Single Autologous Stem Cell Transplantation Research Articles

Salvage High-dose Melphalan With Autologous Stem cell Transplantation as Bridge to Consolidation Therapy for Chemoresistant Aggressive B-cell Lymphoma

BackgroundPatients suffering from refractory aggressive B-cell lymphoma not responding to salvage chemotherapy have a dismal prognosis. CAR T-cells or allogeneic stem cell transplantation (SCT) are potentially curative approaches. However, obtaining a remission, and lowering tumor burden before consolidation seems crucial for long-term efficacy of both treatment modalities. Materials and MethodsIn this retrospective analysis, we reviewed patients with chemoresistant aggressive B-cell lymphoma, defined as being refractory or progressive to at least second line salvage chemotherapy including the regimen immediately preceding autologous stem cell transplantation (ASCT), treated at 2 tertiary centers, who were eligible for intensive treatment using single agent high-dose (HD) melphalan to obtain a remission before consolidating therapy. ResultsWe identified 36 patients that received single agent HD melphalan and ASCT as remission induction followed by CAR T-cells or allogeneic stem cell transplantation (SCT). Thirteen of the evaluable patients (39.4%) achieved a partial remission and 9 patients (27.73%) a complete remission, resulting in an overall response rate (ORR) of 66.7%. High remission rates were seen across all subgroups including patients with primary refractory lymphoma (ORR 58.3%), uncontrolled disease and high tumor burden as indicated by increased LDH levels (ORR 66.7% for patients with elevated LDH above 2 times upper limit of norm). 22 patients proceeded to allogeneic SCT and 5 to CAR T-cell therapy. Treatment related mortality of ASCT was 5.5% (2 patients, both due to infections). Two-year overall survival of all patients was 15.8%, primarily due to a high non–relapse mortality (45.5%) of allogeneic SCT patients treated with myeloablative conditioning chemotherapy. ConclusionSingle agent HD melphalan produces high remission rates in patients with chemoresistant, uncontrolled aggressive B-cell lymphoma and provides a window of opportunity for consolidation therapy. MicroabstractPatient with refractory/relapsed aggressive B-cell lymphoma after salvage therapy are an unmet medical need because of their very poor prognosis. In our retrospective analysis of 36 patients we showed that single agent high-dose melphalan can achieve high response rates (ORR 66.7%) even in uncontrolled disease enabling consolidation therapy e.g. with allogeneic stem cell transplantation or CAR T-cell therapy.

Analysis of the efficacy of autologous peripheral blood stem cell transplantation in high-risk neuroblastoma.

Objective: This study aimed to analyze the efficacy of autologous peripheral blood stem cell transplantation for high-risk neuroblastoma in China.Methods: The data of 90 high-risk neuroblastoma patients treated with the CCCG-NB 2015 regimen were reviewed. The baseline clinicopathological characteristics and prognosis were analyzed and compared. In addition, the prognoses of tandem autologous stem cell transplantation and single autologous stem cell transplantation groups were compared.Results: The results of survival analysis showed that autologous peripheral blood stem cell transplantation based on this pretreatment regimen significantly improved the prognosis of children in the high-risk group. The 3-year event-free survival (EFS) and overall survival (OS) rates for the transplantation group and the nontransplantation group were 65.5% vs. 41.3% (p=0.023) and 77.1% vs. 57.9% (p=0.03), respectively. There was no difference in the distribution of baseline clinical case characteristics between the single transplantation group and the tandem transplantation group (p>0.05), and there was no significant difference in EFS and OS between the two groups (p>0.05).Conclusion: Based on this pretreatment programme, autologous peripheral blood stem cell transplantation is safe and tolerable and significantly improves the prognosis of children in the high-risk group. The value of tandem autologous stem cell transplantation is worthy of further discussion, which should consider various aspects such as the transplantation medication regimen and the patient's state.

Outcomes of Single Versus Tandem Hematopoietic Stem Cell Autologous Transplant in High-Risk Myeloma Patients: A Single-Center Experience

Introduction: Over the past decade, significant advances in the treatment strategy of newly diagnosed multiple myeloma patients (NDMM) have challenged the initial management strategy in transplant-eligible (TE) patients. The value of a single autologous stem cell transplant (ASCT) is established in standard-risk myeloma; however, the role for tandem ASCT reveals conflicting results, especially in patients with high-risk cytogenetic (HR) features. HR changes include at least one of the cytogenetic lesions: t(4;14), t(14;16), t(14;20), del17p, 1q amp +, 1q amp + del 1p. Subgroup analyses of HR patients in the EMN02 study suggest benefits with tandem ASCT.Methods: We retrospectively reviewed our single centre ASCT experience in TE NDMM patients with HR from London, Canada, from January 1, 2007, to April 30, 2021 with the primary objective to compare single versus tandem ASCT for patients with high-risk MM. Secondary objectives include progression-free survival (PFS), overall survival (OS) and the effect of maintenance therapy on survival. OS and PFS were estimated using the Kaplan-Meier method. We also applied univariate and multivariate cox regression to assess the effects of age, hemoglobin, and creatinine on survival.Results: 155 NDMM received at least one ASCT between January 1, 2007 to April 30, 2021. 61/155 (39.3%) patients had HR disease. T(4:14) was seen in 19/61 (31.1%) patients; t(14:16) in 9/61 (9.8%) patients; del 17p in 20/61 (32.7%) patients, 1q amp in 36/61 (59.0%) patients and 1p del + 1q amp in 8/61 (13.1%). Patients with more than one abnormality was seen in 22/61 (36.0%) patients. In this high-risk group, the most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in 58/61 patients (95.0%). 34 (55.7%) patients received single ASCT and 27 (44.2%) patients received tandem ASCT. 18/34 (52.9%) single ASCT patients and 15/27 (55.5%) tandem ASCT patients received maintenance therapy. Maintenance therapy included single-agent lenalidomide (imid) in 14/61 (22.9%); single-agent bortezomib or ixazomib (proteasome inhibitor (PI)) in 8/61 (13.1%), and; imid + PI combination in 11/61(18.0%). Baseline characteristics are summarized in Table 1.Single versus tandem ASCT in HR patients revealed no statistically significant PFS difference at 60 months (p=0.3). Maintenance therapy demonstrated a substantial improvement in PFS regardless of the number of ASCT (single ASCT HR=0.1687, 95% CI range 0.05-0.52, p<0.001) tandem ASCT (HR=0.1319, 95% CI range 0.01-0.96, p=0.019). PFS was similar in patients who did not receive maintenance in tandem ASCT (20 months) or single ASCT (19 months) (p=0.57).At the 60-month follow-up, the median PFS for high-risk patients without maintenance was 18.8 months. In contrast, the PFS for patients on maintenance was not reached (HR=0.1446, 95% CI range 0.05-0.38, p<0.001). There was no difference in OS (p=0.38) with or without maintenance therapy. When comparing single-agent vs. combination strategy with maintenance, there was no PFS (p=0.47) or OS (p=0.68) difference between strategies. All patients were progression-free in those who received any maintenance at 60 months.Conclusion: In our single centre experience, single vs. tandem ASCT in TE NDMM with HR disease did not contribute to long-term survival outcomes, but the presence of any maintenance therapy had a more considerable impact on PFS. Our data does show a longer progression-free survival compared to previous published data, which is likely due to our sample size. [Display omitted] DisclosuresLam: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Amgen: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

