Immunoparesis Recovery As Predictor Marker of Progression after Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4356-4356 ◽  
Author(s):  
Veronica Gonzalez De La Calle ◽  
Eduardo Sobejano ◽  
Julio Davila ◽  
Enrique M Ocio ◽  
Noemi Puig ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
B Lymphocyte ◽  
Disease Stage ◽  
Advisory Committees

Abstract BACKGROUND High dose therapy followed by autologous stem cell transplantation (ASCT) remains the standard of care, especially in Europe, for young and eligible multiple myeloma patients (usually younger than 65 years old). Immunoparesis is defined as a reduction (below the lower normal limit) in the levels of 1 or 2 uninvolved immunoglobulins (Ig) and it is related to a reversible suppression of B lymphocytes that correlates inversely with disease stage. B Lymphocyte reconstitution begins at 3 months after ASCT, with maximum B lymphocyte levels at 1 year after ASCT. AIMS The goal of the present study was to investigate the role of the immunoparesis recovery after ASCT as predictor of relapse or progression in multiple myeloma (MM). METHODS We reviewed medical records of MM patients who underwent to ASCT at University Hospital of Salamanca between 1992 and 2013. The primary endpoint was time to relapse or progression from ASCT. Ig (Ig G, Ig A e Ig M) were collected at the time of diagnosis, before ASCT, every 3 months during the first year after ASCT, and every year up to 5 years after ASCT among eligible patients until the relapse or disease progression. RESULTS 106 multiple myeloma patients who underwent ASCT were included in the analysis. Conventional chemotherapy was administered as induction regimen in 69 patients (65%), whereas novel agents were used in 37 patients (35%). Most patients had immunoparesis at diagnosis (91%) and at the moment of ASCT as well (94%). After a median follow-up of 62 months, median time to progression or relapse (TTP) from ASCT was 31 months (95 % CI: 24.1 - 37.1 months). MM patients with immunoparesis 1 year after ASCT had a significantly shorter median TTP as compared with patients without immunoparesis (33.5 months vs 94.2 months; HR: 2.14, 95% CI: 1.13-4.05; p=0.019). In the group of patients with reduction of both Igs, median TTP was slightly inferior than in the group with reduction of only one of them(33.5 vs 36.4 months, p=0.03). Presence of ISS 3, high-risk cytogenetics at diagnosis, less than partial response achieved before and three months after ASCT were also identified as predictors of progression. Multivariate analysis selected immunoparesis 1 year after ASCT as an independent variable for relapse or progression (HR: 5.97, 95% CI: 1.63-21.88; P=0.007). CONCLUSIONS The lack of immunoparesis recovery at 1 year after ASCT in MM patients is associated with significantly higher risk of relapse or progression and this group of patients could potentially benefit of continuous treatment after ASCT to enhance the immune recovery. Disclosures Ocio: Array BioPharma: Consultancy, Research Funding; Celgene: Consultancy, Honoraria; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy; Mundipharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MSD: Research Funding; Pharmamar: Consultancy, Research Funding; Janssen: Honoraria. Puig:The Binding Site: Consultancy; Janssen: Consultancy. Mateos:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx: Consultancy; BMS: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Upfront Autologous Stem Cell Transplantation for Newly Diagnosed Elderly Multiple Myeloma (MM) Patients: A Prospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1989-1989
Author(s):  
Laurent Garderet ◽  
Cyrille Touzeau ◽  
Anne-Marie Stoppa ◽  
Denis Caillot ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged <65 years. However, at the era of novel induction regimens, and because of better patient selection and supportive care, ASCT may prove to be a valid treatment option even in older MM patients. Therefore, some investigators are questioning the widely used 65 years age limit. Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Safety and Efficacy of Autologous Stem Cell Transplantation in Dialysis-Dependent Myeloma Patients - the Diadem Study from the Chronic Malignancies Working Party of the EBMT

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4574-4574
Author(s):  
Anna Waszczuk-Gajda ◽  
Junfeng Wang ◽  
Liesbeth C. de Wreede ◽  
Tiarlan Sirait ◽  
Zubeyde Nur Ozkurt ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
Safety And Efficacy

