p53 Deletion Yields High Response Rates but Rapid Progression and Poor Overall Survival in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 953-953
Author(s):  
Joseph R. Mikhael ◽  
Jodi Goodwin ◽  
Xiaoying Qi ◽  
Wei Xu ◽  
Keith Stewart ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Plasma Cell ◽  
Induction Therapy ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Cell Leukemia ◽  
Free Survival ◽  
Post Transplant

Abstract Background: The p53 deletion has been documented to confer poor prognosis in patients with multiple myeloma (MM) treated with either conventional chemotherapy or autologous stem cell transplant (ASCT). However, it is not clear whether primary drug resistance and/or rapid relapse account for these adverse outcomes. Objective: Evaluate the impact of the p53 deletion in patients who have undergone ASCT for MM on baseline features, response to initial therapy, progression free survival and overall survival post ASCT. Method: Retrospective review of all patients undergoing ASCT for MM at our institution from January 2000 to July 2007. Results: 31 patients with the p53 deletion intended for ASCT were identified. Four patients did not undergo transplant: 2 patients had plasma cell leukemia (PCL) and died within 4 months of diagnosis, 1 patient had primary refractory disease to all therapy and died in 1 year, and 1 patient’s stem cells could not be collected. The 28 who underwent transplant had a median age of 52 (range 30–76) and 20 (78%) were male. Immunoglobulin subtype was IgG in 14 (52%), light chain in 10 (36%), IgA in 1 (4%), IgD in 1 (4%) and non secretory in 1 (4%). 23 pts (85%) had bony disease. ISS stage was as follows: 13 (52%) stage I, 6 (24%) stage II, and 6 (24%) stage III. Seven patients presented with PCL. All patients were treated with dexamethasone based induction chemotherapy (alone or VAD), with 6 patients also receiving thalidomide. Pre-transplant status after induction therapy was 0 CR, 22 PR (92%), 1 MR (4%) and 1 SD (4%). All patients were conditioned with high dose melphalan 140–200mg/m2. There was one patient who died within 100 days of transplant. Overall responses after completion of ASCT, compared with diagnosis, in evaluable pts (n=22) included 1 CR (5%), 19 PR (86%), 2 MR (9%). Median progression free survival (PFS) for this cohort was 16.9 months (95%CI 9.1–22.3) and median overall survival (OS) was 48.2 months (95%CI 11.3–67.2) post transplant. This is considerably shorter when compared to the full cohort of MM pts transplanted at our institution during the same timeframe (n= 706): median PFS 24.4 months and median OS 76.6 months post transplant. Conclusions: Patients with the p53 deletion have a high incidence of plasma cell leukemia (29%), but most respond well to induction therapy and ASCT. However, the duration of response is short (16.9 months), nearly 8 months less than our overall results with ASCT. Furthermore, median overall survival post transplant is only 4 years, over 2 years shorter than the median of 6.4 years observed in all ASCT patients. ASCT is less effective therapy in patients with this poor prognostic marker; development of novel therapeutic regimens, including targeting p53 dysregulation pathway, may be required to improve the clinical outcome in this subset of MM.

Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy with Interleukin-2 Versus Observation for Patients with Non-Hodgkin’s Lymphoma: Results of a Phase III Randomized Trial by the Southwest Oncology Group (SWOG 9438).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 326-326 ◽  
Author(s):  
John A. Thompson ◽  
Richard I. Fisher ◽  
Michael L. LeBlanc ◽  
Joseph M. Unger ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Grade ◽  
Survival Estimate ◽  
Free Survival ◽  
Post Transplant ◽  
Total Body

