Zon, Rebecca L.

Myeloproliferative neoplasm (MPN) patients are at risk of splanchnic vein thromboses (SVT). Prior studies have failed to demonstrate a benefit of hydroxyurea therapy in preventing recurrent thrombosis after SVT, but are limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. To better assess the impact of cytoreductive therapy on thrombosis recurrence, we performed a retrospective cohort study of MPN-SVT patients from the international GASTRO-MPN Consortium, treating cytoreductive therapy as a time-dependent covariate. We identified 757 patients, of which 43% were treated with cytoreductive therapy. During a median follow-up of 7.4 years, 256 patients (34%) had thrombosis recurrence; 145 (19%) had SVT extension/recurrence/TIPS thrombosis, 138 (18%) an thrombosis recurrence outside the splanchnic bed (74% were venous). Additionally, 262 patients (35%) experienced clinically relevant bleeding and 170 (22%) died. After adjusting for age, sex, prior thrombosis, timing of MPN diagnosis relative to SVT, anticoagulation initiation within 30 days of SVT diagnosis, MPN type, JAK2 status, other cancers and cirrhosis, cytoreductive therapy was associated with a decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). This was driven by a lower risk of SVT extension/recurrence (HR 0.62 95%CI 0.42-0.90, p=0.01) but not by extra-splanchnic thrombosis recurrence (HR 0.97 95%CI 0.72-1.30, p=0.82). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=275), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.07, p=0.09) for recurrent thrombosis. These data support the use of cytoreductive therapy in MPN-SVT patients to prevent recurrent thrombosis, particularly SVT extension/recurrence.

Abstract Immune checkpoint inhibitor–associated immune thrombocytopenia (ICI-ITP) has been described in case reports and small case series, but comprehensive data on its incidence, risk factors, clinical features, treatment, and outcomes are lacking. We reviewed medical records of all adults initiating ICI therapy between 2016 and 2023 at 29 US hospitals across 7 major cancer centers to identify patients with ICI-ITP. Multivariable logistic regression was used to identify risk factors, and Cox modeling was performed to assess the association between ICI-ITP, its severity, and mortality. Among 86 467 patients, ICI-ITP occurred in 214 (0.25%). Independent risk factors included lower baseline platelet count, combination ICI therapy, stage IV cancer, and additional immune-related adverse events. ICI-ITP occurred at a median of 8 weeks (interquartile range [IQR], 4-18) after ICI initiation, with a median nadir platelet count of 41 × 109/L (IQR, 17 × 109/L to 64 × 109/L). Patients were treated with glucocorticoids (n = 106 [49.5%]), immune globulin (n = 39 [18.2%]), and thrombopoietin receptor agonists (n = 29 [13.6%]). Recovery occurred in 161 patients (75.2%) at a median of 2.3 weeks (IQR, 1.0-5.3). Of 76 patients rechallenged with ICIs, 23 (30.3%) developed recurrent ICI-ITP. ICI-ITP and its severity were associated with higher all-cause mortality, with a nearly threefold increase in risk among patients with severe ICI-ITP than those without ICI-ITP (adjusted hazard ratio, 2.96 [95% confidence interval, 2.14-4.08]). These findings establish ICI-ITP as a rare but clinically significant complication of ICI therapy, provide, to our knowledge, the first large-scale description of its risk factors and clinical course, and underscore the importance of timely recognition and management.