Introduction Multiple myeloma (MM) patients with renal impairment (RI), especially dialysis-dependent (DD) RI, have poorer outcomes than MM patients with normal renal function. Autologous stem cell transplantation (ASCT) is a treatment option, but there is concern at a perceived higher risk of complications which may be limiting consideration of the use of ASCT in this population. The evidence is inconsistent among studies and interpretation is complicated by heterogeneous datasets, some dating to before the availability of novel agents. Finally, the reversibility of RI following ASCT is an important prognostic factor for both survival and quality of life. Aim To evaluate the safety and efficacy of ASCT in MM patients with DD RI transplanted in EBMT centres between 1997 and 2017. Methods Baseline characteristics at diagnosis, patient treatment regimens and clinical outcomes were collected using standardised report forms. OS was defined as the period between the date of ASCT and the date of death or the date of last observation. PFS was defined as the period between the date of ASCT and date of progression/relapse or death of any causes or the date of the last observation. Cox proportional hazard regression analysis was applied to assess risk factors for progression and death. Survival curves were plotted by the Kaplan-Meier method and compared using log-rank test. P&lt;0.05 was judged as statistically significant. Results A total of 109,959 adult MM patients are registered in the EBMT database as having undergone ASCT between 1997 and 2017. We further analysed 118 DD MM patients who had a first ASCT during this period. The median (range) age was 57 (27-71) years. Seventy (59%) patients were males. Forty nine patients (49/94 patients, 52%) had Karnofsky score ≥90. One hundred and ten patients were treated with hemodialysis and eight with peritoneal dialysis. A total of 68 (58%) patients had Light Chain MM, 43 kappa and 25 Lambda. In first-line induction therapy, 47/76 (62%) patients received bortezomib-based regimens. Forty-four (37%) patients achieved at least VGPR pre-ASCT. The median time from diagnosis to ASCT was 0.7 years (0.3-4.9). Melphalan doses were as follows: 140 mg/m2 (n=55, 67%), 70-100 mg/m2 (n=15, 18%), and &gt;140 mg/m2 (n=12, 15%). The times to Neutrophil (&gt;0.5) and Platelet (&gt;20) engraftment were 12 (10-37) and 14 (4-128) days, respectively. The 30-day and 100-day transplant-related mortality (TRM) rates were 0.0% and 0.9%, respectively. ASCT was associated with a significant deepening of response (at least VGPR pre- vs post-ASCT: 36/93 (39%) vs 48/93 (52%), p &lt; 0.001). The median PFS was 37 months (95% CI: 24-43) and 5-year PFS was 31% (95% CI: 20-41). The median OS was 102 months (95% CI: 67-129). Five-year OS post-ASCT was 62% (52-72) and 10-year OS 36% (17-55). Thirty-one (26%) DD MM patients achieved dialysis independence. There were no differences in PFS or OS when comparing the 1997-2007 and 2008-2017 cohorts: 5-year PFS - 28% (6-49) vs 31% (19-43) (p=0.7) and 5-year OS - 61% (38-84) vs 63% (51-74) (p=0.9), respectively. On univariate analysis of factors affecting PFS, achievement of an Overall Response Rate (ORR) (CR+VGPR+PR vs. Other) pre-ASCT was associated with a lower risk (HR 0.467, p=0.032) and older age (&gt;55 years) with a higher risk (HR 1.786, p=0.035) of post-ASCT progression. Age higher than 55 (HR 2.033, 95%CI: 0.992 - 4.166, p=0.053) increased and achievement of at least VGPR pre-transplant (HR 0.494, 95%CI: 0.224 - 1.091, p=0.081, on the verge of statistical significance) decreased the risk of death. Conclusion To the best of our knowledge, the DIADEM study is the largest analysis of ASCT in DD MM pts to date. This cohort of 118 unselected patients had an OS comparable to patients without RI. This may reflect patient selection based on younger age, Karnofsky scores and pre-ASCT response. The low TRM and excellent outcomes support consideration of the use of ASCT in pts with DD RI. Notably, more than a quarter of patients became dialysis independent, an outcome likely to confer an improved Quality-of-Life.. These results can also inform the debate around the role of renal transplantation in younger DD MM patients who do not achieve dialysis independence. Disclosures Snowden: IDMC: Honoraria; Kiadis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Mallinckrodt: Honoraria; Jazz: Honoraria; Gilead: Honoraria. Dreger:MSD: Membership on an entity's Board of Directors or advisory committees, Other: Sponsoring of Symposia; AbbVie, AstraZeneca, Gilead, Janssen, Novartis, Riemser, Roche: Consultancy; AbbVie, Gilead, Novartis, Riemser, Roche: Speakers Bureau; Neovii, Riemser: Research Funding. Illés:Takeda, Seattle: Research Funding; Janssen, Celgene, Novartis, Takeda, Roche, Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Basak:Teva: Honoraria; Celgene: Honoraria. Gyan:Pfizer: Honoraria. Hayden:Alnylam: Honoraria; Amgen: Honoraria. Beksac:Amgen: Consultancy; Celgene: Consultancy; Janssen&Janssen: Consultancy; Takeda: Consultancy. Schönland:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Medac: Other: Travel Grant; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Bortezomib- and Thalidomide-Induced Peripheral Neuropathy (PN) in Multiple Myeloma (MM): Clinical and Molecular Analysis of 474 Patients Treated with Thalidomide-Dexamethasone (TD) or Bortezomib-TD (VTD)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1821-1821
Author(s):  
Paola Tacchetti ◽  
Carolina Terragna ◽  
Gioacchino Catania ◽  
Magda Marcatti ◽  
Andrea Nozza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Complete Resolution ◽  
Study Endpoint ◽  
Consolidation Therapy ◽  
Advisory Committees

