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Introduction: Historically, CNS lymphomas have been associated with a very poor prognosis High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated in patients with primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) with promising results in small recent small prospective phase 1/2 results and retrospective series. We hypothesized that the use of R-BuMelTt (rituximab, busulfan, melphalan, thiotepa) conditioning regimen with ASCT regimen will be effective for both patients with PCNSL and SCNSL as used in previously reported promising data by Oh et al 2016 for patients with SCNSL with higher remission and survival rates. Patients and Methods: A retrospective analysis was performed of 6 consecutive patients who had undergone R-BuMelTt conditioning regimen with ASCT for 3 patients with PCNSL and 3 patients with SCNSL from December 2017 to March 2020. The median age of this patient population was 62 years at the time of ASCT. The induction chemotherapy regimen used for patients with SCNSL was R-CHOMP except one patient who received DHAP, and for patients with PCNSL MATRix regimen was used. The median duration of chemotherapy cycles was 4, and all of them had achieved remission prior to transplant based on PET/CT scan/MRI scan. All patients were planned to undergo ASCT using the Conditioning Regimen of Rituximab 375 mg/m2 on Day-7, Thiotepa 250 mg/m2 on Day-6,-5, Busulfan 3.2 mg/kg on Day-4,-3,-2 and Melphalan 100 mg/m2 on Day-1. Supportive cares measures were given at treating physician's discretion. Results: Patients received a median cell dose of 4.4x106 CD34+cells/kg (range: 2.5-5.7), had neutrophil engraftment at 11.5 days (range:9-13), platelet recovery was achieved on days 11,15 and 16 for three patients but was delayed at 27, 46, 89 days for 3 patients. Infectious complications were common with documented bacteremia in in 3 out of 6 patients, 2 patients with c. difficile infection and with significant platelet support due to thrombocytopenia. At a median follow up of 24.5 months (range: 6-30 months), 5 out of 6 patients had complete metabolic response on radiological imaging with PET/CT in conjunction with MRI head. One of the patients with SCNSL died after transplant due to CNS relapse 223 days post ASCT giving an overall survival of 66.6%. Amongst the 2 patients with SCNSL that survived there was no relapse after 30 month follow-up. None of the patients with PCNSL died or relapsed during or after transplant therefore having a 100% overall survival. Although this is a small retrospective study, our results are comparable to current literature. Toxicities included nausea/vomiting, diarrhea, mucositis with 5/6 patients requiring TPN. Also busulfan PK levels were not done. Conclusions: R-BuMelTt regimen can be used successfully as conditioning regimen for ASCT for patients with PCNSL and SCNSL, however with increased hematological toxicity, most notably delayed platelet engraftment. The rate of progression free and overall survival is promising with short median follow up of 24 months. Disclosures Lam: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau.

e22507 Background: We compared toxicity and outcomes of BuMel and TreoMel HDCT consolidation with stem cell rescue in high-risk ES pts prospectively treated in 5 consecutive trials at the Istituto Ortopedico Rizzoli, Bologna, Italy. Methods: Eligible pts had histologically proven diagnosis of ES, high-risk disease defined as localized disease with poor histological/radiological response to standard chemotherapy or lung/pleural metastases or extra-pulmonary metastases or relapsed disease, were aged < 40. All pts received previous standard chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide actinomycin-D) and surgery and/or radiation therapy (RT) as local treatment. From June 1, 2011, TreoMel was used instead of BuMel to avoid potential severe complications related to busulfan, as in case of previous RT on axial skeleton/pelvis. Pts with lung metastases received lung irradiation 12-15 Gy at least 2 months after HDCT. Results: Between January 1, 2007, and September 30, 2018, 98 pts received BuMel or TreoMel: 52 pts with localized disease (7 TreoMel), 26 pts with lung/pleural metastases (5 TreoMel), 10 pts with extra-pulmonary metastases (4 TreoMel) and 10 pts with relapsed disease (1 TreoMel). Median age was 18 yrs (range 3-39 yrs). 14 out of 17 TreoMel pts received previous RT on axial skeleton/pelvis. Median follow up is 4.2 yrs (range 10 mo. - 12 yrs). Pts treated with TreoMel showed a significant lower incidence of grade 3-4 stomatitis (p = < 0.001) and of all grade ≥ 3 non-hematological toxicities (p = < 0.001). One pt died of BuMel-related toxicity (sinusoidal obstruction syndrome/veno-occlusive disease) and none after TreoMel. For localized ES, the 5yr-EFS was 66.7% (95%CI, 47.9-78) for BuMel pts and 66.7% (95CI%, 19.5-90.4) for TreoMel pts. Conclusions: In high-risk ES, TreoMel is significantly less toxic then BuMel. Combining RT on central/axial sites and TreoMel is feasible. In localized ES, results show similar 5yr-EFS between BuMel and TreoMel. TreoMel could be used instead of BuMel when busulfan is contraindicated.

