ABSTRACT
INTRODUCTION: Patients (pts) with blood disorders are at particular risk for severe infection and death from COVID-19. Factors that contribute to this risk, including cancer treatment, have not been clearly delineated. The ASH RC COVID-19 Registry for Hematology is a public-facing, volunteer registry reporting outcomes of COVID-19 infection in pts with underlying blood disorders. We report a multivariable analysis of the impact of cancer treatment and other key variables on COVID-19 mortality and hospitalization among pts with blood cancer. METHODS: Data were collected between April 1, 2020, and July 2, 2021. All analyses were performed using R version 4.0.2. Multivariable logistic regression explored associations between mortality and seven patient/disease factors previously reported as important to COVID-19 outcome. Independent variables included: age (>60);sex;presence of a major comorbidity (defined as any of heart disease, hypertension, pulmonary disease and/or diabetes);type of hematologic malignancy;estimated prognosis of < 6 months prior to COVID-19;deferral of ICU care;and administration of cancer treatment in the previous year (excluding single agent hydroxyurea). A secondary multivariable logistic regression explored associations between the same variables and hospitalization with COVID-19. RESULTS: We included all pts in the registry with a malignant diagnosis except for 3 patients excluded based on a data sharing agreement (N=1029). Median age category was 50-59y (range <5y to > 90y). The sample was 42% female and 28% had major comorbidities. Types of hematologic malignancies were 354 (34%) acute leukemia/MDS, 255 (25%) lymphoma, 206 (20%) plasma cell dyscrasia (myeloma/amyloid/POEMS), 116 (11%) CLL, 98 (10%) myeloproliferative neoplasm (MPN). Most pts (73%) received cancer treatment during the previous year, 9% had a pre-COVID-19 prognosis of <6months, and 10% deferred ICU care. COVID-19 mortality in the entire cohort was 17%. In multivariable analyses, age > 60 (OR 2.03, 1.31-3.18), male sex (OR 1.69, 1.11 - 2.61), estimated pre-COVID-19 prognosis of less than 6 months (OR 6.16, 3.26 - 11.70) and ICU deferral (OR 10.87, 6.36 - 18.96) were all independently associated with an increased risk of death. Receiving cancer treatment in the year prior to COVID-19 diagnosis and type of hematologic malignancy were not significantly associated with death. In multivariable analyses, age > 60 (OR 2.46, 1.83 - 3.31), male sex (OR 1.34, 1.02 - 1.76), estimated pre-COVID-19 prognosis of < 6 months (OR 4.81, 2.45 - 10.50), presence of a major comorbidity (OR 1.57, 1.15 - 2.16), and cancer treatment in the previous year (OR 1.50, 1.10 - 2.06) were all independently associated with an increased risk of a severe COVID-19 requiring hospitalization. Pts with a MPN or plasma cell dyscrasia and COVID-19 were less likely to require hospitalization for COVID-19 compared to patients with CLL, leukemia/MDS, or lymphoma. CONCLUSIONS: These analyses confirm the negative impact of age > 60, male sex, pre-COVID-19 prognosis of < 6 months, and deferral of ICU care on mortality among patients with hematologic malignancy and COVID-19. We did not observe an increased risk of COVID-19 mortality among pts with COVID-19 who received blood cancer treatment in the previous year, although rate of hospitalization was higher. Pts with some hematologic malignancies (MPN, plasma cell dyscrasias), may experience less severe COVID-19 infections than others. Disclosures: Anderson: Celgene: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Desai: Janssen R&D: Research Funding;Astex: Research Funding;Kura Oncology: Consultancy;Agios: Consultancy;Bristol Myers Squibb: Consultancy;Takeda: Consultancy. Goldberg: Celularity: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Aptose: Consultancy, Research Funding;Prelude Therapeutics: Research Funding;DAVA Oncology: Honoraria;Pfizer: Research Funding;Arog: Research Funding;Aprea: Research Funding;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Neuberg: Madrigal Pharmaceuticals: Other: Stock ownership;Pharmacyclics: Research Funding. Radhakrishnan: Janssen India: Honoraria;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Aurigene: Speakers Bureau;Novartis: Honoraria;Johnson and Johnson: Honoraria;Pfizer: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria;Emcure Pharmaceuticals: Other: payment to institute;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;NATCO Pharmaceuticals: Research Funding. Sehn: Genmab: Consultancy;Debiopharm: Consultancy;Novartis: Consultancy. Sekeres: Novartis: Membership on an entity's Board of Directors or advisory committees;Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Kura: Membership on an entity's Board of Directors or advisory committees;Syros: Membership on an entity's Board of Directors or advisory committees;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;NYU Grand Rounds: Honoraria;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria.
