ALBERT

Description: Introduction: Asciminib is a new BCR-ABL1 inhibitor that differs from previous tyrosine kinase inhibitors (TKIs) in that it does not bind to the ATP-binding site of the kinase. Data from different clinical trials has shown an adequate safety and efficacy profile in chronic myeloid leukemia (CML) patients failing previous TKIs. However, no findings have been communicated in real life experience. The aim of our study is to present first results of asciminib in CML patients failing previous TKIs under the current compassionate use program. Methods: We retrospectively collected data from 31 patients treated with asciminib in 25 centers under compassionate use program. Data collecting was performed between October 2018 and June 2020. Patients baseline characteristics are shown in table 1. Most patients were heavily pretreated with 28 patients receiving 3 or more TKIs previous to asciminib. Eleven patients (35.5%) had been treated with ponatinib at some point throughout the disease. Twelve patients showed BCR-ABL1 mutations (only 1 case with T315I mutation). Switch to asciminib was due to intolerance in 22 patients and due to resistance in the remaining 9. Median dose of asciminib was 80mg per day (40mg every 12 hours). Treatment responses were evaluated according to European Leukemia Net recommendations. Data compilation and analysis were performed with REDCap Software and IBM SPSS (Version 25.0). Results: Median time on asciminib for the entire cohort was 35 weeks. Regarding toxicities, 13 patients (42%) experienced mild extra-hematological side effects (grade 1-2) being the most frequent fatigue (19%), joint pain (16%) and nausea (9%). Four patients (12,9%) showed severe (grade 3-4) extra-hematological events: fatigue, hepatotoxicity, hypertension and pericardial effusion (1 patient each). Three patients (9,7%) suffered from grade 4 thrombocytopenia, 2 of them associating grade 4 neutropenia. All toxicities according to previous TKIs adverse effects as well as cross-intolerance data is shown in table 2. Dose reduction had to be carried out in 9 patients (29%), 7 of those with temporary treatment interruptions; most owing to hematological adverse effects. In terms of efficacy (Graph 1), probability of reaching or at least maintaining previous response was 100%, 61.3% and 35.5% for complete hematological response (CHR), complete cytogenetic response (CCyR) and major molecular response (MMR), respectively. Regarding probabilities to improve previous responses, rates of CCyR and MMR were, respectively, 22,2% (2/9) and 22,2% (2/9) for resistant patients and 44% (4/9) and 62,5%. (10/16) for intolerant group. Amid the 11 patients previously treated with ponatinib, 3 patients (27,3%) showed improvement of response achieving at least MMR, 2 of them from the TKI-intolerant group and 1 from the TKI-resistant group. The median follow-up time was 40 weeks, after which 27 patients (87.1%) continued with asciminib. Treatment cessation happened in 2 patients due to progression to blastic phase and in 2 patients due to lack of efficacy. No patients discontinued due to side effects. Conclusion: The data presented, similar to that known from clinical trials, supports the use of asciminib in routine clinical practice in CML patients failing to previous TKIs. Disclosures Garcia-Gutiérrez: Novartis: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Bristol-Myers Squibb: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Pfizer: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding; Incyte: Consultancy, Other: Travel, Accommodation, Expenses, Research Funding.