Impact of Daratumumab-Containing Induction on Stem Cell Mobilization and Collection, Engraftment and Hospitalization Parameters Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Introduction: Advances in induction regimens have significantly improved depth of response and duration of remission in multiple myeloma (MM) patients who are eligible for high-dose therapy and autologous stem cell transplantation (ASCT). Proteasome inhibitor-based induction regimens are standard as part of induction and it has been shown not to have any detrimental effect on stem cell (SC) collection and engraftment. Daratumumab (DARA) is an IgG1k monoclonal antibody directed against CD38 with potent antimyeloma activity. Based on the results of prospective studies DARA is now approved as part of induction therapy. Available data indicate a potential impact of DARA on SC collection but there is limited data on engraftment, duration of hospitalization and infection risk. In this retrospective analysis we evaluated the effect of DARA-based induction on ASCT parameters.Methods: The analysis included consecutive newly diagnosed MM patients that received ASCT between 2016 and 2020, as part of their upfront treatment regimen in our institution (Department of Clinical Therapeutics, Athens, Greece). Per institutional protocol, after 4-6 cycles of induction, pts received low dose cyclophosphamide (2.5 g/m2) followed by G-CSF (10 mcg/Kg/day) to mobilize and collect SCs. Plerixafor was administered on-demand in case of poor mobilization and insufficient first day collection. Large volume leukapheresis was performed in pts with low CD34+ counts in order to increase CD34+ yield. Pts received G-CSF 480 μcg once daily from day +4 after SC reinfusion to ANC >1500/mm3. All pts received antiviral and antifungal but no anti-bacterial prophylaxis.Results: 200 eligible pts were included in the analysis; 40 (20%) pts received DARA as part of PI-based upfront treatment and 160 (80%) pts received PI-based upfront treatment without DARA. Baseline demographics (age, gender, performance status) and disease characteristics (ISS and R-ISS stage, cytopenias, eGFR, lytic bone disease etc) were not different between the two groups. Response after induction was also similar (CR+VGPR rate was 93% vs 95% for non-DARA and DARA-containing regimens respectively).Use of DARA at induction was associated with lower total mean number of collected CD 34+ SCs (10.48 x 10^6/kg vs 16.58 x 10^6/kg, p<0.0001), or SC collection on day 1 (7.99 x 10^6/kg vs 16.27 x 10^6/kg, p<0.0001). Fewer pts in the DARA-treated group achieved the planned yield of at least 5 X 10^6 CD34+/kg, compared to DARA-untreated group (87.5 % vs 96.2%, p=0.047). DARA-treated pts required more often additional SC mobilization with on demand administration of plerixafor (42.5% vs 7.6%, p<0.0001). In order to compensate for a poorer mobilization and lower quality graft (CD34% 0.66% vs 1.26% in apheresis product, p<0.0001) DARA-treated group underwent more often >1 day of SC collection (37.5% vs 6.3%, P <0.0001), resulting in longer duration of collections (689 vs 452 min, p<0.0001) and larger total apheresis volumes (723 vs 557 ml, p<0.0001). However, 97% and 98% of pts in the two groups respectively were able to move to at least a single ASCT. Following ASCT, DARA-treated pts had a slightly delayed hematopoietic recovery (11 vs 10 days to PMN>500/mm3, p<0.001 and 12 vs 11 days for PLT counts> 25x10^9/mm3, p<0.001) and required more transfusions (2 vs 1 for RBCs, p=0.031 and 4 vs 2 for platelets, p<0.001). Rates of neutropenic fever were higher (80% vs 67%, p=0.182), required antibiotics for longer duration (10 vs 8 days, p=0.042) and more often 2 or more lines of antibiotic therapy (53% vs 39%, p=0.003), experienced more often septic shock (12.5% vs 1.3%, p=0.003) and as a results DARA-treated pts had a slightly prolonged hospitalization (21 vs 19 days, p=0.02). However, D100 mortality was not statistically different (<2% in both groups).Conclusion: DARA-containing induction before ASCT is associated with poorer mobilization and frequent need for use of plerixafor. However, similar percentage of patients can move to at least a single ASCT. The use of DARA-containing induction was also associated with slightly increased risk of infectious complications, antibiotics use and blood product transfusions but no increase in the risk of D100 mortality. These data point to the need for certain modifications to ASCT protocol for patients treated with DARA-containing regimens at induction, such as preemptive use of plerixafor, and perhaps prophylactic antibiotics. DisclosuresTerpos: Amgen: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Gavriatopoulou: Takeda: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; BeiGene: Honoraria. Kastritis: Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Janssen: Consultancy, Honoraria, Research Funding.

Myeloma Patients with Deletion of 17p: Impact of Tandem Transplant and Clone Size