ABSTRACT
Background: Predictors of severe infection and outcomes with COVID-19 in patients (pts) with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndromes (MDS) are lacking. Pts with active disease may experience worse outcomes due to overall prognosis and cytopenias. Here we identify risk factors for severe COVID-19 infection and mortality in pts with AML, MDS, and ALL using the ASH RC COVID-19 Registry for Hematology. Methods: The ASH RC COVID-19 Registry for Hematology includes features and outcomes of a laboratory-confirmed or presumptive diagnosis of SARS-CoV-2 infection in adult pts with ongoing or a history of blood disorders. The Registry opened for data collection on April 1, 2020 and is a global effort housed on a secure data platform hosted by Prometheus Research, an IQVIA company. Data are made publicly available and regularly updated on the ASH RC website. Pt characteristics, outcomes, and predictors were analyzed and stratified by disease status (active initial diagnosis and relapsed/refractory vs. remission) and type of hematologic malignancy. Variables included age, comorbidities, type of hematologic malignancy (AML, MDS, ALL), neutrophil and lymphocyte count at time of COVID-19 diagnosis, and active treatment at the time of COVID-19 diagnosis. COVID-19 severity was defined as mild (no hospitalization required), moderate (hospitalization required), or severe (ICU admission required). Categorical pt characteristics for each response group and associations between response groups and characteristics (i.e., alive vs. dead, severity vs. non-severity) were summarized by frequency with differences between response groups evaluated by Fisher's exact test and odds ratios with 95% confidence intervals (CIs) estimated by logistic regression. Multivariable analyses identified independent predictors of outcomes. Results: Analyses were conducted on data from 257 pts with AML (n=135), MDS (n=40), and ALL (n=82);46% were in remission and 44% had active disease (10% unknown). Overall mortality from COVID-19 infection was 21%. Pts with active disease were significantly more likely to present with moderate and severe COVID-19 compared to those in remission (remission vs. active disease, severe 33% (n=20) vs. 67%(n=40), moderate 45% (n=35) vs.55% (n=42), and mild: 67% (n=56) vs. 33% (n=28), p value <0.001) (Figure 1). This was significant when categorized as severe vs. non severe as well (p=0.002). COVID-19 severity was also associated with AML diagnosis, major comorbidities, and neutropenia and lymphopenia at the time of COVID-19 diagnosis. Univariate analyses of increased mortality after COVID-19 diagnosis were significantly associated with advanced age, male sex, pre-diagnosis survival < 6 months, active disease status, neutropenia, lymphopenia and forgoing ICU care. Multivariable analyses in all pts (Figure 1), revealed that increased COVID-19 related mortality was significantly associated with neutropenia at diagnosis (OR 3.15, 95% C.I. 1.31-8.08, p=0.01), estimated pre-COVID-19 prognosis of < 6 months (OR 8.58, 95% C.I. 3.24-24.46, p<0.001) and forgoing ICU care (OR 6.66, 95% C.I. 2.56-18.23, p<0.001). Among hospitalized pts, increased COVID-19 mortality was associated with estimated pre-COVID-19 prognosis of < 6 months (OR 6.77, 95% C.I. 2.34-22.24, p<0.001) and forgoing ICU care (OR 3.98, 95% C.I. 1.45-11.66, p=0.007). Pts who were older, male, smokers, with active disease, or estimated to have pre-COVID-19 survival of < 6 months were more likely to forgo ICU care. Forgoing ICU care (n=37,16%) was associated with a higher COVID-19 mortality in all pts (n=234, OR 15.6, 95% C.I. 6.4-40.9, p<0.001), hospitalized pts (n=143, OR 9.2, 95% C.I., 3.5-26.5, p<0.001) and in pts where ICU admission was indicated and declined (n=61 OR 5.6, 95% C.I. 1.1-56.4, p=0.03)). Neither active disease status nor ongoing cancer treatment were associated with increased mortality among hospitalized patients. Conclusions: These data suggest that patients with active