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Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4895-4895
Author(s):  
Amany R. Keruakous ◽  
Raid Aljumaily ◽  
Daniel Zhao ◽  
Adam S. Asch ◽  
Carrie Yuen

Abstract Introduction: Natural killer (NK) cells are large granular lymphocytes, very potent effector lymphocytes that can induce cytotoxicity against a vast array of tumors without the need for antigen sensitization or antigen presentation by MHC class I. NK cells are believed to play important role in immune surveillance for cancer, limiting neoplastic progression, and effectors of anti-tumor therapies -by introducing Abs that block NK cell inhibitory receptors yielding improved NK cell-mediated lysis- Retrospective studies demonstrated a significant correlation of NK cell recovery after autologous stem cell transplantation (ASCT) in multiple myeloma (MM) and disease outcomes. Higher absolute NK cell count one month after ASCT is associated with longer progression-free survival (PFS) and decreased risk of relapse. We aimed at investigating factors affecting NK cell recovery after ASCT in patients with multiple myeloma. Method: We designed a prospective cohort study, evaluating the potential factors that could affect NK cell recovery after ASCT. We included participants undergoing frontline ASCT for MM. We excluded participants with non-secretory myeloma or other malignancies that require active treatment, or with autoimmune disorders. All participants received conditioning regimen consisted of melphalan 200 mg/m2 on day -2. In patients older than 65 years old given 100mg/m2 for 2 days. Dose reduction to 140 mg/m2 for patients with serum creatinine > 2.0 mg/dL. Hematopoietic growth factor (peg-filgrastim 6 mg once subcutaneously) was given on day +1. Absolute NK cell count (CD3-, CD56+ cells) was determined using flow cytometric immunophenotyping of peripheral blood two-three months after ASCT. To determine variables that affected NK cell recovery after ASCT, absolute NK cell count was dichotomized to less than the lower limit of normal "NK < 76" and normal "NK > or equal 76" following institutional normal reference range which is consistent with ARUP NK cell enumeration reference. Statistical analysis was performed using Fisher-Exact test for categorical variable and Wilcoxon rank test for continuous variables. Results: We analyzed the results of fifteen patients treated with frontline ASCT for multiple myeloma. With a median age at diagnosis of 60 years, ranging from 47 - 70 years. Of which 53 percent females and 47 percent males. Patients' baseline characteristics are described in Table 1 Our data showed that 63 percent of patients with post-transplantation ALC > 1000 (5 of 8 patients), and 73 percent for ALC > 500, (8 of 11 patients), had normal absolute NK cell count; with a correlation coefficient of 0.3 (Pearson Correlation Coefficients), suggesting a moderate linear correlation between absolute NK cell count and ALC two-three months after ASCT. Patients' gender, age at ASCT, and comorbidity index (SORROR score) did not differ between the two groups of patients, P-value= 0.6193, 0.8454, 0.1721, respectively. Additionally, disease burden at the time of diagnosis, presence of CRAB criteria, involved free light chain and monoclonal immunoglobulins; all did not differ between the two cohorts. (Table 2) Medications received before ASCT did affect the absolute NK cell count with a higher proportion of normal absolute NK cell count, and higher mean absolute NK cell in the cohort received double-class (PI plus IMiDs) when compared to triple-class (PI plus IMiDs plus Anti-CD 38 mAb) therapy before transplantation (mean NK cell count 125 and 53 Cell/μL, respectively), with marginal statistical significance P-value= 0.0667 (Fisher's Exact Test). Discussion: Our study showed that the addition of anti-CD38 mAb to myeloma induction regimen, associated with compromised NK cell recovery. Casneuf et al reported similar findings, in daratumumab-treated myeloma patients, total and activated NK-cell counts reduced rapidly in peripheral blood after the first dose, remained low throughout treatment, and recovered after treatment ended. Similar reductions were observed in the bone marrow. Conclusion: Medications received before transplantation potentially affect NK cell recovery in multiple myeloma patients. Although, the addition of anti-CD38 mAb to the myeloma induction regimen is associated with deeper response, its impact on immune reconstitution needs to be investigated on a larger sample size. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3402-3402
Author(s):  
Nirali N. Shah ◽  
Eric S Schafer ◽  
Kenneth Matthew Heym ◽  
Andrew E. Place ◽  
Melissa A. Burns ◽  
...  