IntroductionThe presence of deletion 17p or monosomy 17 (del(17p)/-17) detected by fluorescence in situ hybridization (FISH) is well-established as a high-risk (HR) factor in multiple myeloma (MM). The del(17p)/-17 clone size and the clinical impact in patients that have ≥60% involved nuclei is controversial. Optimal treatment is also controversial, with tandem autologous stem cell transplantation (ASCT) explored but not uniformly adopted in the real world (ENM02, StaMMina). At our center, we have routinely offer tandem transplantation for del(17p)/-17 and now review our experience over a 10-year period, including the significance of del(17p)/-17 genetic variations on outcomes.MethodsWe performed a retrospective chart review of all patients identified with del(17p)/-17 patients who were offered tandem transplant and underwent at least one ASCT at Princess Margaret Cancer Centre from 2009-2019. Patient and disease characteristics, responses, and survival outcomes were collected from the Myeloma and Transplant databases and electronic patient records under REB approval.ResultsPatient, disease, and treatment characteristics.We identified 100 patients with del(17p)/-17 who underwent ASCT at our center. These patients were separated into three groups: those with a deletion of the TP53 locus (57%), those that had monosomy 14 (17%), and those with a relative loss the TP53 locus (eg. aneusomy or polyploidy,13%). The median % of nuclei with del(17p) was 39% (range 5-93%), with 27 (25%) over 60%. 28% of patients carried at least one other cytogenetic abnormality besides del(17p), most commonly t(4;14). All patients were intended for tandem transplant, but only 69 (69%) completed both transplants. Reasons for not proceeding to a second transplant were: patient declined (29%), toxicity (26%), clinical trial (19%), progression prior to the second transplant (13%), with one early death (3%). Median age at transplant was 61 years (range 40-72); most were male (61%) with advanced R-ISS II and III (97%).The most common induction regimen used was cyclophosphamide, bortezomib and dexamethasone (CYBORD)(87%), with 10% requiring a 2 nd induction regimen for inadequate response/progression. Standard conditioning was melphalan 200mg/m 2 for both first and second transplants. Median time from diagnosis to first ASCT was 5.9 months (range 3-24) and time from first to second transplant was 3.3 months (range 1-7). Most patients (90; 84%) received maintenance therapy post-transplant: 47% lenalidomide, 29% multiple agents (commonly lenalidomide and a proteasome inhibitor)Response and survival outcomesAfter induction, the rate of VGPR (very good partial response) or greater was 53%, increasing to 73% after 1 st ASCT, 85% after 2 nd ASCT. At a median follow-up of 32 months (range 3-130), the median PFS for all patients was 39.2 months 95% CI (24.1-46) and median OS was not yet reached (NYR) (95% CI 57.9-NYR). When analyzed by whether single or tandem transplant was performed, median PFS was 21.8 months (95% CI 10.3-43.3) for single ASCT, and 42.1 months (95% CI 32.8-NYR) for tandem ASCT (P=0.0096). The median OS was 57.6 months for single ASCT (95% CI 22.2-86.5), but NYR for tandem ASCT (95% CI 105.6-NYR) (p=0.0022).On subgroup analysis, patients with ≥60% del(17p) achieved a median PFS 45 months (95% CI 14.4-NYR) and median OS 68.5 months (95% CI 20.9-68.5), median was only PFS 24.9 months (95% CI0.4-NYR) and median OS 29.3 months (95% CI 0.4-68.5) for those who received single ASCT. (table1)TP53 signal pattern analysis (table 2) showed the median OS for patients with monosomy 17 was NYR, while it was 105.7 months for patients with deletion, and 86.5 months for those with relative loss. Median PFS was 43.3 months for the monosomy group, 32.8 months for deletion group, and NYR for relative loss.ConclusionsOur experience shows that MM patients with del(17p)/-17 appear to have deeper responses and improved outcomes with more aggressive tandem transplantation. However, approximately 1/3 of our patients intended for tandem transplant did not undergo a second transplant, identifying a focus of future investigation and optimization. Our analysis also suggests that clone size of del(17p) >60% does impact OS negatively, but improved with tandem transplantation. The type of deletion also appears to affect outcomes with deletion having worse PFS but not worse OS. [Display omitted] DisclosuresPrica: Astra-Zeneca: Honoraria; Kite Gilead: Honoraria. Reece: Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Millennium: Research Funding; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Karyopharm: Consultancy, Research Funding; GSK: Honoraria. Trudel: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Roche: Consultancy; Sanofi: Honoraria; Pfizer: Honoraria, Research Funding. Chen: Beigene: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy.

Sustained MRD Negativity Might Predict Successful Maintenance Discontinuation in Patients with Transplant-Eligible NDMM

Background: Multiple myeloma is still an uncurable plasma cell malignancy. Maintenance plays an important role in the MM therapy for decreasing the probability of disease progression. However, prolonged maintenance therapy inevitably brings economic burdens and toxicities to the patients and families. Minimal residual disease (MRD) directed maintenance discontinuation might balance the disease progression and the toxicities. This study aimed to compare the risk of disease progression after maintenance discontinuation between transplant-eligible patients with and without achieving sustained MRD negativity for at least 2 years since post-induction.Methods: One hundred and fifty-seven consecutive patients with newly diagnosed multiple myeloma who had received bortezomib based induction and subsequent single autologous stem cell transplant (ASCT) between 2008 and 2018 in our institute were enrolled. Patients discontinued maintenance was identified during regular follow-up. These patients were then follow-up every 6-12 months until disease progression.Results:Twenty-five patients discontinued their maintenance therapy at the median of 29.3 months post-transplant because of intolerability. For these 25 patients, the median age was 50 years old (range 35-68), and 19 (76%) were male and 6 (24%) were female. The frequencies of IgG, IgA, IgD and light-chain-only subtype of MM were 6 (24.0 %), 7 (28.0 %), 1 (4.0 %) and 11 (44.0 %) patients, respectively. There were 10 (40.0 %), 7 (28.0 %), 8 (32.0 %) patients with ISS stages of 1, 2, and 3, respectively. High-risk iFISH was defined as 17p deletion-positive and/or t (4;14)-positive and/or t (14;16)-positive. Fifteen (60.0 %), four (16.0 %) and six (24.0 %) patients had high-risk, standard-risk and missing iFISH, respectively.With the median follow-up time of 25.4 months after discontinuation, the cumulative disease progression rate was 35%±11% at 2 years after discontinuation (Fig1). Among the 16 patients who had received MRD monitoring since post-induction and thereafter every 3-6 months, 9 achieved sustained MRD negativity since post-induction and maintained for at least 2 years after the transplant. None of these 9 patients had disease progression.No significant difference on age, sex, ISS staging, LDH level and high-risk cytogenetic rate was found between patients with and without sustained MRD negativity. The log-rank analysis showed that patients achieving sustained MRD negativity for at least 2 years since post-induction had significantly lower 2-year disease progression rate after maintenance discontinuation (0% vs. 78.6±17.8%, median time to PD since discontinuation were not reached vs. 14.3 months, as shown in Fig 2).Conclusion: sustained MRD negativity since post-induction and maintained at least 2 years after transplant might predict successful maintenance discontinuation in patients with transplant-eligible NDMM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

Stem Cell Collection with Daratumumab (DARA)-Based Regimens in Transplant-Eligible Newly Diagnosed Multiple Myeloma (NDMM) Patients (pts) in the Griffin and Master Studies

OAB-058: Predictive relevance of sustained MRD negativity and of early loss of MRD negativity during maintenance therapy after transplant in newly diagnosed Multiple Myeloma patients