disease experience significantly higher COVID-19 severity but not increased mortality from COVID-19. Patients who had neutropenia and a pre-COVID-19 prognosis of < 6 months had higher mortality from COVID-19 infection and may be more likely to forgo ICU care. If desired by patients, aggressive support for hospitalized patients with COVID-19 is appropriate regardless of remission status. [Formula presented] Disclosures: Desai: Agios: Consultancy;Janssen R&D: Research Funding;Kura Oncology: Consultancy;Bristol Myers Squibb: Consultancy;Astex: Research Funding;Takeda: Consultancy. Goldberg: AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Aprea: Research Funding;Prelude Therapeutics: Research Funding;Pfizer: Research Funding;Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees;DAVA Oncology: Honoraria;Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees;Arog: Research Funding;Celularity: Research Funding;Aptose: Consultancy, Research Funding. Anderson: Sanofi-Aventis: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees;Janssen: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Millenium-Takeda: Membership on an entity's Board of Directors or advisory committees;Scientific Founder of Oncopep and C4 Therapeutics: Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company;AstraZeneca: Membership on an entity's Board of Directors or advisory committees;Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees. Neuberg: Pharmacyclics: Research Funding;Madrigal Pharmaceuticals: Other: Stock ownership. Radhakrishnan: Emcure Pharmaceuticals: Other: payment to institute;Bristol Myers Squibb: Other: payment to institute;Astrazeneca: Consultancy, Honoraria;Cipla Pharmaceuticals: Honoraria, Other: payment to institute;Pfizer: Consultancy, Honoraria;Johnson and Johnson: Honoraria;Novartis: Honoraria;Aurigene: Speakers Bureau;Roche: Honoraria, Other: payment to institute;Intas Pharmaceutical: Other: payment to institute;Dr Reddy's Laboratories: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen India: Honoraria;NATCO Pharmaceuticals: Research Funding. Roboz: Novartis: Consultancy;Mesoblast: Consultancy;Amgen: Consultancy;Actinium: Consultancy;AbbVie: Consultancy;Janssen: Consultancy;Blueprint Medicines: Consultancy;Astex: Consultancy;Janssen: Research Funding;Daiichi Sankyo: Consultancy;Jazz: Consultancy;Agios: Consultancy;Glaxo SmithKline: Consultancy;Celgene: Consultancy;Otsuka: Consultancy;Astellas: Consultancy;Helsinn: Consultancy;MEI Pharma - IDMC Chair: Consultancy;Jasper Therapeutics: Consultancy;Bristol Myers Squibb: Consultancy;AstraZeneca: Consultancy;Bayer: Consultancy;Pfizer: Consultancy;Roche/Genentech: Consultancy. Sehn: Novartis: Consultancy;Genmab: Consultancy;Debiopharm: Consultancy. Sekeres: Takeda/Millenium: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;BMS: Membership on an entity's Board of Directors or advisory committees. Tallman: Syros: Membership on an entity's Board of Directors or advisory committees;Kura: Membership on an entity's Board of Directors or advisory committees;NYU Grand Rounds: Honoraria;Innate Pharma: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Biosight: Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees;Oncolyze: Membership on an entity's Board of Directors or advisory committees;KAHR: Membership on an entity's Board of Directors or advisory committees;Orsenix: Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Amgen: Research Funding;Rafael Pharmaceuticals: Research Funding;Glycomimetics: Research Funding;Biosight: Research Funding;Orsenix: Research Funding;Abbvie: Research Funding;Mayo Clinic: Honoraria;UC DAVIS: Honoraria;Northwell Grand Rounds: Honoraria;NYU Grand Rounds: Honoraria;Danbury Hospital Tumor Board: Honoraria;Acute Leukemia Forum: Honoraria;Miami Leukemia Symposium: Honoraria;New Orleans Cancer Symposium: Honoraria;ASH: Honoraria;NCCN: Honoraria. Wood: Pfizer: Research Funding;Teladoc: Consultancy;Koneksa Health: Consultancy, Current equity holder in publicly-traded company.