(95% CI: 58-88%), respectively. A formal interim analysis of the Day 90 CR rate was conducted when 65 patients were evaluable, and at that time the Mel only arm was determined to be superior. The study was, therefore, stopped early by the Institutional DSMB. However, with a longer follow up Bu-Mel ultimately resulted in better PFS. Conclusions: Bu-Mel was associated with a significantly lower day 90 CR rate and a significantly higher rate of grade 3-4 non-hematologic toxicity, compared to Mel. However, after a median follow up of 15.7 months, PFS was significantly longer in the Bu-Mel arm. Figure 1 PFS from Day 90 by Treatment Arm

MRD negativity has become an important goal of the initial treatment of MM pts. Our phase 2 multi-center clinical trial, conducted in 10 major Canadian transplant centers, was designed to increase the MRD negativity rate after ASCT by using conditioning with 2 high-dose alkylating agents followed by len maintenance. In addition to conventional response criteria, this trial evaluated serial bone marrow aspirate (BMA) samples for MRD analysis by 8-color multiparameter flow cytometry (MFC) along with serum Hevylite™ assays of the involved HLC that were obtained before and after ASCT and during maintenance therapy. After bortezomib (btz)-based induction therapy off study, pts without MM progression received BuMel (busulfan 3.2 mg/kg IV days -5 to -3 or days -6 to -4 + melphalan 140 mg/m2 day -2 or day -3) conditioning, followed by ASCT on day 0. On day 100 post-ASCT, len 10 mg/day was started, escalated after 3 cycles to 15 mg/day if appropriate, and continued until progression. BMA and serum samples were shipped centrally for MRD and Hevylite analysis before induction therapy, before ASCT, on day 100 post-ASCT, every 3 mos for the 1st year and every 6 mos until progression. Between 03/2013 - 05/2016, 125 newly diagnosed pts provided BMA samples for MRD analysis. To date, 76 pts (target 78), have completed induction therapy and undergone ASCT; 2 pts have provided initial samples and are expected to be enrolled. 46 of the 125 (36.8%) who provided BMA samples did not proceed to BuMel due to: poor samples - 4 (3.2%); MM not confirmed - 3 (2.4%); prior therapy - 1 (0.8%); death during induction - 1 (0.8%); consent withdrawal/opted for standard conditioning - 21 (16.8%); and no ASCT - 16 (12.8%) (8 were unfit, 4 had comorbidities, 2 progressed, 1 failed mobilization and 1 underwent preferential tandem ASCT). Median follow-up is 27.4 mos (range: 10.4-37.6). Median age is 57 (34-69); 65.8% are male. Median serum β2-microglobulin level is 3.07 mg/L (1.5-20) and albumin 37 g/L (2.8-48.1); 34 pts have ISS stage I; 21 stage II; 17 stage III MM and 5 have missing data. Ig isotype includes IgGκ in 34 (44.7%), IgGλ in 16 (21.1%), IgAλ in 10 (13.2%), IgAκ in 9 (11.8%) and κ in 7 (9.2%). Post-ASCT, 26 SAEs have occurred: Grade 2: atrial fibrillation (1) and URI (1); Grade 3: atrial fibrillation (1), acute kidney injury (4), infectious enterocolitis (2), gallbladder infection (1), URI (1), febrile neutropenia (3), bacteremia (1), pain in extremity (1), hypoxia (1), pleural effusion (1), and 3 lung infection (4); and Grade 4: sepsis (1), AML [with spontaneous regression] (1), respiratory distress (1) and acute kidney injury (1). There have been no ASCT-related deaths; 11(14.4%) pts have progressed. The best conventional Ig response post-induction in the 76 