Abstract Purpose: To determine the effect of post-transplant immunotherapy with Interleukin-2 (IL-2) on the progression-free and overall survival of patients with non-Hodgkin’s lymphoma (NHL) after autologous stem cell transplantation and to assess the toxicity of post-transplant IL-2 therapy. Patients and Methods: Patients with previously treated low, intermediate, or high grade NHL (except Working Formulation Groups A and I) were treated with high-dose cyclophosphamide, etoposide, and total body irradiation (TBI) and an autologous peripheral blood stem cell transplant (PBSCT). Twenty-eight to 80 days after PBSCT, patients were randomized to treatment with IL-2 versus observation. Results: Between January 1995 and July 2004, three hundred ninety-four patients with low-grade (n=61) or intermediate-high grade NHL (n=315) were registered at one of 39 SWOG transplant centers. One hundred ninety patients did not proceed to randomization, because of patient refusal (44), grade V toxicity (30), disease progression (28), toxicity (28), or other reasons. Two hundred four patients were randomized to treatment with continuous infusion intravenous IL-2 (9 ×106 units/m2/day for four days followed five days later by 1.6 ×106 units/m2/day for 10 days) versus observation. The 4-year progression-free survival estimate for all eligible patients is 34%, and the 4-year overall survival estimate is 52%. There was no difference in progression-free survival (hazard ratio (HR) of IL-2 to observation = 0.90; p = 0.56) nor in overall survival (HR of IL-2 to observation = 0.88; p = 0.55). There were no deaths related to IL-2 treatment. Grade IV IL-2-related toxicities included hematologic (n=10), cardiovascular (4), renal/bladder (2), flu-like symptoms (1), lung (1), metabolic (1), and neurologic (1) and were reversible in all cases. Conclusions: These results confirm earlier SWOG findings that a regimen of cylophosphamide, etoposide and TBI followed by PBSCT can be administered to patients with relapsed or refractory NHL with acceptable toxicity and with encouraging progression-free and overall survival. Post-transplant therapy with IL-2 given at this dose and schedule of administration had no significant effect on post-transplant relapse, progression-free survival or overall survival.

Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4554-4554
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Osman Ahmed ◽  
Maialen Lasa ◽  
Holger W. Auner ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 4554 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma, resulting in improved survival and response rate compared to conventional chemotherapy. Disease relapse, however, remains almost inevitable and thus the role of two successive (tandem) autologous stem cell transplants has been evaluated in chemorefractory patients as a means of prolonging duration of disease response. We retrospectively analysed the results of nine patients with chemorefractory disease treated at a single UK institution who received tandem ASCT between January 1998 and February 2009. There were six men and three women. Median age at diagnosis was 56 years (range, 42–65 years). Paraprotein isotype was IgG in eight patients and IgA in one patient. Median serum paraprotein level was 41g/L (range 12–73g/L) at presentation. At time of 1st transplant six patients were in stable disease (SD) and three had evidence of progressive disease. Conditioning melphalan dose was 140mg/m2 in all but two patients who received 110mg/m2 and 200mg/m2. Median time between transplants was 3.7 months (range 2.3–6.4 months) with PR and SD being observed in 2/9 and 7/9 patients at time of 2nd transplant. None of the patients reached complete response (CR). One patient received melphalan 140mg/m2 prior to 2nd transplant. The remaining patients received melphalan 200mg/m2. Median follow up after tandem transplant was 54.3 months (range 15.6 –143.6 months). No treatment related mortality was reported. At the time of analysis, six patients were still alive and under follow up with an overall survival (OS) figure for the group of 52% at 10 years from diagnosis (Figure 1). Median progression free survival (PFS) was 20 months from 2nd transplant (range 6.7–62.6 months) (Figure 2). Tandem autologous stem cell transplant in chemorefractory patients has resulted in overall survival similar to autologous stem cell transplant in chemosensitive patients and should be considered in patients with chemorefractory disease. Figure 1: Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 1:. Overall survival from diagnosis in patients receiving tandem autologous stem cell transplant for multiple myeloma Figure 2: Progression free survival following tandem transplant Figure 2:. Progression free survival following tandem transplant Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Different Mobilization Methods on Graft Composition and Outcome after Autologous Stem Cell Transplantation: Implications for Upfront Use of Plerixafor

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1125-1125
Author(s):  
LaQuisa Hill ◽  
Oluchi C. Ukaegbu ◽  
Bipin N. Savani ◽  
Salyka Sengsayadeth ◽  
Stacey Goodman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Partial Remission ◽  
Progression Free Survival ◽  
Free Survival ◽  
Disease Response ◽  
Graft Composition