Abstract INTRODUCTION Immune checkpoint inhibitors (ICIs) have emerged as a cornerstone of cancer therapy. However, despite their efficacy, ICIs can cause a unique spectrum of autoimmune toxicities known as immune-related adverse events (irAEs). In contrast to irAEs involving other organ systems, hematologic irAEs such as ICI-associated immune thrombocytopenia (ICI-ITP) are less common. As a result, existing data on ICI-ITP are largely confined to isolated case reports, single-center case series, and pharmacovigilance databases lacking granular clinical data. To address this key knowledge gap, we sought to comprehensively characterize the incidence, risk factors, clinical features, treatments, and outcomes associated with ICI-ITP. METHODS We performed a multicenter cohort study of adult patients who initiated ICI therapy at 29 hospitals across 7 major cancer centers in 11 geographically diverse states in the US between 2016-2023. ICI-ITP was defined as a decline in platelet count to <100 x109/L in the absence of an alternative more plausible etiology of thrombocytopenia. Patients with hematologic malignancies were excluded, as were those who received cytotoxic chemotherapy within 30 days prior to thrombocytopenia onset. For each patient identified as having ICI-ITP, we collected data on demographics, comorbidities, medications, laboratory values, treatments, and outcomes. All data were extracted by manual chart review. To identify risk factors for ICI-ITP and to examine its association with death, for each case of ICI-ITP we also collected data on two control patients who initiated ICI therapy at the same site and in the same year but without development of ICI-ITP. We used multivariable logistic regression to identify independent risk factors for ICI-ITP and its recovery (the latter defined according to criteria established by the ITP International Working Group). We used a multivariable Cox model to examine the association between ICI-ITP and its severity with all-cause mortality. RESULTS We identified a total of 214 patients who developed ICI-ITP among 86,648 examined (0.25%). The incidence was highly consistent across sites (range, 0.15–0.30%). Risk factors for ICI-ITP included simultaneous receipt of two different classes of ICIs, additional irAEs, and a lower baseline platelet count. ICI-ITP developed at a median of 8 weeks (IQR, 4–18) following ICI initiation. The median nadir platelet count was 41 x109/L (IQR, 17–64). Six out of 214 patients (2.8%) developed a major bleed, and 16 patients (7.5%) developed a clinically relevant non-major bleed. Cell-bound anti-platelet antibody testing was positive in 6 of 8 patients (75.0%) for whom it was assessed, and median circulating thrombopoietin levels (201 pg/mL [IQR, 178–295]) were similar to those seen in primary ITP. Treatments used included glucocorticoids (49.5%), immune globulin (18.2%), and thrombopoietin receptor agonists (13.6%). Overall, 161 patients (75.2%) recovered from ICI-ITP at a median of 2 weeks (IQR, 1–5) following ICI-ITP onset. Predictors of recovery included additional irAEs and a higher nadir platelet count. Treatment response was observed in 57.0%, 56.4%, and 58.3% of patients within 60 days following initiation of glucocorticoids, immune globulin, and thrombopoietin receptor agonists, respectively. Of 76 patients rechallenged with an ICI, 23 (30.3%) developed recurrent ICI-ITP at a median of 9 weeks (IQR, 2–15); 17 of these 23 patients (73.9%) recovered. Finally, ICI-ITP and its severity were monotonically associated with a higher risk of death (adjusted hazard ratio 2.96 [95% CI, 2.14–4.08] for those with severe ICI-ITP compared to those without ICI-ITP). CONCLUSION In this multicenter study involving patients treated with ICIs at 29 hospitals across the US, we identified 214 patients with ICI-ITP. For the first time, we characterize in detail the incidence, risk factors, clinical features, treatments, and outcomes of ICI-ITP, a relatively novel disease entity. We found that more than half of patients responded to conventional ITP-directed therapies, and that most patients rechallenged did not develop recurrent ICI-ITP. We also found that ICI-ITP was independently associated with an increased risk of death, including a nearly 3-fold increased risk in those with severe ICI-ITP. These findings highlight ICI-ITP as a rare but clinically significant complication of ICI therapy that hematologists must be equipped to recognize and manage.