ABSTRACT
Background: Waldenström macroglobulinemia (WM) is a rare, indolent B-cell lymphoproliferative disorder. After the STiL-1 trial (Rummel MJ. Lancet. 2013;381(9873):1203-1210) demonstrated significant benefit in a subgroup analysis as well as reduced toxicity using bendamustine and rituximab (BR) compared to R-CHOP (N=41 enrolled WM patients), BR became the preferred immunochemotherapy (IC) regimen for all patients with symptomatic treatment naïve (TN) WM in British Columbia (BC) since 2014. Prior to the introduction of BR, the combination of rituximab, cyclophosphamide, vincristine, and prednisone (RCVP), was the standard of care in BC for this population since 2004, given its widespread use across a broad range of indolent B-cell lymphomas. We report a population-based analysis evaluating outcomes in TN-WM patients comparing BR with RCVP. Methods: The BC Cancer Centre for Lymphoid Cancer Database was used to identify TN-WM patients treated with BR or RCVP as their first systemic therapy between August 1, 2004 - August 1, 2020. A period of observation but no prior to systemic therapy was permitted. All patients had clinicopathologically confirmed lymphoplasmacytic lymphoma and measurable monoclonal IgM. Event-free survival (EFS) was defined as time from start of IC to progression, relapse, initiation of alternative therapy, histologic transformation, or death due to any cause. Early progression (POD24) was defined as relapse or progression, death from lymphoma, or treatment toxicity within 24 months of initiation of systemic therapy. Outcomes were compared with a historical cohort of patients treated with frontline RCVP. Responding patients were eligible to receive maintenance rituximab (MR) every 3 months for 2 years since 2006;however this was discontinued in 2020 when a subgroup analysis of the MAINTAIN trial (Rummel MJ. Blood 2019;134 (Supplement_1): 343), showed a lack of PFS benefit after BR, coupled with safety and vaccine response concerns during the COVID-19 pandemic. Results: A total of 111 patients with WM were identified;57 treated with BR, 54 treated with RCVP. Median age was 69 years (range 33-89) and baseline characteristics (Table 1), were well-balanced. A higher proportion of RCVP-treated patients received >4 cycles of chemotherapy (81% vs 65%, p=0.049). After IC, 75 (68%) received MR, with 36 (63%) and 39 (72%) in the BR and RCVP groups respectively (p=0.3). Median follow-up from diagnosis for all living patients was 5.9 years (range 0.8-19.2), with median 4.4y vs 9.8y for BR and RCVP respectively. EFS estimates at 4-years achieved with BR were 57% (95% CI 40-71%) compared to RCVP 60% (95% CI 45-72%), p=0.5 (Figure 1). Median EFS was established for RCVP due to longer duration of follow up at 6.3 years (95% CI 3.6-11.8y). Overall survival (OS) estimates at 4-years were 74% (95% CI 57-85%) and 81% (95% CI 67-89%) for BR and RCVP patients respectively, p=0.6. Worse performance status (≥2) was the only pre-treatment factor identified as significant for inferior EFS. A sub-analysis limited to patients that received >4 cycles of IC also showed no clear difference in outcomes between BR and RCVP. Median time to transformation was 6.5y (5.5-13y), with only 3 late biopsy-proven events. Early progression (POD24) has occurred in 19 (18%) patients, with inferior survival observed in patients that had an early event compared with a reference cohort (2-years event free), however this did not reach statistical significance (p=0.3) (Figure 1). Conclusion: This population-based analysis of TN-WM patients treated with upfront IC confirms the excellent outcomes that can be achieved with a finite course of therapy. In contrast to prior studies, similar outcomes were observed with RCVP and BR. Further, regardless of front-line therapy, POD24 may be associated with inferior outcome but larger studies are needed. To our knowledge, this study is the first to make a direct comparison between BR and RCVP, and one of the largest restricted to IC-treated TN-WM. This data supports RCVP as a viable option, and should