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In: Transplantation and Cellular Therapy, Elsevier BV, ( 2023-11)

Type of Medium: Online Resource

ISSN: 2666-6367

URL: Article

DOI: 10.1016/j.jtct.2023.11.010

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 3056525-X

In: Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 2 ( 1998-02), p. 141-144

Type of Medium: Online Resource

ISSN: 0148-7043

URL: Article

DOI: 10.1097/00000637-199802000-00006

Language: English

Publisher: Ovid Technologies (Wolters Kluwer Health)

Publication Date: 1998

detail.hit.zdb_id: 2063013-X

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4899-4899

Abstract: Introduction: High-dose chemotherapy and autologous hematopoietic cell transplant (HDT-AHCT) is considered a standard-of-care (SOC) consolidation therapy for patients with aggressive systemic non-Hodgkin (NHL) and Hodgkin lymphomas (HL). This therapy is associated with improved survival in relapsed/refractory NHL and HL as well as in first complete remission in mantle cell lymphoma. The most widely used HDT regimen consists of carmustine, etoposide, cytarabine and melphalan (BEAM). Although potentially curative, significant morbidities occur with HDT, especially in older patients. Aside from the expected severe hematologic toxicities, the most common clinically meaningful morbidities include signs and symptoms related to severe alimentary tract mucositis such as CTCAE Grade ≥ 3 nausea/vomiting, diarrhea and oral mucositis and febrile neutropenia (FN). The majority of FN, other infectious complications and sepsis are thought to occur due to translocation of the normal gut flora into the peripheral circulation in the presence of oral/GI mucositis. In the present study, we retrospectively analyzed patients undergoing HDT-AHCT for lymphoma in a contemporary cohort from 2 academic transplant centers, focusing on rates of oral/GI severe regimen related toxicity (SRRT) and febrile neutropenia. Methods: We conducted a retrospective analysis of 143 consecutive adult patients from 2 transplant centers undergoing HDT-AHCT as SOC consolidation for a diagnosis of NHL or HL between 2018 and 2020. The protocol was approved by the IRB at both institutions. Standard prophylactic and supportive care were provided as per institutional guidelines for HDT-AHCT. Toxicities were graded by CTCAE v5 criteria. SRRT was defined as oral/GI grade 3 or higher (G≥3) including adverse events related to alimentary tract mucositis. Partial response (PR) and complete response (CR) were defined by Lugano criteria. Statistics presented are descriptive only with no multiplicity adjustments. Results: 143 patients were included in the analysis, 99% (n=141) of whom received BEAM for the HDT regimen, while 1% (n=2) received BeEAM (bendamustine in place of carmustine) (Table 1). 71% had NHL, while 29% had HL. Median prior lines of therapy were 2 (range, 1-4). Median CD34+ cell count was 4.3 x10 6 cells/kg (range, 1.9-19.6). Oral/GI SRRT occurred in 45% (n=65) of patients, with the most common G≥3 GI toxicities being diarrhea (26%), nausea / vomiting (20%), and oral mucositis (10%) (Table 2). Importantly, rates of SRRT were higher among patients ≥65 (63% vs 41%, p=0.031). The predominant differences were higher rates of G≥3 diarrhea (44% vs 21%, p=0.011), nausea (28% vs 18%, p=0.214) and oral mucositis (16% vs 8%, p=0.215). Considering only oral/GI SRRT of oral mucositis, nausea / vomiting, diarrhea (SSRT4), the overall rate of SRRT4 was 41%, with 56% and 37% occurring in patients ≥65 yo and & lt;65 yo respectively. Rates of SRRT were similar regardless of gender, disease, number of prior lines of therapy or best response at the time of HDT-AHCT (Table 3). Interestingly, rates of FN were also numerically higher among older adults (75% vs 64%, p=0.247). Consistent with the notion that GI toxicity predisposes to bacterial translocation from the gut, patients with SRRT had numerically higher rates of FN compared to those without (74% vs 60%, p=0.088). Time to engraftment and length of hospital stay did not appear to vary by age group (Table 4). Conclusion: We identify severe GI toxicities including alimentary mucositis as a significant source of morbidity in patients receiving HDT-AHCT for lymphoma. Older age increases risk with 63% of the elderly experiencing ≥G3 GI toxicities and 72% experiencing FN. New therapies that have the potential to revive the alimentary tract repair mechanism will not only have impact on reducing severe oral/GI toxicities but will also enhance innate immunity by preventing translocation of bacteria into the bloodstream from the GI tract, as indicated by the association between SRRT and FN in our cohort of patients. Figure 1 Figure 1. Disclosures Shouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Aggarwal: Kadmon: Current equity holder in publicly-traded company, Ended employment in the past 24 months; Angiocrine Bioscience: Current Employment, Current holder of stock options in a privately-held company. Kavalerchik: Angiocrine Bioscience: Current Employment, Current holder of stock options in a privately-held company. Frazer: Angiocrine Bioscience: Current Employment, Current holder of stock options in a privately-held company. Finnegan: Angiocrine Bioscience: Current Employment, Current holder of stock options in a privately-held company. Fakhri: Loxo/Lilly: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-151018