Abstract Background Patients with myeloproliferative neoplasms (MPNs) are at risk of splanchnic vein thrombosis (SVT). Prior studies failed to demonstrate a benefit of hydroxyurea in preventing SVT extension/recurrence, but these were limited by small sample sizes and inability to account for starting, stopping, or switching of cytoreductive therapies. We therefore investigated the role of cytoreduction as a time-dependent covariate on thrombosis recurrence in a large, international cohort of MPN-SVT patients. Methods We performed a retrospective cohort study of MPN-SVT patients included in the international GASTRO-MPN consortium. Patients diagnosed with MPN at any time before, concurrently with, or up to 60 days after initial SVT were included. Primary outcome was time from initial SVT to first thrombosis recurrence, defined as the composite of SVT extension/recurrence, transjugular intrahepatic portosystemic shunt (TIPS) thrombosis, or venous/arterial thrombosis outside the splanchnic veins. Secondary outcomes included SVT extension/recurrence, TIPS thrombosis or extra-SVT thrombosis individually, clinically relevant bleeding (composite of major and clinically relevant non-major bleeding), MPN progression to myelofibrosis or blast phase, and death. Cytoreductive therapy was treated as a time-dependent covariate to account for discontinuation and therapy changes. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results A total of 757 patients were included for this analysis. Median age was 51 years (IQR 38-62), 59% were female. SVT involved the portomesenteric veins in 558 (77%) patients, hepatic veins in 95 (13%), and both in 54 (7.4%). MPN was known prior to initial SVT in 316 patients (42%) and diagnosed concurrently or up to 60 days after SVT in 441 (58%). Polycythemia vera (PV) was the most common MPN subtype (43%), followed by essential thrombocythemia (ET) in 24%, and primary myelofibrosis in 14%. JAK2V617F mutation was present in 86% and CALR in 2.9%. 13% had prior non-SVT thrombosis. 607 patients (83%) were treated with cytoreduction. At time of SVT, 131 patients (17%) were already on cytoreduction; in those who started after SVT, median time to initiation was 54 days after SVT, and median duration of cytoreduction per patient was 63 months. Cytoreductive therapies used at any point in treatment included hydroxyurea in 504 (69%), ruxolitinib in 182 (25%), and interferon-based in 85 (12%) patients. Anticoagulation (AC) was started within 30 days after SVT in 504 (68%) patients. Median duration of any AC per patient was 24.6 months. During a median follow up of 7.4 years, 245 patients (33%) had thrombosis recurrence; 143 (20%) had SVT extension/recurrence/TIPS thrombosis, 129 (18%) extra-SVT thrombosis (of which 74% venous), 237 patients (32%) experienced clinically relevant bleeding, and 163 (22%) died. After adjusting for age, sex, timing of MPN diagnosis relative to SVT diagnosis, AC within 30 days of SVT, PV/ET vs other MPN, JAK2 mutation, previous thrombosis, non-MPN cancer, and cirrhosis, cytoreductive therapy was associated with a significantly decreased risk of recurrent thrombosis (HR 0.67 95%CI 0.50-0.89, p=0.01). Age was associated with an increased risk of recurrent thrombosis (p=0.01). When considering types of recurrent thrombosis, cytoreduction was associated with a decreased risk of SVT extension/recurrence/TIPS thrombosis (HR 0.62 95%CI 0.42-0.90, p=0.01), but not thrombosis outside the splanchnic veins (HR 0.97 95%CI 0.72-1.30, p=0.82). There was no association between cytoreduction and bleeding (HR 1.10 95%CI 0.82-1.47, p=0.52). Similarly, there was no association between cytoreduction and time to MPN progression (p=0.24) or overall survival (p=0.30). In a subgroup of patients without erythrocytosis/thrombocytosis at initial SVT (n=271), cytoreductive therapy was associated with a HR 0.65 (95%CI 0.40-1.10, p=0.09) for recurrent thrombosis. Limited sample size and low event-rate precluded evaluation of the impact of individual cytoreductive therapies. Conclusions In the largest cohort of MPN-SVT patients to date, we show for the first time that cytoreductive therapy is associated with a decreased risk of thrombosis recurrence, driven largely by decreased SVT extension/recurrence/TIPS thrombosis. Collectively, these findings support use of cytoreductive therapy in individuals with MPN-SVT to prevent recurrent thrombosis.

