Marrow Transplant Recipients Research Articles

Hyperpigmented Folliculocentric Papules in a Bone Marrow Transplant Recipient: Answer.

Hyperpigmented Folliculocentric Papules in a Bone Marrow Transplant Recipient: Answer.

Factors Affecting Platelet Transfusion Response Following Haploidentical Stem Cell Transplant

A mainstay of therapy for certain hematologic malignancies and non-malignant disorders is allogeneic stem cell transplant. One known complication is post-transplant thrombocytopenia which results in a significant bleeding risk. Although prophylactic platelet transfusions reduce the severity of thrombocytopenia, refractoriness to transfusions often develops. Several studies have examined clinical and laboratory factors that are associated with poor platelet response in the general hematologic malignancy and hematopoietic stem cell transplant population, which include lymphocytotoxic antibodies, bleeding, medications and infection. Only a few detailed studies have examined factors which specifically affect platelet transfusion response in patients who have undergone haploidentical stem cell transplant (HI SCT).This was a single center retrospective analysis of 721 platelet transfusions from 110 HI SCT patients to determine risk factors associated with platelet refractoriness. During the Jefferson 2-step HI SCT, the recipient receives myeloablative or reduced intensity conditioning followed by donor lymphocyte product infusion (DLI). Cyclophosphamide is given 2-3 days after DLI for tolerization, followed in 2 days by CD34+ stem cell product infusion. Patient-specific, transplant-specific and transfusion-specific data were collected and analyzed within 28 days following the 2-step HI SCT. Patient- and transplant-specific data included patient age, gender, body surface area, indication for transplant, conditioning regimen, date of transplant, pre-transplant CMV antibody status, pre-transplant anti-HLA antibodies, number of prior pregnancies, history of splenectomy or splenomegaly, and patient co-morbidities according to the Hematopoietic Cell Transplantation-Specific Co-morbidity Index. Transfusion-specific data included major ABO or Rh mismatch between bone marrow transplant (BMT) recipient and platelet product, major ABO or Rh mismatch between BMT donor and platelet product, age of platelet product at the time of transfusion, pre- and post-transfusion platelet count, and time from BMT to transfusion.Corrected count increments (CCI) were calculated according to standard formula, CCI=(post-transfusion - pre-transfusion platelet count) x body surface area / number of platelet transfused. The date and time of each platelet transfusion were recorded along with pre- and post-transfusion counts. CCI measures were modeled as a function of time from BMT using a linear mixed effects model allowing for the patient-specific trajectories by incorporating random effects in the intercept and slope for time from BMT.Our analysis identified significant associations with recipient gender, splenomegaly, coronary artery disease/congestive heart failure (CAD/CHF) and time from BMT to transfusion. CCI was on average lower by 23% in male compared to female recipients (95%CI: 13%, 33%; p<0.001), and by 40% in patients with splenomegaly (95%CI: 29%, 49%; p<0.001). When assessing CCI trends over time, transfusions further out from BMT were shown to have improved CCI versus those closer to BMT with significant improvement in patients without CAD/CHF (average 2.8% CCI improvement per day in non-CAD/CHF patients versus 0.8% in CAD/CHF patients; p=0.034). The effect of pre-transplant class 1 anti-HLA antibodies was not significant (p=0.510).This study confirms results from prior studies which indicate that male gender and splenomegaly are important contributors to post-transplant platelet transfusion refractoriness. Previous findings indicating the impact of anti-HLA antibodies in the pre-transplant setting were not confirmed by this study. We hypothesize that the marked increase in sensitivity that characterizes current-generation anti-HLA antibody testing may have lowered the predictive value of this test. Associations between platelet responsivity, CAD/CHF and time from transplant are novel findings and will require confirmation in future studies. DisclosuresNo relevant conflicts of interest to declare.

