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 ◽  
...  

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.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4323-4323
Author(s):  
Kevin Song ◽  
Heather J. Sutherland ◽  
John D. Shepherd ◽  
Yasser Abou Mourad ◽  
Michael J Barnett ◽  
...  

Abstract 4323 Introduction Allogeneic stem cell transplant has been considered the only potentially curative treatment for patients with myeloma. Due to the high treatment related mortality associated with myeloablative allogeneic stem cell transplantation, non-myeloablative allogeneic stem cell transplantion is being investigated. Methods Between May 2003 and June 2008, 23 patients received a non-myeloablative allogeneic stem cell transplant (NMT) using a fully matched sibling as the donor. All had received a previous autologous stem cell transplant (ASCT). 17 received the NMT as a part of a planned tandem transplant post ASCT. Six received the NMT after relapse post ASCT. Conditioning chemotherapy was a combination of cyclophosphamide 1000 mg/m2 daily x 2 days and Fludarabine 25mg/m2 daily for 5 days. Survival was measured from the date of allogeneic stem cell infusion. Results Median age at NMT was 52 years. Eight were female. Immunoglobulin isotype was 13 IgG; 5 IgA; 1 IgD; 4 light chain. ISS stage was 10 – stage 1; 8 – stage 2; 3- stage 3; 2 – insufficient information. 9/21 had del 13q; 3/9 t (4;14); 1/7 del 17p. Disease status at the time of NMT were 5 CR/nCR, 11 PR, 1 SD, 3 relapse chemo-sensitive, 3 relapse chemo-resistant. Median follow-up is 29 months (7 – 65 months). Median event free survival (EFS) for all patients is 17 months (95 % CI 8-26 months). Median EFS for the 17 patients who received NMT as a part of a planned tandem procedure was 18 months. Median overall survival (OS) for all patients is 29 months (95% CI unable to calculate). At the time of analysis 17 patients remain alive. Five patients are alive in continuous remission at a median of 40.9 months from NMT (13.5-47.6 months). Twelve patients have active disease requiring treatment. Three patients have died of myeloma, one of graft-versus-host-disease (GVHD) and two of other causes. Nineteen patients (83%) developed GVHD at some time post-transplant. Of 14 patients who have relapsed, eleven patients had GVHD at the time of relapse. Of the 6 patient who received the NMT after relapse post ASCT, 5 have relapsed post NMT and one died of GVHD within 9 months. Conclusion Non-myeloablative sibling allogeneic stem cell transplantation for myeloma produces short progression free survival in-spite of the presence of graft-versus-host-disease and only a limited number of patients benefit. Patient who receive this treatment after relapse from prior autologous stem cell transplant do particularly poorly. Improved overall survival is primary due to improvements in post-relapse myeloma therapy.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5497-5497
Author(s):  
Kamal Kant Singh Abbi ◽  
Sonya Behrends ◽  
Margarida Silverman ◽  
Umar Farooq ◽  
Kalyan Nadiminti ◽  
...  