Description: Introduction. The combination of lenalidomide and rituximab (or R2) has been demonstrated to be an effective frontline treatment for patients with advanced stage follicular lymphoma (FL), and it has been increasingly used over the last few years. However, limited data exist regarding the management and outcome of patients who relapse and/or progress after frontline R2. Methods. In a retrospective study of patients with advanced stage FL grade 1-3A treated with frontline R2 at MD Anderson Cancer Center between 08/2008 and 01/2020, we examined treatment strategies and outcomes for patients who progressed/relapsed and required salvage therapy. Response was retrospectively assessed according to 2014 Lugano response criteria. Survival outcomes were calculated from time of first salvage therapy. Results. Among 156 patients with advanced stage FL treated with frontline R2, 33 (21%) relapsed/progressed and required salvage therapy, with a median time to first salvage therapy of 33 months (range, 1-122 months); 12 (8%) patients relapsed within 24 months, and no patients showed transformation at time of first relapse. At time of first relapse/progression, 12 (36%) patients were older than 60 years, 19 (57%) were male, 9 (27%) had high risk FLIPI, and 1 relapsed with localized disease. Overall, the median number of salvage systemic therapies after R2 was 1 (range, 0-4), and maintenance following any line of salvage was used in 7 (21%) patients; 1 (3%) patient each had autologous or allogeneic stem cell transplant, both had progressed within 24 months of frontline R2. First salvage therapy was: bendamustine with an anti-CD20 monoclonal antibody (MAb) in 8 (24%) patients, RCHOP in 8 (24%), an anti-CD20 MAb alone in 8 (24%), a clinical trial in 6 (18%), repeated R2 in 2 (7%), and radiotherapy (XRT) in 1 patient with localized disease. Thirty-two patients were evaluable for response after first salvage therapy: the overall response rate was 78% and complete response rate was 72%. After a median follow-up of 51 months (95%CI, 27-75 months) from time of first salvage therapy initiation, 17 patients progressed/died, and median PFS was 38 months (95% CI, 1-82 months). None of the baseline characteristics collected at time of first salvage therapy were significantly associated with PFS. Median PFS was significantly longer in patients who received chemoimmunotherapy (CIT) as compared to biological therapy (BIO) at relapse (99 vs 25 months, p=0.004)(Figure). Transformation was identified in 2 (7%) patients, 2 and 20 months after initiation of first salvage therapy. At most recent follow-up, 2 (7%) patients died (1 of unknown cause, 1 of transformed FL), and median OS has not been reached (Figure). Second cancers (excluding transformation) were diagnosed in 1 (2%) patient after first salvage chemotherapy, and was represented by a pancreatic adenocarcinoma, after 74 months. Discussion. Chemoimmunotherapy is an effective treatment strategy for patients with FL who relapse after frontline R2. The optimal salvage therapy for these patients needs to be prospectively investigated. Tissue samples derived from patients included in this study are being analyzed at our institution, and changes occurring in the tumor microenvironment are being characterized. Figure Disclosures Westin: Kite: Consultancy; Genentech: Consultancy; 47 Inc: Consultancy; MorphoSys: Consultancy; Unum: Consultancy; Juno: Consultancy; Curis: Consultancy; Novartis: Consultancy; Janssen: Consultancy. Lee:Guidepoint Blogal: Consultancy; Celgene: Research Funding; Oncternal Therapeutics: Research Funding; Takeda: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Aptitude Health: Speakers Bureau. Neelapu:Celgene: Other: personal fees, Research Funding; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Takeda Pharmaceuticals: Patents & Royalties; Cellectis: Research Funding; Adicet Bio: Other; Calibr: Other; Unum Therapeutics: Other, Research Funding; Poseida: Research Funding; Incyte: Other: personal fees; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Acerta: Research Funding; Allogene Therapeutics: Other: personal fees, Research Funding; Karus Therapeutics: Research Funding; Pfizer: Other: personal fees; N/A: Other; Novartis: Other: personal fees; Cell Medica/Kuur: Other: personal fees. Vega:NCI: Research Funding. Fowler:TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding. Nastoupil:Karus Therapeutics: Research Funding; Gamida Cell: Honoraria; Celgene: Honoraria, Research Funding; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Pfizer: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Genentech, Inc.: Honoraria, Research Funding; Bayer: Honoraria.