Abstract Abstract 1821 Introduction: PN is an important complication of MM and its incidence has been further increased after the introduction of the novel agents thalidomide and bortezomib. In a phase 3 trial comparing TD with VTD as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation for previously untreated MM patients, the VTD arm was significantly superior over TD in terms of improved rates of complete or near-complete response (CR/nCR) (the primary study endpoint) and progression free survival (PFS). Toxicity of VTD and TD regimens, including PN, was a secondary study endpoint. Methods: We performed a subanalysis of the study to assess the frequency, reversibility, risk factors and molecular markers associated with treatment-emergent PN. PN was graded by use of National Cancer Institute's Common Toxicity Criteria (NCI CTCAE) version 3.0. Since grade 1 PN could be misinterpreted and does not interfere with the daily activities, only patients who developed PN of at least grade 2 were evaluated. A total of 474 patients (of whom, 236 randomized to the VTD arm and 238 to TD) were stratified according to the development or not of grade ≥2 neurological adverse events (NAEs). Gene expression profiles (GEP) of pre-treatment CD138+ bone marrow plasma cells (BMPCs) were analyzed in a subset of 127 VTD-treated patients for whom biological samples taken at diagnosis were adequate for genomic analysis. GEP experiments were performed using the Affymetrix HG-U133 Plus 2.0 platform and class comparison of groups of array was done with one-way ANOVA Partek Genomic Suite (version 6.4). Results: Occurrence of PN throughout the entire treatment program was significantly higher in the VTD arm compared with TD. In particular, the rate of grade ≥2 PN was 35% vs 10% (p<0.001), and grade ≥3 was 15% vs 2.5% (p<0.001), respectively. Most of NAEs occurred during the induction phase (52% in VTD and 70% in TD arms), while a minority were seen during consolidation therapy (6% in VTD and 8% in TD). Median time to onset of grade ≥2 PN was 83 days in the VTD arm compared with 37.5 days in TD arm (p=0.04). Overall, 89% of patients on VTD and 95% on TD had a complete resolution of PN within a median of 70 and 61 days (p=0.6), respectively. An improvement to at least grade 1 was recorded in 94% of patients in the VTD arm and in 95% on TD within a median of 78.5 and 61 days (p=0.4), respectively. Three patients (1%) on VTD and none on TD discontinued treatment due to neurological toxicity. Notably, development of grade ≥2 PN did not affect the rates of CR/nCR, and both time to progression (TTP) and PFS. By univariate analysis, characteristics of patients at baseline, including age, MM isotype, ISS stage and cytogenetic abnormalities such as del(13q), t(4;14) or del(17p), did not influence the development of grade ≥2 PN in both arms. GEP were analyzed in 127 patients assigned to the VTD arm (44 with and 83 without treatment-emergent grade ≥2 PN). Patients experiencing a grade ≥2 PN were characterized by the differential expression of 184 genes (p<0.01). The genes showing the highest change in expression included NRN1 (involved in the axonal regeneration), GSTM1 (involved in the detoxification of electrophilic compounds by conjugation with glutathione), DCTN1 (whose mutations are associated in specific types of disease-associated axonal degeneration). GeneGO® pathway analysis of differentially expressed genes showed enrichment for genes mainly implicated in the regulation of cytoskeleton rearrangement and the axonal guidance: indeed, several genes, which are involved in the signal transfer from semaphorin and ephrin to the cytoskeletal and motor proteins resulted differentially expressed in patients who developed grade ≥2 PN (SEMA6A, SEMA4B, ACTA2, EPHA5, NEB). Conclusions: Although VTD incorporated into double ASCT was associated with a higher incidence of grade ≥2 PN compared with TD, the probability of complete resolution or improvement to at least grade 1 was comparable in both VTD- and TD-treated groups. Importantly, NAEs did not adversely affect the rate of CR/nCR, and TTP and PFS. No relationship between development of PN and both patient demographics and disease characteristics was observed. Conversely, GEP analysis of BMPCs from patients with VTD-induced PN showed the significant deregulated expression of genes involved in the nervous system function. Disclosures: Off Label Use: Bortezomib and Thalidomide as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation in newly diagnosed multiple myeloma. Tosi:Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Baccarani:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Mayers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria. Cavo:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Incidence and Clinical Features of Extramedullary Multiple Myeloma in Patients Who Underwent Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5746-5746
Author(s):  
Matthew Weinstock ◽  
Yosra Aljawai ◽  
Irene M. Ghobrial ◽  
Elizabeth A. Morgan ◽  
Jacob P. Laubach ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Medical Center ◽  
Academic Medical Center ◽  
Advisory Committees ◽  
Treatment Regimens

Abstract Background: Extramedullary disease (EMD), strictly defined as an infiltrate of clonal plasma cells at an anatomic site distant from the bone marrow or adjacent soft tissue in a patient with underlying multiple myeloma, is an uncommon manifestation of multiple myeloma. Comparatively little is known about this disease entity, with no large case series published in the last decade. Patients and Methods: 663 consecutive patients with multiple myeloma who underwent autologous or allogeneic stem cell transplantation at a single, large, academic medical center in the United States from January 2005 to December 2011 were assessed for the presence or absence of EMD, as well as baseline demographic and biochemical characteristics, treatment regimens, and response to therapy. Results: A cohort of 55 patients with biopsy-proven EMD was identified, comprising 8.3% of the total study population. Among the patients with EMD, 13 (23.6%) were found to have EMD at the time of initial presentation, while the remainder developed EMD during the course of their illness. Patients with EMD received a median of 5 different treatment regimens during the course of their illness, most commonly with combinations of dexamethasone, thalidomide, lenalidomide, and bortezomib, as well as autologous hemotopoietic stem cell transplantation. Patients had received a median of 3 lines of therapy prior to experiencing an extramedullary relapse. Patients with EMD had markedly elevated maximum serum LDH levels (median 613.5 units/L) and low minimum hemoglobin levels (median 7.8 g/dL). Common cytogenetic abnormalities included deletion 13q, deletion 11q, t(11;14), and deletion 17p. Available immunohistochemical data suggest that EMD specimens had frequent expression of CXCR4, CD44, and CD56. The median overall survival data of these patients was 3.2 years (range, 0.9-9.5) and the median time from diagnosis of EMD to death was 0.5 years (range, 0.002-3.2). Conclusions: This report describes a large series of multiple myeloma patients with EMD who were treated in the era of stem cell transplant at a single academic medical center. Further studies to examine the molecular characteristics of extramedullary multiple myeloma are necessary to better define this entity and characterize therapeutic options that can prolong survival in this otherwise very vulnerable population. Disclosures Ghobrial: Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Laubach:Novartis: Research Funding; Onyx Pharmaceuticals: Research Funding. Schlossman:Millennium: Consultancy. Mitsiades:Millennium Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Research Funding; Johnson & Johnson: Research Funding; DFCI: patent submission on stromal co-culture technologies Patents & Royalties.

