PURPOSE Chemotherapy-induced thrombocytopenia (CIT) leads to delay or reduction in cancer treatment. There is no approved treatment. METHODS We conducted a phase II randomized trial of romiplostim versus untreated observation in patients with solid tumors with CIT. Before enrollment, patients had platelets less than 100,000/μL for at least 4 weeks, despite delay or dose reduction of chemotherapy. Patients received weekly titrated romiplostim with a target platelet count of 100,000/μL or more, or were monitored with usual care. The primary end point was correction of platelet count within 3 weeks. Twenty-three patients were treated in a randomization phase, and an additional 37 patients were treated in a single-arm, romiplostim phase. Resumption of chemotherapy without recurrent CIT was a secondary end point. RESULTS The mean platelet count at enrollment was 62,000/μL. In the randomization phase, 14 of 15 romiplostim-treated patients (93%) experienced correction of their platelet count within 3 weeks, compared with one of eight control patients (12.5%; P < .001). Including all romiplostim-treated patients (N = 52), the mean platelet count at 2 weeks of treatment was 141,000/μL. The mean platelet count in the eight observation patients at 3 weeks was 57,000/μL. Forty-four patients who achieved platelet correction with romiplostim resumed chemotherapy with weekly romiplostim. Only three patients (6.8%) experienced recurrent reduction or delay of chemotherapy because of isolated CIT. CONCLUSION This prospective trial evaluated treatment of CIT with romiplostim. Romiplostim is effective in correcting CIT, and maintenance allows for resumption of chemotherapy without recurrence of CIT in most patients.

Leukocytosis is a common feature of malignancies. While controversial, there appears to be an association between the degree of tumor-related leukocytosis and prognosis. In this paper, we provide evidence supporting an untapped clinical paradigm linking G-CSF secretion to the induction of leukocytosis and expansion of myeloid-derived suppressor cells, providing an explanation for the association between leukocytosis, elevated neutrophil-to-lymphocyte ratios and prognosis in non-small cell lung cancer. Clinically validating this mechanism may identify MDSCs and G-CSF as dynamic markers of early disease progression and therapeutic response, and shed light onto novel therapeutic avenues for the treatment of patients with non-small cell lung cancer.

Summary Incidence of venous thromboembolism (VTE) varies across different regimens in newly diagnosed multiple myeloma (NDMM) patients. Limited data exist on the use of direct oral anticoagulants as thromboprophylaxis in the setting of haematologic malignancies, specifically multiple myeloma. In this retrospective study of 305 NDMM patients, VTE rates in those treated with carfilzomib, lenalidomide, dexamethasone (KRD) + aspirin (ASA), bortezomib, lenalidomide, dexamethasone (RVD) + ASA, and KRD + rivaroxaban were statistically significant, 16·1%, 4·8%, and 4·8%, respectively. The findings confirm a higher incidence of VTE when using KRD induction compared to RVD induction and reveal that the use of low‐dose rivaroxaban thromboprophylaxis can mitigate this risk without an observable increase in bleeding rates.

Background Low‐molecular‐weight heparin has been the preferred treatment of cancer‐associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs). Objectives The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT. Methods From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway. Results The 6‐month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%‐5.7%) and 2.2% (95% CI, 1.1%‐3.2%), respectively. The incidence of clinically relevant non–major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI,  3.7%‐7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6‐month cumulative mortality rate was 22.2% (95% CI, 19.4%‐24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years. Conclusion Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

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