evaluable pts is CR in 6 (7.9%), VGPR in 29 (38.2%), PR in 35 (46.1%), MR in 5 (6.6%) and SD in 1 (1.3%). At day 100 after ASCT, the Ig response in the 73 evaluable pts is CR in 9 (12.3%), VGPR in 41 (56.2%), PR in 22 (30.1%) and MR in 1 (1.4%). The rates of MRD negativity also increased from 29% after btz-based induction to 41%, while the rates of achievement of a normal HLC ratio were 50% after induction and 48% at day 100 (Table 1). Among evaluable pts, 77.3% of those after induction and 53.3% of those at day 100 who were MRD-negative also had had normal involved HLC ratios, while 38.9% and 44.2% of those, who were MRD-positive, respectively, had had normal involved HLC ratios. At month 6 and 12 post-ASCT, 43% and 35% of evaluable pts, respectively, are MRD-negative. Individual patient patterns of len dose, MRD negativity and involved HLC ratios are under assessment and will be presented. Conclusions: 1) IV BuMel conditioning + ASCT is well-tolerated with few SAEs and no ASCT-related deaths; 2) at day 100 post-ASCT, 98.6% had achieved ≥ PR (≥ VGPR in 68.5% and CR in 12.3%); 3) MRD negativity rates improved from 29% to 41% after ASCT; 4) the rates of normalization of the involved HLC ratio remained stable (50% to 48%) pre- and post-ASCT; 4) conventional Ig and MRD responses were often discordant as only 41% of CR pts were MRD-negative at day 100; 5) the majority of MRD-negative patients (53.3%) also had normalization of their involved HLC ratios; 5) with a median follow-up of over 2 years, only 14% of pts have progressed; 6) the serial marrow samples mandated by this study will allow determination of relationships between len dose, conventional Ig response rates, MRD status and involved HLC ratios as these pts are followed for longer periods of time. Disclosures Reece: Takeda: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Merck: Research Funding; BMS: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. White:Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria. Venner:Takeda: Honoraria; Celgene: Honoraria, Research Funding; J+J: Research Funding; Janssen: Honoraria; Amgen: Honoraria. Stakiw:Roche: Research Funding; BMS: Honoraria; Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Jansen: Honoraria, Speakers Bureau. Sebag:Celgene: Honoraria; Novartis: Honoraria; Janssen: Honoraria. Comeau:Seattle Genetics: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Song:Otsuka: Honoraria; Janssen: Honoraria; Celgene: Honoraria, Research Funding. Louzada:Pfizer: Honoraria; Bayer: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. McCurdy:Celgene: Honoraria. Kukreti:Celgene: Honoraria. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Celgene: Honoraria; Novartis: Honoraria; Oncoethix: Research Funding. Prica:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:Novartis: Honoraria; Takeda Oncology: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; BMS Canada: Honoraria. Chen:Takeda: Research Funding; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

11000Background: EE99R2Loc (ISRCTN61438620) was conducted in 12 countries, by 4 cooperative groups: GPOH, SFCE/GSF, UK-CCLG, and EORTC. It evaluated effects on event-free (EFS, main endpoint) and o...

11001Background: EE99R2pul (ISRCTN61438620) was conducted in 16 countries, by 5 cooperative groups: COG, SFCE/GSF, GPOH, UK CCLG, EORTC. It evaluated the effect on event-free (EFS, main endpoint) a...