ser e to inform clinicians, patients, and policy makers in decision-making when considering upfront therapeutic options, and when considering indefinite alternative regimens such as BTK inhibitors. [Formula presented] Disclosures: Gerrie: AbbVie: Honoraria, Research Funding;Janssen: Honoraria, Research Funding;Astrazeneca: Honoraria, Research Funding;Sandoz: Honoraria;Roche: Research Funding. Savage: Servier: Consultancy, Honoraria;Astra-Zeneca: Consultancy, Honoraria;BMS: Consultancy, Honoraria, Other: Institutional clinical trial funding;Seattle Genetics: Consultancy, Honoraria;Merck: Consultancy, Honoraria, Other: Institutional clinical trial funding;Takeda: Other: Institutional clinical trial funding;AbbVie: Consultancy, Honoraria;Roche: Research Funding;Beigene: Other: Institutional clinical trial funding;Genentech: Research Funding. Villa: Roche: Honoraria;Janssen: Honoraria;Lundbeck: Honoraria;Celgene: Honoraria;Seattle Genetics: Honoraria;AbbVie: Honoraria;AstraZeneca: Honoraria;Gilead: Honoraria;NanoString Technologies: Honoraria. Scott: BC Cancer: Patents & Royalties: Patent describing assigning DLBCL COO by gene expression profiling–licensed to NanoString Technologies. Patent describing measuring the proliferation signature in MCL using gene expression profiling.;Abbvie: Consultancy;Janssen: Consultancy, Research Funding;AstraZeneca: Consultancy;Rich/Genentech: Research Funding;Celgene: Consultancy;Incyte: Consultancy;NanoString Technologies: Patents & Royalties: Patent describing measuring the proliferation signature in MCL using gene expression profiling. Craig: Bayer: Consultancy. Slack: Seagen: Consultancy, Honoraria. Sehn: Debiopharm: Consultancy;Novartis: Consultancy;Genmab: Consultancy. Freeman: Amgen: Honoraria;Celgene: Honoraria;Sanofi: Honoraria, Speakers Bureau;Incyte: Honoraria;Abbvie: Honoraria;Teva: Research Funding;Roche: Research Funding;Bristol Myers Squibb: Honoraria, Speakers Bureau;Janssen: Honoraria, Speakers Bureau;Seattle Genetics: Honoraria.
ABSTRACT
Background: Cytokine release syndrome (CRS) is a potentially serious complication of T-cell engaging immunotherapy. Effective measures are needed to reduce the rate and severity. In a multicenter Phase I/II study (NCT02500407), the CD20xCD3 bispecific antibody mosunetuzumab (Mosun) showed durable complete responses (CR) and had manageable safety in patients (pts) with late-line R/R B-NHL (Schuster et al. ASH 2019). IV administration with Cycle (C) 1 step-up dosing was an effective strategy for mitigating CRS during C1 (Bartlett et al. ASCO 2019). Fixed-dose SC administration was also a viable strategy for CRS mitigation, owing to the slower rate of Mosun absorption compared with IV (Matasar et al. ASH 2020). A combination of both strategies could further improve the CRS profile. We present safety and efficacy data from the initial cohorts investigating SC Mosun administration with C1 step-up dosing in the Phase I/II study. Methods: All pts had R/R B-NHL with ≥1 prior line of systemic therapy and ECOG PS ≤1. SC Mosun was given in 21-day cycles using two step-up dosing schedules (C1 day [D]1/C1D8/C1D15 and D1 of subsequent cycles: 5/15/45mg or 5/45/45mg). Mosun was discontinued after C8 in pts who achieved a CR, while pts with a partial response or stable disease continued Mosun for a total of 17 cycles, unless progressive disease or unacceptable toxicity occurred. Primary objectives included evaluation of safety, tolerability, and pharmacokinetics (PK). Responses were evaluated by investigator-assessment of PET/CT scans using Cheson 2007 criteria. CRS is reported using ASTCT criteria (Lee et al. Biol Blood Marrow Transplant 2019). Results: As of June 21, 2021, 74 pts had been enrolled (5/15/45mg: 38 pts;5/45/45mg: 36 pts). Median age was 67.0 years (range: 41-88). The most common NHL subtypes were DLBCL (31 pts), FL (21), transformed (tr) FL (10), and MCL (3). 70.0% of pts had Ann Arbor stage III or IV disease. Median number of prior lines of therapy was 3 (range: 1-9). 