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2502-2502

Abstract: Introduction: Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) or other B-cell lymphomas. However, the potent anti-lymphoma effect of CAR-T is balanced by the risk of acute toxicities, namely cytokine release syndrome (CRS) and Immune effector cell-Associated Neurotoxicity Syndrome (ICANS), as well as the variable length of progression-free survival (PFS) after CAR-T. Tools to better risk-stratify for adverse outcomes and to guide targeted interventions are lacking. Sarcopenia (loss of lean muscle mass) is an important cause of age-related functional decline in the general population and is an independent predictor of health outcomes in patients with solid and hematologic cancers, irrespective of age or comorbidity. Advances in software technology have facilitated the near real-time integration of body composition measurements into imaging studies obtained as part of standard clinical care. To date, there have been no studies to examine the association between sarcopenia and outcomes after CAR-T therapy. Methods: Using a retrospective cohort design, 280 consecutive patients with DLBCL or B-cell lymphoma, age ≥18y, and treated with CAR-T therapy between 2015 to 2020 at a single center were included in the study. This analysis was restricted to 226 (80.7%) patients with available computed tomography scans ≤60d from CAR-T. Skeletal muscle area was ascertained from abdominal scans using an automatic image analysis software (APACS; Voronoi Health Analytics; Vancouver, Canada); 3rd lumbar vertebra was used as a landmark because of its high correlation with whole-body muscle mass (J Clin Oncol 2016 34:1339); Figure. Trained researchers blinded to patient demographics and outcomes manually validated these measurements (SliceOmatic; Tomovision; Quebec, Canada). Skeletal muscle index (SMI) was calculated as the ratio of skeletal muscle area (cm 2) divided by height (m). Sarcopenia was defined according to sex-based cutoffs (lowest SMI tertile). Kaplan-Meier method was used to examine PFS at one-year. Multivariable regression was used to calculate the hazard ratio (HR) for PFS and odds ratio (OR) for toxicities with 95% confidence intervals (CI), adjusted for covariates (demographics [age, race/ethnicity], disease characteristics [largest lymph node diameter, blood lactate dehydrogenase] , CAR-T product, ECOG performance status). Results: Median age at CAR-T was 63y (range: 18-84); 65.9% were male; 50.9% were non-Hispanic white; 8.8% had ECOG ≥2; 80.5% had a diagnosis of DLBCL; CAR-T products: axicabtagene ciloleucel (51.3%), lisocabtagene maraleucel (31.9%), other (16.8%); 46.9% were treated on a clinical trial; median residual lymph node diameter prior to CAR-T was 2.3cm (range: 0-17.2); 8.0% underwent HCT & lt;1 year after CAR-T and follow-up was censored at HCT. Outcomes: 59.1% developed CRS (18.2% grade ≥2) and 30.1% developed ICANS (15.9% grade ≥2). In adjusted analyses, the odds of developing CRS or ICANS was 1.9-fold (CRS: 1.89 [95%CI: 1.02-3.5], ICANS: 1.93 [1.06-3.51] ) higher among patients who were sarcopenic (reference: normal body composition). Average length of hospitalization was also longer (25.6d vs. 21.9d; p=0.037) among patients with sarcopenia. Survival: One-year PFS for the overall cohort was 50.1% (±4.2); PFS was significantly worse for patients who were sarcopenic compared to those with normal muscle mass (35.1% [±6.2] vs. 57.7% [±4.3] , p=0.005; Figure). In adjusted analyses, sarcopenia was associated with inferior one-year PFS (HR=1.73 [CI: 1.12-2.68]) compared to those with normal muscle mass. Conclusion: Sarcopenia is an important and independent predictor of outcomes after CAR-T with potential downstream health-economic consequences, including increased burden of acute toxicities and prolonged length of hospitalization. Taken together, these data form the basis for real-time decision making prior to CAR-T (e.g. pre-habilitation, consideration of alternative treatments), or during/shortly after CAR-T (e.g. increased supportive care, rehabilitation), setting the stage for innovative strategies to improve outcomes after CAR-T therapy. Figure 1 Figure 1. Disclosures Artz: Radiology Partners: Other: Spouse has equity interest in Radiology Partners, a private radiology physician practice. Budde: Merck, Inc: Research Funding; Amgen: Research Funding; Astra Zeneca: Research Funding; Mustang Bio: Research Funding; Novartis: Consultancy; Gilead: Consultancy; Roche: Consultancy; Beigene: Consultancy. Herrera: Merck: Consultancy, Research Funding; Gilead Sciences: Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Karyopharm: Consultancy; Kite, a Gilead Company: Research Funding; Seagen: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy; Tubulis: Consultancy; Genentech: Consultancy, Research Funding. Popplewell: Novartis: Other: Travel; Pfizer: Other: Travel; Hoffman La Roche: Other: Food. Shouse: Kite Pharmaceuticals: Speakers Bureau; Beigene Pharmaceuticals: Honoraria. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Forman: Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company; Allogene: Consultancy; Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-149784

