Non-Small Cell Lung Cancer: What It Is, Symptoms, and More
Obesity Linked To Acute Kidney Injury After HDMTX For Hematologic Cancer
Some patients with hematologic cancer and obesity are at higher risk of acute kidney injury (AKI) after receiving high-dose methotrexate (HDMTX) in the outpatient setting, suggesting a differential drug clearance and the need for guidelines specific to obese patients. These results were published in Hematology, Transfusion and Cell Therapy
HDMTX (500 mg/m2 or higher) is a key part of chemotherapy regimens for the treatment of hematologic cancers; however, AKI is a major drug-induced toxicity that can result in critical organ damage and death when not detected early and treated.
Therefore, HDMTX is administered in the hospital allowing for postadministration monitoring. But in resource-poor areas, it is administered in the outpatient clinic without drug monitoring.
This retrospective study of 302 patients was conducted to review the toxicity data after outpatient administration of HDMTX without drug monitoring. Data were from patients aged 16 years and older with a hematologic cancer who had received at least 1 infusion of HDMTX without drug-level monitoring during a 10-year period. A total of 840 infusions were administered, with a median 2 infusions per patient.
Hospitalization was reported in 8.6% of the patients, and 25 patients experienced AKI after HDMTX administration, which correlated to 3% of the infusions and 8.3% of the patients. The most common diagnoses in the patients with AKI was HIV-associated Burkitt lymphoma (28%) and diffuse large B-cell lymphoma (28%).
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A higher BMI was associated with [methotrexate]-induced AKI in our cohort suggesting a differential drug clearance and the need for specific guidelines for obese patients.
Baseline factors related to AKI after administration of HDMTX included age (older than 44 years), body surface area 1.76 m² and greater, and body mass index (BMI) 23.8 kg/m² and higher, as well as estimated glomerular filtration rate (eGFR) and thrombocytopenia (more than 150×10⁹/L).
Additionally, only 9 of the 25 patients with AKI had their methotrexate serum level measured at the event. This demonstrates low clinician awareness of this complication, explained the researchers. They also noted that thrombocytopenia, neutropenia, and hyperbilirubinemia grade 3 or higher were found in 36%, 64% and 36% of patients, respectively, and 22 of the 25 patients required hospitalization.
The findings indicated that age, BMI, eGFR, and baseline thrombocytopenia were statistically significant for AKI, but the strongest correlation was with BMI. The researchers wrote that this highlights the need for more studies on methotrexate pharmacokinetics, especially in overweight patients.
"Our data showed a similar rate of AKI after HDMTX to that reported in the literature, even without drug monitoring," the researchers wrote in conclusion. "However, patients who developed AKI in our cohort fared worse than expected, with more hospitalizations and deaths. A higher BMI was associated with [methotrexate]-induced AKI in our cohort suggesting a differential drug clearance and the need for specific guidelines for obese patients. Careful selection for this procedure is warranted."
This article originally appeared on Hematology Advisor
Gilead Ends Development Of Magrolimab For Hematologic Cancers
Gilead has decided to end its phase 3 ENHANCE-3 study evaluating magrolimab in patients with acute myeloid leukemia (AML).
Magrolimab is an investigational monoclonal antibody that binds to CD47 and blocks the inhibitory CD47-signal regulatory protein (SIRPα) interaction. This enhances the ability of macrophages and other phagocytes to identify and destroy cancer cells.
The phase 3 ENHANCE-3 study (ClinicalTrials.Gov Identifier: NCT05079230) compared the efficacy and safety of magrolimab to placebo, in combination with venetoclax and azacitidine in newly diagnosed, previously untreated patients with AML who are ineligible for intensive chemotherapy. The primary endpoint was overall survival.
Following a planned interim analysis, a decision to discontinue the trial was made based on the recommendation of an independent data monitoring committee. Findings showed the magrolimab combination demonstrated futility and increased the risk of death, primarily from infections and respiratory failure.
Gilead has already discontinued 2 other trials evaluating magrolimab in hematologic cancers. The phase 3 ENHANCE study (ClinicalTrials.Gov Identifier: NCT04313881) included 520 adult patients with higher-risk myelodysplastic syndromes (MDS). A decision was made to end the trial due to futility based on a planned analysis.
