The effect that β-lactam antibiotics have on progression free and overall survival in multiple myeloma patients undergoing autologous stem cell transplantation.

e20518 Background: Gut microbiome dysbiosis is correlated with graft-versus-host disease (GVHD) in allogeneic stem cell transplant (allo-SCT) patients. In the allo-SCT population, antibiotics have been associated with increased risk for GVHD mortality and relapse due to loss of gut obligate anaerobes . It has been shown that antibiotics may negatively impact the efficacy of checkpoint inhibitors for patients with solid tumors. Based on these studies, we performed a retrospective analysis to determine if antibiotic treatment affects outcomes of multiple myeloma (MM) patients after autologous SCT (ASCT). Methods: This is a single institution retrospective study at Hackensack University Medical Center. A list of consecutive MM patients treated from 1/2012 to 12/2015 was obtained and an electronic medical record review of the first 217 who received ASCT was performed. Baseline characteristics, treatment history, transplant course and antibiotic treatment (including β-lactams, fluoroquinolones, macrolides, metronidazole, and vancomycin) were reviewed. Prophylactic antibiotics were excluded. Response was defined using the IMWG criteria. Median progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log rank tests were used to compare the difference in survival between stratified groups. The LASSO cox regression analysis method was used for multivariate analyses of PFS and OS. Results: Of the 217 patients, 205 patients were available for analysis. Median age at ASCT was 61. β-lactams were associated with decreased median PFS (1.95 vs 4.77 years (yrs), p < 0.01) and decreased median OS (7.51 vs 13.45 yrs, p = 0.01). Multivariate analysis adjusting for lasso-selected age, gender, complete remission (CR) after ASCT, and ISS demonstrated independent progression risk associated with β-lactam use (HR = 2.00, 95% CI, 1.28–3.12, p < 0.01). β-lactams were associated with worse OS in multivariate analysis adjusting for lasso-selected age, gender, CR after ASCT and high risk cytogenetics (HR = 1.89, 95% CI, 1.07–3.40, p = 0.03). Conclusions: In this preliminary study, β-lactams predicted for decreased PFS and OS compared to patients who did not receive β-lactams in MM patients undergoing ASCT. The study was limited by its retrospective nature but demonstrates one of the first evaluations of antibiotic effect on the ASCT population in MM. Prospective studies evaluating the impact of antimicrobials on patient outcomes and the gut microbiome are ongoing.

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Depth of Response with Stem Cell Transplantation and Outcome for Multiple Myeloma in the Era of Novel Agents.

Blood ◽

10.1182/blood.v114.22.1228.1228 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1228-1228

Author(s):

David Dingli ◽

Francesca Gay ◽

Francis Buadi ◽

Angela Dispenzieri ◽

Suzanne R Hayman ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Novel Agents ◽