Infection-Related Mortality in Adults and Children Undergoing Allogeneic Hematopoietic Cell Transplantation: An Australian Registry Report

Infection-related mortality (IRM) is the most common non-relapse-related cause of death reported after allogeneic hematopoietic cell transplantation (HCT). Information on the incidence and timing of specific infective organisms and the risk factors for IRM is essential to developing prevention strategies. This report provides the first account of IRM in adults and children undergoing HCT in Australia. Between 2013 and 2018, 2705 adult and 689 pediatric first HCTs were identified from the Australasian Bone Marrow Transplant Recipient Registry database, associated with 1075 (39.7%) total overall deaths in adults and 134 (19.4%) in children. Demographics and causes of death, including infectious etiology and causative organisms, were extracted from the database for adults and children for analysis. At day +100 and 1 year post-HCT, IRM was the leading cause of early post-HCT mortality in adults, accounting for 6.2% and 9.8%, respectively; in children, IRM was the leading cause of post-HCT mortality at day +100 at 2.5% and the second highest cause of post-HCT mortality at 1 year post-HCT at 4.9%, following relapse at 5.8%. In adults, older age, transplantation not in a first complete remission (non-CR1), the use of antithymocyte globulin (ATG) or alemtuzumab, donor-positive/recipient-negative cytomegalovirus (CMV) serostatus, and acute graft-versus-host disease were significant risk factors for IRM. However, in children, age >5 years, acute lymphocytic leukemia as the primary disease, and mismatched unrelated or haploidentical donor source were predictive of IRM. Of the deaths in which an infectious etiology was reported in adults (52.4%), 49.3% were attributed to bacteria, 25.3% to fungus, 21.7% to viruses, and 3.6% to post-transplantation lymphoproliferative disorder (PTLD). The most common organisms were Pseudomonas spp, Enterococcus spp, Candida spp, Aspergillus spp, and CMV. In children where an infectious etiology was reported (64%), 13% were attributed to bacteria, 26% to fungus, 45% to viruses, and 16% to PTLD. This report highlights that IRM was the leading cause of death early post-HCT in Australia. Strategies to reduce IRM, such as individualized pre-transplantation infection risk assessment, rapid diagnostics, and prevention management strategies should be explored to determine whether these outcomes can be improved. In addition, improving the completeness and accuracy of reported data, particularly for infectious pathogens, could assist in directing management strategies to reduce IRM in HCT.

Considerations for immunotherapy in patients with cancer and comorbid immune dysfunction.

Immune checkpoint inhibitors have been widely incorporated for cancer treatment in a variety of solid and hematologic malignancies. Multiple clinical trials have demonstrated the efficacy of PD-1/PD-L1 and CTLA-4 axis inhibition in the metastatic and adjuvant settings. Due to the risks of autoimmune toxicity with these agents, stringent inclusion/exclusion criteria were employed in those initial clinical trials. These criteria led to exclusion or underrepresentation of a variety of patient populations with underlying immune dysfunction. These populations included patients with preexisting autoimmune diseases, solid organ or bone marrow transplant recipients, patients with HIV or viral hepatitis infections, patients receiving concurrent chronic steroid therapy, as well as patients who were elderly, pregnant, or had poor performance status. Thus, established guidelines on the use of immune checkpoint inhibitors in these patients are lacking, and evidence to support efficacy or toxicity are overall limited to retrospective studies and case series. Fortunately, ongoing clinical trials are now including these patients and are shedding light on whether these underrepresented populations can also safely benefit from immune checkpoint inhibitor therapies. In this review, we summarize the most clinically relevant available data on the use of checkpoint inhibitors in immunocompromised patient groups with a primary focus on safety.