Abstract Background: Therapeutic options for patients with Multiple myeloma (MM) whose disease has relapsed after a prior autologous stem cell transplant (SCT) include an expanding armamentarium of novel agents, often combined with traditional chemotherapy, or a second SCT, with no clear standard of care. Upfront tandem transplantation has been shown to improve both progression free survival and overall survival. But currently, there is little data regarding the application of tandem SCT in relapsed multiple myeloma patients. Methods: We retrospectively analyzed the outcomes of patients who underwent salvage melphalan-based tandem SCT for relapsed MM at University of Iowa Hospitals and clinics. Progression free survival (PFS) was defined as the time from date of the first salvage SCT to disease progression or death, whereas overall survival (OS) was defined from the date of the first salvage SCT to the date of death from any cause. Results: Between 2012 and 2015, 12 patients with MM received tandem autograft (total 24 transplants) for relapsed disease at our center. Conditioning was with VDT-melphalan 200mg/m2 (21/24), VDT-MEL 140mg/m2 (2/24) and Velcade, gemcitabine, BCNU, melphalan and dexamethasone (1/24). The median age at the salvage SCT was 48 years (range 37-58); 7 patients were female. 17% had high risk cytogenetics (including t(4;14), +1q, p53 loss) at the time of salvage SCT. Median time between previous transplant and progression of disease was 34 months (range 8-108). Of the 7 patients, who received re-induction therapy, 71% had chemotherapy refractory disease prior to salvage SCT. Response was assessed at 2-3 months post-SCT. Overall response rate was 92%. 7/12 (58%) patients achieved stringent complete remission, one patient achieved CR, one patient achieved near CR, 2/12 patients achieved VGPR and 1/12 had stable disease (SD). Following salvage tandem SCT, all patients received consolidation therapy with three drug combination, intended to be given for two years. Three patients have shown progressive disease at the time of analysis. The median PFS was 390 days (range 265- 1085) (Table-1); the median OS was 517 days (range 338-1085) (Table-2). Rate of progression free survival in the 10 evaluable patients at one year was 80%. There was no transplant related mortality. One patient died of progressive disease. Conclusions: Salvage tandem SCT is an effective strategy for relapsed MM and is especially effective in patients who had received less intensive therapy initially (single transplant and no maintenance therapy). Incorporation of novel agents (monoclonal antibodies and high doses of carfilzomib) into maintenance strategies may further improve outcomes. Figure 1. Progression free survival for all the patients Figure 1. Progression free survival for all the patients Figure 2. Overall survival for all the patients Figure 2. Overall survival for all the patients Disclosures Farooq: Kite Pharma: Research Funding.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7623-7623
Author(s):  
P. B. Johnston ◽  
B. P. O’Neill ◽  
S. M. Ansell ◽  
D. J. Inwards ◽  
L. F. Porrata ◽  
...  

7623 Background: Survival for patient with primary CNS lymphoma (PCNSL), in general, is poor with patients requiring frequent chemotherapy treatments or receiving whole-brain radiation therapy, which can potentially result in significant neurologic decline and dementia. Because of the improved survival of high risk patients with aggressive lymphoma undergoing autologous stem cell transplant (ASCT), we began ASCT for patients with PCNSL in first or later remission with chemotherapy sensitive disease. We now report on outcomes of patients who have had at least 1 year follow up post ASCT. Methods: Between June, 2000 and September, 2004, 11 patients underwent ASCT for PCNSL. The medical records of consenting patients were abstracted for the following information. Median age at transplant was 47 years old (range 30–67). Median number of prior treatments 1 (range 1–3). Median time from diagnosis to transplant was 7.5 months (range 2.9 to 75.8). Median International Extranodal Working Study Group Prognostic Score: 2 (range 0–3). Disease status at transplant: First CR 5 patients, later CR or PR 6 patients. Results: Eleven patients underwent ASCT for PCNSL and have a minimum of 1 year follow-up. All patients received BEAM conditioning. Median follow up was 28.3 months. Four patients have relapsed at a median of 200 days (range 40–523). Of the patients who relapsed, one has died of disease progression and the remaining three are alive after additional therapy. Median overall survival and progression free survival from transplant have not been reached. Two year overall and event free survival are 89% and 61%, respectively. Conclusions: Although limited by patient selection and retrospective biases, this review suggests that ASCT for PCNSL demonstrates improved overall survival when compared to historical controls with similar PCNSL Prognostic Scores (2 year survival for patients from diagnosis with PS 2–3 was 48% in a prior published study). ASCT in first remission in patients with PCNSL appears promising and may limit the need for additional therapy which can be myelosuppressive or result in neurologic decline. No significant financial relationships to disclose.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20509-e20509
Author(s):  
Christopher Lemieux ◽  
Lori S. Muffly ◽  
David Joseph Iberri ◽  
Andrew Rezvani ◽  
Robert Lowsky ◽  
...  