Description: Introduction: Mantle cell lymphoma commonly presents as classic variant histology, however 10-30% patients (pts) can transform into an aggressive histology (blastoid and/or pleomorphic variants). We have previously reported that genomic profile and clinical outcomes of transformed MCL pts are distinct from classic variant pts who never transformed (CNT) and that transformed pts have poor clinical outcomes. In this study, we analyzed the factors at initial diagnosis which can predict the time to transformation and the risk for transformation in a cohort of 369 pts with MCL. Methods: We analyzed charts from 369 pts with MCL (293 were CNT and 76 were transformed MCL). Statistical analysis was performed from baseline pt characteristics collected from the time of initial diagnosis in CNT group and at the time of initial diagnosis of classic variant MCL who later transformed (t-MCL). Time to transformation (TTT) was calculated from initial diagnosis to the date of transformation in those who transformed and last follow up in those who never transformed. Univariate and multivariate (MVA) logistic regression modeled the risk of transformation. Classification and regression tree (CART) analysis was performed to identify optimal cut off in categorical variables predictive of TTT. Results: Among the 369 pts, the median age was 62 yrs (range 34-90). Ki-67% values were available in 133 pts (36% of total) and median Ki-67% was 25% (range 1-80). Three hundred eight pts (84%) had initial bone marrow involvement and 66 pts (18%) had leukemic phase at diagnosis. The median follow up was 133 months and the median overall survival (OS) was 95 months and 43% were alive at the time of this analysis. Discernible difference were noted in pts who belong to t-MCL group compared to pts in the CNT group, pts in t-MCL group exhibited - higher values of median Ki-67% (30% vs 20% in CNT; p=0.04), higher LDH levels, higher proportions of pts with high risk simplified MIPI risk score, leukemic phase at initial diagnosis, complex karyotype and lower hemoglobin. First line treatments received by both groups were similar. Eleven pts got anti-CD19 CART therapy at some point and 7 pts were t-MCL and 4 were CNT group. The median time to transformation in months for those who transformed was 39 (range 5-240 months) while in CNT it was 51 months (1-257 months). We further identified that incremental Ki-67% was significantly associated with TTT and OS (Figure-1A-B). Using CART analysis we identified Ki-67% ≥60 is significantly associated with shorter TTT (HR, 6.26; 95% CI 2.58-15.21; p 729 IU/L), higher platelet count 〉 180 and high absolute lymphocyte count 〉 5000 k/ul were predictive of shorter TTT. Logistic regression model showed factors associated with the risk of transformation. In univariate analysis, higher risk was significantly associated with Ki-67% as a continuous variable - OR 1.03 (95% CI 1.01-1.05; p=0.006), leukemic phase at diagnosis, high risk MIPI score and complex cytogenetics. First line treatment with ibrutinib compared to R-HCVAD, was associated with decreased risk of transformation. In MVA, ibrutinib/BTK inhibitor therapy (n=51) as first line therapy was associated with decreased risk of transformation while CNS involvement was associated with higher risk of transformation. Conclusions: Routinely available clinical variables can help determine the risk for transformation of MCL and time to transformation. Progressive increase in Ki-67 and high MIPI risk score is associated with shorter TTT and increases the risk for transformation. Earlier usage of BTK inhibitor therapy may reduce the risk of developing histologic transformation in MCL pts. Disclosures Lee: Seattle Genetics: Research Funding; Takeda: Research Funding; Aptitude Health: Speakers Bureau; Oncternal Therapeutics: Research Funding; Guidepoint Blogal: Consultancy; Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Vega:NCI: Research Funding. Flowers:Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Research Funding; OptumRx: Consultancy; TG Therapeutics: Research Funding; BeiGene: Consultancy; Denovo Biopharma: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Kite: Research Funding; Bayer: Consultancy. Wang:Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Beijing Medical Award Foundation: Honoraria; Dava Oncology: Honoraria; Molecular Templates: Research Funding; Verastem: Research Funding; InnoCare: Consultancy; Nobel Insights: Consultancy; OncLive: Honoraria; Loxo Oncology: Consultancy, Research Funding; MoreHealth: Consultancy; Oncternal: Consultancy, Research Funding; Targeted Oncology: Honoraria; Acerta Pharma: Research Funding; Guidepoint Global: Consultancy; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Lu Daopei Medical Group: Honoraria; Juno: Consultancy, Research Funding; VelosBio: Research Funding; BioInvent: Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding.