Immature platelet fraction as a predictor of platelet count recovery following allogeneic bone marrow transplantation

The immature platelet fraction (IPF) is a marker of increased platelet production. An increase in IPF is associated with increased marrow production; therefore, a subsequent increase in a bone marrow transplant recipient during the pancytopenic phase may correlate with platelet recovery and engraftment. We performed a retrospective cohort study and evaluated 32 patients who underwent allogeneic bone marrow transplantation. Patients had platelet count, neutrophil count, platelet transfusion and IPF recorded over a period extending from stem cell infusion, day 0, to day 30. The outcomes analysed were platelet count versus time and IPF versus time to establish the predictive ability of the IPF to determine platelet count recovery. Further analysis was performed to confirm the strength of the correlation and the sensitivity of the IPF in predicting a platelet count greater than 50 at day 30. The IPF was shown to rise 5 days prior to platelet count increase. An IPF rise was also shown to correlate with higher average platelet counts at day 30 of transplant. The utility of the IPF in predicting a platelet count of over 50 at day 30 was strongest between days 11 and 15 with an area under the curve (AUC) of 0.79. An IPF of 2.0 or above had 69% sensitivity and 85% specificity for predicting a platelet count of greater than 50 by day 30. In allogeneic bone marrow transplantation, the IPF is a reliable predictor of platelet recovery. The mean IPF between day 11 and day 15 is the most sensitive in predicting a robust platelet count of greater than 50 by day 30.

Australia and New Zealand (ANZ) outcomes of high-dose chemotherapy and stem cell transplantation for relapsed or refractory germ cell tumors (GCT) from 1999 to 2019: Multicenter registry-based study with ABMTRR.

382 Background: High dose chemotherapy (HDCT) with autologous stem-cell transplant (ASCT) is effective in advanced germ cell tumours (GCT) that are refractory to, or progress after, first-line therapies. Five-year overall survival in North American and European series range from 48-60%1,2,3. This study aimed to assess ANZ outcomes for quality assurance. Methods: Retrospective multi-centre audit of all male patients with GCT who underwent HDCT and ASCT from 1999-2019. Patients were identified from the Australasian Bone Marrow Transplant Recipient Registry. Primary outcomes included overall and progression- free survival (OS, PFS). Results: 111 patients were identified at 13 centres, each treating a median (range) of 7 (1-27) patients. Median (range) age was 30 (14-68) years. 88 (79%) had testicular primary. 16% were pure seminoma. Median time from first diagnosis to first stem cell cycle was 11 months (range 3 months-38 years). Prior to ASCT, 35% had primary refractory disease and 65% had relapsed. IPFSG risk score was very low in 5%, low in 13%, intermediate in 36%, high in 25%, and very high in 21%. HDCT regimen was CE in 78% (as part of TI-CE regimen in 38%), Carbop-EC-T in 6%, ICE in 6%, CEC in 5% and other in 4%. 89% completed all planned HDCT and ASCT cycles. Five treatment related deaths occurred. Progressive disease on treatment occurred in 14%. At median follow-up time 4.4 years (95% CI: 2.9 to 6.0), 51% were disease-free, 13% alive with disease, 34% deceased. 3 patients displayed late progression over 2 years after ASCT. The estimated 1, 2 and 5-year PFS rates were 62%, 57% and 52% respectively and OS rates were 73%, 65% and 61%. Survival by IPFSG and IGCCG risk categories are displayed in the table below. Conclusions: This is the first registry-based audit of HDCT for metastatic GCT from ANZ, which has demonstrated our outcomes are comparable with best international practice.

Efficacy of Rezafungin in Prophylactic Mouse Models of Invasive Candidiasis, Aspergillosis, and Pneumocystis Pneumonia.