<h3>Background</h3> sustained MRD negativity is emerging as a surrogate biomarker of patients (pts)' outcome in clinical trials. We implemented this tool in our clinical practice and we analyzed outcome according to sustained MRD negativity in MM pts treated with autologous stem cell transplantation (ASCT) at our Institution. <h3>Methods</h3> We retrospectively analyzed the outcome of 77 newly diagnosed MM pts (median age 61 years) diagnosed between January 2015 to December 2019 in ≥ VGPR after ASCT. Bone marrow samples were collected for MRD by 8-color FCM (Sn 10-5) at day +100 after ASCT, before maintenance. Sustained 1 year MRD negativity was also evaluated and the prognostic impact of MRD status on PFS and OS was analyzed. <h3>Results</h3> out of 77 pts, 28 (36%) were ISS stage 3 and 18 (23%) showed high risk cytogenetics. Patients were treated with the following induction regimens: VTD 51, VRD 5, Dara-VRD 5, KRD 14, KCD 2. Single ASCT with MEL200 conditioning was performed in 49 pts (64%), whereas 28 pts (36%) received double ASCT. Subsequent maintenance was performed with lenalidomide (70), daratumumab-lenalidomide (5), carfilzomib-lenalidomide (2). Response rates were VGPR 26%, CR 61% and sCR 13%. MRD before maintenance was positive in 20 pts (26%) and negative in 57 (74%). Sustained MRD negativity lasting ≥ 1 year was documented in 49 pts (64%), whereas early loss of MRD negative status was observed in 8 (10%) of cases. After a median follow up of 40.2 months, PFS was significantly longer in pts with sustained MRD negativity (≥1 year) compared to MRD positive patients before maintenance: median NR vs 41.4 months, p 0.0002, HR 0.17 (0.044-0.65). The worst PFS (24.7 months) was observed in pts with early loss of MRD negativity (<1 year) and was significantly inferior if compared both to pts with sustained MRD negativity (p<0.0001, HR 0.06; 0.01-0.54) and to MRD positive pts before maintenance (p 0.03, HR 0.35; 0.11-0.16), with significantly different outcome of the three subgroups (p<0.0001). Different OS trend was also observed among the three subgroups: NR in sustained MRD negative pts, 58.5 months in MRD positive pts and 35.3 months in pts with early loss of MRD negativity (p<0.0001), although OS difference between sustained MRD negativity (≥ 1 year) and MRD positive pts was not statistically significant on a direct comparison (p 0.054). The worst OS observed in pts with early loss of MRD negativity (<1 year) was significantly inferior if compared both to pts with sustained MRD negativity (p<0.0001, HR 0.05; 0.003-0.80) and to MRD positive pts before maintenance (p 0.020, HR 0.21; 0.035-1.26). <h3>Conclusion</h3> we confirm the predictive value of MRD assessment after ASCT and therefore the importance of achieving sustained MRD negativity regardless of different treatment strategies. Moreover, the detection of early loss of MRD negativity can help the physician to identify pts with particularly poor prognosis

Real World Outcomes of Newly Diagnosed High-Risk Multiple Myeloma Patients Treated at Princess Margaret Cancer Centre: A Retrospective Chart Review

Background: In the era prior to the availability of novel agents, we have previously reported that the median progression-free survival (PFS) and overall survival (OS) of high-risk (HR) multiple myeloma (MM) patients (pts) undergoing a single autologous stem cell transplant (ASCT) was only 9.9 and 18.3 months, respectively (Chang H et al., Bone Marrow Transplant, 36 (2005), 793). The current study expands our experience in newly diagnosed HR pts and focuses on the outcomes in pts treated with single or tandem ASCT.Methods: A retrospective chart review of myeloma pts was conducted based on pt information retrieved from the Princess Margaret Myeloma Database. 245 pts with HR MM diagnosed and treated in our centre from Oct 1998 to Dec 2016 were identified. Survival rates were calculated using the Kaplan-Meier product-limit method and the log rank-statistic was used for comparison of survival curves.Results: Pts were considered HR based on the presence of any one of the cytogenetic features: t(4:14) (71%), t(14:16) (36%), and chromosome 17p deletion (42%). Characteristics at the time of MM diagnosis of the 245 pts identified as HR are summarized in Table 1. The median age was 60.9 years. First-line therapy included the following: tandem ASCT in 86 pts (35%), single ASCT in 84 pts (34%), and no ASCT in 75 pts (31%). Of the 170 pts who underwent single or tandem ASCT, 119 (70%) received maintenance therapy post-ASCT, including 84% of the tandem ASCT pts and 56% of the single ASCT pts.Median follow-up was 29.3 months (range 1.1-123.7). The median PFS from date of diagnosis of all HR pts was 33.1 months [95% CI 29.3-37.0 months], while the median OS was 79.2 months [95% CI 58.3-90.9 months]. Both PFS (p= 0.0003) and OS (p= 0.0011) were significantly affected by first-line therapy with a median PFS of 53.1 vs 32.9 vs 21.8 months and median OS of 88.5 vs 71.9 vs 55.0 months in pts treated with tandem ASCT, single ASCT and no ASCT, respectively. Tandem ASCT pts had improved PFS and OS survival at 1, 2, and 5-years compared to single and non-transplant pts (Fig. 1A & B). Age at diagnosis significantly affected the PFS (p= 0.0003) and marginally affected the OS (p= 0.0748), likely due in part to our policy for the preferential use of fixed-duration non-ASCT as first-line therapy in older individuals (typically ≥70 years of age). On the other hand, serum beta 2- microglobulin levels correlated significantly with OS (p= 0.0023) while the association with PFS was not significant. Among ASCT pts, those who received tandem ASCTs vs single ASCT demonstrated a significantly better PFS (p= 0.0039) and showed a trend for improved OS (p= 0.0707). Amongst pts who received single ASCT, those with maintenance vs no maintenance demonstrated significantly better PFS (p=0.0082). Finally, pts with both t(4:14) and 17p deletion (28 pts) had a significantly decreased PFS (p= 0.0414) and a trend for decreased OS (p= 0.0621) compared to those with only one abnormality (Fig. 1C & D).Conclusions: Although adverse factors such as older age and co-morbidities likely affected the ability to perform 1 or 2 autografts and likely introduced bias into our analysis, our data nevertheless suggest that tandem ASCT is an effective approach in extending PFS and OS among HR MM pts when compared to single transplants or none at all in the real-world setting. Multivariate analysis is underway to further delineate the factors contributing to PFS and OS in HR pts. As in other transplant studies, the PFS is improved in pts who receive maintenance therapy after single ASCT. Efforts should be made to offer newly diagnosed HR MM pts a program that includes tandem transplantation, if feasible, as well as maintenance therapy post-transplant. Pts with “ultra HR” MM, i.e., those with both t(4;14) and 17p deletion, require new innovative approaches. [Display omitted] DisclosuresReece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Paid expert testimony, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Paid expert testimony, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka: Research Funding. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbvie: Honoraria; Amgen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:BMS Canada: Honoraria; Celgene: Honoraria; Takeda Oncology: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Trudel:Janssen: Research Funding; Amgen: Consultancy, Honoraria; Astellas: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Honoraria; GlaxoSmithKline: Research Funding.