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 2637-2637

Abstract: Introduction: Comorbidities are common in CLL and associated with shorter overall survival (OS) and disease specific survival (Rotbain, Leukemia, 2021). Using an ensemble machine learning approach, we identified the comorbidities most strongly associated with event free survival (EFS) in CLL in order to construct the CLL-CI (Gordon et al, 2021). Our initial report included heterogeneously-treated derivation (N=570) and validation (N=167) cohorts of patients with CLL. Median EFS in the derivation cohort was 58, 33 and 20 months for low, intermediate and high-risk CLL-CI groups, respectively (p & lt;0.001). We now report on the performance of CLL-CI in patients treated with targeted therapies and conduct additional validation of the score using a National Registry. Methods: In our multicenter CLL cohort, we retrospectively analyzed patients from 10 academic centers who received targeted therapies, e.g. ibrutinib, acalabrutinib, idelalisib and venetoclax. Secondly, we now compiled a validation cohort which included patients from the Danish National CLL registry. CLL-CI score was assigned as previously reported (Gordon et al, 2021). Briefly, one point was assigned, if present, for any cumulative illness rating scale (CIRS) vascular comorbidity, moderate/severe upper gastrointestinal CIRS comorbidity and moderate/severe endocrine CIRS comorbidity, for a total maximum score of 3 (Fig. 1A). A score of 0 signifies low risk disease, 1-intermediated risk and 2-3-high risk. The Kaplan-Meier method and Cox models were used to estimate the association between CLL-CI, EFS (defined as death or next therapy) and OS. Results: CLL patients treated with targeted therapies (N=448) had a median age of 68 years (range, 26-91), 124 pts (28%) had TP53 aberrancy, 268 (60%) were treated in the relapsed/refractory (R/R) setting and 398 (89%) received ibrutinib. By CLL-CI group, 194 (43%) were low risk, 173 (39%) intermediate risk and 81 (18%) high risk. Median EFS was 57, 35 and 17 months for low, intermediate and high-risk groups, respectively (p & lt;0.001; Fig. 1B). Estimated 2-year OS was 93%, 86% and 55%, respectively (p & lt;0.001: Fig. 1C). In multivariable models, CLL-CI was independently associated with EFS and OS when adjusted for TP53 aberrancy, age, prior lines of therapy and Rai stage (high risk vs. low risk HR, 3.31; p≤0.001 and HR 2.42; p=0.02, respectively). There was no observed difference in survival comparing ibrutinib to non-ibrutinib treated patients. The validation cohort (N=4975) included patients from the Danish CLL registry. Median age was 71 years, 1630 (33%) had low risk CLL-IPI and 425 (8.5%) had high or very-high risk CLL-IPI; 87% received chemoimmunotherapy. From time of diagnosis, in low, intermediate and high risk CLL-CI groups the median OS was not reached, 8.5 and 6 years, respectively (p & lt;0.0001). The median EFS from time of diagnosis was 8.4, 4.4 and 2.2 years, respectively (p & lt;0.0001). CLL-CI was associated with time to first treatment: 56% of high risk patients vs. 20-30% of low and intermediate risk patients received treatment within 4 years of diagnosis (p & lt;0.0001), and independently associated with OS when adjusted for CLL-IPI category. Furthermore, CLL-CI risk group was associated with OS from time of first treatment: medians of 8.2, 6.0, and 4.4 years (p & lt;0.0001) and EFS medians of 3.6, 2.9, and 1.9 years (p=0.0064), respectively. Interestingly, high CLL-CI score, compared to low/intermediate, was associated with unmutated IGHV (46% vs. 30%), TP53 aberrancy (10% vs. 5%), elevated