To study the impact of dose modification and temporary interruption of ibrutinib in routine clinical practice, we conducted a retrospective study of consecutive CLL patients treated with ibrutinib outside the context of a clinical trial at Mayo Clinic, (Rochester, MN) from 11/2013 to 12/2017. Of 209 patients, 131 (74%) had unmutated IGHV, 38 (20%) had TP53 disruption, and 47 (22%) were previously untreated. A total of 87/209 (42%) patients started reduced dose ibrutinib (<420 mg daily; n = 43, physician preference; n = 33, concomitant medications; and n = 11, other). During 281 person‐years of treatment, 91/209 patients had temporary dose interruption (54%, nonhematologic toxicity; 29%, surgical procedures; 10%, hematologic toxicity; and 7%, other). After a median follow‐up of 24 months, the estimated median event‐free survival (EFS) was 36 months, and median overall survival (OS) was not reached. On multivariable analyses, temporary ibrutinib interruption (hazard ratio [HR]: 2.37, P = .006) and TP53 disruption at ibrutinib initiation (HR: 1.81, P = .048) were associated with shorter EFS, whereas only TP53 disruption (HR: 2.38, P = .015) was associated with shorter OS. Initial ibrutinib dose and dose modification during therapy did not appear to impact EFS or OS. These findings illustrate the challenges associated with continuous oral therapy with ibrutinib in patients with CLL.

Infectious complications following immunosuppressive therapy increase morbidity and mortality in patients combatting malignancy. 1 The inverse relationship between circulating leukocyte levels and infection potential places patients with prolonged and profound neutropenia at greatest infection risk. 2 Granulocyte colony stimulating factor (GCSF) after aggressive chemotherapy is a supportive measure recommended to reduce neutropenia intensity and ultimately abrogate infection.Chimeric antigen receptor T-cell (CAR-T) therapy represents a major advancement in the management of refractory or relapsed malignancies. 3 Patients receiving CAR-T therapy have multiple factors that impair their immunity and increase infection risk. 4 The theoretical potential for GCSF to exacerbate cytokine release syndrome (CRS) prompted guidelines to recommend against administering GCSF within 14 days after CAR-T infusion. 5 However, few studies exist that characterize outcomes after CAR-T therapy and the ultimate impact of concurrent GCSF remains unknown. 6 Our primary objective was the comparison of neutrophil kinetics between patients who did and did not receive GCSF after axicabtagene ciloleucel. Secondary outcomes included comparing CAR-T therapy-related toxicity characteristics and infection rates. This Mayo Foundation Institutional Review Board approved retrospective analysis evaluated consecutive, adult cancer patients who received commercial axicabtagene ciloleucel between January 2018 and December 2020. Patients actively participating in a CAR-T clinical trial, considered a vulnerable population, or refusing research participation were excluded. All patients provided written informed consent or had consent provided for them by their legal power of attorney prior to data collection. The electronic health record (EHR) data was compiled utilizing a standardized form developed by the investigators. Baseline criteria were established immediately prior to lymphodepleting chemotherapy. Lymphoma diagnosis with subtyping was reported according to World Health Organization classification criteria. 7 Relevant laboratory values, medications, and microbiology were abstracted from the time of CAR-T infusion through disease relapse, death, or a maximum of CORRESPONDENCE E399