The Effect and the Cost of Tandem Transplantation in Multiple Myeloma Patients with Adverse Cytogenetics

Introduction:Autologous stem cell transplantation (ASCT) plays a major role in the treatment of multiple myeloma. However, the result of STaMINA trial showed no extra benefit of second transplantation or consolidation therapy in addition to single ASCT; there is still argue about the optimal intensity of the treatment in patients with high-risk cytogenetic abnormalities. We analyzed retrospectively, the effect of the tandem ASCT and the cost.Methods:We analyzed multiple myeloma patients with Adverse Cytogenetics who were treated with ASCT in National Center for Global Health and Medicine Hospital from January 2010 to the end of March 2017. Most patients were treated with bortezomib based induction therapy. Patients who failed to achieve very good partial remission or better after the first ASCT proceeded to the second ASCT. Most patients received consolidation therapy and/or maintenance therapy. Overall Survival (OS) and progression free survival (PFS) was analyzed using the Kaplan-Meier methods, and the log-rank test. Also, cumulative cost for the treatment was evaluated. Adverse cytogenetics were defined as hypodiploidy, del(17p), t(4;14), and t(14;16).Results:Ten patients were treated with tandem ASCT, and fifteen patients were treated with single ASCT. Twenty-one patients were treated with BD regimen, two patients with CyBorD regimen, and two patients with VAD regimen. The median number of induction therapy was 4 cycles (4-6). The PFS of the tandem ASCT group (3yrs PFS was 87.5%) was superior to the single ASCT group (3yrs PFS was 37.2%) (P = 0.0038). The OS of the tandem ASCT group (3yrs PFS was 100%) was superior to the single ASCT group (3yrs OS was 49.5%) without statistical significance (P = 0.057). We compared cumulative costs of tandem ASCT patients with single ASCT patients. We plotted the average cumulative cost of every 3 months in each group. The first 21 months and beyond 54 months, the rate of cost increment was apparently higher in the single ASCT group than tandem ASCT group. A regression line was calculated for the average cumulative cost of single ASCT group and tandem ASCT group. Regression analysis revealed that overall inclination of the regression line of the cost in single ASCT was significantly larger than that of the cost in tandem ASCT (P = 0.0024).Conclusion:The outcome of tandem ASCT was superior to single ASCT in patients with adverse cytogenetics. Also, the total cost in patients with tandem ASCT was lower than that with single ASCT. Tandem ASCT may reduce the rate of relapse and the cost for salvage treatment. Therefore, tandem ASCT should be considered for multiple myeloma patients with adverse cytogenetics from a cost-benefit point of view. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic Impact of Tandem Autologous Stem Cell Transplantation (ASCT) in Different Response Subgroups after 1st ASCT

Prognostic Impact of Tandem Autologous Stem Cell Transplantation (ASCT) in Different Response Subgroups after 1st ASCT

Double Autologous Stem Cell Transplantation Significantly Prolongs Progression-Free Survival and Overall Survival in Comparison with Single Autotransplantation in Newly Diagnosed Multiple Myeloma: An Analysis of Phase 3 EMN02/HO95 Study

Background The role of single vs double autologous stem cell transplantation (ASCT) for newly diagnosed (ND) multiple myeloma (MM) continues to be debated in the novel agent era. Methods The phase III EMN02/HO95 study was designed to administer 3-4 cycles of bortezomib-cyclophosphamide-dexamethasone as induction therapy for NDMM and afterwards to randomize eligible patients to receive (randomization 1, R1) standard-dose intensification treatment with bortezomib-melphalan-prednisone (VMP) for four 42-day cycles or high-dose intensification treatment with melphalan at 200 mg/m2 (HDM) plus ASCT. A second randomization to receive or not receive consolidation therapy was planned after the intensification phase, followed by lenalidomide maintenance in both arms. In centers committed to a double ASCT policy, patients were randomized (1:1:1) to receive VMP or single ASCT (ASCT-1) or two sequential courses of HDM (administered 2 to 3 months apart) plus double ASCT (ASCT-2) in order to prospectively compare ASCT-1 vs ASCT-2, which was an additional study objective. For this purpose, and for consistency with the primary study end point, progression-free survival (PFS) from R1 was evaluated. Results A total of 1503 patients aged ≤65 years were registered and 1192 were eligible for R1. By study design, 618 patients who received the diagnosis of MM in centers with a double ASCT policy were randomly assigned to VMP (n=203) or ASCT-1 (n=208) or ASCT-2 (n=207). 415 of these patients who were randomized to receive ASCT-1 or ASCT-2 were included in the current pre-specified analysis. Median age was 58 years for patients in the ASCT-1 group and 57 years for those in the ASCT-2 group. The frequency of ISS stage III was 19% in both groups. According to IMWG criteria, a high-risk (HiR) cytogenetic profile defined by t(4;14) ± t(14;16) ± del(17p) positivity (HiR-cyto-3) was detected in 26% and 21% of patients who were evaluable in ASCT-1 (80%) and ASCT-2 (86%) groups. The presence of amp(1q) ± del(1p) ± 1 or more of t(4;14), t(14;16) and del(17p) identified a HiR cytogenetic profile (HiR-cyto-5) which was detected in 55% of patients in ASCT-1 arm and 50% of those in ASCT-2 arm. Median follow-up from R1 was 38 (IQR: 29-47) months for the overall patient population (36 and 39 months for patients randomized to ASCT-1 and ASCT-2, respectively). On an intention-to-treat basis, 3-year estimate of PFS was 73% (95% CI=66-79) for ASCT-2 group vs 64% (CI=57-71) for ASCT-1 group (HR=0.70; CI=0.50-0.98; P=0.040), which represented a 30% reduced risk of progression or death in the ASCT-2 group compared with the ASCT-1 group (Fig. 1a). PFS benefit associated with ASCT-2 was confirmed in subgroups of patients with HiR-cyto-3 (HR=0.42; CI=0.21-0.84; P=0.014), revised ISS (R-ISS) stage II+III (HR=0.64; CI=0.43-0.97; P=0.034), age >55 years (HR=0.64; CI=0.43-0.96; P=0.033); HiR-cyto-5 (HR=0.65; CI=0.42-1.01; P=0.059) and best ≥VGPR (HR=0.64; CI=0.44-0.94; P=0.023). Importantly, ASCT-2 overcame the adverse prognosis conferred by HiR-cyto-3 (3-year PFS: 76% vs 69% for patients with standard-risk cytogenetic profile; P=0.482) (Fig. 1b). In particular, 3-year PFS estimate for patients randomized to ASCT-2 and carrying or lacking del(17p) was 72% vs 73%, respectively (P=0.534). The corresponding PFS values in the ASCT-1 group were 43% vs 67%, respectively (P=0.014). In a multivariate Cox regression analysis, randomization to ASCT-2 (HR=0.65; CI=0.44-0.95; P=0.029), R-ISS I (HR=0.60; CI=037-0.98; P=0.042), absence of HiR-cyto-5 (HR=0.35; CI=0.22-0.55; P Conclusions Randomization to ASCT-2 was superior over ASCT-1 in terms of prolonged PFS and OS for the overall patient population and for poor prognosis subgroups of patients with advanced R-ISS disease stage and HiR cytogenetic profile. Incorporation of bortezomib into ASCT-2 abrogated the increased risk of progression or death imparted by t(4;14) ± t(14;16) ± del(17p), and in particular by del(17p) positivity. Disclosures Gay: Amgen: Honoraria; Mundipharma: Membership on an entity9s Board of Directors or advisory committees; Roche: Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria; Seattle Genetics: Membership on an entity9s Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria. Bringhen: Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Amgen: Membership on an entity9s Board of Directors or advisory committees; Mundipharma: Membership on an entity9s Board of Directors or advisory committees; Karyipharm: Membership on an entity9s Board of Directors or advisory committees. Musto: janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria; BMS: Honoraria. Palumbo: Takeda: Consultancy, Employment, Equity Ownership, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding; Binding Site: Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Genmab A/S: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Sonneveld: Celgene Corporation, Amgen, Janssen, Karyopharm, PharmaMar, SkylineDx: Honoraria; Celgene, Amgen, Janssen, Karyopharm, Takeda: Consultancy, Honoraria, Research Funding; Celgene Corporation, Amgen, Janssen, Karyopharm, SkylineDx, PharmaMar: Consultancy.