Prognostic Impact of Cytogenetic Abnormalities On Outcomes of Newly Diagnosed Multiple Myeloma Patients Treated with Thalidomide-Dexamethasone Incorporated Into Double Autologous Stem-Cell Transplantation: An Analysis of 593 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3562-3562 ◽  
Author(s):  
Elena Zamagni ◽  
Nicoletta Testoni ◽  
Carolina Terragna ◽  
Paola Tacchetti ◽  
Mauro Fiacchini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Prognostic Impact ◽  
Advisory Committees ◽  
Cytogenetic Abnormalities ◽  
Cox Regression Analysis

Abstract Abstract 3562 Aim of the present study was to evaluate the clinical outcome of a large series of younger patients with symptomatic multiple myeloma (MM) who were enrolled in two subsequent clinical trials of thalidomide-dexamethasone (thal-dex) incorporated into double autologous stem-cell transplantation (ASCT) to support high-dose melphalan (200 mg/m2). In both studies, thal (100 mg/day for the first 14 days and then 200 mg/day) and pulsed dex (between 480 and 160 mg per cycle), were administered from the onset until the second ASCT. The analysis was performed on an intention-to-treat basis on a total of 593 patients who were followed for a median of 36 months. The best VGPR and CR rates were 69% and 35%, respectively. The median duration of CR was 66 months. Median TTP and PFS were 53 and 44 months, respectively. The 5-year projected rates of TTP and PFS were 46% and 38%, respectively, while the corresponding value for OS was 67%. More than 80% of the patients were screened at diagnosis for the presence of cytogenetic abnormalities by FISH analysis. Forty-five percent of patients had del(13q), while t(4;14) and del(17p) were found in 16 % and 7 % of patients, respectively. The presence of del(17p) and/or t(4;14) was associated with a significantly shorter 5-year projected TTP, PFS and OS in comparison with the absence of these abnormalities, indifferently from the presence or absence of del(13q) (TTP: 30% vs 53%, respectively P=0.0000; PFS: 28% vs 45%, respectively, P=0.0000; OS: 53% vs 69%, respectively, P=0.0000). OS and PFS curves of patients carrying del(13q) alone were almost superimposable to those of patients without cytogenetic abnormalities, while TTP was significantly shorter for patients with del(13q) alone (5-year projected rates: 40% vs 53%, respectively, P=0.04). Patients carrying del(17p) in the absence of t(4;14) had similar 5-year projected TTP and PFS as compared with t(4;14) positive but del(17p) negative patients. However, OS was significantly shorter for the subgroup with del(17p) and absence of t(4;14) in comparison with that of patients carrying t(4;14) without del(17p) (5 year projected rates: 18% vs 70%, respectively, P=0.03). In a multivariate analysis, presence of del(17p) and high beta2-m at baseline were the most important variables adversely influencing TTP (HR: 2.3, P=0.001 and HR: 1.8, P=0.002, respectively), PFS (HR: 2.0, P=0.001 and HR: 1.9, P=0.001, respectively), and OS (HR: 3.9, P=0.000 and HR: 2.0, P=0.005, respectively). Additional variables predicting for shorter TTP and PFS were the presence of t(4;14) (HR: 1.8, P=0.004) and of del(13q) (HR: 1.6, P= 0.009). Also the quality of best response to the overall treatment program influenced clinical outcomes. In particular, patients achieving CR had a significantly longer PFS and OS than those achieving a VGPR (PFS: median 68 vs 40 months, respectively, P=0.007; 5-year projected OS rates: 84% vs 70%, respectively, P=0.01). In conclusion, incorporation of thal-dex into double autotransplantation failed to overcome the poor prognosis conferred by del(13 q), t(4;14) and del(17p). In a multivariate Cox regression analysis, del(17p) and high levels of serum beta2-m at diagnosis were the strongest variables adversely influencing PFS and OS. In comparison with the presence of t(4;14) but absence of del(17p), patients carrying del(17p) without t(4;14) had a significantly shorter OS, possibly due to their worst outcome after relapse. Presence of del(13q) alone conferred a significantly shorter TTP, but did not have an adverse impact on OS due to the favorable role of effective salvage therapies incorporating either bortezomib or lenalidomide. Disclosures: Off Label Use: use of first line thalidomide in preparation for ASCT. Cavo:Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, no; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, no.

scholarly journals Evaluating the PET Parameters SUVmax and TMTV in the Setting of Autologous Stem Cell Transplantation for DLBCL

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Rachel Brown ◽  
Alessandro Lambertini ◽  
Michael S Hofman ◽  
Mathias Bressel ◽  
Michael P Macmanus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
Relative Change