Antifungal prophylaxis is recommended to prevent invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii in patients at risk for opportunistic infections, such as allogeneic blood or marrow transplant recipients, patients with hematological disease undergoing chemotherapy, or patients on immunosuppressive therapies. Current approaches to antifungal prophylaxis require multiple agents to cover these key fungi. Rezafungin, a novel echinocandin designed for next-generation properties (e.g., greater stability and long-acting pharmacokinetics for once-weekly dosing), has demonstrated in vitro activity against Candida and Aspergillus spp. and efficacy against Pneumocystis spp. biofilms. Rezafungin was evaluated in in vivo studies of prophylactic efficacy using immunosuppressed mouse models of invasive candidiasis, aspergillosis, and Pneumocystis pneumonia. Rezafungin reduction of Candida CFU burden was generally greater with increasing drug concentrations (5, 10, or 20 mg/kg) and when rezafungin was administered closer to the time of fungal challenge (day -1, -3, or -5). Similarly, in the aspergillosis model, survival rates increased with drug concentrations and when rezafungin was administered closer to the time of fungal challenge. Against Pneumocystismurina, rezafungin significantly reduced trophic nuclei and asci counts at all doses tested. Rezafungin prevented infection at the two higher doses compared to vehicle and had comparable activity to the active control trimethoprim-sulfamethoxazole at human equivalent doses for prevention. These findings support phase 3 development of rezafungin and the potential for single-agent prophylaxis against invasive fungal disease caused by Candida spp., Aspergillus spp., and Pneumocystis jirovecii.

375 - The Incidence of Viral Upper Respiratory Tract Infection in Allogeneic Bone Marrow Transplant Recipients during the COVID Pandemic

375 - The Incidence of Viral Upper Respiratory Tract Infection in Allogeneic Bone Marrow Transplant Recipients during the COVID Pandemic

489 - Trends and Outcomes in Australia and New Zealand in Autologous Stem Cell Transplantation in Older Patients with Multiple Myeloma: An Australasian Bone Marrow Transplant Recipient Registry Study

489 - Trends and Outcomes in Australia and New Zealand in Autologous Stem Cell Transplantation in Older Patients with Multiple Myeloma: An Australasian Bone Marrow Transplant Recipient Registry Study

483 - Allogeneic Haematopoietic Cell Transplantation for Mantle Cell Lymphoma Can Achieve Durable Remission and Myeloablative Conditioning Is Associated with Inferior Survival: An Australasian Bone Marrow Transplant Recipient Registry Study

483 - Allogeneic Haematopoietic Cell Transplantation for Mantle Cell Lymphoma Can Achieve Durable Remission and Myeloablative Conditioning Is Associated with Inferior Survival: An Australasian Bone Marrow Transplant Recipient Registry Study

142 - Improvement in Non-Relapse Mortality Following Allogeneic Transplantation for Chronic Lymphocytic Leukaemia in Australia and New Zealand: An Australasian Bone Marrow Transplant Recipient Registry Study

142 - Improvement in Non-Relapse Mortality Following Allogeneic Transplantation for Chronic Lymphocytic Leukaemia in Australia and New Zealand: An Australasian Bone Marrow Transplant Recipient Registry Study

482 - Allogeneic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma Can Achieve Durable Remissions: An Australasian Bone Marrow Transplant Recipient Registry Study

482 - Allogeneic Stem Cell Transplantation for Diffuse Large B Cell Lymphoma Can Achieve Durable Remissions: An Australasian Bone Marrow Transplant Recipient Registry Study

Associations between urinary 3-indoxyl sulfate, a gut microbiome-derived biomarker, and patient outcomes after intensive care unit admission.

3-indoxyl sulfate (3-IS) is an indole metabolism byproduct produced by commensal gut bacteria and excreted in the urine; low urinary 3-IS has been associated with increased mortality in bone marrow transplant recipients. This study investigated urinary 3-IS and patient outcomes in the ICU. Prospective study that collected urine samples, rectal swabs, and clinical data on 78 adult ICU patients at admission and again 72h later. Urine was analyzed for 3-IS by mass spectrometry. Median urinary 3-IS levels were 17.1μmol/mmol creatinine (IQR 9.5 to 26.2) at admission and 15.6 (IQR 4.2 to 30.7) 72h later. 22% of patients had low 3-IS (≤6.9μmol/mmol) on ICU admission and 28% after 72h. Low 3-IS at 72h was associated with fewer ICU-free days (22.5 low versus 26 high, p=0.03) and with death during one year of follow-up (36% low versus 9% high 3-IS, p<0.01); there was no detectable difference in 30-day mortality (18% low versus 5% high, p=0.07). Low urinary 3-IS level 72h after ICU admission was associated with fewer ICU-free days and with increased one-year but not 30-day mortality. Further studies should investigate urinary 3-IS as an ICU biomarker.