Bortezomib and High-Dose Melphalan Vs. High-Dose Melphalan As Conditioning Regimen before Autologous Stem Cell Transplantation in De Novo Multiple Myeloma Patients: A Phase 3 Study of the Intergroupe Francophone Du Myelome (IFM 2014-02)

Bortezomib and High-Dose Melphalan Vs. High-Dose Melphalan As Conditioning Regimen before Autologous Stem Cell Transplantation in De Novo Multiple Myeloma Patients: A Phase 3 Study of the Intergroupe Francophone Du Myelome (IFM 2014-02)

A Single Autologous Stem Cell Transplant (ASCT) Followed By Two Years of Post-Transplant Therapy Is Safe in Older Recently Diagnosed Multiple Myeloma (MM) Patients. Preliminary Results from the Prospective Phase II Trial (NCT01849783)

Introduction: The median age at diagnosis of MM patients is around 70. The current standard of treatment for younger eligible MM patients is ASCT after initial induction chemotherapy. Multiple studies have shown that age by itself is not necessarily an exclusion criterion for transplant and that elderly eligible patients derive benefits from ASCT. While melphalan 200mg/m2 has been the standard preparative regimen for ASCT, more studies are currently evaluating the role of including novel agents along with melphalan to improve outcomes. We previously reported the safety and efficacy of VDT-Mel in patients mostly younger than 65 years. Here we report the tolerability of the same regimen in elderly patients.Methods and patients: A total of 41 eligible patients above the age 65 were prospectively enrolled in the IRB approved phase II trial beginning in June 2013. After an induction chemotherapy and stem cell collection, ASCT was performed with a preparative chemotherapy consisting of VDT-Melphalan 200mg/m2. Early after engraftment, patients were started on maintenance for 2 years with triple agent therapy. Primary end points include PFS, frequency of severe toxicities, ICU admissions, and percentage of patients able to complete the full course of maintenance.Results: Of the 41 patients enrolled, 37 patients had at least day 100 follow up post-transplantation and were included in this analysis. Six have been removed from study due to relapse (N=2), development of acute leukemia (N=1), failure to collect stem cells (N=1) or failure to comply with therapy (N=2). Toxicity and best response were assessed at day 100. Median age was 68 (range: 65 to 75). Median follow up was 21 months (3.5 months - 3.7 years). Major non-hematologic toxicities ≥ grade 3 were related to infections (25%), diarrhea (16%) and mucositis (11%). Median time to ANC and platelet engraftment was 11 and 17 days, respectively. 18 patients achieved a stringent CR (sCR) by day 100 restaging (50%). There was one death within day 100 related to candida sepsis. Only 2 patients were re-hospitalized within 100 days. Thirty-five patients started maintenance therapy. Median time to start post-transplant therapy was 66 days (range: 42 to 174 days).Conclusion: This is the first trial to prospectively evaluate the feasibility of combined intensified preparative regimen with two years of maintenance using triple agent therapy in elderly MM patients. Toxicity and mortality were not increased compared to the younger patients (median age 59) receiving a similar regimen. It is too early to comment on the efficacy of this approach, but we are encouraged by the high frequency of sCR, early after transplantation. DisclosuresNo relevant conflicts of interest to declare.