B2 microglobulin (31% vs. 13%) and Binet stage B or C (29% vs. 18%; P & lt;0.001 for all). Conclusions: Here we report that a novel comorbidity index, CLL-CI, predicts outcomes in patients with CLL treated with targeted therapies. Furthermore, we validate this index in a large National Registry. Thus, CLL-CI is a validated measure of comorbidity in CLL which provides important prognostic information for patients with early stage disease treated with a watch and wait approach and in patients with advanced stage disease receiving targeted therapies or chemoimmunotherapy. Figure 1 Figure 1. Disclosures Rotbain: Abbvie: Other: travel grants; AstraZeneca: Consultancy, Other: travel grants; Janssen: Other: travel grants . Shouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Mei: Morphosys: Research Funding; BMS: Research Funding; Epizyme: Research Funding; TG Therapeutics: Research Funding; EUSA: Honoraria; Janssen: Honoraria; Beigene: Research Funding. Brander: Ascentage: Research Funding; Pfizer: Consultancy, Other: Biosimilars outcomes research panel; ArQule: Research Funding; DTRM: Research Funding; Genentech: Consultancy, Research Funding; BeiGene: Research Funding; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; LOXO: Research Funding; MEI Pharma: Research Funding; TG Therapeutics: Consultancy, Research Funding; AstraZeneca: Research Funding; Verastem: Consultancy; NCCN: Other: panel member; Novartis: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding; ArQule/Merck: Consultancy. Hill: Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Gentenech: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Celgene (BMS): Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Epizyme: Consultancy, Honoraria; Beigene: Consultancy, Honoraria, Research Funding. Choi: Abbvie: Other: Institution: Research Grant/Funding; Pharmacyclics: Other: Institution: Research Grant/Funding; Oncternal: Other: Institution: Research Grant/Funding; Velosbio: Other: Institution: Research Grant/Funding; Merck: Other: Institution: Research Grant/Funding; Geron: Other: Institution: Research Grant/Funding. Cohen: Genentech, BMS/Celgene, LAM, BioINvent, LOXO, Astra Zeneca, Novartis, M2Gen, Takeda: Research Funding; Janssen, Adicet, Astra Zeneca, Genentech, Aptitude Health, Cellectar, Kite/Gilead, Loxo, BeiGene, Adaptive: Consultancy. Stephens: Abbvie: Consultancy; Novartis: Research Funding; JUNO: Research Funding; Mingsight: Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees; Arqule: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy; CSL Behring: Consultancy; Celgene: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding. Patel: Kite Pharma: Consultancy, Speakers Bureau; MEI Pharma: Consultancy; TG Therapeutics: Consultancy, Speakers Bureau; Abbvie: Consultancy; Janssen: Consultancy; Genentech: Consultancy; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy; Morphosys: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; ADC Therapeutics: Consultancy; Lilly: Consultancy. Shadman: Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab: Research Funding; Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune , Mustang Bio and Atara Biotherapeutics: Consultancy. Niemann: Novo Nordisk Foundation: Research Funding; CSL Behring, Genmab, Takeda, Octapharma: Consultancy; Abbvie, AstraZeneca, Janssen: Consultancy, Research Funding. Danilov: Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Rigel Pharm: Honoraria; Gilead Sciences: Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Takeda Oncology: Research Funding; Bayer Oncology: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-148253