Cell Transplant ◽

Time To Progression ◽

Depth Of Response ◽

The Impact

Abstract Abstract 1228 Poster Board I-250 Background It is generally believed that a ‘deeper’ response in multiple myeloma is associated with an improved outcome, including time to progression (TTP) as well as overall survival. Before the advent of novel agents such as IMiDs or bortezomib, complete responses (CR) were rare in the absence of stem cell transplantation (ASCT). In that era, the depth of response achieved before ASCT tended to be dwarfed by the impact of the conditioning used for stem cell transplant. Hence, the time to progression in patients achieving CR before ASCT was not different from those who achieved CR after ASCT. With novel agents, CR rates are higher and again raises the question of whether patients who achieve CR before ASCT benefit from consolidation with ASCT. The purpose of this analysis was to determine whether CR achieved before ASCT still benefit when consolidated with ASCT Methods After approval from the Institutional Review Board at Mayo Clinic Rochester, the transplant dysproteinemia database was searched for all patients treated with novel agents and patients who achieved CR before or after ASCT were identified. In addition, we identified patients with IMiDs induction therapy and achieved CR but did not proceed with ASCT. Relevant demographic, clinical and laboratory characteristics were determined at the time of ASCT. Comparisons between groups were performed with non-parametric tests. Overall survival and TTP were determined from the time of ASCT using the Kaplan-Meier method. Results A total of 354 patients who underwent ASCT within a year from diagnosis of multiple myeloma were identified. Of these, 24 achieved CR before proceeding to ASCT while another 100 patients achieved CR after ASCT. There were no differences between the two cohorts with respect to age (58 vs 57.5 yr, p=0.14), gender, number of treatment regimens (1 vs 1, p=0.83), time to ASCT (6.5 vs 6.3 months, p=0.80), b2M (2.41 vs 2.26, p=0.58) and ISS (p=0.23). Patients who achieved CR before ASCT had a lower plasma cell burden (1.0 vs 5.0%, p<0.0001) and lower labeling index (0 vs 0, p=0.0007). Aneuploidy was present in none of the patients with CR before transplant compared to 10% in patients who achieved CR after ASCT (p=0.11). The median TTP for patients with CR before ASCT has not been reached (71% at 70 months) compared to 30 months for patients who achieved CR after ASCT (p=0.07). After a median follow up of 70 months, 21 of 24 patients (88%) with CR before transplant are alive compared to 76 of 100 patients with CR after ASCT (p=0.44). In contrast, for patients who achieved CR with IMiDs but did not proceed with ASCT, 55% have not progressed at 51 months and 71.7% are alive at 51 months (Gay et al ASH, 2009). Conclusion Our results suggest that patients who achieve CR before ASCT benefit from high-dose therapy and experience prolonged TTP without the need for maintenance therapy. ASCT after achieving CR can result in a deeper response with improvement in disease free and overall survival. Disclosures Lacy: celgene: Research Funding. Gertz:celgene: Honoraria; genzyme: Honoraria; millenium: Honoraria; amgen: Honoraria.

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

Blood ◽

10.1182/blood.v120.21.595.595 ◽

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.

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Lenalidomide maintenance after second autologous stem cell transplant improves overall survival in multiple myeloma

Leukemia & Lymphoma ◽

10.1080/10428194.2020.1749603 ◽

2020 ◽

Vol 61 (8) ◽

pp. 1877-1884 ◽

Cited By ~ 1

Author(s):

Dipenkumar Modi ◽

Jie Chi ◽

Seongho Kim ◽

Lois Ayash ◽

Asif Alavi ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

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Dose Intensive Induction Chemotherapy Does Not Decrease Tumor Contamination of Autograft or Improve Survival for Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant.

Blood ◽

10.1182/blood.v106.11.2932.2932 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2932-2932

Author(s):

Farzana A. Sayani ◽

Nizar J. Bahlis ◽

Peter Faris ◽

Mary Lynn Savoie ◽

Ahsan Chaudhry ◽

...

Keyword(s):

Stem Cells ◽

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Small Sample ◽

Cell Transplant ◽

Intensive Chemotherapy ◽

Kaplan Meier ◽

Significant Difference ◽

Time To Relapse

Abstract Multiple dose intensive chemotherapy regimens have been used for induction/mobilization of stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma. However, the exact role and regimens of such dose intensive chemotherapy has not been clearly defined. We therefore did a retrospective study to determine if dose intensive cyclophosphamide (Cyclo) 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in improved relapse rate and survival compared to standard mobilization with only Cyclo 2 g/m2. Between January 1998 and March 2004, a consecutive series of 57 newly diagnosed multiple myeloma patients receiving DICEP (38) or Cyclo (19) for in-vivo purging/mobilization were analyzed. Both groups were similar in regards to age and sex. There were no significant differences in IPI score, Durie-Salmon stage, B2 microglobulin, calcium, creatinine and albumin levels between treatment groups. Outcomes included time to relapse and time to death. Median follow up time was 799 days. Kaplan-Meier plots for time to relapse showed no significant difference (p=0.0992). Median relapse time in the DICEP group was 905 days (95% CI 580–1604) compared to 1112 days (95% CI 742-infinity) in the Cyclo group. Kaplan-Meier plots for overall survival showed no significant difference between both groups (p=0.8664). The median survival times have not yet been reached in either group and are not reported. Analysis revealed no discernable confounding risk factors. Effects of treatment on outcomes were not altered after adjusting for IPI score and Durie-Salmon staging using the stratified log-rank test. Small sample size and short duration of followup are potential limiting factors for this study, however, preliminary analysis of a larger sample of 91 multiple myeloma patients receiving either DICEP or a less intense induction/mobilization regimen, also revealed no significant difference in disease free or overall survival. Monoclonal plasma cell contamination of stem cell products was not significantly different between both groups (DICEP 42.9%, Cyclo 56.3%, p=0.5573). This study therefore suggests that the very intense DICEP induction/mobilization regimen results in no significant difference in survival outcomes. The more intense regimen does not significantly decrease tumor contamination of autograft stem cells. Overall, our experience suggests that novel induction therapies such as bortezomib, lenolidomide etc. should be pursued in preference to any further study of high dose cytotoxic chemotherapy induction. Figure Figure