Impact of Active Maintenance Treatment (MT) Compared to No MT on the Quality of Life (QoL) of Patients with Multiple Myeloma (MM) Following First Autologous Stem Cell Transplant (ASCT)

Background: Evidence supports that MT after ASCT provides a progression free and overall survival advantage in MM compared to placebo in phase III trials. Lenalidomide was recently approved for this purpose by both the Food and Drug Administration and the European Medicines Agency in 2017. However, there is the potential that continual treatment will have a negative impact on patient QoL. Very few studies have assessed this; although a recent study found no significant QoL differences between patients receiving MT vs no MT post ASCT. Further data are required to confirm this.Objective: To assess the impact of active MT vs. no MT on the QoL of patients with MM following first ASCT.Methods: A non-interventional, cross-sectional study was conducted with patients recruited from 13 centers in the United States and Canada. All patients had received a single ASCT and three groups were identified and compared: •Patients within 30-100 days of ASCT and had not commenced any MT (baseline patients)•Patients at >100 days post ASCT and currently receiving any MT therapy (MT patients)•Patients at >100 days post ASCT and currently not receiving MT (no MT patients)Patients were excluded from this analysis if they had experienced clinical progression post ASCT.Demographics, clinical characteristics, comorbidities, treatment and symptoms were captured via a case report form. Patients completed a questionnaire containing the EuroQoL five dimension (EQ-5D), the European Organization for Research and Treatment of Cancer QoL Questionnaire Core 30 (EORTC QLQ-C30) and the QoL Questionnaire Myeloma 20 module (QLQ-MY20). Differences in QoL between baseline, MT and no MT patients were explored with ordinary least squares regressions, controlling for age, sex, body mass index, time since diagnosis, stage at diagnosis, comorbidities, Eastern Cooperative Oncology Group performance status and country.Results: Between 2016 - 2017, 13 sites in the US and Canada enrolled 303 patients (excluding 3 patients who had progressed). Mean age was 62.0 years, 45% were female. There were 84, 141 and 78 baseline, MT and no MT patients respectively. Baseline patients were a mean of 83.7 days post ASCT whereas mean days post-transplant was 868.6 for MT patients and 905.2 for no MT patients. The majority of MT patients (81.6%) received lenalidomide either as monotherapy or combination therapy. Unadjusted mean EQ-5D scores were 0.77 for baseline patients, 0.81 for MT patients and 0.79 for no MT patients, with higher scores indicating better QoL.In the adjusted analysis, EQ-5D and the majority of EORTC scores did not significantly differ between the three patient groups. However, EORTC global scores demonstrated a significant QoL improvement relative to baseline for both MT (+9.62, p=0.0178) and no MT (+10.06, p=0.0435) patients. A similar pattern was observed for social functioning (MT vs. baseline; +12.65, p=0.0106. No MT vs. baseline; +16.94; p=0.0055) and the MY-20 body image domain (MT vs. baseline, +16.78, p=0.0053; No MT vs. baseline, +19.31, p=0.0083). Only the diarrhea domain from the EORTC-QLQ C30 and future perspectives from the MY-20 (measuring concerns about outlook and future health) differentiated between MT vs. no MT patients; with patients on MT reporting higher scores for diarrhea (greater problems, [+9.43; p=0.0358]) and lower scores for future perspectives (poorer outlook, [-11.39; p=0.0196]).Conclusion: QoL after ASCT improves from baseline for both MT and no MT patients as measured by the global health status and social functioning domains of the EORTC QLQ-C30, and the body image domain from the MY-20. Only outcomes on future perspectives and diarrhea differentiated between MT and no MT patients. Collectively, the results suggest that MT is not associated with a notable QoL detriment. DisclosuresVij:Takeda: Honoraria, Research Funding; Abbvie: Honoraria; Bristol-Meyers-Squibb: Honoraria; Janssen: Honoraria; Jazz: Honoraria; Celgene: Honoraria; Amgen: Honoraria, Research Funding; Konypharma: Honoraria. Norkin:Celgene: Honoraria, Research Funding. Kumar:Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Skyline: Honoraria; Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding. Roberts:Adelphi Real World: Employment. White:Amgen, Celgene, Janssen, Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wood:Adelphi Real World: Employment. Blanthorn-Hazell:Adelphi Real World: Employment. Rossi:Thrassos: Consultancy; Celgene: Consultancy. Dhanasiri:Celgene Corporation: Employment, Equity Ownership. Zafar:Celgene Corporation: Employment. Newhouse:Celgene: Employment. Arleigh:Celgene: Honoraria.

Tandem versus single autologous stem cell transplant: A patient-reported outcome.

e20026 Background: Whether tandem autologous stem cell transplant (ASCT) is superior to single ASCT for new diagnosed multiple myeloma (MM) patients remains a subject of discussion in the era of novel agents. This project analyzed patient-reported outcomes to single ASCT and tandem ASCT utilizing an online patient-centered platform. Methods: We analyzed patient-reported treatment outcomes pertaining to tandem ASCT and single ASCT from HealthTree Cure Hub ( www.healthtree.org ). In this study, we examined whether patients reported a reduction or no reduction in their myeloma after their tandem or single ASCT. The association between stem cell transplant and myeloma outcome was compared by chi-squared test. Results: In this retrospective analysis of 945 MM patients, we compared two groups, those that reported receiving a tandem ASCT (n = 75) and those that reported receiving a single ASCT (n = 870). Our analysis revealed an association between patients who reported receiving a tandem ASCT and a reduction of their myeloma (chi-square (1) = 3.87, p = .04), compared to patients who reported receiving a single ASCT. Conclusions: Tandem ASCT was perceived by patients to be superior over single ASCT in regard to myeloma reduction for the HealthTree patient population. A more in-depth analysis of the patient-provided health data from HealthTree could aid in determining factors related to survival as well as help to quickly answer lingering questions related to tandem ASCT, such as timing, genetic factors, progression free survival, and more.[Table: see text]

Subcutaneous bortezomib-containing regimens as up-front treatment of newly diagnosed transplant-eligible multiple myeloma patients: a retrospective, non-interventional observational study

Subcutaneous (SC) bortezomib-based regimens represent the standard induction therapy prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients. Published data are based principally on intravenous (IV) administration: this retrospective observational study aimed to define patients’ outcomes upon SC bortezomib administration, before and after ASCT. Of 131 enrolled patients, 86% received bortezomib-dexamethasone plus thalidomide (VTD), 5% plus cyclophosphamide (VCD), and 9% alone (VD), for a median of 4 cycles induction therapy, followed by single (52%) or double (48%) ASCT. 48 patients received consolidation with the same induction regimen. 35% had at least one adverse event, mainly gastrointestinal disorders and peripheral neuropathy (PN). ORR was 93.1%, 97.7% and 100%, after induction, ASCT(s) and consolidation, respectively. Median PFS and PFS2 were 55.8 months and 72 months, respectively, (median follow-up 45.3 months), while median OS was unreached. Concluding, SC bortezomib has similar efficacy with reduced PN than IV administration.

Pediatric high risk neuroblastoma with autologous stem cell transplant - 20 years of experience.