Description: Background - We investigated the efficacy and safety of using a combination of ibrutinib plus rituximab (IR) followed by short course (4 cycles) of R-HCVAD/MTX-ara-C as consolidation in previously untreated young (age ≤ 65 years) patients (pts) with mantle cell lymphoma (MCL). Using a chemo-free induction may reduce the toxicities, complications and the risk of second cancers which were observed with intensive chemoimmunotherapy regimen in MCL pts. Methods - We enrolled 131 previously untreated pts in this single institution, single arm, phase II clinical trial - NCT02427620. Pts received IR induction (part-A), until they achieved complete remission (CR) for up to a maximum of 12 cycles, followed by a maximum of 4 cycles of R-HCVAD/R-MTX-ara-C (part-B) as consolidation. None of the pts received stem cell transplant or maintenance therapy. The primary objective was to assess overall response rate (ORR), [defined as either a partial response (PR) or a complete response (CR)] after part A. Adverse events were coded as per CTCAE version 4. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response, clonal evolution and MRD using circulating tumor DNA (ctDNA), whole exome (WES) and bulk RNA sequencing from baseline tissue samples was performed. Results - Among the 131 pts, the median age was 56 yrs (range - 35-65). High Ki-67 (≥30%) in 58/117 (49.5%) pts, 10 pts (8%) had high risk simplified MIPI score, 15 pts (11%) had aggressive MCL (blastoid/pleomorphic) and 114 pts (87%) had initial bone marrow involvement. Seventeen pts (13%) had had complex karyotype and 83% had positive SOX-11 expression. Baseline PET scan was available in 101 pts and 97 pts had PET positive disease. Median number of cycles on IR in part A was 7 (1-12). At week 16 on part A, the ORR was 95% (15% CR and 80% PR) and 5% pts had stable disease. Overall best response (ORR) on part A of therapy was 100% (88% CR and 12% PR) and at the time of last follow up after completion of part A and part B, ORR was 100% (98% CR). Median time to CR was 5 months (range 1-16). Pts with CR within 6 months are "early" CR (n=66) and those with CR ≥ 6 months were "late" CR (n=49) while pts who never had CR were grouped as no CR (n=13). With a median follow up of 37 months, the median PFS and OS were not reached (3 year 82% and 95% respectively). Twenty two pts (17%) relapsed after treatment, including 6 who transformed to aggressive MCL. PFS among pts with high and low Ki-67% was 58 months vs not reached (P=0.03) while no difference was observed in OS. PFS was significantly shorter in pts with aggressive histology (p=0.003) but not the OS. Overall 6 pts died (2 with progression, 2 due to disease transformation, one on study due to multiple complications including splenic hematoma, cardio-pulmonary arrest and progression and the last one expired outside and came off study due to encephalitis). Forty two pts came off study for various reasons [16 disease progression (including 4 transformation), 20 pt choice, 3 intolerance, two second cancer and one lost to follow up]. Grade 3-4 toxicities on part A were 4% myelosuppression and 8% each with fatigue, myalgia and rashes and 4% mucositis. None had grade 3-4 atrial fibrillation or bleeding. WES in 76 pts revealed deletions of BANK1, CCND1, TP53, UBR5, ATM, RB1, CDKN2A and BCL2 in late CR (n=14) (≥ 6 months) and no CR (n=12) pt groups vs early CR (〈 6 months; n=30). KMT2C, NCOR2 SMARCA4 and NSD2 mutations were significantly different in late CR vs early CR groups. Furthermore, 68 pts had bulk RNA sequencing and a differential gene expression pattern was identified separating early vs late vs no CR groups. Immune response pathways were overexpressed in early CR pts while oncogenic signaling pathways were clustered in late CR and no CR groups. Conclusions - Chemo-free induction with IR induced durable and deep responses in young MCL pts in the frontline setting. Short course R-HCVAD chemotherapy minimized toxicities and consolidated responses. This combined modality treatment approach may significantly improve young MCL pts outcomes across all risk groups. Pathway analysis demonstrated immune response pathways to be associated with early CR on IR. Detailed analyses on MRD using ct-DNA will be reported. Disclosures Wang: Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; MoreHealth: Consultancy; Pulse Biosciences: Consultancy; Molecular Templates: Research Funding; OncLive: Honoraria; VelosBio: Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Acerta Pharma: Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding; Nobel Insights: Consultancy; Guidepoint Global: Consultancy; Lu Daopei Medical Group: Honoraria; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Beijing Medical Award Foundation: Honoraria; Verastem: Research Funding; Dava Oncology: Honoraria. Lee:Celgene: Research Funding; Guidepoint Blogal: Consultancy; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Aptitude Health: Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Research Funding. Westin:BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; Amgen: Consultancy; 47: Research Funding; Kite: Consultancy, Research Funding. Nastoupil:TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Celgene: Honoraria, Research Funding; Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gamida Cell: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Karus Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Gilead/KITE: Honoraria. Vega:NCI: Research Funding. Flowers:Millennium/Takeda: Consultancy, Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; TG Therapeutics: Research Funding; OptumRx: Consultancy; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; Burroughs Wellcome Fund: Research Funding; Gilead: Consultancy, Research Funding; Eastern Cooperative Oncology Group: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy; AbbVie: Consultancy, Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Celgene: Consultancy, Research Funding.