Abstract Introduction: Vincristine intensification has the potential to improve outcomes in ALL, but severe neurotoxicity has prohibited escalation beyond standard capped doses. Vincristine sulfate liposome injection, VSLI (Marqibo®) is a liposomal formulation of aqueous vincristine that optimizes pharmacokinetics, prolongs circulating half-life, increases tissue penetration, and may be better tolerated than standard vincristine. VSLI received accelerated FDA approval for adults with relapsed/refractory (r/r) ALL, at a dose of 2.25 mg/m 2/dose without a dose cap. A phase I trial of VSLI in children and young adults with r/r ALL demonstrated safety, tolerability, and evidence for single-agent activity (Shah NN, et al. Pediatric Blood Cancer, 2016). Studies of VSLI with combination chemotherapy in children have not been conducted. With emerging data supporting improved outcomes for patients (pts) with r/r ALL who proceed to immunotherapy with low-burden disease, identifying safe and effective reinduction regimens to reduce disease burden remains a priority. Methods: This multicenter pilot study conducted through the TACL consortium was designed to assess safety and feasibility of VSLI as replacement for standard vincristine with combination chemotherapy for individuals between the ages of 2-21 years with r/r ALL. Two dose levels of VSLI were utilized without a dose cap: Dose level 1 (DL1) 1.5 mg/m 2/dose; and Dose level 2 (DL2) 2.0 mg/m 2/dose. Treatment success was determined by both 1) the absence of a dose-limiting toxicity (DLT) (as defined by any > Grade 3 regimen related non-hematologic toxicity which precluded completion of the pre-specified treatment course or from proceeding to subsequent therapy within 7 weeks) and 2) completion of the prescribed treatment regimen. Adverse event grading was based on CTCAE v4.03. Bone marrow aspirate was used for standard morphologic assessment of response with central flow cytometric analysis for minimal residual disease (MRD) determination with a cut-off of <0.01% of mononuclear cells considered as MRD negative. This analysis reports the toxicities and feasibilities for Cohort A which constituted the 4-drug UK ALL-R3 induction regimen consisting of VSLI, dexamethasone, mitoxantrone, and asparaginase (pegaspargase or Erwinia). Results: A total of 10 pts with r/r B-ALL, median age 13.4 (range 5.0-17.3 years) were treated on Cohort A. Pts were heavily pre-treated, with 3 having relapsed after prior allogeneic stem cell transplantation; 8 of 10 had an M3 marrow (>/= 25% blasts). The first 4 pts were treated at DL1. All 4 were evaluable for toxicity and response and met the criteria for treatment success, facilitating dose escalation to DL2. At DL2, 4 pts were treated, with 2 experiencing DLT, including one grade (Gr) 5 event (Table 1). Two additional pts were subsequently treated at DL1 and achieved treatment success, confirming safety and feasibility of DL1 with a VSLI dose of 1.5 mg/m 2 in combination with UK ALL-R3 4-drug induction. Nine of 10 (90%) pts achieved a morphologic complete remission (CR), 5 of which were MRD negative. The median VSLI dose administered at DL1 was 2.3 mg (range, 1.8-3.2 mg) and at DL2 was 2.2 mg (range, 1.5-3.3 mg) demonstrating the feasibility of dosing beyond the standard vincristine dose-cap of 2 mg. Transient aspartate aminotransferase (AST) and alanine aminotransferase (ALT) elevations were seen in 8 pts, 6 of whom had a grade 1-2 toxicity. Gr 3 hepatic toxicities were seen in 3 pts: 1 each with ALT elevation and hyperbilirubinemia; ALT and AST elevation; gamma-glutamyl transferase elevation. Toxicities were generally consistent with the UK ALL-R3 regimen. Conclusions: In children with r/r ALL, the combination of UK ALL-R3 with VSLI was highly effective with an acceptable safety profile. DL1 (1.5 mg/m 2/dose) was found to be the maximum tolerated dose in combination with this intensive re-induction regimen. The trial continues to enroll at DL1 in the expansion phase to obtain additional safety and response data with this 4-drug regimen. Additionally, 2 cohorts have been added to gain further experience with VSLI in combination with 3-drug induction (Cohort B: UK ALL-R3 without mitoxantrone) and with ALL maintenance chemotherapy (Cohort C: dexamethasone, methotrexate, mercaptopurine). VSLI has potential as a vincristine dose-intensification strategy in combination with reinduction chemotherapy for r/r ALL in pediatric patients. Figure 1 Figure 1. Disclosures Hermiston: Novartis: Consultancy; Sobi: Consultancy. Whitlock: Amgen; Jazz Pharmaceuticals: Honoraria; Novartis: Research Funding; Sobi Pharmaceuticals: Consultancy. Silverman: Takeda, Servier, Syndax, Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Wayne: Spectrum/Acrotech: Research Funding; KITE/Gilead: Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2329-2329
Author(s):  
Kelli McCrum ◽  
Justin LaPorte ◽  
Asad Bashey ◽  
Scott R. Solomon ◽  
Lawrence E Morris ◽  
...  