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 6633-6634

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-160157

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3633-3634

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-159805

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3558-3558

Abstract: Background. Despite advances in targeted and cellular therapy, outcomes among patients with RT and tNHL remain dismal. Copanlisib (COPA) is a selective, small molecule, PI3K inhibitor which preferentially targets the p110αδ isoforms . COPA has shown clinical efficacy in NHL and is an approved therapy for follicular lymphoma (FL). Nivolumab is a PD-1 antagonist which has demonstrated activity in Hodgkin lymphoma as well as NHL. Furthermore, combined targeting of PI3K and PD-1 has demonstrated synergy in pre-clinical lymphoma models. Here we report initial results of a phase 1 study of COPA in combination with nivolumab in patients with R/R RT or tNHL (NCT03884998). Methods. This ongoing multicenter, open-label, phase I, investigator-sponsored study is enrolling patients with RT or tNHL, age ≥18 years, whose disease had relapsed or was refractory to ≥1 prior line of therapy. The phase I portion of the study followed a standard 3+3 design with three planned dose levels of COPA administered IV (dose level [DL]1 - 45 mg on days 1, 8 and 15; DL2 - 60 mg on days 1, 8 and 15; DL "-1" - 45 mg on days 1 and 15 of a 28-day cycle). Nivolumab 240 mg was given IV on days 1 and 15. Patients received up to 24 cycles of therapy. The primary study objective was to evaluate the maximum tolerated dose (MTD) of the combination; secondary objectives included preliminary measures of efficacy by Lugano criteria including PET/CT scans. Exploratory objectives included pharmacodynamic endpoints. Dose limiting toxicities (DLT) were defined as grade ≥4 hematologic & gt; 7 days or grade ≥3 non-hematologic toxicities. Results. Of the eleven patients enrolled, 8 had RT and 3 had transformed FL (tFL); 91% (10/11) were men. Median age was 70 (43-77) years, 82% (9/11) had an ECOG performance status ≤1. Patients had received a median of 3 prior lines of therapy (range, 1-8), including three patients (1 RT, 2 FL) who had undergone CAR T cell therapy. Eight patients were treated at DL1 (45 mg COPA), of which 2 patients did not complete the DLT period due to rapidly progressive disease and were replaced. No DLTs were observed at this dose level. At DL2 (60 mg COPA), three DLTs (grade 4 febrile neutropenia and grade 4 thrombocytopenia in another patient) were observed among the three patients treated. Therefore, the MTD and recommended phase 2 dose (RP2D) of COPA in combination with nivolumab was determined to be 45 mg on days 1, 8, 15. The most common treatment-related adverse events (AEs, any grade) were anemia and neutropenia (Table 1). Five pts discontinued therapy due to progressive disease; one due to intercurrent infection (coccidiomycosis, unrelated to study drugs), two due to DLTs noted above. Three patients remain on treatment. Among the seven efficacy-evaluable patients who completed at least one cycle of therapy, median time on treatment was 2 months (range, 2-9 months). Of these, four patients achieved a response per the investigators' assessment (tFL: 2 partial responses; RT: 1 complete response and 1 partial response). Efficacy assessment is ongoing and will be reported at the meeting. Discussion. We identified COPA 45 mg IV on days 1, 8 and 15 as the MTD/RP2D in combination with nivolumab in patients with R/R RT and tFL. This combination was well-tolerated at the MTD/RP2D, and the study is currently enrolling patients in an expansion cohort to further characterize the efficacy of this regimen. Figure 1 Figure 1. Disclosures Shouse: Beigene Pharmaceuticals: Honoraria; Kite Pharmaceuticals: Speakers Bureau. Siddiqi: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Juno therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Other: DSM Member, Speakers Bureau; PCYC: Speakers Bureau; Jannsen: Speakers Bureau; Dava Oncology: Honoraria; ResearchToPractice: Honoraria. Popplewell: Pfizer: Other: Travel; Novartis: Other: Travel; Hoffman La Roche: Other: Food. Kittai: Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy; Abbvie: Consultancy. Davids: MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; AbbVie: Consultancy; BeiGene: Consultancy; Merck: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Eli Lilly and Company: Consultancy; BMS: Consultancy, Research Funding; Janssen: Consultancy; Celgene: Consultancy; Astra-Zeneca: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Research to Practice: Consultancy; Verastem: Consultancy, Research Funding; Takeda: Consultancy; MEI Pharma: Consultancy; TG Therapeutics: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Danilov: Genentech: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria, Research Funding; SecuraBio: Research Funding; Bristol-Meyers-Squibb: Honoraria, Research Funding; Rigel Pharm: Honoraria; Takeda Oncology: Research Funding; Bayer Oncology: Consultancy, Honoraria, Research Funding; Gilead Sciences: Research Funding; Pharmacyclics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; TG Therapeutics: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-149320