Description: Introduction: Acalabrutinib is an irreversible BTK inhibitor (BTKi) in the treatment of relapsed patients (pts) with mantle cell lymphoma (MCL). We and others have previously reported that ibrutinib resistant MCL have poor outcomes and BTK mutations are uncommon in ibrutinib resistant MCL. However, the outcomes, causes of discontinuation, management and mutational landscape in MCL pts who discontinued acalabrutinib are not described. Methods: We reviewed charts from all relapsed MCL pts treated with acalabrutinib (n=26) in the relapsed setting and identified 21 pts who discontinued acalabrutinib, described in this analysis. Outcomes and management of patients after discontinuing acalabrutinib are reported. Whole-exome sequencing (WES) with SureSelect Human All Exon V6 was performed in 9 pts who progressed on acalabrutinib (10 tumor specimens and 5 matched germline samples); among these pts, 4 tumors were collected before acalabrutinib and 6 were collected after progression on acalabrutinib. One patient had paired sample at both time points (baseline and progression). Results: Among the 21 pts who discontinued acalabrutinib, 15 (71%) discontinued due to disease progression (2 pts transformed from classic to pleomorphic MCL at progression) and 6 discontinued due to intolerance (one for fatigue and idiopathic encephalopathy, one due to unrelated severe aortic stenosis, 2 others due to therapy related myelodysplasia and 2 due to cardiac issues). Two pts with cardiac issues had pre-existing coronary artery disease and one of them developed new onset atrial fibrillation. Overall, the median number of prior treatments was 2 (range, 1-3); all had prior chemo-immunotherapy and none with ibrutinib. The median duration on treatment with acalabrutinib was 8.3 months (1 to 50 months) and the median number of cycles of acalabrutinib treatment was 8 (range, 1-53). Thirteen pts had complete remission (CR) as their best response on acalabrutinib, 5 were primary refractory and 3 achieved partial remission. At the time of starting acalabrutinib, 12 pts had classic and 9 pts had blastoid (n=6) or pleomorphic (n=3) features, the median Ki-67 expression was 50% (range, 10-100). Pts who progressed, received acalabrutinib for a median duration of 8.3 months (range, 1-50) while those with intolerance, received acalabrutinib for a median duration of 9.4 months (range, 4-31). Median follow up after discontinuation was 38 months and the median post acalabrutinib survival was 24 months (not reached for progression and 7.4 months for intolerance; p =0.02, Figure-1A-B). Patients who discontinued due to intolerance could not get subsequent treatment for MCL. Among the 15 pts who progressed on acalabrutinib, 14 pts received systemic therapies for MCL [eight received ibrutinib based therapies (4 non responders, 3 achieved CR and 1 were PR and all pts progressed subsequently), 5 got chemo-immunotherapy, bortezomib, lenalidomide and progressed and one pt did not receive any treatment and was lost to follow up and died. Among the 15 pts who progressed on acalabrutinib, 6 patients who received anti-CD19 CAR-T therapy had significantly longer survival compared to those who did not get CART therapy; p = 0.007, Figure-1C. For all pts, at the time of last follow up, 10 pts were alive and in remission under follow up while 11 were dead. Recurrently mutated genes in these tumors included ATM (6/10; 60%), TP53 (4/10; 40%), KMT2C (3/10), MYCN (2/10), NOTCH1 (2/10), NOTCH3 (2/10), and MEF2B (2/10) (1-D). We did not detect any mutation or copy number alterations in BTK, PLCG2, TRAF2/3 and MYD88 that have been reported previously to be associated with ibrutinib resistance. To investigate the mutation evolution on acalabrutinib treatment, mutation profiles, particularly the mutation variant allelic fractions (VAFs), were compared between the baseline and progression samples from one patient. Mutation of MYCN, MEF2B, ATM, and NOTCH1 were identified in both tumors at similar VAFs, whereas mutation of CARD11 (two mutations), NLRC5 and B2M were detected only at progression. Conclusions: Relapsed MCL pts who fail acalabrutinib