Abstract Older patients make up the majority of those diagnosed with acute myeloid leukemia (AML), however, many of these patients are not able to tolerate intense induction chemotherapy regimens. The use of lower intensity induction such as hypomethylating agents (HMA) with or without venetoclax or other targeted therapies has widened the scope of patients who are able to receive induction chemotherapy and move towards a hematopoietic stem cell transplant. Recent data from the Center of International Blood and Marrow Transplant research showed that patients aging >64 years accounted for 26% of all allogeneic transplantations in 2019 compared to only 9% in 2009. We have previously published a report showing that induction with FLAG +/- Idarubicin (FLAG+ IDA) results in better post remission survival than '7+3'induction (Solh et al, Leuk res 2020). In order to determine how induction chemotherapy affects post-remission outcomes among older patients with AML, 289 patients over the age of 55 year who received either FLAG±IDA, 7+3, or HMA based induction at a single institution were analyzed. Median follow up was 48 months. Patient and disease characteristics were as follows: Median age 64 (55,83) years, secondary AML (10%), abnormal cytogenetics (49%), and NCCN non-favorable risk (76%). Induction regimens included FLAG+/- Ida (n=208, 72%), 7+3 (n=60, 21%) and HMA based (n=21, 7%). A total of 248 patients (86%) achieved CR/Cri after induction with a median time from induction to CR of 28 days. Patients who received induction with FLAG±IDA reached a higher rate of CR after one cycle (92% vs 75% vs 62%) and had a shorter time to CR (27 vs 33vs 55 days) compared to '7+3' or HMA based therapy (p<0.001 for both). FLAG±IDA had better overall survival and DFS 3 years post-remission compared to '7+3' and HMA OS (50%, 45%, 22%, p=0.021) and DFS (45%, 37%, 8% p=0.01) respectively. A total of 133 patients received allogeneic transplantation. Transplant rate was similar between FLAG+/- IDA (n=100) and 7+3 (n=29) at 48% and was significantly better than HMA-based induction 19% (n=4) (p=0.03). Post-transplant survival and DFS was not significantly different between FLAG+/-Ida and 7+3, however both were better compared to HMA based induction with OS (54%, 44%, 25%) and DFS (51%, 44%, 25%) . On multivariate analysis on post remission survival and disease free survival, NCCN risk and age were both associated with OS ( high risk NCCN vs others HR 3.63, P<0.001; Age per 5 year increment HR 1.16, p=0.049) and NCCN risk was the only factor associated with worse DFS ( high vs others HR 2.4, p<0.0001). The choice of induction regimen did not significantly impact post-remission survival outcomes. In conclusion, Older patients with AML achieve higher rates of complete remission, shorter time to remission and better post-remission survival with FLAG+/-IDA than 7+3 or HMA-based induction. Disclosures Solh: BMS: Consultancy; Partner Therapeutics: Research Funding; Jazz Pharmaceuticals: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1635-1635
Author(s):  
Yuxin Liu ◽  
Bohm Kywe ◽  
Lake Crawford ◽  
Federico Lora ◽  
Noffar Bar ◽  
...  