Introduction Where tolerated,high dose chemotherapy supported by autologous stem cell transplantation (ASCT) is the standard of care for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL). Disease recurrence post-ASCT however is common and carries an extremely poor prognosis, highlighting the need for improved pre-transplant prognostic stratification. This study investigates the prognostic utility of the PET parameters total metabolic tumour volume (TMTV) and standardised uptake value (SUV)max in the peri-transplant setting. Methods 125 patients underwent ASCT for relapsed or refractory DLBCL between 1/1/2002 and 31/1/2017 at the Peter MacCallum Cancer Centre. All patients received multi-agent salvage immuno-chemotherapy before proceeding to ASCT. 58 patients were treated with peri-transplant radiotherapy, with indications including incomplete response post-salvage therapy, and bulky and/or localised disease. 122 patients had their treatment response assessed with PET. TMTV and SUVmax were measured at time of primary disease relapse/progression prior to salvage immuno-chemotherapy (pre-salvage PET) and post-salvage immuno-chemotherapy prior to ASCT (pre-ASCT PET). 93 patients had pre-salvage and pre-ASCT PETs available for TMTV and SUVmax measurement. Results Median follow up was 5.6 years. The 5-year progression free survival (PFS) and overall survival (OS) were 52% (95% CI: 42-60) and 65% (95% CI: 56-73). In patients demonstrating complete metabolic response (CMR) and non-CMR on pre-ASCT PET the 5-year PFS was 58% (95% CI: 44-70) and 44% (95% CI: 29-57) respectively. The 5-year OS with CMR and non-CMR on pre-ASCT PET was 73% (95% CI: 59-83) and 54% (95% CI: 39-67). TMTV and SUVmax were investigated as potential prognostic factors in the peri-transplant setting. In this patient group, pre-salvage TMTV and SUVmax were not found to be of prognostic significance. Pre-salvage TMTV and SUVmax PFS hazard ratios (HR)s were 1.06 per 100ml (95% CI:0.96-1.17; p = 0.27) and 1.00 (95% CI: 0.98-1.03; p = 0.78) respectively, and OS HRs were 1.10 per 100ml (95% CI: 0.86-1.18; p = 0.07) and 1.02 (95% CI: 0.96-1.04 p = 0.24). In contrast, pre-ASCT TMTV was a significant negative prognostic factor for both PFS (HR = 1.22 per 100ml; 95%CI: 1.10-1.37; p &lt; 0.001) and OS (HR = 1.96 per 100ml; 95% CI: 1.38-2.79; p &lt; 0.001). Pre-ASCT SUVmax similarly demonstrated a negative association with PFS (HR = 1.07; 95% CI: 1.04-1.10; p &lt; 0.001) and OS (HR of 1.08 ; 95% CI: 1.04-1.11; p &lt; 0.001). In addition to the TMTV and SUVmax absolute values, the relative change from pre-salvage to pre-ASCT PET was investigated for prognostic value. No significant association with PFS or OS was demonstrated for the relative change of either parameter. The relative change in TMTV had a HRs of 1.21 (95% CI: 0.54- 2.72; p = 0.65) and 1.15 (95% CI: 0.45-2.93; p = 0.77) for PFS and OS respectively, and relative change in SUVmax had a HRs of 1.30 (95% CI: 0.68- 2.50; p = 0.43) and 1.20 (CI 95% 0.57-2.54; p = 0.64) for PFS and OS. Conclusion As prognostic tools, pre-ASCT TMTV and SUVmax were both predictors for PFS and OS. In contrast, pre-salvage TMTV and SUVmax did not demonstrate an association with PFS or OS, reinforcing the prognostic significance of the pre-ASCT PET scan. The relative change in SUVmax and TMTV were similarly not associated with PFS and OS. These findings indicate that in the context of TMTV and SUVmax measurement, residual disease on pre-ASCT PET may be of greater predictive value than degree of response to salvage immuno-chemotherapy. While TMTV and SUVmax have primarily been studied in the context of first-line therapy for DLBCL, these results suggest a promising prognostic role for these PET parameters in the peri-transplant setting. Disclosures Seymour: AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; F. Hoffmann-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Consultancy; Nurix: Honoraria; Mei Pharma: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria. Dickinson:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck Sharp & Dohme: Consultancy; Gilead: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals A Phase I Trial of Venetoclax in Combination with BEAM Conditioning Chemotherapy (V-BEAM) with Autologous Stem Cell Transplantation in Non-Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5705-5705
Author(s):  
Allison M. Winter ◽  
Kirsten M Boughan ◽  
Jack Khouri ◽  
Paolo Caimi ◽  
Faiz Anwer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Dose Level ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Advisory Committees ◽  
Level 2

Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is a standard treatment both as consolidation after induction chemotherapy and as second-line therapy depending on the histologic subtype of NHL. BEAM (BCNU, etoposide, cytarabine, and melphalan) is a commonly used conditioning regimen for NHL but often fails to produce durable remission, likely due to inherent chemoresistance. Many B-cell NHL subtypes including diffuse large B-cell lymphoma and double-hit lymphoma are resistant to chemotherapy-induced apoptosis by overexpression of Bcl-2. Venetoclax is an orally administered selective Bcl-2 inhibitor with significant single agent activity in CLL and mantle cell lymphoma. In addition, the efficacy of venetoclax is potentiated by combination with rituximab [Seymour 2018, Kater 2018] and multiple lines of preclinical data show synergistic efficacy with a range of both novel and conventional antineoplastic agents [Johnson-Farley 2015, Li 2015]. Study Design and Methods: This is a single arm, open-label, dose-escalation phase I trial to evaluate the safety of venetoclax in combination with BEAM (V-BEAM) conditioning chemotherapy. Key inclusion criteria include patients with pathologically confirmed NHL, regardless of specific histology, who have received one prior systemic therapy and are eligible for and proceeding with HDCT followed by ASCT. The trial employs a standard 3+3 cohort-based dose escalation design of venetoclax (800 mg daily days -7 through -6 on dose level 1, 800 mg daily days -7 through -5 on dose level 2, 800 mg daily days -7 through -4 on dose level 3, 800 mg daily days -7 through -3 on dose level 4, and 800 mg daily days -7 through -2 on dose level 5) with standard doses of BEAM followed by ASCT. The primary objectives are to assess safety, describe dose-limiting toxicities, engraftment of stem cells and to identify the recommended phase II dose. Secondary objectives include evaluation of progression-free survival (PFS) and overall survival (OS) compared to historical controls treated with BEAM as part of ASCT. Neutrophil and platelet engraftment will be estimated with cumulative incidence and compared to controls with Gray test. OS and PFS will be estimated with Kaplan-Meier and compared to controls with the log-rank test. As of 8/1/2019, the first dosing cohort of 3 patients have been enrolled and successfully completed study treatment. There are 3 patients in screening to be enrolled in dose level 2. Additional accrual will be presented at the time of the meeting. Clinical trial information: NCT03713580. Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Gerds:Celgene Corporation: Consultancy, Research Funding; Sierra Oncology: Research Funding; Pfizer: Consultancy; Incyte: Consultancy, Research Funding; CTI Biopharma: Consultancy, Research Funding; Roche: Research Funding; Imago Biosciences: Research Funding. Majhail:Nkarta: Consultancy; Atara Bio: Consultancy; Mallinckrodt: Honoraria; Incyte: Consultancy; Anthem, Inc.: Consultancy. Hill:TG therapeutics: Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Research Funding; Kite: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria; Takeda: Research Funding; Amgen: Research Funding. OffLabel Disclosure: Our trial in progress is investigating the use of venetoclax in combination with BEAM conditioning chemotherapy prior to autologous stem cell transplantation. Venetoclax is not currently approved in this setting.

scholarly journals Depth of Response and Outcomes in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4619-4619 ◽  
Author(s):  
Gunjan L. Shah ◽  
Kenneth Seier ◽  
Sean M Devlin ◽  
David J. Chung ◽  
Michael Scordo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Partial Remission ◽  
Research Funding ◽  
Advisory Committees ◽  
Depth Of Response

Abstract Background: For multiple myeloma (MM) patients, depth of response after induction therapy and after autologous hematopoietic stem cell transplantation (AHCT) has been shown to be important for progression free (PFS) and overall survival (OS) in some studies. Furthermore, the impact of minimal residual disease (MRD) on outcomes and treatment decisions has been widely discussed. We aimed to evaluate outcomes by depth of response after induction and AHCT. Methods: MM patients who received their first AHCT within 1 year of starting induction were identified from the institutional registry. MRD was assessed by non-10 color flow cytometry. Response was defined by the International Myeloma Working Group criteria. Summary statistics were used to describe the population. Kaplan-Meier methodology estimated PFS and OS by response status pre-AHCT and at post-AHCT restaging. Results: Between 2012 - 2014, 182 MM patients met our inclusion criteria, with 83% alive at last follow-up. The median age at AHCT was 60 years (range 29-76) with 57% male. By the International Staging System (ISS), 50% were stage I, 26% stage II, and 24% stage III. High risk cytogenetics were detected in 24%. Isotype was IgG in 55%, IgA 21%, Kappa Free Light Chain (KFLC) 11%, and lambda FLC (LFCL) 9%. First induction therapy included bortezomib in 90% and lenalidomide in 79%. Median time to AHCT was 5.5 months (range 2.8-11.7). The median follow-up from AHCT was 3.7 years (range 0.22 - 4.6 years), with 84% of patients receiving lenalidomide maintenance, and 9% receiving an additional autologous or allogenic transplant at relapse. Response prior to the initial AHCT was a complete remission (CR) in 13.7% (MRD negative 6.6%, positive 4.4%, unknown 2.7%), very good partial remission (VGPR) 38%, partial remission (PR) 40%, stable disease (SD) 5%, and progressive disease (PD) 4%. At post-AHCT restaging, responses had improved to 42% CR (MRD negative 23%, positive 6%, unknown 13%), 35% VGPR, 19% PR, 2% SD, and 3% PD. Median PFS from AHCT for the entire cohort was 3.2 years (95% CI 2.4 - 4 years) with 1-year and 3-year PFS 85% and 52%, respectively. Median OS was not reached (NR) (95% CI 4.4 years - NR) with 1-year and 3-year OS 97% and 88%, respectively (Figure 1). PFS from AHCT was significantly longer in patients with an MRD negative CR prior to AHCT with median PFS not reached (95% CI 1.7 - NR) compared to MRD positive/unknown CR, VGPR, and ≤ PR [3.64 years (95% CI 1.09-3.64), 3.46 years (95% CI 2.4 - NR), and 2.44 years (1.68-3.56 years), respectively, p=0.048] (Figure 2A). From post-AHCT restaging, PFS was also significantly longer in patients with an MRD negative CR prior to AHCT with median PFS not reached compared to MRD positive/unknown CR, VGPR, and ≤ PR [3.49 years (95% CI 0.86-3.49), 3.56 years (95% CI 2.5 - NR), and 2.4 years (1.6-3.33 years), respectively, p=0.026] (Figure 2B). However, there was no difference in PFS based on the post-AHCT restaging with median PFS in MRD negative CR, MRD positive/unknown CR, VGPR, and ≤ PR of 3.49 years (95% CI 2-NR), not reached (95% CI 1.4-NR), 2.96 years (95% CI 1.7-NR), and 2.86 years (95% CI 1.7 - NR) (p=0.78, Figure 2C), respectively. OS from AHCT was not significantly different by pre-AHCT response, and the median was not reached in any group (p=0.33, Figure 3A). Finally, the median OS from post-AHCT restaging by pre-AHCT response or by post-AHCT response was also not reached in any group (p=0.32 and 0.31, respectively; Figure 3B & C). Conclusion: For MM patients, AHCT deepened responses and increased the CR rate. We were unable to show a significant difference in outcomes at post AHCT restaging, which may be due to the effect of maintenance therapy, the small numbers of MRD negative patients, or the sensitivity of the MRD assay available during this time period, though potentially show that MRD positive patients do as well as MRD negative patients after AHCT. We plan to add additional patients treated in the more recent years who were assessed by more sensitive methods. Disclosures Shah: Janssen: Research Funding; Amgen: Research Funding. Korde:Amgen: Research Funding. Lesokhin:Janssen: Research Funding; Genentech: Research Funding; Takeda: Consultancy, Honoraria; Serametrix, inc.: Patents & Royalties: Royalties; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Squibb: Consultancy, Honoraria. Mailankody:Janssen: Research Funding; Physician Education Resource: Honoraria; Takeda: Research Funding; Juno: Research Funding. Smith:Celgene: Consultancy, Patents & Royalties: CAR T cell therapies for MM, Research Funding. Landgren:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