have poor outcomes. Advent of CART therapy has significantly improved survival of these heavily refractory pts. In this small cohort, we did not observe BTK mutations associated with acalabrutinib resistance in MCL pts. Further studies are ongoing to determine acalabrutinib resistance mechanism in MCL. Disclosures Lee: Takeda: Research Funding; Aptitude Health: Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding; Seattle Genetics: Research Funding; Oncternal Therapeutics: Research Funding; Guidepoint Blogal: Consultancy; Celgene: Research Funding. Westin:Astra Zeneca: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Morphosys: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Amgen: Consultancy; Kite: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; 47: Research Funding. Nastoupil:LAM Therapeutics: Research Funding; TG Therapeutics: Honoraria, Research Funding; Merck: Research Funding; Novartis: Honoraria, Research Funding; Gilead/KITE: Honoraria; Gamida Cell: Honoraria; Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Vega:NCI: Research Funding. Flowers:Denovo Biopharma: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Pharmacyclics/Janssen: Consultancy; Celgene: Consultancy, Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Research Funding; Bayer: Consultancy; Eastern Cooperative Oncology Group: Research Funding; AbbVie: Consultancy, Research Funding; Millennium/Takeda: Consultancy, Research Funding; Kite: Research Funding; Spectrum: Consultancy; National Cancer Institute: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Burroughs Wellcome Fund: Research Funding; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; BeiGene: Consultancy; Acerta: Research Funding. Wang:AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Nobel Insights: Consultancy; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; VelosBio: Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; Oncternal: Consultancy, Research Funding; Molecular Templates: Research Funding; Beijing Medical Award Foundation: Honoraria; OncLive: Honoraria; Dava Oncology: Honoraria; Verastem: Research Funding; Guidepoint Global: Consultancy; Lu Daopei Medical Group: Honoraria; InnoCare: Consultancy; Acerta Pharma: Research Funding; BioInvent: Research Funding; Juno: Consultancy, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Pulse Biosciences: Consultancy; Loxo Oncology: Consultancy, Research Funding; Targeted Oncology: Honoraria; OMI: Honoraria, Other: Travel, accommodation, expenses.

Description: Introduction: Complex karyotype (Cx) refers to ≥3 unrelated cytogenetic abnormalities in addition to t(11;14) in MCL patients (pts). In limited pts treated with chemotherapy, pts with Cx exhibited poor outcomes compared to non-Cx group. Prognostic impact of Cx in pts treated with BTKi is unclear. We present the largest and most comprehensive analysis on the prognostic impact of Cx in MCL pts. Methods: We analyzed charts from 396 MCL pts with karyotype data. (271 were non-Cx and 125 were Cx). Karyotype status at initial MCL diagnosis was denovo (DN) while previously treated pts were secondary (S). Among Cx, n=80 pts were DN-Cx and 45 were S-Cx while in non-Cx group, 224 were DN-non-Cx and S-non-Cx were 47 pts. TP53 mutation/FISH data was available (n=134; 46 positive, 88 negative). Pt characteristics were obtained from the time of karyotype testing (at initial diagnosis in DN and at the time of testing in S group). Overall survival (OS) was calculated from test date to the last follow up and progression free survival (PFS) after first line therapy from treatment date to date of progression/death. Univariate and multivariate logistic regression modeled the risk of event and treatment response. Results: Cx pts had significant differences compared to non-Cx, including median Ki-67 (40 vs 20%), sMIPI (median 6 vs 4), poor performance status (p.s.), CNS involvement (7 vs 2%), blastoid (22 vs 7%), pleomorphic (12 vs 3%), higher LDH, WBC, ALC and β2M levels and low Hb and platelet counts, prior BTKi (35 vs 15%), TP53 positive (75 vs 17%), shorter median follow up from the test date (18 vs 33 months). Overall, 70 (56%) in Cx and 70 (26%) in non-Cx had died. Univariate analysis for OS showed, advanced age, higher values of Ki-67, WBC, LDH, β2M, MIPI scores, number of chromosomal aberrations, B symptoms, splenomegaly, CNS involvement, poor p.s., prior BTKi, blastoid/pleomorphic histology, TP53 positive status, non-responder to first line therapy and Cx (median 35 months vs 101 months in non-Cx respectively; p