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Early Lymphocyte Recovery Predicts Superior Survival after Autologous Peripheral Blood Stem Cell Transplantation (ASCT) in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v106.11.5487.5487 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5487-5487

Author(s):

Devendra K. Hiwase ◽

Anthony P. Schwarer ◽

Geraldine M. Bollard ◽

Smita D. Hiwase ◽

Michael Bailey

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Prognostic Factors ◽

Prognostic Marker ◽

Lymphocyte Count ◽

Progressive Disease ◽

Prognostic Indicator ◽

Cell Transplant ◽

The Difference

Abstract Aim: ASCT has improved survival in patients with multiple myeloma although most patients develop progressive disease. Absolute lymphocyte count recovery at day 15 (ALC-15) following ASCT has been reported as an independent prognostic indicator of overall survival (OS) and progression free survival (PFS) for patients with multiple myeloma. It is not only a good prognostic marker but may also have therapeutic significance. We evaluated absolute lymphocyte recovery on day 15 (ALC-15), day 30 (ALC-30), day 60 (ALC-60) as a prognostic marker following ASCT in patients with multiple myeloma. Method: Between 1992 and 2004, 119 consecutive patients underwent ASCT. ALC-15, ALC-30, ALC-60 were evaluated for impact on OS and PFS following ASCT. Information on known prognostic factors for multiple myeloma including age, BM plasma cells (PC), paraprotein (PP), international staging system (ISS staging) and disease response following stem cell transplant were also evaluated. Result: There were 119 (M/F, 79/43) patients and median age was 57 (30–70) years. Most patients (N=100) received melphalan 200 mg/m2 as conditioning chemotherapy. The median CD34 dose infused was 3.95 x 106/kg (1.30–33.7). Median ALC-15 was 190 (0–254) cells/ul, median ALC-30 was 1000 (60 to 5590) cells/ul and ALC-60 was 1290 (50–6570). There were 28% of patients in complete remission (CR) & 67% in partial remission (PR) following ASCT. On Multivariate analysis: ALC-30 was significantly associated with OS. Although there was higher PFS with higher lymphocyte count, the difference was not statistically significant. Other known prognostic factors such as ISS staging, PC at diagnosis, age at transplant and CR response following ASCT were also significantly correlated with OS & PFS. Survival analysis: Median OS was 64 (0.2 to 175) months and PFS 32 (1.7 to 175) months following PBSCT. In patients with ALC-30 >500 cells/ul median OS was 80 months and 53 months in patients with ALC-30 < 500 cells/ul (P= 0.0147). Fig 1: Overall survival following ASCT in months Fig 1:. Overall survival following ASCT in months PFS was 43 months in patients with ALC-30 > 500 cells/ul and 31 months in patients with ALC-30 < 500 cells/ul (P=0.39). Median ALC-30 was 1309 cells/ul in patients who were alive at last follow up while median ALC-30 was 879 cells/ul in patients who were deceased (P=0.0072) and in most of the patients (35/45, 77%) progressive disease was responsible for their demise. There was no significant correlation between CD34+ stem cells dose and lymphocyte dose in autograft with ALC-30 recovery (P=0.26). Conclusions: ALC-30 was an independent prognostic indicator of OS following ASCT in patients with multiple myeloma. There was trend for longer PFS in patients with ALC-30 >500 cells/ul, although the difference was not statistically significant. This may be due small sample size and needs to be evaluated further in prospective study. We could not find a correlation between lymphocyte dose or CD34 dose in autograft with ALC-30 recovery. Lower ISS stage, less extensive marrow infiltration at diagnosis and complete response following PBSCT positively influences OS & PFS.