Janus Kinase Inhibitors and Non-Melanoma Skin Cancer.

JAK (janus kinase) inhibitors are becoming increasingly prescribed for various conditions from dermatologic diseases to graft versus host disease in bone marrow transplant recipients. This class of drugs has been found to be truly life-changing for many, though they are not without potential adverse effects. While JAK inhibitors have not been shown to significantly increase the risk of non-melanoma skin cancer (NMSC) in large scale clinical trials, NMSC is one of the most concerning possible adverse events, and there have been several reported cases of aggressive squamous cell carcinomas, especially in our already immunosuppressed patient populations. In these patients, it is incredibly important that patients are on the lowest possible dosage of the JAK inhibitor. In addition, these patients must be routinely screened by a dermatologist with a comprehensive skin exam to ensure early detection if skin cancer was to develop. For those patients diagnosed with skin cancer, early intervention is key to optimize outcomes, and at times, multi-disciplinary care coordination is needed. In the future, large-scale studies with longer follow-up of patients would help determine whether JAK inhibitors significantly increase the risk of NMSC.

Cyclosporine-induced Leukoencephalopathy Precipitated Following Interaction with Ciprofloxacin.

ABSTRACTA bone marrow transplant recipient on cyclosporine initiated on ciprofloxacin for a renal abscess presented with encephalopathy, right hemiparesis, and multiorgan dysfunction. Imaging revealed white matter signal changes characteristic of cyclosporine leukoencephalopathy. This case illustrates the potential drug interaction of cyclosporine with ciprofloxacin and the need to exercise caution while prescribing antibiotics with cyclosporine.

Rezafungin: A Novel Antifungal for the Treatment of Invasive Candidiasis

Rezafungin is a novel echinocandin with exceptional stability and solubility and a uniquely long half-life allowing for front-loaded drug exposure with once-weekly dosing. Rezafungin has been shown comparable to other echinocandins, with activity against Candida spp. and Aspergillus spp. including subsets of echinocandin-resistant Candida auris and azole-resistant Aspergillus isolates. Available clinical data show robust safety and promising efficacy. Phase III trials will provide data on efficacy of rezafungin for the treatment of candidemia and invasive candidiasis and for the prevention of invasive fungal disease in blood and bone marrow transplant recipients. Rezafungin is a promising new candidate in the antifungal arsenal that opens up clinical possibilities based on its impressive half-life, such as early hospital discharge for stable patients and use as prophylaxis in immunocompromised patients.

1284. Outcomes by Baseline Pathogens and Susceptibility in the STRIVE Phase 2 Trial of Once-Weekly Rezafungin for Treatment of Candidemia and Invasive Candidiasis Compared with Caspofungin

BackgroundRezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. This analysis of the completed Phase 2 STRIVE trial (NCT02734862) of RZF treatment was conducted to evaluate outcomes based on baseline pathogen and susceptibility.MethodsIn STRIVE, adults (≥ 18 y) with systemic signs and mycological evidence of candidemia and/or IC were randomized to either RZF once weekly or caspofungin (CAS) once daily for ≥ 14 days (Fig. 1). The primary efficacy endpoint was Overall Response (resolution of clinical signs of infection + mycological eradication) at Day 14. For this analysis, outcomes by treatment group were stratified by Candida species and by its in vitro susceptibility (CLSI broth microdilution MIC values; M27-Ed4).Figure 1. Treatment Groups of the Phase 2 STRIVE Trial ResultsA total of 196 Candida isolates were recovered from 183 patients across all treatment groups (Fig. 2). C. albicans was the most common species, followed by C. glabrata, C. parapsilosis, and C. tropicalis; non-albicans Candida comprised 54% of all baseline isolates (Fig. 2). Among all clinical isolates, MIC distributions and ranges for RZF were generally lower than or comparable to those for CAS (Table 1). The rate of Overall Response (as defined above) against C. parapsilosis was lower for CAS than for RZF (Table 2). Overall, outcomes by Candida species and MIC did not appear to be affected by MIC values for either RZF or CAS (Table 1).Figure 2. Candida Species Distribution and MIC ranges in the Phase 2 STRIVE Trial (mITT) Table 1. Overall Response Rates (%) for Most Frequently Isolated Candida Species at Baseline by Treatment Group and MIC Values (mITT) Table 2. Overall Response Rates (%) for Most Frequently Isolated Candida Species at Baseline by Treatment Group (mITT) ConclusionThis analysis demonstrated RZF efficacy across multiple Candida species. RZF outcomes were similar to or better than those for CAS regardless of species identified. There was no clear correlation between increased MICs and clinical outcomes although, based on MICs, all isolates exhibited a wild-type in vitro susceptibility profile. These findings from STRIVE, together with future analyses from the ongoing Phase 3 trial of RZF treatment of candidemia and IC (ReSTORE; NCT03667690), will further our understanding of the relationships between MIC values and clinical outcomes in patients with candidemia or IC.Disclosures Jeffrey B. Locke, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Rolando Viani, MD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Mahmoud Ghannoum, PhD, Amplyx (Grant/Research Support)Cidara (Grant/Research Support)Scynexis (Consultant, Grant/Research Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)

1286. Pharmacokinetics, Excretion, and Mass Balance of [14C]-Rezafungin Following Intravenous (IV) Administration in Healthy Adults

BackgroundRezafungin is a once-weekly novel echinocandin antifungal currently in Phase 3 development for treatment of candidemia and invasive candidiasis (ReSTORE) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients (ReSPECT). Nonclinical ADME studies in rats and monkeys show rezafungin is primarily excreted unchanged in feces, with urine as a minor route. This study was conducted to characterize the routes of elimination of [14C]-rezafungin and the pharmacokinetics of total radioactivity and plasma rezafungin in humans.MethodsNine healthy male subjects received a single IV 400-mg rezafungin infusion containing 200 µCi of [14C]-rezafungin. Serial blood samples, urine, and feces were collected at specified times over 60 days; subjects were initially confined in the clinical research unit (CRU) for 17 days postdose and returned for two follow-up visits (days 29 and 60). During the period of time subjects were away from the CRU, recovery of radioactivity was estimated by linear interpolation.ResultsRezafungin exhibited a long plasma half-life and was mainly excreted in feces unchanged. Cumulative recovery of radioactivity from excreta collected through the first 17 days was 52% (38% in feces, 14% in urine), reinforcing the slow overall elimination of rezafungin. Overall recovery of the administered dose by day 60 was estimated to be 88.3% (65.6% in feces, 22.7% in urine) (Figure 1). Mean blood/plasma concentration ratios ranged from 0.860 to 1.02 through the last collection time point (day 60), which indicated low association of radioactivity with blood cells. Rezafungin was the predominant compound measured in plasma and feces across all collected time points. In the urine, as observed in rat and monkey metabolite profiling studies, low level, inactive, oxidative metabolites were identified as 2-, 3-, 4-hydroxylpentyl rezafungin, and despentyl-rezafunginFigure 1 ConclusionResults from this human excretion balance, metabolism and PK study are consistent with nonclinical results, which showed fecal excretion as the major route of elimination of rezafungin. Rezafungin was the predominant compound in plasma and feces.DisclosuresVoon Ong, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder)

637. Outcomes by Body Mass Index (BMI) in the STRIVE Phase 2 Trial of Once-Weekly Rezafungin for Treatment of Candidemia and Invasive Candidiasis Compared with Caspofungin