e20509 Background: We evaluated outcomes of patients with multiple myeloma (MM) ≥ 70 years who were seen for Autologous Stem Cell Transplant (ASCT) consult, based on whether they underwent transplant vs. non-transplant treatment. Methods: 138 patients with MM ≥ 70 years (median 71, range 70-78) were evaluated in the BMT clinic from 1/2010 to 11/2019 for a transplant consult. Results: Of the 138 patients, 53 proceeded to ASCT. ASCT was not pursued in 85 patients despite most (79%) being eligible for transplant. Reasons for deferring ASCT in eligible patients included patient preference (48%, n = 32) and physician preference (52%, n = 35). 68 patients were seen during first-line therapy, of which 29 underwent upfront transplant. The remainder were seen at second-line or beyond. There was no difference in baseline characteristics among the 113 patients with available follow-up (ASCT = 53, non-ASCT = 60), including median age (71 vs. 72 years, p = 0.4), high-risk cytogenetics (41% vs. 31%, p = 0.4), high-risk HCT-CI (32% vs. 20% p = 0.2), and ISS stage III (34% vs. 27%, p = 0.6). In the 53 patients who underwent transplant, conditioning melphalan dose was 200 mg/m2 (75%, n = 40) and 140 mg/m2 (25%, n = 13). Day 100 transplant related mortality was 0% (n = 0). Progression-free survival (PFS) and overall survival (OS) were compared in patients who were seen for consultation within 1 year of diagnosis (n = 80). With a median follow-up of 27 months, median PFS amongst patients ≥ 70 years undergoing ASCT (n = 39) was 47 months compared to 34 months in the non-ASCT (n = 41) group, p = 0.006. Median OS was not reached in either group. Estimated 5-years OS was 76% in the ASCT group and 82% in the non-ASCT group (p = 0.6). There was no difference in PFS of patients ≥ 70 undergoing ASCT compared to a cotemporaneous cohort of patients < 70 (n = 639) from our institution (47 vs. 57 months, p = 0.3). Conclusions: Selected patients ≥ 70 years with MM undergoing ASCT have better PFS compared to patients with similar characteristics who do not undergo ASCT. ASCT is safe in this older population and outcomes were similar compared to younger patients. [Table: see text]


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5699-5699
Author(s):  
Neelakanta Dadi ◽  
Venkata Vosuri ◽  
Samip R Master ◽  
Richard Preston Mansour

Background: Salvage autologous stem cell transplant (SAT)is an alternative treatment option for relapsed multiple myeloma patients that offers additional progression-free survival (PFS2) and overall survival (OS2) advantage over salvage chemotherapy. We conducted a meta-analysis to evaluate the outcomes of salvage transplant in patients with relapsed multiple myeloma after initial transplant. Methods: This meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search on PubMed, Embase, Cochrane and Web of Science was conducted up to December 31st, 2018. Two independent reviewers screened the literature and extracted data. All studies including randomized, retrospective or prospective studies in multiple myeloma patients who underwent salvage autologous transplant were included. Abstracts, posters, review articles, case reports and studies with syngeneic and tandem transplant were excluded. Articles were excluded if they did not provide transplant related outcomes data. The search terms included "Salvage autologous stem cell transplantation", "Second autologous stem cell transplantation", "multiple myeloma". 'Meta' and "Metafor' libraries in R software (CRAN Project) were used for the analysis. Pooled estimates and 95% confidence intervals were calculated using DerSimonian-Laird (DL) random effects model. Heterogeneity between studies was evaluated using Q test and sensitivity analysis. Results: The search strategy identified over 3260 articles; 16 studies (n = 1113 patients; 1 randomized trial; 15 retrospective studies) were selected for this meta-analysis. The sample size of the studies varied between 25 and 200 patients. All studies used melphalan conditioning for salvage transplant. A significant number of patients in about 10 studies received maintenance after initial transplant. Only one study included patients who received maintenance therapy after salvage transplant. Pooled rate of patients achieving partial response or more(≥PR) after salvage transplant was 76% (95%CI: 68-83; I2=84%). Pooled rate of transplant related mortality (TRM2) was 5.5% (95%CI: 2.6-9.3; I2=78%). The pooled estimates showed a median progression free survival (PFS2) 13.5 months (95%CI: 11.3 - 15.6; I2=100%), overall survival (OS2) 34.3 months (95%CI: 27.9 - 40.7; I2=100%). The results are shown in figures 1&2. Conclusion: SAT approach had favorable outcomes of achieving durable PFS and OS in relapsed myeloma patients. A Higher TRM was observed with salvage transplant than in upfront transplant. Prospective randomized trials are needed to define benefits of SAT in comparison with "best non-ASCT" therapy in patients with MM who relapse after primary therapy. Figure 1 Disclosures Mansour: Abbvie: Other: Stock; Astra Zeneca: Other: Stock; Bluebird Bio: Other: Stock; CRISPR: Other: Stock; Editas: Other: Stock; Johnson and Johnson: Other: Stock; Novartis: Other: Stock.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3512-3512
Author(s):  
Firoozeh Sahebi ◽  
Laurent Garderet ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Gösta Gahrton ◽  
...  