The phase 3 ENHANCE-2 study (ClinicalTrials.Gov Identifier: NCT04778397) compared the effectiveness of magrolimab in combination with azacitidine, to physician's choice of venetoclax plus azacitidine or intensive chemotherapy in patients with previously untreated TP53 mutant AML. Findings showed the investigational therapy was unlikely to provide a survival benefit over standard of care.
Given the outcomes of these trials, Gilead has decided not to pursue further development of magrolimab in hematologic cancers. Additionally, the Food and Drug Administration has placed all magrolimab studies in MDS and AML, including related expanded access programs, on full clinical hold.
"The complexity of treating blood cancer is highlighted in these results," said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. "We are incredibly grateful to all the patients and investigators for their participation in the ENHANCE studies."
Detailed results from ENHANCE-3, along with a sub-analyses for efficacy and safety, will be shared and submitted in upcoming medical conferences.
An Expert Explains Why Black Men Are At A Greater Risk For Prostate Cancer
Dr. Shaal Patel, a board certified physician in hematology, oncology, and internal medicine, spoke with Healthline about how prostate cancer affects Black men, including rate of diagnosis, survival, the role of genetics, and screening guidelines.
One in 6 Black men will have prostate cancer in their life compared to 1 in 8 men overall.
Prostate cancer is the second most common cancer in men, at 14.1% of new cancer cases annually. Among all men, prostate cancer accounts for 6.8% of cancer deaths annually. This makes prostate cancer the fifth highest cause of cancer mortality in men.
Prostate cancer accounts for 37% of all cancer diagnoses among Black men. It also accounts for 17% of cancer mortality, which is the second highest after lung cancer.
In 2020, there were nearly 1.4 million new cases of prostate cancer worldwide. According to a 2022 review, African American men have the highest incidence of prostate cancer in the world.
In the United States, Black men have the highest incidence and mortality rates from prostate cancer than any other ethnic group. Specifically, the incidence and mortality rates of prostate cancer among Black men are more than twice as high (60%) as rates among white Americans and 3 to 4 times higher than rates among Asian Americans.
African American men develop prostate cancer at a younger age and have more active or aggressive forms of prostate cancer compared to their white counterparts. On average, the diagnosis of prostate cancer in an African American man occurred 3 years earlier than it did in white men of a similar age in the United States.
One explanation for this is that Black men may develop symptoms from their prostate cancer earlier (for example, symptoms of an enlarged prostate) compared to other racial groups.
Another explanation points to African American men experiencing puberty earlier than their white counterparts. This can be a risk factor because prostate cancer is fueled by testosterone. When males go through puberty, there's a testosterone surge. If a man experienced puberty earlier in life, they have been exposed to testosterone for a much longer period than someone who began puberty later on.
Prostate cancer has the second highest death rate of all cancers among Black men. It accounts for approximately 17% of the cancer deaths in Black men. However, the discrepancy in survival rates by stage for Black men versus white men who have prostate canceris not as large as in other types of cancer.
The 5-year survival rates for prostate cancer at various stages are as follows:
Yes, but not all of the time. Inherited gene mutations (those you're born with) can be found in up to 10% of patients with prostate cancer. Family linkage in a diagnosis of prostate cancer does exist, but it's not always strong.
However, a man who has a father or brother with prostate cancer is more than twice as likely to be diagnosed with prostate cancer. The risk is higher for men with a brother as opposed to a father who has had prostate cancer.
The higher number of relatives who have been affected by the disease increases a person's risk of developing prostate cancer. This is especially the case if your relative with prostate cancer was diagnosed when they were young.
The death rate of prostate cancer is 2.3 times higher in African American men compared to white men. Risk factors that influence the higher death rate of prostate cancer in African American men compared to the other racial groups include:
In general, prostate cancer screening is controversial and is a decision between the patient and the physician.
The American Urological Association recommends prostate cancer screening for Black men around age 40, which is earlier than other racial groups. Other cancer organizations recommend that discussion about screening start around age 45. This is earlier than age 50, which is the recommended age to begin discussions about prostate cancer screening in a man with no risk factors.
There are no specific recommendations for frequent screenings simply because a patient is Black.
Dr. Sheel Patel is an ABMS board certified physician in hematology, oncology, and internal medicine. Dr. Patel is a practicing physician at the Orlando VA Medical Center in Florida. He specializes in genitourinary oncology.
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