Abstract Introduction: Multiple myeloma (MM) is an incurable yet highly heterogeneous disease of clonal plasma cells. The role of induction therapy is to achieve a complete response, thereby reducing the number of malignant plasma cells in the bone marrow. Partial responses or less are considered suboptimal and are associated with poorer outcomes. Following the approval of monoclonal antibody (mAb) therapies in MM, little is known of their effect on primary refractory and suboptimal responses in real-world populations. Methods: This retrospective cohort study included patients with clinical MM who were diagnosed and treated within the Yale New Haven Health System between 2009-2019. Our primary aim was to evaluate the overall survival (OS) in patients with primary refractory (PriRef) or suboptimal responding disease compared to those who achieved at least a very good partial response (≥VGPR). PriRef disease was assessed following three months of induction therapy, and was defined as a partial response, stable disease, or progressive disease based on International Myeloma Working Group (IMWG) criteria. A stricter cutoff of less than a VGPR was chosen for our definition of PriRef, because deeper responses, including MRD-negative status, have demonstrated increasingly important prognostic value. Descriptive statistics and OS analysis were performed with 2-tailed contingency χ²-tests, t-tests, Kaplan Meier, and log-rank tests using GraphPad Prism v8. Results: 246 patients (pts) with adequate response data following 3 months of induction therapy were identified. Clinical features included median age at diagnosis of 61 years (range, 34-92), 26.8% of whom were 70 years or older, 54.9% male, 63.4% Caucasian, 24.3% Black or African American, and 11% Hispanic. 46.8% had International Staging System (ISS) stage II or III disease and 41.1% had Revised International Staging System (R-ISS) stage II or III disease. 33.3% of patients had high-risk cytogenetics, which was defined as a del17/17p, t(4:14), t(4;16), t(4;20), gain or amplification of 1q, deletion of 1p, and chromosome 1 translocations. 81.7% of this cohort received a triplet or quadruplet induction regimen. The majority of patients received triplet induction regimens that included immunomodulatory and proteasome inhibitor combinations, and only two patients were prescribed quadruplet therapy. 44.7% of patients received autologous stem cell transplant (ASCT) at some point in their treatment course, with 79.1% (87/110) in the upfront setting and 20.9% (23/110) having delayed ASCT (Table 1). In this cohort, 122 pts (49.6%) achieved ≥VGPR and 124 pts (50.4%) were PriRef. There were no significant differences in the baseline demographics, ISS, R-ISS, or cytogenetic characteristics between ≥VGPR and PriRef. PriRef patients were less likely to have been treated with at least a triplet induction regimen than ≥VGPR (74.2% vs. 89.3%, p <0.01), and they were also less likely to have undergone ASCT (37.1% % vs. 52.5%, p = 0.02). When the two cohorts were stratified by upfront versus delayed ASCT, PriRef pts still demonstrated lower rates of ASCT in both settings, but the differences were not statistically significant (Table 1). There was no significant difference in OS between PriRef and ≥VGPR pts. Median OS for PriRef was 102.9 months compared to 114.9 months in ≥VGPR (p = 0.27) (Figure 1). Out of the 124 PriRef pts, 78 (62.9%) went on to receive subsequent lines of therapy. 39.7% of these PriRef pts received a mAb, such as daratumumab, elotuzumab or isatuximab, in the 2 nd or 3 rd line setting. When stratified by whether they received mAb therapy, median OS of PriRef pts who did not receive a mAb was 86.6 months, whereas median OS was not reached for the PriRef pts who received a mAb (p=0.98) (Figure 2). Conclusions: Our cohort analysis showed that early primary refractoriness to induction in newly diagnosed MM patients was not associated with a lower overall survival, despite lower utilization of triplet regimens and ASCT. Treatment with monoclonal antibodies in the 2 nd and 3 rd line setting may explain this finding. Since the approval of mAbs for myeloma, OS appears to be beneficially impacted. However, the effect of this class of therapy is yet to be fully appreciated in the real-world setting. Therefore, longer follow up data is needed to better assess the true impact of monoclonal antibodies on primary refractory multiple myeloma patients. Figure 1 Figure 1. Disclosures Neparidze: GlaxoSmithKline: Research Funding; Janssen: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 460-460
Author(s):  
Alfredo De La Torre ◽  
Eshetu G Atenafu ◽  
Adam C. Smith ◽  
Vishal Kukreti ◽  
Anca Prica ◽  
...  

