therapy following response assessment by their treating hematologist, typically around day 100 following HDT, and were categorized based on the intent of that discussion; length of maintenance and dose reductions were not evaluated. PFS and OS were calculated from date of transplant and OS was also estimated from Dx. Timing of HDT was restricted to within one year of MM Dx (early HDT). Results 300 pts had available FISH and underwent early HDT. Median age at dx was 60 (23-75), and median follow up from Dx was 40 months (7.5-90) with 229 (76%) alive at time of analysis. The median time to HDT from Dx was 5.8 months (95% CI 5.4-8.0). At the time of HDT 249 pts (83%) were in a partial response or better. Overall, 73 pts (24%) had adverse risk FISH from dx as described, 154 pts (51%) had at least one trisomy, and 32 pts (10.7%) had a concomitant adverse FISH abnormality and a trisomy. Of all pts, 112 (37%) received maintenance therapy of some sort, most commonly single agent lenalidomide (n=67 pts) or bortezomib (n=36). Of the 73 pts with adverse FISH, 54 (74%) received maintenance therapy following initial HDT compared with 58 of 227 pts (26%) with non-adverse FISH. Among pts with adverse FISH, median PFS and OS was 21 months (95% CI 16-24) and 57 months (95% CI 41-NR) respectively, compared with 24 months (95% CI 21-26) and not met respectively for pts with no adverse FISH (p =0.08 and p=0.04). The OS from Dx was 63 months (95% CI 46-NR) and not met, respectively for pts with adverse FISH and no adverse FISH (p=0.04). Among adverse FISH pts, PFS following initial HDT was improved with any maintenance therapy (23 months (95% CI 18-33) versus 13 months (95% CI 6-22), p=0.0016). OS was not statistically different among pts with adverse FISH whether or not they received maintenance therapy, both from date of HDT as well as from Dx. For pts with non-adverse FISH at Dx similar findings were observed, with an increase in PFS following HDT with any maintenance therapy (30 months (95% CI 23-48) versus 22 months (18-24)), without a difference in OS. Further analysis of the group of pts with adverse FISH status revealed the PFS benefit seen with maintenance therapy was greatest for a subgroup of pts with concomitant trisomies (29 months (95%CI 18-38) versus 14 months (95%CI 8-16) p=0.0003) as compared to pts with adverse FISH without concomitant trisomies (19 months (95%CI 13-35) versus 12 months (95% CI 3-24) p=0.204) (figure 1). However, OS either from HDT or Dx did not differ for pts with adverse FISH with or without concomitant trisomies regardless of maintenance status. Conclusions Our data support an improvement in PFS with maintenance therapy following initial HDT amongst adverse risk FISH MM pts, however no OS benefit was observed with maintenance therapy irrespective of FISH status. Among pts with adverse FISH, maintenance strategies improve PFS for pts with a concomitant trisomy. No PFS benefit was seen with maintenance therapy in pts without concomitant trisomies. Future trials of maintenance therapy post HDT should consider evaluating and reporting on the subgroup of adverse FISH pts with concomitant trisomies. Figure 1 Figure 1. Disclosures Kumar: Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi-Aventis: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Millennium: The Takeda Oncology Co.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals High-dose therapy and autologous stem cell transplant in older adults with multiple myeloma

2015 ◽  
Vol 50 (8) ◽  
pp. 1075-1082 ◽  
Author(s):  
T M Wildes ◽  
J D Finney ◽  
M Fiala ◽  
F Gao ◽  
R Vij ◽  
...  
Keyword(s):  
Older Adults ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy

Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2345-2350 ◽  
Author(s):  
Ranjit K. Dasgupta ◽  
Peter J. Adamson ◽  
Faith E. Davies ◽  
Sara Rollinson ◽  
Philippa L. Roddam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Glutathione S Transferase ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
The Impact

Abstract Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates, including melphalan, and have an altered outcome following treatment for multiple myeloma. We have assessed the impact of GSTP1 codon 105 polymorphisms in 222 patients entered into the Medical Research Council (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose therapy). In the standard-dose arm, patients with the variant allele (105Val) had an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile homozygotes; P for trend = .04); this was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome by genotype was found for patients treated with high-dose therapy. However, the progression-free survival advantage of the high-dose arm was seen only in patients homozygous for 105Ile (P = .008). (Blood. 2003;102:2345-2350)

Favorable Responses to Novel Agents for Multiple Myeloma in African American Patients,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4213-4213
Author(s):  
Santosh Saraf ◽  
Pritesh R. Patel ◽  
Howard Ozer ◽  
David Peace ◽  
Sangeetha Nimmagadda ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African Americans ◽  
Induction Therapy ◽  
Partial Remission ◽  
Disease Risk ◽  
Conflicts Of Interest ◽  
High Dose Chemotherapy ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant

Abstract Abstract 4213 Multiple myeloma (MM) accounts for 10% of hematologic malignancies in the U.S. African Americans (AA) have twice the risk of developing multiple myeloma and, in previous studies, a higher mortality rate when compared to non-African Americans (non-AA). In recent years, clinical outcomes for patients with MM have improved as a result of new agents, such as immunomodulatory drugs (IMiDs) and bortezomib. However, the therapeutic impact of these new therapies in AA vs. non-AA patients has not been evaluated. In this study, 53 consecutive patients (23 AA, 30 non-AA) with newly diagnosed MM were retrospectively analyzed after induction treatment with thalidomide/dexamethasone (n=22), lenalidomide/dexamethasone (n=8), bortezomib/dexamethasone (n=5), bortezomib/thalidomide/dexamethasone (n=3), lenalidomide/bortezomib/dexamethasone (n=12), or an IMiD plus melphalan (n=3). AA and non-AA patients were comparable for age, immunoglobulin isotype, MM stage of disease, serum β2microglobulin and albumin levels, and cytogenetic abnormalities including del13 (27% vs. 38%, respectively, p=NS). When measured according to international uniform criteria, the response rate to induction therapy was not statistically different between AA and non-AA patients: complete remission (CR, 22% vs. 21.4%), very good partial remission (VGPR, 26% vs. 21.4%), or partial remission (PR, 43.4% vs. 32.1%). However, the rate of stable/progressive disease following induction therapy was significantly higher in non-AA patients (p = 0.03). Of 53 patients, 34 received high-dose chemotherapy followed by autologous stem cell transplant (ASCT). In this group, the CR + VGPR rate following ASCT was significantly higher in AA compared with non-AA patients (59% vs. 35%, p=0.0007). At a median follow up of 47 months, the relapse rate was 59% in AA and 46% in non-AA patients (p=NS) and the median time to progression (TTP) was 9.1 months in both groups. Five patients (9%) died. All deaths occurred in the non-AA cohort and in 4/5 cases death was due to disease progression. In conclusion, our findings demonstrate that despite their increased disease risk, AA patients with MM have a favorable outcome that is equivalent to that of non-AA patients when treated with IMiDs and/or bortezomib. Disclosures: No relevant conflicts of interest to declare.

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