Abstract Early lymphocyte recovery (ELC) is associated with improved outcomes of hematologic malignancies after autologous hematopoietic stem cell transplantation (auto-SCT). ELC, its composition and impact on outcome depends on many variables; however there is limited data on ELC after different mobilization strategies (G-CSF [G] vs. G + high dose cyclophosphamide [GC] vs. G + plerixafor [GP]). Results from a recent study showed that GP based mobilization can affect the number and subsets of immune competent cells contained in the graft. We studied whether these differences are associated with immune reconstitution (ELC), engraftment, or long-term outcomes. We retrospectively identified patients undergoing auto-SCT at the Nashville VA Transplant Center between January 2000 and December 2010 in our CIBMTR database. Disease response was determined by standard CIBMTR response criteria. At our center, GP mobilization is reserved for patients who failed prior mobilization, to rescue G or GC mobilization, or as upfront usage in heavily pre-treated patients. Our patient cohort primarily included patients with multiple myeloma (MM) and lymphoma (LY). We had evaluable data on 333 patients (MM=196; LY=127; others=10). Comparative analysis of different mobilization methods are summarized in Table 1. Median number of regimens pre-SCT for MM was 2 (range 1-5) and for lymphoma 2 (range1-7). Among LY patients, 60 (47.3%) patients were in complete remission (CR), 58 (45.7%) in partial remission (PR) and 9 (7%) had stable disease (SD). Among MM patients, 69 (35.2%) were in CR or very good partial remission (VGPR) pre-transplant, 105 (53.5%) were in PR, and 14 (7.1%) had SD. There was no significant difference between disease response status among different mobilization methods for either the MM or LY patients. A higher absolute WBC count was seen in grafts after GP mobilization compared to G or GC (p=0.01), despite a majority of patients having received GP mobilization after failed G or GC mobilization, or as a rescue regimen (n=20 [89%]). Similarly, absolute lymphocyte counts were higher in grafts mobilized after GP compared to G or GC (p=0.01). All patients engrafted and there was no difference in time to WBC or platelet engraftment between mobilization methods. Although the GP cohort was more heavily treated than the other cohorts (>2 regimens for GP 82%, vs. G 72% vs. GC 58% [p=0.02]), progression-free survival (PFS) and overall survival (OS) of G vs. GC vs. GP at 2-years was not significantly different between MM and LY cohorts (Table 1). In summary, grafts mobilized with GP exhibited major differences in graft composition in conjunction with favorable post- transplant outcomes compared with grafts mobilized with G or GC. GP mobilization accelerated lymphocyte engraftment in this heavily treated group compared to G or GC. For patients proceeding to transplant heavily pre-treated, GP is a better mobilization method to ensure a robust graft is collected while avoiding the need for multiple stem cell collections and providing similar outcomes as patients less heavily treated and mobilized by G or GC. A prospective randomized controlled trial would elucidate whether progression free survival and overall survival might be improved by utilizing GP mobilization as a first-line therapy rather than as a rescue method. Table 1. Graft composition and outcomes of different stem cell mobilization methods Variable G (n=97) GC (n=213) GP (n=23) P value Numbers of regimens pre-SCT, median 2.2 (95% CI, 2.0-2.4) 1.9 (1.8-2.0) 2.3 (1.9-2.7) 0.02 WBC in graft, median (range) 184.8 (12-777.7) 138.6 (11-542) 286.1 (186-400.3) 0.01 Absolute lymphocyte in graft (x103), median (range) 128.1 (13-321.1) 73.9 (3.4-433.6) 161.2 (47.4-302.0) 0.01 ANC >500 (days), median (range) 16 (11-25) 15 (7-86) 18 (13-24) 0.16 Platelets >20 (days), median (range) 13 (9-22) 12 (7-18) 12 (10-21) 0.07 OS (2 year) Lymphoma 74.5 77.9 72.7 0.054 Multiple myeloma 89.6 74.4 72 0.76 PFS (2 year) Lymphoma 58.2 57.6 46.1 0.1 Multiple myeloma 66.3 49 60 0.21 Disclosures No relevant conflicts of interest to declare.

The Survival of Multiple Myeloma Patients: A Single Institution Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5223-5223
Author(s):  
Zwi N. Berneman ◽  
An-Sofie Verstraete ◽  
Alain Gadisseur ◽  
Ann Van de Velde ◽  
Wilfried A. Schroyens
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
Free Survival