Background: Myeloproliferative neoplasms (MPNs) are chronic leukemias with increased thrombotic risk. Venous thrombosis in MPN often occurs in atypical sites, such as splanchnic vein thrombosis (SVT), defined by thrombosis in the portal, hepatic, mesenteric, or splenic veins. Data to guide anticoagulation management of SVT in MPN patients is lacking. Objectives: The purpose of this study is to evaluate outcomes as well as the safety and efficacy of different anticoagulation strategies in MPN patients with SVT. Methods: A retrospective cohort study of MPN patients with SVT from 10 international centers was conducted. All centers performed systematic identification of adults with a World Health Organization 2016 diagnosis of an MPN (polycythemia vera [PV], essential thrombocythemia [ET], myelofibrosis [MF], prefibrotic MF, MPN-unclassifiable [MPN-U]) and confirmed SVT. Inclusion criteria were met if first SVT occurred after or within one year before MPN was diagnosed. The primary outcome was 1-year cumulative incidence of recurrent venous (VT) or arterial thrombosis (AT). Secondary outcomes included 1-year cumulative incidence of (1) major and clinically relevant non-major bleeding (CRNMB) by International Society on Thrombosis and Hemostasis criteria, (2) SVT recanalization; and (3) 1-year overall survival. Death as a competing risk was used for cumulative incidence analyses of recurrence and bleeding. Results: 486 MPN patients (median age at first SVT 51 years; 62.3% female) were identified. MPN diagnosis preceded SVT in 35.2% of patients (median time 4.8 years) and occurred simultaneously or within 1 year of first SVT in 64.8% of patients. 43.8% of patients had PV, 23.7% ET, 14.2% MF, 3.1% prefibrotic MF and 13.2% MPN-U. The most common driver mutation was in JAK2 (90.7%) followed by CALR (4.4%) and MPL (1.6%). SVT localization was isolated to portal (25.7%), hepatic (15.4%), mesenteric (1.9%), and splenic veins (4.3%), and in 51.2% of cases SVT occurred in multiple vessels. Prior VT or AT occurred in 8.8% and 4.1% of subjects, respectively. Cytoreduction (most commonly hydroxyurea [36.9%], interferon [9.6%] or JAK inhibitor [6.8%]) was started after SVT in 58.7% of newly diagnosed MPN patients and 40.6% of those with known MPN. 57.6% of patients were anticoagulated, 3.5% of patients were treated with an antiplatelet agent, and 11.7% were treated with both. The most common initial anticoagulants were vitamin K antagonists (VKA) (29.2%), direct oral anticoagulants (DOAC; 20.4%), and low-molecular-weight heparin (LMWH; 10.5%). DOACs were more commonly used in the USA and Asia than Europe (21.2%, 52%, and 13.5%; p<0.001). The median duration of anticoagulation was 23.9 months, with 62.8% still on anticoagulation after 3 years or at last follow-up. 1-year cumulative incidence of recurrent VT and AT was 14% (95% CI 11-18) (5.8% for recurrent SVT [95% CI 3.9-8.3]; 6.3% for other VT [95% CI 4.3-8.8]; 2.4% for AT [95% CI 1.3-4.2]), with an overall time to event 89 (IQR 34-193) days. Thrombosis incidence was similar in patients initially treated with VKA (13%), DOAC (15%) or LMWH (16%) (p=0.93); in comparison, individuals not treated with anticoagulation had 1-year thrombosis incidence of 13% (p=0.22). 1-year major and CRNMB cumulative incidence in all patients was 5.8% (95% CI 3.9-8.2) and 8.5% (95% CI 6.1-11), with median time to event 68 (IQR 13-150) days. Incidence of major bleeding was similar in VKA, DOAC, and LMWH-treated patients (5.9%, 6.6%, and 4.0%; p=0.89). 1-year cumulative incidence of SVT (partial) recanalization was 13% (95% CI 9.8-16) in all patients, with a median time to recanalization of 127 (IQR 40-323) days; recanalization rates were similar in anticoagulated and non-anticoagulated patients (p=0.76). There was a trend toward higher recanalization rates in patients treated with DOAC (26.9%) than with VKA (21.5%) or LMWH (13.6%; p=0.28). 