Description: Background/Purpose The recognition of the contribution of Helicobacter pylori (H. pylori) (Carmel et al Am J Gastroenterol 2001 96: 63.), plasma cell dyscrasias (Baz et al Cancer 2004 101:790.), autoimmune polyendocrine syndromes (APS), and other autoimmune disease to vitamin B12 absorption and pernicious anemia has lead to an appreciation of a more varied presentation of the disease. The purpose of this study is to document the spectrum of the disease as manifest in a cohort of patients diagnosed with pernicious anemia in a rheumatology clinic. Methods A retrospective chart review of history and physical, laboratory and x-ray studies was conducted among patients diagnosed with pernicious anemia over a 10 year period. Pernicious anemia was diagnosed on the basis of having had a low vitamin B12 level and the presence of intrinsic factor (IF) and/or anti-parietal cell antibodies (APA). Results A total of 150 patients, 106 female and 44 males ranging in age from 32-101 (mean 77.8) were diagnosed. Initial referral was based on acute fracture in 41, rheumatoid arthritis-30, arthritis-30, osteoporosis-16, pain-15, autoimmune disease-9, systemic lupus erythematosus-7, psoriasis-2. There was a history of major osteoporotic fracture in 55, heartburn-73, past peptic ulcer disease-16, thyroid disease-42, type 1 diabetes-12, and vitiligo-2. Fifty patients were taking a PPI. 101 patients had a sensory deficit at the level of the ankle including 38 with findings of glove and stocking sensory loss. Seventy one patients had IF antibodies, 53 had APA, and 26 had both IF and APA antibodies. Only 25 patients were anemic with 2 patients having an MCV 〉100 fL and 5 with a low iron. Folic acid was 8 ng/mL〈 in 9 patients with a predominance of IF antibodies (p=0.039). Vitamin D was

Description: Background: Compared to other peripheral T cell lymphomas (PTCLs), patients with AITL have an aggressive clinical course and poor outcomes with conventional chemotherapies. Previous studies reported overall survival (OS) of

Description: Introduction: The current coronavirus disease- 2019 (COVID-19) pandemic has caused a sudden increase in pneumonia cases, with a case-fatality rate of 10.9% in Mexico. Two inpatient groups have been defined, with different clinical evolution: cases of severe pneumonia and those with life-threatening disease (Acute respiratory distress syndrome [ARDS], invasive mechanical ventilation [IMV] requirement, and multiorgan involvement). Currently, there is no effective treatment. Convalescent plasma (CP) has been used to treat another viral infections and outbreaks since the last century. The rationale is that neutralizing antibodies contained in CP suppress viremia and produce immunoregulation. However, an established therapeutic dose during this pandemic is lacking. Aim: To evaluate in a phase I trial the minimum effective dose of CP in severe and life-threatening disease patients and then carry out a phase II study to establish the effectiveness (overall survival at 30 days) comparing it with a non-randomized control group. Methods and design. Our study is an open-label, multicenter, non-randomized and started in May, 2020 and was approved by the ethics committee at HGE & HCN Pemex; respectively. CP donor selection: pre-donors who were infected by SARS-CoV-2 were evaluated on +30 day by serum titration (≥1:320 IgG antibody); then connected to apheresis machine to obtain 600 ml of CP that were fractionated in 200 ml bags and stored. Patients: Two groups were formed: severe and life-threating disease. CP was offered to patients who were admitted on two hospitals. Patients should meet the following criteria: SARS-CoV-2 positive for qRT- PCR, respiratory rate〉 30 per minute or Kirby index