Abstract Background: For a long time, multiple myeloma has been a disease with a poor outcome. High dose (melphalan) chemotherapy followed by autologous stem cell transplantation has been reported to improve the overall and progression-free survival of these patients. Objective: To determine the survival of multiple myeloma patients treated with conventional chemotherapy and compare it with that of patients treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation. Design/Methods: 83 myeloma patients treated at a single institution were included in this retrospective study. They were divided into two groups: one group of patients who were received high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (n=42) and one group of patients who only received conventional chemotherapy and were eventually also treated with thalidomide and/or corticosteroids (n=41). The distribution of the stages of the disease according to Salmon and Durie were similar in both groups of patients. For both groups, the overall and progression-free survival was calculated. Results: In the general analysis, myeloma patients who underwent an autologous transplant had a significantly longer overall survival (58.8 vs. 52.2 months, p=0.036) and progression-free survival (39.6 vs. 11.8 months, p < 0.001) in comparison with the conventional chemotherapy group. If analysis was restricted to those patients who were transplanted as a first-line treatment, there was no significant difference in overall survival in comparison with conventional chemotherapy (51.8 vs. 52.2 months, p= 0.422); progression-free survival was significantly better in the first-line transplant arm as compared to the conventional chemotherapy arm (35.4 vs. 11.8 months, p= 0.003). As the median age in the transplant arm was significantly lower than in the conventional chemotherapy arm, we also performed a sub-analysis of patients who were between 60 and 70 years of age at diagnosis; there was no significant difference in overall survival between the two groups (60.7 vs. 69.5 months, p= 0.656), while the progression-free survival was again better in the autologous transplant group as compared to the conventional chemotherapy group (41.0 vs. 8.4 months, p= 0.020). Conclusion: High-dose chemotherapy and autologous stem cell transplantation in the treatment of myeloma is associated with improved progression-free survival and in the general analysis, with improved overall survival. The overall survival of patients who were only treated with conventional chemotherapy is somewhat higher (more than 4 years) as compared to that of historical controls (2–3 years).

Analysis of Outcome after Autologous Stem Transplantation in Patients with Newly Diagnosed Myeloma: Comparison of Different Induction Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3079-3079 ◽  
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Background: Autologous stem cell transplantation (SCT) improves survival in patients (pts) with multiple myeloma (MM). We have previously demonstrated that the degree of response at transplant does not impact on the outcome of transplant. However, newer induction regimens such as thalidomide and dexamethasone (Thal-Dex) result in higher response rates compared to previously used regimens such as single agent dexamethasone or vincristine, doxorubicin, and dexamethasone (VAD). We examined the outcome of SCT following three different induction therapies for newly diagnosed MM, namely VAD, single agent Dex, and Thal-Dex. Patients and Methods: 340 patients with MM who received their SCT within 12 mos of diagnosis (median 5.8, range 3–12) were studied. Patients receiving more than one induction therapy as well as those in whom thalidomide was added to dexamethasone for lack of response were excluded from the analysis. There were 105 pts in the VAD group, 140 in the Dex group and 95 in the Thal-Dex group. Responses were defined using standard criteria. Results: The study cohort consisted of 209 males (59%), with a median age of 57 years (range 30–76) at transplant. Baseline characteristics were similar in the 3 groups, except for lower age in the VAD group (median 55.8) compared to Dex (59.6) and Thal Dex (57.4) and shorter time to transplant in the Dex group (5.4 m) compared to VAD (6.4) and Thal Dex (5.9). Markers of disease activity pre-transplant, including B2M and marrow plasma cell percentage were higher in the Dex group compared to either VAD or Thal Dex. The proportion of patients with any response to induction therapy was lower in the Dex group compared to the other two. All pts in the Dex and the Thal-Dex groups received melphalan only conditioning compared to 70% in the VAD group, the rest receiving Melphalan/TBI. An objective response was achieved after SCT in 96%, 97%, and 98% of pts in the VAD, Dex and Thal-Dex groups respectively (P=0.8). A complete response to SCT was seen in 49% of patients in VAD group, 45% among those in the Dex group and 38% among those in the Thal Dex group (P=0.38). There was no difference in the median progression free survival after transplant (P=0.21) or overall survival from diagnosis (P=.34) between the three groups. The proportion free from progression at 2 years post transplant was 54%, 55% and 46% for Dex, VAD and Thal-Dex respectively. The proportion surviving at 4 years from diagnosis was 64%, 65.4% and 72% respectively for the three groups. Conclusion: We did not observe any difference in the response rates including complete responses to SCT in the three groups with nearly all pts in each group achieving a response. The progression free survival and overall survival appear to be comparable between the three groups. The results from initial therapy cannot be compared between the three regimens since the study population is restricted to patients reaching stem cell transplant. Within the limits of the study, there does not appear to be any long term impact of the initial therapy for the patients going onto an early stem cell transplant. Figure Figure