1-year overall survival was 94.2% (95% CI 91.8-96.1) and similar between treatment groups (VKA 96.7%, DOAC 95.6%, LMWH 89.7%; p=0.11) and for no anticoagulation (82.3%; p=0.32). Conclusions: This is the largest contemporary cohort of MPN patients with SVT. MPN patients with SVT remain at risk for short-term thrombosis and bleeding complications regardless of treatment. We found no significant differences in outcomes between anticoagulation strategies, including in patients treated with DOACs compared to VKA or LMWH.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Abstract Background : Patients (pts) with COVID-19 are reported to have increased risk of venous thromboembolism yet bleeding has been an under recognized complication. Rates of bleeding remain unexamined in all patients especially in pts with cancer and COVID-19. Aim: To estimate the incidence of bleeding complication in patients with cancer and COVID 19 Methods: The CCC19 international registry (NCT04354701) aims to investigate complications of COVID-19 in pts with cancer. Our aim was to investigate the frequency of bleeding in hospitalized adult pts with cancer andCOVID-19, enrolled between March 16, 2020 and Feb 8, 2021. The incidence of bleeding complications was captured as defined by CCC19 and included both major and non major bleeding . Associated baseline clinic-pathologic prognostic factors and outcomes such as need for mechanical ventilation, intensive care unit (ICU) admission and mortality rates were assessed Results :3849 pts met analysis inclusion criteria. Bleeding was reported in 276 (7%) pts with median age of 70years; incidence was 6.6 % in females and 7.6 % in males, 6.5% in non-Hispanic white pts, 8.2 % in non-Hispanic Black pts, and 7.8 % in Hispanic pts. 74% had solid cancer and 29% had hematologic malignancies, 33% had received anti-cancer therapy in preceding 30 days, and 8% had surgery within 4weeks. In pts taking antiplatelet or anticoagulant medications at baseline, 7.2% developed bleeding. Need for mechanical ventilation, ICU admission, 30-day mortality, and total mortality were significantly higher in those with bleeding complications compared to those without, p<0.05 Conclusion : We describe the incidence of bleeding in a large cohort of pts with cancer and COVID-19. Bleeding events were observed in those with adverse outcomes including mechanical ventilation, ICU admission, and high mortality; the overall mortality of 43% in patients with bleeding complications is especially notable. This important complication may reflect underlying COVID-19 pathophysiology as well as iatrogenic causes. Figure 1 Figure 1. Disclosures Kumar: Diagnostica Stago: Honoraria. Zon: AMAGMA AND RLZ: Consultancy, Current holder of individual stocks in a privately-held company. Byeff: Pfizer, BMS, Takeda,Teva, Merck, United health: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Nagaraj: Novartis: Research Funding. Hwang: astrazaneca,Merck,bayer, Genentech: Consultancy, Research Funding. McKay: Myovant: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Calithera: Membership on an entity's Board of Directors or advisory committees; Tempus: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tempus: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Dendreon: Consultancy; Caris: Other: Serves as a molecular tumor board ; Vividion: Consultancy; Sorrento Therapeutics: Consultancy; Bayer: Research Funding. Warner: Westat, Hemonc.org: Consultancy, Current holder of stock options in a privately-held company. Connors: Pfizer: Honoraria; CSL Behring: Research Funding; Alnylam: Consultancy; Bristol-Myers Squibb: Honoraria; takeda: Honoraria; Abbott: Consultancy. Rosovsky: Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Inari: Consultancy, Membership on an entity's Board of Directors or advisory committees; Dova: Consultancy, Membership on an entity's Board of Directors or advisory committees.