79.5% of pts were refractory to prior anti-CD20 therapy and 82.4% were refractory to their last prior therapy. Median follow-up for safety was 2.5 months (range: 0.2-7.2). No dose-limiting toxicities were observed during dose-escalation. Common all-Grade (Gr) adverse events (AEs;≥10% of pts) were injection site reaction (52.7%;Gr 1: 47.3%;Gr 2: 5.4%), CRS (24.3%), fatigue (21.6%), headache (17.6%), rash (13.5%), and pyrexia (10.8%). CRS mostly occurred in C1 and was low Gr in all pts (Gr 1: 17.6%;Gr 2: 6.8%);no Gr ≥3 CRS occurred. Gr 2 CRS occurred with a similar frequency in the 5/15/45mg and 5/45/45mg cohorts (7.9% vs 5.6% of pts, respectively). In the 5/15/45mg cohort, the 3 Gr 2 CRS events occurred after each of the C1 doses, while in the 5/45/45mg cohort, the 2 Gr 2 CRS events occurred after the first 45mg dose. Median duration of CRS was 2 days (range: 1-6) and all events resolved without sequelae. Neutropenia occurred in 12.2% of pts (Gr 2: 2.7%;Gr 3: 6.8%;Gr 4: 2.7%). Febrile neutropenia occurred in only 1 pt (Gr 3). Serious infections occurred in 3 pts (2 pneumonia, both resolved;1 COVID-19, fatal outcome). No Mosun-related Gr 5 (fatal) AEs or Mosun-related AEs leading to Mosun discontinuation occurred. The PK profile of SC Mosun was consistent with that previously reported, with high bioavailability (>85%), a slow absorption rate, and a blunted C max. IL-6 and IFN-y kinetics in plasma were similar in both SC cohorts, with modest and delayed increases observed after the initial dose, contrasting with the more marked and rapid increases observed with IV dosing, and consistent with the low frequency and severity of CRS observed. At data cut-off, 38 pts were efficacy evaluable. Responses were observed in 19 pts across all histologies, including 8/10 (80%) pts with R/R FL and 6/17 (35.3%) pts with R/R DLBCL/trFL. Conclusions: SC Mosun administration with C1 step-up dosing has a favorable safety profile in pts with late-line and highly refractory B-NHL, enabling an outpatient treatment schedule without mandatory hospitalizations. Encouragingly, the 5/45/45mg schedule had a low rate of CRS that was similar to the 5/15/45mg schedule, allowing the target dose to be reached earlier. Early response data suggest that the efficacy of Mosun is not compromised by SC dosing. Compared with IV, SC Mosun is likely to improve convenience for pts and efficiency for healthcare providers. Updated efficacy data with longer follow up and depth of response will be presented. Disclosures: Bartlett: Affimed: Research Funding;Autolus: Research Funding;Bristol-Myers Squibb: Research Funding;Celgene: Research Funding;Forty Seven: Research Funding;Janssen: Research Funding;Kite Pharma: Research Funding;Merck: Research Funding;Millennium: Research Funding;Pharmacyclics: Research Funding;Genentech, Inc./F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding;Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding;ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding;Washington University School of Medicine: Current Employment. Giri: Royal Adelaide Hospital: Current Employment. Budde: Genentech, Inc.: Consultancy;Merck, Inc: Research Funding;Amgen: Research Funding;AstraZeneca: Research Funding;Mustang Bio: Research Funding;Novartis: Consultancy;Gilead: Consultancy;Roche: Consultancy;Beigene: Consultancy. Schuster: Celgene: Consultancy, Honoraria, Research Funding;Nordic Nanovector: Consultancy;Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding;Abbvie: Consultancy, Research Funding;Acerta Pharma/AstraZeneca: Consultancy;Alimera Sciences: Consultancy;BeiGene: Consultancy;Juno Theraputics: Consultancy, Research Funding;Loxo Oncology: Consultancy;Tessa Theraputics: Consultancy;Genentech/Roche: Consultancy, Research Funding;Pharmaclyclics: Research Funding;Adaptive Biotechnologies: Research Funding;Merck: Research Funding;Incyte: Research Funding;TG Theraputics: Research Funding;DTRM: Research Funding. Assouline: Johnson&Johnson: Current equity holder in publicly-traded company;Gilead: Speakers Bureau;Amgen: Current equity holder in publicly-traded company, Research Funding;Novartis: Honoraria, Research Funding;Eli Lilly: Research Funding;Roche/Genentech: Research Funding;Jewish General Hospital, Montreal, Quebec: Current Employment;Takeda: Research Funding;BeiGene: Consultancy, Honoraria, Research Funding;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;AstraZeneca: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria, Research Funding, Speakers Bureau;Janssen: Consultancy, Honoraria;Pfizer: Consultancy, Honoraria. Matasar: Merck Sharp & Dohme: Current holder of individual stocks in a privately-held company;Juno Therapeutics: Consultancy;Janssen: Honoraria, Research Funding;Daiichi Sankyo: Consultancy;Genentech, Inc.: Consultancy, Honoraria, Research Funding;Bayer: Consultancy, Honoraria, Research Funding;Merck: Consultancy;Teva: Consultancy;TG Therapeutics: Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;Takeda: Consultancy, Honoraria;GlaxoSmithKline: Honoraria, Research Funding;Seattle Genetics: Consultancy, Honoraria, Research Funding;Memorial Sloan Kettering Cancer Center: Current Employment;IGM Biosciences: Research Funding;Pharmacyclics: Honoraria, Research Funding;Rocket Medical: Consultancy, Research Funding;ImmunoVaccine Technologies: Consultancy, Honoraria, Research Funding. Canales: Takeda: Consultancy, Honoraria, Speakers Bureau;Incyte: Consultancy;Sandoz: Honoraria, Speakers Bureau;iQone: Honoraria;Sanofi: Consultancy;Novartis: Consultancy, Honoraria;Karyopharm: Consultancy, Honoraria;Eusa Pharma: Consultancy, Honoraria;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria;Gilead/Kite: Consultancy, Honoraria;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau;Janssen: Consultancy, Honoraria, Speakers Bureau. Fay: St Vincent's Hosptial, Sydney, ustralia: Current Employment. Cheah: BMS: Consultancy, Research Funding;Abbvie: Research Funding;Janssen: Consultancy, Honoraria;MSD: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Ascentage Pharma: Consultancy, Honoraria;AstraZeneca: Consultancy, Honoraria;Lilly: Consultancy, Honoraria;TG therapeutics: Consultancy, Honoraria;Beigene: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Roche: Consultancy, Honoraria, Other: travel, Research Funding. Marlton: BeiGene: Honoraria, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees;AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Queensland Health: Current Employment;Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wiebking: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company;F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Yin: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. To: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Li: Genentech, Inc.: Current Employment, Current holder of individual stocks in a privately-held company. Huang:F. Hoffmann-La Roche Ltd: Current Employment. Zhou: Fibrogen China: Ended employment in the past 24 months;Roche Pharma Product Development: Current Employment. Penuel: Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. O'Hear: Genentech, Inc.: Current Employment;F. Hoffmann-La Roche Ltd: Current holder of individual stocks in a privately-held company. Sehn: Novartis: Consultancy;Debiopharm: Consultancy;Genmab: Consultancy. OffLabel Disclosure: Mosunetuzumab is a CD20xCD3 bispecific antibody that redirects T cells to engage and eliminate malignant B cells. Mosunetuzumab is an investigational agent.
ABSTRACT
The emergence of the covid-19 disease pandemic caused by the 2019 novel coronavirus has required a re-evaluation of treatment practices for clinicians caring for patients with chronic lymphocytic leukemia (cll). The American Society for Hematology (ash) has provided a series of recommendations for the treatment of patients with cll during the pandemic, covering a range of topics, including testing for covid-19, cll treatment initiation and selection, use of immunoglobulin therapy, in-person monitoring, and treatment of patients with cll and covid-19. We summarize the ash recommendations and discuss their applicability as guidelines for the treatment of cll during the covid-19 pandemic in Canada.