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A Phase II Study of Sequential Velcade/Thalidomide/ Dexamethasone (VTD) as Maintenance Therapy Post Single Autologous Peripheral Stem Cell (PSCT) in Patients with Multiple Myeloma.

Blood ◽

10.1182/blood.v114.22.3403.3403 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3403-3403

Author(s):

Firoozeh Sahebi ◽

Amrita Krishnan ◽

George Somlo ◽

Leslie Popplewell ◽

P. Parker ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Peripheral Neuropathy ◽

Maintenance Therapy ◽

Phase Ii ◽

Phase Ii Study ◽

Disease Stage ◽

Cell Transplant ◽

Grade Iii

Abstract Abstract 3403 Poster Board III-291 Autologous PSCT remains standard treatment in younger patients (pts) with multiple myeloma. However, relapse is the major cause of treatment failure. Several studies have reported improved progression-free survival (PFS) and possibly overall survival with thalidomide alone or in combination with steroid and chemotherapy as maintenance/consolidation therapy post autologous PSCT. We performed a phase II study investigating the role of sequential velcade/thalidomide/dexamethasone (VTD) as maintenance therapy post single PSCT. The objectives were to examine the toxicities of prolonged course of sequential VTD, CR rate, PFS and overall survival following single autologous PSCT. Within 4-8 weeks of autologous PSCT using melphalan 200mg/m2, pts received weekly velcade (vel) at 1.3mg/m2 /wk x 3 weeks with 1 week rest and dexamethasone (dex) at 40mg/d x 4 d for 6 months, followed by thalidomide (thal) at 50 -200mg/d and dexamethasone (dex) at 40mg/dx4 d for 6 more months. Single agent thalidomide was then continued until disease progression. Twenty-eight pts have been enrolled. Median age is 54 years (29-66). Median time from diagnosis is 7.9 mo. (4.2 – 145). Disease stage at diagnosis; by Salmon-Durie (II/III 6/22) and by ISS (I/II/III 11/9/7/missing data in 1 pt). Pts received induction treatment with thal/dex (14), velcade based (15) and revlimid based regimens (7). Median B2M at enrollment is 1.75 mg/L (1.14 -5.3). Disease status at enrollment; CR (7) VGPR (9), PR (11), SD (1). Three pts have chromosome 13 abnormalities (1 pt by karyotype and 2 pts by FISH). Results: All pts have undergone transplant. Four pts were unable to start planned maintenance therapy due to development of grade II or more neuro toxicities (3), and persistent thrombocytopenia (1) after PSCT. Twenty-four pts started maintenance vel/dex within 4-8 weeks of PSCT. Nine pts have completed 6 months of vel/dex. Two pts stopped vel/dex because of low WBC (1) or PN (1). With a median F/U of 5.2 mo. (1.2 -17.3) nine of 28 pts (33%) have achieved CR post PSCT and six out of 11 evaluable pts (55%) have achieved CR after vel/dex. Six out of 9 pts (66%) who have completed 6 mo. of vel/dex achieved CR. Two out of 9 pts (22%) have upgraded their response with vel/dex. Four pts have completed 6 month of thal/dex and are beyond 1 year post PSCT. Two out of 4 pts remain in CR at one year post PSCT. One pt is in PR and 1 pt has progressed. Two pts could not complete thal/dex phase of therapy because of relapse (1) and grade III GI toxicity (1). Three pts have relapsed of whom 1 pt died of relapsed myeloma (leptomeningeal disease). No grade IV toxicity has been noted. Grade III toxicities have occurred in 4 pts; low platelet (1), fatigue (1), mood alteration (1), GI (severe constipation) (1). Thirteen pts have peripheral neuropathy (PN). Ten pts had PN grade I at enrollment. Only 3 pts have developed PN on the study and all are grade I - II. Median velcade dose is 1.3 mg /m2/wk and thalidomide dose is 100mg /d. Conclusion: Prolonged sequential velcade/thalidomide/dexamethasone maintenance therapy post single autologous PSCT is well tolerated with no severe peripheral neuropathy. Fifty-five percent of pts have achieved CR and 22% have upgraded their response after six months of velcade/dexamethasone therapy suggesting this is an active and well tolerated maintenance strategy post PSCT. Disclosures: Sahebi: Celgene: Honoraria; Millennium Pharmaceutical: Research Funding. Off Label Use: The use of bortezomib(Velcade)in combination with thalidomide and dexamethasone is investigated as maintenance therapy post autologuous stem cell transplant in patients with multiple myeloma.