Abstract Abstract 3512 Recent studies in multiple myeloma patients using reduced intensity conditioning (RIC) allograft following autologous stem cell transplant in a planned tandem fashion (auto-allo) have reported low transplant related mortality (TRM) in a range of 10–15% and long term disease control in approximately one third of the patients. Similar results are reported with reduced intensity allogeneic stem cell transplant either as upfront or salvage treatment for patients who have failed prior autologous stem cell transplant. It is not clear if RIC allograft without preceding autologous stem cell transplant can produce the same outcome. The objectives of this retrospective study are to evaluate and compare the results of planned tandem autologous-RIC allograft (auto-allo) and early RIC allograft as first transplant in order to address whether or not cytoreductive autologous stem cell transplant (ASCT) is needed in patients who are candidates for RIC allograft and patients can be spared from morbidities of autologous stem cell collection and transplant. Study: We performed a retrospective analysis of the EBMT database. Five hundred and four multiple myeloma patients were identified as auto-allograft or early RIC allograft recipient between 1998 – 2007. Three hundred and fifty six patients were assigned to planned tandem auto-allograft and 148 patients received early RIC allograft as their first transplant. All patients underwent transplant within 1 year from diagnosis. Two hundred and fifty-three of 356 patients in the auto-allo group received their planned allograft, 88 patients did not undergo the planned allograft and 15 patients had a second autologous stem cell transplant. There were no significant differences in disease stage, disease subtype, sex, use of T-cell depleted allograft and donor type (sibling vs. unrelated donor) between the 2 groups. However patients in the early RIC group were younger (median age 51 vs. 53 years old P=0.03), received transplant in earlier calendar period (51% between 1998–2002 vs. 33% P <0.001), had longer interval from diagnosis to transplant (9 vs. 6 mo. P=0.0001) and were more in CR at the time of transplant (17% vs. 9% P=0.008). The B2 microglobulin and cytogenetic data were missing in the majority of patients and therefore not included in this analysis. Results: Results are reported on an intention to treat (ITT) analysis. With a median follow up of 52 mo. (48-55) in the auto -allo and 48 mo. (39-55) in the early RIC group best response occurred more frequently in the auto-allo group than early RIC with complete response rate of 62% vs. 47% respectively. Progression-free survival at 3 and 5 years were significantly better in the auto-allo group (43% and 31% respectively) as compared to the early RIC group (30% and 17% respectively, P<0.001). Overall survival was also significantly improved in favor of the auto-allo group with 3 and 5 year OS of 68% and 60% as compared to 52% and 37% in the early RIC group (P<0.001). Non Relapse Mortality (NRM) rates at one year were 9% and 18% in the auto-allo and early RIC group respectively (p <0.001). There were no differences in the incidence of acute GVHD (41% vs. 43% P=0.13) and chronic GVHD (60% vs. 56% P=0.19) between the auto-allo and RIC groups respectively. Given the differences in the calendar year we compared the PFS and overall survival between the two groups within the same calendar period (1998-2002 and 2003–2007). Log rank test confirmed significantly better outcome in favor of the auto-allo group in each calendar period suggesting that the observed differences between the 2 groups were independent of the calendar period. (P<0.001). Conclusion: This large retrospective study on an ITT analysis suggest cytoreductive autologous stem cell transplant (ASCT) prior to RIC allograft is associated with improved disease free survival and overall survival in patients with multiple myeloma who are candidates for RIC allograft. Disclosures: Sahebi: Millennium Pharmaceuticals, Inc: Research Funding.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 828-828
Author(s):  
Vittorio Montefusco ◽  
Francesco Spina ◽  
Francesca Patriarca ◽  
Massimo Offidani ◽  
Benedetto Bruno ◽  
...  