Stem Cell Transplant in Multiple Myeloma: Impact of Response Failure in the Era of Novel Therapies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1878-1878
Author(s):  
Morie A Gertz ◽  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
David Dingli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Progression Free Survival ◽  
Novel Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
Novel Agent

Abstract Abstract 1878 Poster Board I-900 Autologous stem cell transplant as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplant. Previously published medical literature has showed that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplant. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after induction therapy with a regimen that contains a novel agent. Unlike patients in reports published previously—before novel agents—patients who do not achieve partial remission have a significantly shorter overall survival from transplant (74.0 vs 43.5 months) and a shorter progression-free survival (22.6 vs 13.1 months; P<.001). Absence of a response to induction therapy with a novel agent predicts a poorer outcome after high-dose therapy.{abstabft}.b CR+VGPR for plateau, P<.001 compared with other 3 categories. Failure to respond to novel-agent induction leads to shorter posttransplant progression-free survival (PFS). Failure to respond to novel-agent induction leads to shorter posttransplant overall survivalDisclosures: Gertz: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kumar: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lacy: celgene: Honoraria; millenium: Honoraria.TableMultivariable Analysis of Posttransplant Progression-Free SurvivalVariableP ValuePlateau vs relapsed-refractory.003Albumin.86Sex.94b2-Microglobulin.89Bone marrow plasma cells.18Age.75Abnormal cytogenetics.002CTX mobilization.51Labeling index.002

Monoclonal and Oligoclonal Bands After Single Autologous Stem Cell Transplantation in Patients with Multiple Myeloma: Impact On Overall Survival and Progression-Free Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 595-595
Author(s):  
Victor Hugo Jimenez-Zepeda ◽  
Norman Franke ◽  
Andrew Winter ◽  
Suzanne Trudel ◽  
Christine I. Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Prognostic Factor ◽  
Light Chain ◽  
Progression Free Survival ◽  
Oligoclonal Bands ◽  
Cell Transplant ◽  
Free Survival

Abstract Abstract 595 Multiple myeloma is a malignancy of terminally differentiated plasma cells in which the malignant plasma cell clone usually produces a single abnormal unique monoclonal antibody with a constant isotype and light chain-restricted paraprotein. Recently, the occurrence of oligoclonal and monoclonal bands (OB/MB) not related to the original clone has been reported in patients with multiple myeloma who undergo autologous stem cell transplant (ASCT) and/or receive treatment with novel agents. Based on this data, the aim of our study was to assess the impact of monoclonal (MB) and oligoclonal bands (OB) occurrence on overall survival (OS) and progression-free survival (PFS) for MM patients undergoing single ASCT at Princess Margaret Hospital (PMH). Patient and Methods: All consecutive patients with documented MM undergoing single ASCT at PMH from 01/00 to 12/07 were evaluated. Oligoclonal banding (OB) was defined as the development of two or more concurrent monoclonal-type bands on the serum electrophoretic pattern, with either a different heavy or light chain component from the original M-protein band at day+100 post-ASCT. A new monoclonal band (MB) was defined as a heavy and/or light chain immunoglobulin distinct from the initially diagnosed MM. All cases with OB/MB in our series fulfilled the criteria of secondary monoclonal gammopathy of undetermined significance (MGUS). Multivariate analysis was performed with the Cox proportional hazard model. All analyses were performed using the SPSS 13.0 software. Results: Between January 2000 and December 2007, 788 patients were identified. Clinical and laboratory characteristics are listed in Table 1 Ninety-six patients (12.1%) developed OB/MB at 3 months from ASCT: 32 patients (33.3%) had OB, and 64 patients (66.7%) had a new MB. The median duration of the OB/MB was 12 months (range 4–52 months). OB and MB emerged after ASCT in 14% (60/409) of patients receiving VAD, 7.0% of patients receiving bortezomib (6/86) and 8.6% of patients receiving thalidomide (6/69) containing regimens as induction therapy. Thirty-seven (38%) patients with subsequent development of an OB/MB had achieved ≥VGPR after induction and this rate improved to 79% (76/96) at day +100 post-ASCT. Patients who did not develop OB/MB had a ≥VGPR rate of 28% and 58% after induction and day+100 post-ASCT, representing a lower rate than patients with OB/MB (p=0.07 and 0.002, respectively). At the time of this analysis, 65 (67.7%) of the cohort patients who developed OB/MB are alive and 68 have already progressed (70.8%). Median overall survival for patients who did not develop OB/MB at day+100 post ASCT was 74.5 months compared to 115.5 months for those who developed OB/MB (p=0.0098). Multivariate analysis shows developing of OB/MB as an independent prognostic factor for OS and PFS (p=0.006 and 0.021, respectively). (Fig1a-b) The duration of the OB/MB did not affect OS and PFS. In conclusion, OB/MB occurrence is an important prognostic factor in MM patients who undergo ASCT, the biological significance and its impact on clinical outcomes should be prospectively validated. Disclosures: Chen: Roche: Honoraria; Johnson & Johnson, Lundbeck, Celgene: Consultancy; Johnson & Johnson, Celgene, GlaxoSmithKline: Research Funding. Tiedemann:Janssen: Honoraria; Celgene: Honoraria. Kukreti:Roche: Honoraria.