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Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) Scores Correlates with Increased Readmissions and Days In Hospital In Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplant

Blood ◽

10.1182/blood.v116.21.4748.4748 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4748-4748

Author(s):

Szwed A. Ellen ◽

Jack W. Hsu ◽

Wei Hou ◽

Randy A. Brown ◽

Christopher R. Cogle ◽

...

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Conditioning Regimens ◽

Comorbidity Index ◽

The Impact

Abstract Abstract 4748 Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) Scores Correlates with Increased Readmissions and Days in Hospital in Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation. Ellen Szwed, Jack W. Hsu, Wei Hou, Randy A. Brown, Christopher R. Cogle, John W. Hiemenz, W Stratford May, Jan S. Moreb, Baldeep Wirk, John R. Wingard. The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed to assess the impact of comorbidities in allogeneic stem cell transplant (AlloSCT) recipients. It has been shown to correlate with non-relapse mortality and overall survival in both the myeloablative, non-myeloablative (NMA), and reduced intensity (RIC) settings, regardless of graft source. However, the economic impact of allogeneic transplant in patients with comorbidities has not been assessed. We retrospectively analyzed 181 consecutive patients who underwent AlloSCT from an HLA identical sibling following either myleoablative (n= 109) or NMA/RIC (n=71) conditioning regimens between January 2001 and December 2008. The HCT-CI score was calculated according to the method of Sorror, et al. (Sorror ML, et al. Blood. 2005 106: 2912–2919). Median follow-up of the entire cohort was 2 years. As previously published, there was a statistically significant correlation between HCT-CI and both non-relapse mortality (HR = 1.147, p = 0.0170,) and overall survival (HR = 1.152, p=0.0001) at 2-years of 23% and 50% respectively. We found statistically significant correlations between the HCT-CI score and total number of hospital readmissions (mean = 1.92; r=0.192; p = 0.0098) and total days in hospital after initial discharge from hospital after stem cell infusion (mean = 22.4 days; r=0.156; p = 0.036). Interestingly, the correlation for number of hospital days did not become statistically significant until 180 days or greater after transplantation. There was no correlation between HCT-CI with graft source, relapse or graft-vs.-host disease. When we stratified the HCT-CI to either myeloablative (N=109) or NMA/RIC (N=71) conditioning regimens, the correlations between the HCT-CI and both non-relapse mortality and overall survival were still statistically significant. The differences in days of hospitalization remained statistically significant in the myeloablative setting, but not in the NMA/RIC setting. In conclusion, our analysis of AlloSCT recipients found a correlation between the HCT-CI and the number of readmissions and hospital length of stay for myeloablative but not NMA/RIC conditioning regimens, suggesting a higher HCT-CI score results in greater use of hospital resources and costs. The increase in resource utilization is greater after the immediate post-transplant period. Whether these conclusions also apply in other transplant settings will need to be investigated. Disclosures: No relevant conflicts of interest to declare.

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Tandem Autologous Stem Cell Transplantation in Chemorefractory Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4554.4554 ◽

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.

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Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽

10.1182/blood.v120.21.4548.4548 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4548-4548

Author(s):

Catherine Garnett ◽

Chrissy Giles ◽

Maialen Lasa ◽

Osman Ahmed ◽

Marco Bua ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Disease Progression ◽

Cell Transplantation ◽

Median Time ◽

Autologous Stem Cell Transplantation ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

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Reduced Intensity Allogeneic Stem Cell Transplant In Patients With Multiple Myeloma: A Comparison Of Planned Autologous-Reduced Intensity Allogeneic Stem Cell Transplant (Auto-Allo) and Reduced Intensity Allogeneic Stem Cell Transplant (RIC) As Upfront Transplant In Patients With Multiple Myeloma, An EBMT Analysis