Abstract Introduction The 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. Methods We 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. Results Patient, 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 outcomes After 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. Conclusions Our 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. Figure 1 Figure 1. Disclosures Prica: 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.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2915-2915
Author(s):  
Melhem Solh ◽  
Asad Bashey ◽  
Lawrence E Morris ◽  
H. Kent Holland ◽  
Xu Zhang ◽  
...  

Abstract The routine use of autologous stem cell transplantation (ASCT) in first remission have significantly improved outcomes for patients with mantle cell lymphoma (MCL) (Hermann et al, jco 2009). The choice of the most appropriate induction regimen prior to transplant remains a controversial topic. Adding high dose cytarabine to RCHOP among young patients (<65 years) results in superior PFS, higher toxicity but no improvement in overall survival when compared to RCHOP alone (Hermine O et al, Lancet 2016). The use of bendamustine/Rituxan (BR) compared to RCHOP in 2 randomized studies showed lower toxicity, higher PFS but similar overall survival. In this study, we investigated the effect of induction regimen intensity and the use of high dose cytarabine on post autologous stem cell transplant outcomes among MCL patients treated at our center. 59 patients who received ASCT for MCL between 2010 and 2020 were included in this analysis. Data were retrieved from our database where it was entered prospectively. Median age at diagnosis was 60 (45,76) years, stage IV (85%), B symptoms (32%), MIPI score (low 17%, intermediate 47%, high 28%) and ECOG performance 0-1 (81%). Induction regimen included BR (n=14), RCHOP (n=11), R-Hyper CVAD (n=14), RBAC(n=2) and RCHOP/RDHAP (n=18). 85% of patients were in CR and 15% in PR at time of transplant. All patients underwent chemo mobilization with a median time from diagnosis to transplant of 251 (119,1372) days. 30 patients (51%) received post-transplant rituximab maintenance. Patients were compared into 2 groups based on the use of high dose cytarabine in their induction regimen (table 1). Patients who received high dose cytarabine were younger and had a shorter time from diagnosis to transplant that patients who were treated without cytarabine. Survival endpoints for cytarabine based and no cytarabine based induction at 5 years post-transplant were as follows OS (82% vs 69%), DFS (65% vs 50%), Non-relapse mortality (4% vs 9%) and relapse (31% vs 41%) respectively ( figure 1). A multivariable cox analysis for OS, DFS, NRM and relapse showed that cytarabine had no effect on any of the endpoints. For OS, B symptoms and worse ECOG performance at Diagnosis (>=2) were associated with worse OS. For relapse, higher MIPI score and no use of Rituxan maintenance resulted in higher relapse. In conclusion, our data shows that among MCL patients receiving ASCT, the use of more intensive cytarabine based induction does not clearly improve long-term outcomes It is possible that use of ASCT compensates for the use of a less intense induction regimen. Disease (MIPI), Patient (ECOG)characteristics and use of post-transplant maintenance are factors that contribute to post transplant outcomes. Figure 1 Figure 1. Disclosures Solh: Jazz Pharmaceuticals: Consultancy; Partner Therapeutics: Research Funding; BMS: Consultancy; ADCT Therapeutics: Consultancy, Research Funding.


Author(s):  
J Slobodan ◽  
I Pecuh ◽  
J McCombe ◽  
F Morneau-Jacob ◽  
P Smyth ◽  
...  

Background: Rituximab is a B-cell-depleting monoclonal antibody whose off-label use is funded in Alberta by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric central nervous system (CNS) inflammatory disorders in Alberta. Methods: Rituximab applications for CNS inflammatory indications in patients < 18 years of age were identified from the STEDT database between January 1, 2012 – December 31, 2019. Patient information was linked to other provincial datasets, including the Discharge Abstract Database, Pharmaceutical Information Network, and provincial laboratory data. Analysis was descriptive. Results: 51 unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis (other than anti-NMDA receptor encephalitis; n=20, 39%). Most children were approved for a two-dose (n=33, 66%) or four-dose (n=16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets. Conclusions: The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring, as well as regional disparities in use.


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