Bortezomib-Based Regimens As Consolidation Therapy after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Single Center Experience from Oran (Algeria)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5121-5121 ◽  
Author(s):  
Souad Talhi ◽  
Soufi Osmani ◽  
Mohamed Brahimi ◽  
Kamila Amani ◽  
Hafida Ouldjeriouat ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Progression Free Survival ◽  
Consolidation Therapy ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Significant Difference

Abstract INTRODUCTION: Autologous stem cell transplant (ASCT) is the standard of care in transplant-eligible multiple myeloma (MM) patients and is associated witha significant improvement in progression-free survival (PFS), complete remission rates (CR), and overall survival (OS). However, the majority ofpatientsrelapse. This study compares the efficacy of autologous hematopoietic stem cells followed by consolidation bybortezomibbased regimens to the no consolidation therapy in adult patients. PATIENTS AND METHODS: This is a retrospective study over a period of 7 years (2009-2015). All patients less than 65 years with a newly MM diagnosis were included. The protocol used in induction was VD (n=47) treatment whichconsisted of four 3-week cycles of 1.3 mg/m2 bortezomib administered subcutaneously (SC) on days 1, 4, 8, and 11 and 40 mg dexamethasone on days 1Ð4 and 9Ð12. Therapy with VTD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 100 mg/day thalidomide administered orally. Therapy with VCD was composed of four 3-week cycles of SC bortezomib and dexamethasone at the same doses and schedules as for the VD regimen plus 500 mg/m2 cyclophosphamide administered orally on days 1, 8, and 15. Recommended concomitant medications included bisphosphonates, antibiotics, and antiviral prophylaxis. Acetyl salicylic acid was systematically used in the VTD arm. Stem cells were mobilized with 15 or 10 microg/kg G-CSF alone. Leukapheresis to harvest stem cells was performed on day -2 and -1. The grafts were kept in a conventional blood bank refrigerator at 4¡C until reinfusion on day 0. The target yield was 2 x106 CD34+ cells/kg. Following induction therapy, all patients had to proceed to ASCT. The conditioning regimen consisted of melphalan 200 mg/m2 in all patients.The consolidation regimen consisted of two cycles of VD or VCD or VTD after autologous stem- cell transplantation. In our study patients were divided into two groups: Group1 (ASCT plus consolidation) and Group 2 (ASCT alone). The therapeutic evaluation focused on the overall response (CR + VGPR) and progression free survival (PFS) and overall survival (OS) calculated by the Kaplan-Meier method. RESULTS: Over a period of 7 years, 153 patients were collected divided in two group: G1 (n=71) and G2 (n=82). Baseline characteristics are summarized in Table 1. No significant difference was observed between the 2 groups. In terms of CR, 58% of the patients in the G1 achieved a CR after consolidation vs 33% in the G2 after ASCT alone (p=0.007). In terms of VGPR, 31% of the patients in the G1 achieved a least a VGPR vs 17% in the G2 (p=0.04). The relapse rate was significantly lower in the G1 (10%) than the G2 (39%), (p=0.0001). The median follow-up period was 23,4 months. PFS was significantly higher in the G1, median no reached vs 37 months in the G2 (p=0.02) but no significant difference was observed in terms of OS rate between the 2 groups, 91% (G1) versus 82% (G2) at 27 months (p=0.7). CONCLUSION: We conclude thatbortezomib-based regimens as consolidation therapy after ASCT in patients with MM was effective in the improvement of PFS and response rate. Table Patients characteristics. Table. Patients characteristics. Disclosures No relevant conflicts of interest to declare.

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