Abstract Abstract 828 Introduction: Patients with multiple myeloma (MM) relapsing or progressing after allogeneic stem cell transplantation (alloSCT) have limited therapeutic options. Donor lymphocyte infusions (DLI) are used to exploit the graft-versus-myeloma effect, and pilot studies have shown that cytoreduction before DLIs could increase their efficacy. These patients are often chemo-refractory or frail, so the new drugs are an attractive option in this setting. Based on experimental and pilot studies showing the high efficacy of bortezomib in alloSCT relapse of MM, we designed a prospective multicenter study to treat these patients with 3 cycles of bortezomib-dexamethasone (VD) followed by escalating doses of DLIs (VD-DLI). The primary objective was the efficacy in terms of response as defined by IMWG criteria. Secondary objectives were to assess the incidence of GVHD, the incidence of graft failure, the progression free survival (PFS), the overall survival (OS), and the safety. Methods: Patients with relapsing or progressive MM after alloSCT were enrolled. Treatment consisted of three 21-day cycles with bortezomib 1.3mg/sqm/day iv at days 1, 4, 8, 11, and oral dexamethasone 20mg/day at days 1–2, 4–5, 8–9, 11–12, followed by 4 DLIs at escalating cell doses administered every 6 weeks. The DLIs started from 5×10^6 CD3+/kg cell dose for HLA-identical sibling donors, or 5×10^5 CD3+/kg for mismatched siblings, matched unrelated (MUD), or haploidentical donors. For every patient, the cell dose was escalated by 0.5 Log at each DLI until a maximum of 1×10^8 CD3+/kg and 1×10^7 CD3+/kg dose at the fourth DLI for HLA identical and alternative donors, respectively. DLIs were stopped anytime in case of acute GVHD, or if patients achieved >=CR after at least 2 DLIs. A safety interim analysis was run after the enrollment of the first 10 patients. Here we presented the final analysis of the study. Results: Nineteen patients were enrolled at 4 Italian transplant centers between 2007 and 2010. Sixteen patients had ISS stage I MM, two had ISS stage II, and one had ISS stage III MM. FISH data were not available. Median patients' age was 58 years (range, 34–68 years), 8 patients were female. Patients had been treated with a median of 2 lines of therapy (range, 2–5 lines): all the patients had received at least one autologous transplant, 10 had received thalidomide, 4 patients had received bortezomib and none of them was bortezomib-refractory. Two patients had grade (G) 1 peripheral neuropathy (PN) owing to previous treatments. Fifteen alloSCT donors were HLA identical siblings, 3 were MUD and one was haploidentical. One patient received one VD, one 2 VD, and 17 patients all the 3 planned VD. Two patients received one DLI, 1 patient 2 DLIs, 6 patients 3 DLIs, and 8 patients 4 DLIs. The median follow-up of the 15 (79%) surviving patients is 22 months (range, 12.5–55 months). Overall response rate (ORR) to VD was 63%: 3 patients achieved PR, 7 patients VGPR, 1 patient CR and 1 sCR; patients with SD were 5. The 17 patients receiving VD and DLIs had a 71% ORR, with 1 patient achieving PR, 7 patients achieving VGPR, 2 patients CR and 2 sCR; disease was stable in 4 patients. Twelve patients (63%) eventually progressed at a median time of 8.7 months (range, 1–22 months). Progression-free survival was 47% at one year and 33% at both 2 and 3 years of follow-up (median PFS, 12 months). Overall survival was 90% at 1 year and 79% at both 2 and 3 years of follow-up (median not reached). The incidence of aGVHD was 18% (3 patients: 2 had grade 1 and one grade 2). Five patients (29%) had limited cGVHD, none had extensive cGVHD. None of the patients experienced graft failure. During VD, 2 patients experienced G2 hematologic toxicity (thrombocytopenia). PN occurred in 5 patients (26%): 4 patients had G2 PN, and one patient had G3 PN. Other extra-hematologic toxicities more than G2 occurred only in one patient (G3 infection event). During DLI there were no >G2 hematologic or extra-hematologic toxicities. There were no treatment-related mortalities. Conclusion: This prospective study shows that VD-DLIs is feasible, well tolerated, and it can offer a high remission rate to patients with MM relapsed or refractory after alloSCT. Interestingly, the PFS and OS curves show a plateau, suggesting the achievement of a response more prolonged respect to the series previously published, relative to the non allotransplant setting. [protocol EudraCT number: 2006-004815-24]. Supported by Janssen-Cilag. Disclosures: Off Label Use: Bortezomib and Thalidomide as post autotransplantation consolidation therapy in myeloma.


2019 ◽  
Vol 58 (12) ◽  
pp. 2327-2339
Author(s):  
Avinash K. Persaud ◽  
Junan Li ◽  
Jasmine A. Johnson ◽  
Nathan Seligson ◽  
Douglas W. Sborov ◽  
...  

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