BackgroundThere is increasing evidence of antifungal underdosing in the treatment of invasive disease, particularly in special populations such as the obese. Body size is often an important variable affecting drug exposure, and pharmacokinetic (PK) models of antifungal dosing have suggested size-based dose adjustments to achieve target drug exposure.Rezafungin (RZF) is a novel echinocandin in Phase 3 development for treatment of candidemia and invasive candidiasis (IC) and for prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis in blood and marrow transplant recipients. Distinctive PK properties of RZF (e.g., long half-life, extensive tissue distribution, and front-loaded drug exposure) lend themselves to RZF once-weekly (QWk) dosing and antifungal efficacy. In this sub-analysis of the Phase 2 STRIVE trial of RZF in the treatment of candidemia and/or IC, outcomes based on patient BMI were evaluated.MethodsThe STRIVE trial (NCT02734862) compared the safety and efficacy of RZF QWk compared with once-daily caspofungin (Fig. 1). For this subanalysis, data were stratified by BMI categories of < 30 kg/m2 and ≥ 30 kg/m2. Efficacy (overall response [resolution of clinical signs of infection + mycological eradication], mycological response, and investigator assessment of clinical response) and safety (treatment-emergent adverse events [TEAEs]) endpoints by treatment group were evaluated, as well as PK data (area under the curve [AUC]) from RZF-treated patients.Figure 1. ResultsMean BMI values were similar across treatment arms (26.9 kg/m2 in RZF Group 1 and 26.8 kg/m2 in RZF Group 2 and CAS arms). Efficacy outcomes at Day 14 were similar between BMI categories (Table 1). Rates of TEAEs were generally similar between BMI categories as well (Table 2), with no concerning safety trends. Following one dose of RZF 400 mg (Week 1), the ranges of AUCs by BMI category overlapped and there was a minor mean difference of ~20% (lower for those with BMI ≥ 30 kg/m2) (Fig. 2).Table 1 Table 2 Figure 2. ConclusionThe safety, efficacy, and PK of RZF in the Phase 2 STRIVE trial was consistent across BMI categories. These results suggest that dose adjustments in obese patients are not necessary. These findings contribute to the evaluation of RZF in a range of patient populations and its ongoing development.Disclosures Shawn Flanagan, PhD, Cidara Therapeutics, Inc. (Employee, Shareholder) Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Taylor Sandison, MD, MPH, Cidara Therapeutics, Inc. (Employee, Shareholder) Patrick M. Honore, MD, PhD, FCCM, Cidara Therapeutics, Inc. (Scientific Research Study Investigator)

COVID-19 Vaccination for Cancer Patients, What Oncologists and Cancer Patients Need to Know?

As the current evidence is accumulating in support of multiple COVID-19 vaccine in general population while the final regulatory approvals are still pending, multiple vaccine candidates have already received temporary authorization for emergency use. The mRNA vaccines are new to the clinical practice and global regulators must balance the lack of medium to longer-term data on these novel mRNA COVID-19 vaccines.The inactivated vaccines have been used in cancer patients in the past with excellent safety profile and they may be theoretically the safest vaccine for cancer patients. Currently there are no formal COVID-19 vaccine trial designed specifically for cancer patients. Some of the current major trials excluded cancer patients while others did not explicitly excluded malignancies. Early reports indicate that some cancer patients were able to enroll in some of the vaccine trials, yet no clear information if these patients were on active systemic therapies or surveillance. There is a need for a dedicated COVID-19 vaccine trials for cancer patients. The UK Independent report by the “ Joint Committee on Vaccination and Immunisation for the Priority groups for coronavirus (COVID-19) vaccination” recommended “bone marrow and stem cell transplant recipients and people with specific cancers” to receive priority vaccination, without further clarification which “specific cancers” were referred to. Until further data are available, recommendations for vaccination for COVID-19 for cancer patients cannot be routinely recommended. At the current time evaluation of cancer patients who wish to consider COVID-19 vaccination should be done in the context of clinical trials, if there is no access to clinical trials; This should be addressed “case by case” basis with clear discussion about potential benefits, risks and uncertainties surrounding COVID-19 vaccination for cancer patients at the current time.