Background and ObjectiveNeuroblastoma is the most common extracranial solid tumor found in pediatric patients. High-risk neuroblastoma (HR-NBL) can be characterized by metastasis, age, and other tumor characteristics that result in an adverse outlook for this patient cohort. The standard of care includes induction chemotherapy, surgery, followed by stem cell autologous transplant (ASCT), and later, antidisialoganglioside (anti-GD2) antibodies. In this study, we provide the survival and toxicity data of our HR-NBL patients treated with a single ASCT.MethodsWe retrospectively analyzed pediatric HR-NBL patients treated with single ASCT after a carboplatin, etoposide, and melphalan (CEM) regimen in our institution between January 1993 and December 2014.ResultsThere were 99 evaluable patients with male predominance. The median age at diagnosis was 3 years. Most of our HR-NBL patients were stage 4 (88%). All patients received ASCT. Peripheral blood was the graft source in 58% of the patients. Time for hematological count recovery with bone marrow as a graft source was prolonged but not statistically significant when compared with PBSCs. Of all the patients, 58% received radiation therapy to residual disease. Overt secondary leukemia was not seen in any of these patients. Three-year overall survival (OS) was 68.5% ± 5.2% and the 3-year event-free survival (EFS) was (48.3% ± 5.2%).ConclusionOur HR-NBL patients tolerated high-dose chemotherapy well followed by single autologous stem cell transplant. Tandem transplant is a feasible option in our patient cohort. Apart from secondary solid tumors, there were no long-term complications seen.

Long-Term Follow-up of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Children and Young Adults with Metastatic or Relapsed Ewing Sarcoma: A Single-Institution Experience

Forty-seven patients with metastatic disease at diagnosis or recurrent Ewing sarcoma (EWS) received high-dose chemotherapy (HDC) followed by tandem (n=20, from February 13, 1997, to October 24, 2002) or single (n=27, from October 1, 2004, to September 5, 2018) autologous hematopoietic stem cell transplantation (ASCT). To our knowledge, this is the largest single-institution study with sustained long-term follow-up exceeding 10 years. All patients who underwent single ASCT received a novel conditioning regimen with busulfan, melphalan, and topotecan. The overall survival (OS) and disease-free survival (DFS) were 46% and 37% at 10 years and 42% and 37% at 15 years, respectively. Disease status at transplant and the time to disease relapse prior to ASCT were identified as important prognostic factors in OS, DFS, and risk of relapse. At 10 years, patients who underwent transplantation in first complete response (1CR) had an excellent outcome (OS 78%), patients in 1CR/second complete response (2CR)/first partial response (1PR) had an OS of 66%, and patients at third or more complete response, second or more partial response, or advanced disease had an OS of 26%. Ten-year OS for patients without a history of relapse, with late relapse (≥2 years from diagnosis), or with early relapse (<2 years from diagnosis) was 75%, 50%, and 18%, respectively. Selected patients in 1CR, 2CR, 1PR, and with late relapse had excellent, sustained 10- and 15-year OS and DFS.

Relapse from MRD Negativity As Indication for Treatment in Multiple Myeloma - the Remnant Study

Background: Early intervention can reduce the rate of progression and improve overall survival (OS) in smouldering multiple myeloma (SMM) patients (pts) (1, 2). The most powerful predictor of prognosis in active MM is whether pts achieve minimal residual disease (MRD) negativity in bone marrow with treatment (3), however treating MRD relapse has not been evaluated in a randomized fashion. The REMNANT study will evaluate whether treating MRD relapse after first line (1.L) treatment prolongs progression free survival (PFS) and OS for MM pts versus treating relapse after 1.L. treatment at progressive disease (PD) (4). To establish a homogenous group of MRD negative pts after 1.L treatment including autologous stem cell transplantation (ASCT), pts are enrolled at diagnosis and treated with Norwegian standard of care (SOC) 1.L treatment. MRD negative pts will move on to the randomized part. Methods: The REMNANT study is an academic, multicenter, open-label, randomized phase II/III study of NDMM pts eligible for ASCT (see Figure 1). 391 pts across Norway will be included in the phase II part of the study and receive SOC 1.L treatment according to Norwegian national guidelines; VRd (V: 1,3 mg/m2 SC Days 1, 4, 8, 11; R: 25 mg PO Days 1-14; d: 20 mg PO Days 1, 2, 4, 5, 8, 9, 11, 12) for 4 pre-transplant induction and 4 post-transplant consolidation cycles (all 21-d cycles). After induction pts will undergo tandem or single ASCT, depending on toxicity and response to first ASCT. The primary endpoint of the phase 2 part of the study is the number of pts who achieve MRD negative (Euroflow NGF 10 -5) complete response (CR) 30-45 days post consolidation. Safety evaluations and pts-reported outcome assessment will be measured. Pts (176) achieving MRD negative CR will be randomly assigned in a 1:1 ratio to receive 2.L treatment at MRD reappearance (arm A) or at progressive disease (PD) as defined by the IMWG criteria (4) (arm B). Randomization will be stratified by R-ISS stage at diagnosis and single vs tandem ASCT. Pts in arm A will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative CR. Pts in arm B will be followed up by standard criteria and start 2.L treatment at PD. Both arms will receive the same 2.L treatment; KdD (all 28-d cycles) (K: 70mg/m2 iv Days 1,8,15 d: 40 mg Days 1, 8, 15, 22 D: 1800 mg SC Days 1, 8, 15 during C 1-2, Days 1, 8 during cycle 3-6, Day 1 from cycle 7,). 2.L treatment will continue until disease progression, unacceptable AEs or patient withdrawal. In arm A MRD Euroflow will be assessed after 6 and 18 months of 2L therapy. In arm B MRD Euroflow will be assessed if &amp;gt;CR is achieved but not before 6 months of 2 L therapy, and again after 12 consecutive months. The co-primary endpoint is progression and death by any cause (PFS) and death by any cause alone (OS). Secondary endpoints includes TTNT and the proportion pf pts who achieve MRD negative CR during 2.L treatment in arm A and arm B, safety evaluations and pts-reported outcome. The trial is approved and will start enrollment Q3 2020. 1. Mateos MV, Hernandez MT, Giraldo P, de la Rubia J, de Arriba F, Corral LL, et al. Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial. Lancet Oncol. 2016;17(8):1127-36. 2. Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. 2020;38(11):1126-37. 3. Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, et al. Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis. JAMA Oncol. 2017;3(1):28-35.5. 4. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016;17(8):e328-e46. Disclosures Schjesvold: Amgen, Celgene, Janssen, MSD, Novartis, Oncopeptides, Sanofi, SkyliteDX, Takeda: Honoraria; Celgene, Amgen, Janssen, Oncopeptides: Research Funding; Amgen, Celgene, Janssen, MSD, Novartis, Oncopeptides, Sanofi, Takeda: Consultancy. OffLabel Disclosure: Carfilzomib-dexamethason-daratumumab (KdD) as second line treatment