scholarly journals Prospective Analysis of Bortezomib, Fludarabine and Melphalan As Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1020-1020
Author(s):  
Phyllis McKiernan ◽  
David S Siegel ◽  
David H. Vesole ◽  
Tracy Andrews ◽  
Noa Biran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Research Funding ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Significant Difference ◽  
Grade 3

Abstract Background: Despite advances in novel myeloma treatments and autologous hematopoietic stem cell transplantation (ASCT), allogeneic HSCT (alloSCT) remains the only curative option for patients (pts) with multiple myeloma (MM). Questions remain as to the timing of alloSCT, toxicity risks and optimal conditioning regimen. The addition of bortezomib (Vel) to fludarabine (Flu) and melphalan (Mel) for conditioning prior to alloSCT is based on the demonstrated safety of Vel in combination with melphalan prior to ASCT, the synergistic effect of Vel with Mel, and the ability of Vel to selectively eliminate allo-reactive T-cells. Methods: We present a prospective Phase II study using Flu/Mel/Vel (FMV) as a conditioning regimen for alloSCT. The primary endpoint is overall survival (OS), and secondary endpoints include progression free survival (PFS), incidence of graft-versus-host disease (GVHD) and transplant related mortality (TRM). For related donors, the conditioning regimen was Flu 30 mg/m2 days -5, -4, -3, -2, Vel 1.6 mg/m2 days -4, -1, Mel 140 mg/m2 day -2. For unrelated donors, rabbit ATG 4 mg/kg was given in divided doses days -3, -2, -1. GVHD prophylaxis consisted of methotrexate and tacrolimus. We compared pts receiving FMV to historical controls of pts receiving FM at the same dose and schedule without Vel. We also compared pts receiving FMV to all pts with MM treated with alloSCT including all regimens and donor types. The response criteria from the IMWG and M-Smart criteria were used to determine response and risk, respectively. Chi-square tests of association and Wilcoxon rank sum tests were performed to test for differences across groups. OS/PFS probabilities were calculated using the Kaplan-Meier product limit estimator with log rank-tests. Multivariate Cox proportional hazard models examined factors associated with OS/PFS. Results: Of the 54 pts who received FMV, 35 (65%) were male and the median age was 56 years. Twenty-seven pts had an HLA matched sibling donor and 27 had an unrelated donor. At the time of alloSCT, 5 pts were in a CR, 27 in a VGPR, 13 in a PR, 9 had < PR. Twenty eight pts (52%) had high risk disease. Twenty-nine pts (53%) received alloSCT as salvage, defined as relapsed or refractory to ASCT, and 25 pts (46%) as consolidation after ASCT. OS was 42% at 10 years. While 32 pts developed aGVHD, only 2 had ≥ Grade 3. Of the 31 pts who developed cGVHD, 23 were graded as extensive. TRM was 5% at day 100, and 15% over 10 years. Pts in the control groups had similar baseline characteristics to the FMV group. The only significant difference was 47 pts (72%) who received FM were transplanted as salvage, and 18 (28%) as consolidation after ASCT (p=0.035). The total number of pts who did not receive FMV (non FMV) was 121, with 66 pts receiving FM. Compared to pts who received FMV, there was no difference in OS for pts who received FM or the non FMV group, 35% (p=0.55) and 48% (p=0.855) respectively. There was no difference in pts who developed aGVHD, however 9 pts (13%) had ≥ grade 3 aGVHD in the FM group (p=0.004) and 15 (12%) in the non FMV group (p=0.006). The cumulative incidence of cGVHD was similar with 51% for pts receiving FM and 60% for FMV pts (p=0.32). TRM was similar to pts who had received FMV; 18% for FM and 17% for non FMV. There were no differences between the 3 groups across disease risk, donor type, or disease status at the time of alloSCT. Multivariate analysis of the 3 groups, shows achieving a CR after alloSCT (p=0.0006) or having cGVHD (p=0.0004) predicts for improved OS, while severe aGVHD (p=0.0002) predicts for decreased OS. Discussion: While FMV was associated with a lower incidence of severe aGVHD, the addition of bortezomib to the FM backbone did not improve PFS or OS. Day 100 TRM was low for all regimens, and the addition of Vel did not impact overall TRM. For all 175 pts, those who achieve a CR after alloSCT had a significantly improved OS. This prompts the question of whether strategies should be employed post alloSCT to maximize response to a CR, and the role of achieving MRD negativity after alloSCT also needs to be elucidated. Figure Figure. Disclosures Siegel: BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Biran:Amgen: Consultancy, Speakers Bureau; BMS: Research Funding; Merck: Research Funding; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Skarbnik:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

scholarly journals Hospital in the Home Delivery of Supportive Care for Autologous Stem Cell Transplantation: A Novel Single Centre Patient Focused Approach