10528Background: The COG conducted a groupwide study of a Busulfan/Melphalan (BuMel) myeloablative regimen in patients with newly diagnosed, high-risk neuroblastoma (ANBL12P1). Previously used in S...

e21009 Background: High dose chemotherapy with ASCR is a key component of therapy for patients (pts) with HRNB, but the optimal ASCR regimen is not defined. CEM is the current US standard; however, European data suggest that BuMel may improve outcomes with less toxicity. Published data regarding toxicities associated with CEM and BuMel within current-era HRNB therapy are limited. Methods: Pts with HRNB who underwent single ASCR with CEM or BuMel from 6/1/10-6/30/13 were identified in the Pediatric Health Information System (PHIS) database. RU data for 60 days (d) from the start of BuMel or CEM were compared using a Wilcoxon 2-sample test. A retrospective chart review of contemporaneously treated pts was conducted at Children’s Hospital of Philadelphia (CHOP) to evaluate toxicities that could not be identified in PHIS, such as sinusoidal obstruction syndrome (SOS). Data were analyzed using Fisher’s exact test. Results: Total inpatient days were greater in the PHIS BuMel group (n=59) than in the CEM group (...

Conventional immunoglobulin (Ig) markers have been used to define multiple myeloma (MM) responses, but assessment of marrow for minimal residual disease (MRD) may provide better information on disease status/prognosis (Paiva B, et al. Blood 2008; 112: 4017). We therefore initiated a national multi-center ASCT trial with the goal of producing a high rate of MRD-negativity by using bortezomib (btz)-based induction, enhancing the conditioning regimen and utilizing post-ASCT maintenance. This phase 2 open label-trial was conducted in 10 Canadian centers. After btz-based induction (usually CyBorD) in the absence of disease progression, patients (pts) received BuMel conditioning (IV busulfan 3.2 mg/kg days -5 to -3 or days -6 to -4 + melphalan 140 mg/m2 day -2 or day -3), followed by ASCT on day 0. On day 100 post-ASCT, lenalidomide (len) 10 mg/day was commenced, escalated to 15 mg/day after 3 cycles if appropriate, and continued until disease progression. Bone marrow aspirate (BMA) samples were shipped centrally for MRD analysis by 15-color multiparameter flow cytometry (MFC) before any therapy, prior to ASCT, on day 100 post-ASCT, every 3 mos for the 1st year and every 6 mos thereafter until progression. Between 03/2013 - 07/2014, 99 newly diagnosed MM pts provided untreated BMA samples for MRD analysis. To date, 42 of a planned target of 78 pts have completed induction therapy have undergone ASCT and 39 are evaluable so far. 25 of the 99 (25%) who provided initial marrow samples did not meet criteria for enrollment: 3 (3%) had poor BMA samples; 3 (3%) did not have confirmed MM; 6 (6%) did not proceed with ASCT (1 due to progression); 1 (1%) had received dexamethasone prior to MRD analysis; 1 (1%) died during induction and 11 (11%) withdrew consent/opted for standard conditioning. Median age of the 39 evaluable pts is 53 (39-67); 64% are male. Median serum β2-microglobulin level is 3.64 mg/L (1.7-20) and albumin 37 g/L (2.8-48.1); 17 pts have ISS stage I; 9 have stage II; 9 have stage III MM and 4 have missing data. Ig subtype includes IgGκ in 16 (40%), IgGλ in 4 (10%), IgAκ in 5 (13%), IgAλ in 8 (21%), IgMλ in 1 (3%), κ in 1 (3%); non-secretory in 2 (5%) and no data in 2 pts (5%). Post-ASCT, only 4 SAEs have occurred: atrial fibrillation (2), acute kidney injury (1) and sepsis (1). There have been no ASCT-related deaths, and no pt has progressed at a median follow-up of 7.8 mos (range: 4.8-10.1). The best Ig response post-induction in the 31 pts with available restaging data is CR in 5 (16%), VGPR in 9 (29%), PR in 13 (42%), and SD in 1 (3%). 27 pts have reached day 100 post-ASCT and 8 pts have been formally evaluated. In these 8, the Ig response is CR in 2 (25%), VGPR in 5 (63%) and PR in 1 (12%). Table 1 summarizes MRD results to date. Table 1. Comparison of conventional Ig response rates and achievement of MRD negativity # Conventional Ig Responses [# MRD negative] Time point of assessment #Evaluable Total # MRD negative CR VGPR PR MR After btz-based induction 31 6 5 [3] 9 [1] 13 [2] 0 Day 100 post-ASCT 8 2 2 [2] 5[0] 1[0] 0 During len maintenance 5 1 0 5 [1] 0 0 Conclusions: 1) MFC performed on pre-therapy marrow samples to allow subsequent evaluation for MRD was successful in 97% of pts using a central lab; 2) IV BuMel was well-tolerated with few SAEs and no ASCT-related deaths; 3) MRD and conventional Ig responses may not correlate well; 4) Further F/U is required to determine the dynamics of MRD achievement and long term outcomes with this approach. Disclosures Reece: Novartis: Honoraria, Research Funding; BMS: Research Funding; Merck: Research Funding; Millennium: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Amgen: Honoraria. Off Label Use: Lenalidomide maintenance after ASCT. Venner:Celgene: Honoraria, Research Funding; Janssen: Honoraria. White:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Sebag:Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Song:Celgene: Honoraria; Otsuka: Honoraria; janssen: Honoraria. Tay:Celgene: Honoraria; Janssen: Honoraria. Kukreti:Celgene: Honoraria. Trudel:Glaxo Smith Kline: Honoraria, Research Funding; Novartis: Honoraria; Celgene: Honoraria; Oncoethix: Research Funding. Tiedemann:Celgene: Honoraria; Janssen: Honoraria. Chen:Millennium: Research Funding; Janssen: Honoraria; Celgene: Honoraria, Research Funding.