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 10573-10574

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-162373

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 570-570

Abstract: Introduction: CAR T-cell therapy has revolutionized the treatment of relapsed/refractory B cell lymphomas, providing hope to patients who previously faced dismal outcomes. Despite unprecedented efficacy including high response rates and a significant proportion of durable responses, significant toxicities are still prevalent. Toxicities related to immune therapy including cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) along with infections and hematologic toxicity, complicate the post CAR T-cell infusion course. Innate patient-related factors including presence of comorbidities, advanced physiologic age, and poor fitness, likely contribute to poor short-term outcomes, however no validated risk scores incorporating these factors have been validated in patients receiving CAR T-cell therapy for lymphoma. In the present study we identified the ability of a patient to walk 500 feet (ft) or more during the 6 Minute Walk Test (6MWT) at baseline as a predictive marker for poor short-term outcomes after CAR T-cell infusion. Methods: We retrospectively analyzed charts of 78 patients who received commercially available CAR T-cell products for the treatment of lymphoma between May, 2019 and March, 2021 who had baseline assessment by physical therapy at the time of admission for CAR T-cell therapy. CRS and ICANS were scored by ASTCT guidelines. Demographics were analyzed with descriptive statistics. Univariate analysis was performed by Chi Squared. Results: The analysis included 78 patients with a median age of 63 (range, 21-82), 37% (n=29) were female. Patients were treated for DLBCL (64%, n=50), transformed follicular lymphoma (tFL; 29%, n=23), primary mediastinal B cell lymphoma (PMBCL; 4%, n=3), and mantle cell lymphoma (MCL; 3%, n=2). Patients received axicabtagene ciloleucel (94%, n=73), tisagenlecleucel (4%, n=3), or brexucabtagene autoleucel (3%, n=2). Patients had a median of 3 prior lines of therapy (range 2-7) and 53% (n=42) received bridging chemotherapy. Among the 70 patients who completed the 6MWT, the mean distance was 909 ft (range, 20-2045), 8 patients were unable to compete the assessment due to debility and were included in the analysis as a 0 distance. Patients who were unable to complete 500 feet (n=17) were deemed to have poor endurance (PE). The PE group of patients were 3.6 times more likely to have a prolonged length of stay (p=0.02), while they were 1.5 times less likely to be alive at 100 days post CAR T infusion (p = 0.002). Patients also tended to have higher rates of ICANS (76% vs 41%), lower overall response rates (ORR) (78% vs 98%), and higher 30 day mortality (18% vs 2%), although these did not reach statistical significance, p=0.08, 0.06, and 0.07, respectively. CRS did not appear to be related to PE status, neither did age, or prior lines of therapy. Conclusions: Within the limitations of a retrospective study, we demonstrate that the baseline physical therapy-assessed measure of function and endurance, namely the 6MWT, correlates with several critical short-term outcomes in CAR T patients with lymphoma. These include prolonged length of stay, survival at day 100, and there is suggested correlation with ORR, ICANS, and 30-day survival as well. These findings illustrate the potential for early recognition of deconditioned patients that may do poorly after CAR T-cell therapy. Identification of these patients could allow for therapeutic interventions prior to CAR T infusion or during their post-infusion hospital stay, designed to enhance their strength and endurance, and potentially improve these short-term outcomes. Prospective intervention studies are planned based on these findings. Disclosures Shouse: Kite Pharma: Speakers Bureau; Beigene: Honoraria. Budde: Kite Pharma: Consultancy; AstraZeneca: Research Funding; Genentech: Consultancy, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-150858

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7