Blood ◽

10.1182/blood.v122.21.920.920 ◽

2013 ◽

Vol 122 (21) ◽

pp. 920-920 ◽

Cited By ~ 1

Author(s):

Firoozeh Sahebi ◽

Simona Iacobelli ◽

Anja Van Biezen ◽

Liisa Volin ◽

Peter Dreger ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Allogeneic Stem Cell Transplant ◽

Allogeneic Hsct ◽

Autologous Hsct ◽

Reduced Intensity

Abstract Background Despite the advances in the treatment of multiple myeloma using new targeted therapies and autologous hematopoietic stem cell transplant (HSCT) the disease remains largely incurable. Recent efforts in using reduced intensity allogeneic HSCT have been hampered by increased allograft-related morbidity and mortality. Several prospective studies comparing single or tandem autologous HSCT with planned tandem autologous-reduced intensity allogeneic HSCT (auto-allo) have shown no overall survival advantage despite improvements in progression-free survival (PFS) and lower relapse rates with reduced intensity allograft, mainly due to increased non-relapse related mortality (NRM) rates. However, two of these prospective studies; the European Group for Blood and Marrow Transplantation NMAM 2000 and the Italian group study with long term follow-up reported PFS and overall survival (OS) benefits in favor of the auto-allo arm. Currently allogeneic HSCT is recommended within the context of clinical trials and only in high risk multiple myeloma patients who continue to have a very poor outcome with autologous HSCT. While such clinical trials are ongoing there remains a need to address the role of autologous HSCT prior to reduced intensity allogeneic HSCT. The objective of this retrospective study is to evaluate the role of upfront cytoreductive autologous HSCT prior to allograft in the outcomes of patients who have undergone allograft following induction therapy. Study We performed a retrospective analysis of the EBMT database comparing the outcomes of patients who were planned to receive auto-allograft to those who underwent reduced intensity allograft (early RIC) without a prior autologous HSCT within one year from diagnosis. The data in 504 patients were previously reported at the ASH meeting 2010 (abstract 3512). We subsequently included additional patients and requested more information from the participating EBMT centers and updated the study. From 1996 to 2013 a total of 689 patients were registered as reduced intensity allograft. 517 patients were registered as planned auto-allograft; however, 73 did not receive the planned allograft. A total of 172 patients received reduced intensity allograft after induction treatment without prior auto-HSCT. Median age at first transplant was 53 years (range 20-72) in the auto-allo and 51 years (range 31-77) in the early RIC group. Median time from diagnosis was 6.6 months (range 2-156 months) in the auto-allo and 7.7 months (2.8-12.0) in the early RIC group. The disease status at the time of first transplant for the auto-allo group was CR - 8%, PR - 67%, other or missing - 25%; and for the RIC group was CR - 15%, PR - 62%, other or missing - 23%. Donors were HLA matched siblings in 88% and matched unrelated in 12% for the auto-allo group, and 84% siblings and 16% matched unrelated in the RIC group with no significant differences between the two groups. Results With a median follow-up of 93 months in the auto-allo and 84 months in RIC groups, PFS rates were significantly better at 3 and 5 years in the auto-allo group (45.6% and 34.2%) as compared to the RIC group (33.9% and 22.0%, p<0.001). Overall survival was also significantly improved in favor of the auto-allo (3 yr and 5 yr OS 67.9% and 58.9%) as compared to the RIC group (54.3% and 42.7%, P = 0.001). The non-relapse mortality (NRM) rates were lower in the auto-allo group as compared to RIC: 1 yr and 3 yr NRM were 8.1% and 14.1% in the auto-allo and 20.3% and 27.4% in early RIC group, p<0.001. We examined potential differences in outcomes based on use of novel agents, and used the year 2004 as a surrogate for introduction of novel agents to routine clinical practice. There were no significant differences by multivariate analysis in outcomes for patients transplanted before or after 2004. Conclusion This large multicenter retrospective study suggests that cytoreductive autologous HSCT prior to allograft is associated with improved PFS and OS. We are in the process of conducting an extended analysis to control for possible confounders. If the results are confirmed, future studies should be conducted to verify the importance of autologous stem cell transplant as part of the allograft treatment strategy. Disclosures: No relevant conflicts of interest to declare.

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