7612 Background: Auto-SCT is the preferred treatment modality for MM. From the results of IFM 9502 (Moreau et al. Blood, 2002) melphalan 200 mg/m2 was considered the new standard as conditioning regimen due to its lower toxicity. However, many chemotherapy regimens have been tested. We present our results with two cohorts of consecutive patients (pts) diagnosed of MM and treated with Auto-SCT between 1996 and 2005 in our BMT Unit. Methods: Following induction chemotherapy (median of 6 courses) 20 pts were conditioning with busulfan 16 mg/kg + melphalan 140 mg/m2 (BuMel) and 23 (since September-2002) with melphalan 200 mg/m2 (Mel-200). Clinical features: median age (BuMel vs Mel-200) 55 vs 58 (p=0.5); female sex 10 vs 10; Bence-Jones MM 5 vs 5; renal failure (B) 2/20 (10%) vs 7/23 (30%)(p=0.48); previous treatment with local irradiation 6/20 vs 3/23; status previous Auto-SCT (complete remission, CR) 7/20 (35%) vs 6/23 (26%), p=0.5. A median of 4.8 vs 4.4 x 10e6/kg CD34+ cells were infused, respectively (p=0.15). Results: Four toxic deaths: 2 pts by hemorrhagic cystitis-enterocolitis (at day +84 and +96), 1 pt with disseminated candidiasis (day +7), and 1 pt by pulmonary fibrosis (day +452). At 3 months following Auto-SCT, 13/19 (68%) treated with BuMel and 12/23 (52%) of those treated with Mel-200 achieved CR (p=0.28). At 24 months, probability of remaining disease free was 87% for BuMel group and 55% for Mel-200 (p=0.08). Conclusions: 1) Conditioning regimen BuMel was associated with a higher toxicity than Mel-200, as well as a higher mortality treatment related. 2) However, a trend for higher CR rates and probability of disease free progression were shown in BuMel group without statistical significance [Table: see text] No significant financial relationships to disclose.