Background: Two-year follow-up from ZUMA-1 trial for axicabtagene ciloleucel (axi-cel) CD19 chimeric antigen receptor T-cell (CART) in aggressive non-Hodgkin lymphoma (NHL) demonstrated that patients (pts) achieving complete remission (CR) as their best response have the longest progression free survival (PFS), while PFS remained poor for others. Majority of the best response are achieved by month 3 post-infusion. Moreover, a subset of pts who do not achieve CR by month 1 may still achieve CR while others will progress within months. Having a clinically available test to predict for durable response can assist clinicians in selecting pts who can be observed for continued response vs. those who may need intervention earlier. Peak CAR-T expansion has been correlated with best clinical response to axi-cel. However there is no clinically available test to quantify CART cells post treatment. Given the prolonged lymphotoxic effect of the lymphodepletion (LD) chemotherapy administered before CART infusion, we hypothesize that the peak expansion of absolute lymphocyte count (ALC, ALCpeak) after infusion likely corresponds to CART expansion. We examined for correlation between ALCpeak and clinical response at month 3 post-infusion for pts who received axi-cel. Methods: Data was collected from pts who received axi-cel between June 2016 and March 2019 at Mayo Clinic Rochester (NCT02348216, NCT03153462, and standard of care). All infused pts were included in the intention to treat analysis for response and event-free survival (EFS). Lugano 2014 criteria were used for clinical response. EFS was defined as the date of infusion until progression or death due to any cause and evaluated using Kaplan Meier curves with log-rank test. Comparison between subgroups was investigated using Fisher's exact test and Wilcoxon test for categorical and continuous variables, respectively. Statistical analysis performed using JMP Pro 14.1. Results: Of the thirty-six NHL pts treated with axi-cel, the median age was 56 yrs (range 26-65); 78% (28) were male; 44% (16) had DLBCL; the median number of prior therapies was 3 (2-6), 47% (17) had stem cell transplant. Nineteen (53%) pts received bridging therapy after leukapheresis. All pts received fludarabine and cyclophosphamide for LD chemotherapy and achieved ALC nadir by the day of CART infusion (median 0.03 x 10^9/L, range 0.01-0.11). As CART expansion were found to peak within the first two weeks in ZUMA-1 trial, we examined ALC trend over 15 days post infusion and found that ALCpeak generally happened within the same timeframe (median ALCpeak day: 9, range 6-15). At 3 months post infusion, 33.3% (12/36) of pts achieved CR, 8.3% (3/36) pts were in partial remission (PR). No correlation was found between CR response and clinical characteristics: age >60 years, stage III/IV, B symptoms, elevated LDH, IPI score 3-4, number of previous treatments, use of bridging therapy, peak CRP and ferritin. However, the ALCpeak was significantly different between CR and non-CR pts (median, range: 1.09, 0.35-2.55; 0.67, 0.15-1.03; p=0.04). Using receiver operator curve (ROC)-derived area under the curve (AUC) estimates, ALCpeak 1.08 x 10^9/L was identified as the best threshold to discriminate patients at different likelihood to achieve CR at month 3. Pts achieving ALCpeak ≥ 1.08 showed a strong increased likelihood of achieving CR at month 3 (OR 2.8; 95% CI, 1.12-6.99; P=0.02). There was no statistical difference between the ALCpeak high and low groups in terms of use of bridging therapy, occurrence of any grade or higher grade cytokine release syndrome or neurotoxicity, or the use of tocilizumab or steroid. Interestingly, for pts who had changes in clinical response from month 1 to month 3, all 3 pts who converted to CR by month 3 had ALCpeak≥1.08, while the 13 of the 15 pts who had progressed by month 3 had ALCpeak<1.08. In addition, EFS was significantly different between pts who had ALCpeak above and below 1.08 (6 months EFS rate 75% vs. 25%, respectively, Figure 1). Conclusions: We found that the ALC expansion occurred in the first 15 days post axi-cel infusion, consistent with the known time frame for CART expansion. Higher ALCpeak level in this timeframe correlated with higher likelihood of achieving CR, and is associated with conversion to CR. This study is limited by the small sample size and limited follow-up, but the results are promising for further prospective investigation in a larger cohort of patients. Disclosures Paludo: Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding; Celgene: Research Funding; Celgene: Research Funding. Ansell:Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding. Bennani:Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Seattle Genetics: Other: Advisory board; Adicet Bio: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Other: Advisory board; Purdue Pharma: Other: Advisory board. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Karyopharm: Research Funding; Rigel: Consultancy. Kapoor:Celgene: Honoraria; Janssen: Research Funding; Cellectar: Consultancy; Sanofi: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Glaxo Smith Kline: Research Funding. Kenderian:Novartis: Patents & Royalties, Research Funding; Tolero: Research Funding; Humanigen: Other: Scientific advisory board , Patents & Royalties, Research Funding; Lentigen: Research Funding; Morphosys: Research Funding; Kite/Gilead: Research Funding. Kumar:Takeda: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.

Background: The patient/caregiver experience during CAR-T therapy is stressful, overwhelming, terrifying, and often a patient’s last treatment option. The Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery Innovation and Design team has worked with the CAR-T therapy clinical team to develop a patient experience that provides patients with a sense of caring, supportive environment, timely knowledge, and realistic expectations. Using a human-centered design approach, the Innovation and Design team worked with patients and caregivers to understand latent and unspoken needs in order to develop an ideal CAR-T therapy patient journey. Methods: With qualitative interviewing techniques, patient observation, and low fidelity experimentation, 21 patients/caregiver pairs were interviewed throughout their CAR-T therapy experience in 2018. Patients were interviewed at several touch points as well as encouraged to reach out to the Innovation and Design team at any point with reflections on their experiences. Patients were recruited as they began their evaluation phase for CAR-T therapy. The interviews were unscripted to allow for a breadth of discovery by not constraining the conversations to previously developed themes. As themes emerged from patient/caregiver interviews, artifacts and interventions were designed to alleviate pain points and improve the patient/caregiver experience. These artifacts and interventions were integrated into the clinical processes in real time and patient/caregivers were interviewed to understand the impact of these activities. Results: Several themes emerged from qualitative interviews with patients and caregivers. From the themes, interventions were developed. We were able to demonstrate a qualitative improvement in patient/caregiver experience through these interventions (Figure 1). Conclusions: Patients/caregivers undergoing CAR-T therapy have unique issues surrounding the logistics of care, emotional burden, and physical effects of treatment. We implemented processes to address these issues and observed a qualitative improvement via patient interviews/feedback. Ongoing work includes optimizing remote monitoring, digital platforms for patient education, and a quantitative study looking at patient reported outcomes (PROs) in such patients. To our knowledge, this is the first report for care delivery optimization in real-world practice for this new therapy.

There were no significant differences in hematologic outcomes in newly diagnosed AML patients who received linezolid for extended gram-positive antimicrobial coverage following induction chemotherapy. This study provides new insight with a primary focus on the effects of hematologic outcomes when using linezolid in a well-defined acute leukemia population. Further study is warranted with larger populations to assess the potential adverse effects linezolid may have in patients with acute leukemia.