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1834-1834
Author(s):  
David Routledge ◽  
Simon J Harrison ◽  
Trish Joyce ◽  
Seok Lim ◽  
Michael Montalto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Supportive Care ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Advisory Committees ◽  
Royal Melbourne Hospital ◽  
Bed Days

Abstract Introduction: High dose therapy with Autologous Stem Cell Transplantation (ASCT) has traditionally been performed as an inpatient procedure. However, with improvements in care and patient selection it is possible to safely deliver conditioning chemotherapy and supportive care in an Daytherapy setting (Kodad SG et al., 2019). While deemed an "outpatient procedure" this method is often delivered on large day units which requires the patient to attend daily, often only spending overnight at home. To reduce these daily visits the Clinical Haematology Department of Peter MacCallum and Royal Melbourne Hospital (CHD) in collaboration with the Hospital in the Home department (HIHD) at Royal Melbourne Hospital developed an innovative program to safely deliver supportive care for Myeloma Patients undergoing ASCT at home (HIH-ASCT). The HIHD is an acute inpatient unit that exists as a "virtual" inpatient ward. Patients are reviewed daily by a HIHD Doctor with twice daily visits by a HIHD Nurse for administration of supportive care measures (e.g. intravenous electrolyte and fluid replacement) in the comfort of their home. Here we report on the safety outcomes of our HIH-ASCT program, specifically patient complications and outcomes. Methods: A retrospective case note audit identified 54 consecutive HIH-ASCT patients who received HIH-ASCT for Myeloma between 2018 and 2021 under HIHD. Patients were eligible for our HIH-ASCT program if they had Myeloma requiring ASCT; an ECOG ≤1; had not been admitted to ICU previously; lived within 30 minutes drive of the hospital; had a safe home environment (for both the patient and visiting staff) and a carer who could stay with them throughout their HIH-ASCT. While undertaking HIH-ASCT patients did not receive prophylactic antibiotics and they were not routinely given GCSF to minimise the risk of engraftment fevers. Results: Of those treated as HIH-ASCT patients the median age was 60 years (range 33-72). 39% patients were female (n=21) and 61% male (n=33). Underlying disease groups included IgA (n=8; 15%), IgG (n=35; 64%), IgM (n=1; 2%), Light Chain (n=9; 17%) and Oligosecretory (n=1; 2%). 43% had High-risk Cytogenetics. ASCT-1 (n=48; 88%), ASCT-2 (n=5; 9%) and one patient underwent a ASCT-Tandem (both under HIHD). Conditioning regimes included Melphalan200 (n=37; 68%), Velcade-Melphan200 (n=13; 23%) and Carfilzomib-Melphalan200 (n=5; 9%). The average stem dose was 3.80 x10 6/kg (range 2.14-8.4). Median time to Neutrophil engraftment was 12 days (range = 10-21) and Platelet engraftment 12 days (range = 8-18). The total number of bed days saved through the HIH-ASCT program was 466, with a median length of stay (LOS) under the HIHD team of 9 days (Range = 3-14). In addition, 3 patients were not readmitted to the hospital (6%) and were discharged directly from the HIHD team. The most common reason for readmission was fever (n=43; 80%), of which only 11 were culture positive, and diarrhoea (n=44; 81%). Only 1 patient required intensive care support. There were no deaths. The median LOS as an inpatient once readmitted was 6 days (range = 2-27). In regards to cost savings, an acute inpatient bed under the CHD is approximately $1300 USD versus $900 USD per day for a HIHD bed. This equated to a potential cost saving for the CHD of approximately $186000 USD. Conclusion: The delivery of supportive care for patients undergoing HIH-ASCT in is both safe and effective with comparable outcomes for what would be expected for an inpatient cohort. It resulted in a median of 9 bed days saved per patient (total number of bed days saved = 466). This is important as it allowed our department to increase bed capacity across the unit without the associated costs of building a new ward. In addition, during our COVID-19 outbreaks the HIH-ASCT program has allowed us to continue to deliver optimal patient care, while minimising the infection risk for our patients. More recently we have introduced remote monitoring (e.g. temperature, heart rate, blood pressure and oxygen saturations) with video reviews with the aim of increasing the capacity of our HIHD and further improving the HIH-ASCT experience for our patients. Disclosures Routledge: Amgen: Honoraria, Speakers Bureau; Sandoz: Consultancy, Honoraria, Speakers Bureau; BMS: Honoraria. Harrison: Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusa: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/ Juno/ BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Terumo BCT: Consultancy, Honoraria; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ritchie: CRISPR Therapeutics: Research Funding; Amgen Inc: Honoraria, Research Funding; Novartis: Honoraria; CSL: Honoraria; BMS: Research Funding; Takeda: Research Funding.

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