A simple change may help prevent anemia associated with PARP inhibitors for some patients

Clinicians may need to rethink folic acid in select patients with cancer. A new study published in the latest issue of the journal Blood Red Cells & Iron suggests that routine screening and treatment with folic acid may help many patients treated with PARP inhibitors avoid blood transfusions, hospitalizations and interruptions to their cancer treatment.PARP inhibitors are used to treat multiple cancers, including ovarian, breast, prostate and pancreatic cancers associated with BRCA gene mutations. These agents have transformed treatment options for many patients. However, they commonly cause anemia. The long held belief was that the anemia caused by PARP inhibitors was mainly due to a drug class effect that causes bone marrow suppression.Corresponding author Dr. Noa Rippel, chief fellow in Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai in New York, said anemia in this patient population has always been treated reactively. “Clinicians responded by reducing, holding or stopping PARP inhibitor treatment, and providing red blood cell transfusions when needed. While these strategies helped stabilize patients in the short-term, they didn’t identify nor address the underlying cause of the anemia.” This is the first study to systematically evaluate folate deficiency in patients receiving PARP inhibitors. Previous reports had been limited to individual case studies. The researchers reviewed the records of 512 patients with BRCA-mutated cancers treated with PARP inhibitors. They found that 3.1% developed folate deficiency anemia, more than six times the estimated rate seen in the general population. Nearly 30% of patients also developed unexplained macrocytic anemia. Analysis of those patients with new folate deficiency on PARP inhibitors, showed that none had known malabsorptive risk, concurrent vitamin B12 deficiency, or uncontrolled hypothyroidism. More than 60% of patients with folate deficiency anemia required blood transfusions, many were hospitalized and 12 of 16 (75%) experienced interruptions in their cancer treatment. The encouraging finding was that treating the folate deficiency was highly effective. Grade 4 anemia requiring packed red blood cell (PRBC) transfusions occurred in 10 of 16 patients (62.5%) who developed folate deficiency. This was significantly higher compared with 72 of 496 patients (14.5%) who did not. Patients who received oral folic acid supplements recovered their folate levels, allowing them to safely resume their PARP inhibitor therapy. Among the 512 patients (median age 65.0 years), the most common tumour types treated with PARP inhibitor therapy were ovarian (62.7%), breast (31.4%), fallopian tube (17.4%), prostate (14.3%) and pancreatic (4.3%) cancer. The most frequently used PARP inhibitor was olaparib (72.7%). The researchers found evidence suggesting that starting folic acid supplements when PARP inhibitor treatment begins may help prevent this complication. “These findings have the potential to change how oncologists evaluate anemia in patients taking PARP inhibitors,” said Dr. Rippel. “Folic acid supplementation is a low-risk, low-cost intervention that should be considered by treating oncologists.”As PARP inhibitors continue to be approved for more types of cancer, the researchers believe greater awareness of a folate deficiency could benefit many thousands of patients annually. “We expect that this study will fundamentally change how clinicians evaluate and manage PARP inhibitor-associated anemia. Folate deficiency is a previously unrecognized, readily diagnosable, and highly treatable cause of severe anemia in patients with BRCA-mutated cancers,” said Dr. Rippel. “A simple, inexpensive intervention may reduce transfusions, hospitalizations, treatment interruptions, and unnecessary discontinuation of life-prolonging cancer therapy.”Building on these findings, it is hoped that prospective studies can evaluate the impact of prophylactic folic acid supplementation at the time of PARP inhibitor initiation, using close serial monitoring of folate levels throughout treatment. This type of study could help determine whether maintaining adequate folate status can reduce the incidence and severity of anemia in this patient population. “This approach would represent a paradigm shift by transforming a common, dose-limiting toxicity into a preventable complication through routine nutritional optimization,” said Dr. Rippel, who is originally from Vancouver and completed her undergraduate degree at the University of British Columbia before beginning her medical career.Dr. Lauren Prescott, MD, a gynecologic oncologist at Vanderbilt University in Nashville, said the prevalence of anemia in cancer patients is high and the workup and management of anemia are suboptimal. “This is the first study to show an increased prevalence of folate deficiency in patients using PARP inhibitors and therefore a very interesting thought provoking study on the role of folate deficiency,” Dr. Prescott told the Medical Post. “I think this has significant implications for evaluation and management of patients particularly on PARP inhibitors and perhaps more rigorous monitoring of folate levels may help decrease severity of anemia and keep patients on treatment.”She noted that currently there are studies looking at using PARP inhibitors in a variety of cancers. Research scientist Mads Daugaard, professor and head of Molecular Pathology & Cell Imaging Laboratory at UBC said PARP inhibitors are by far the most successful class of targeted cancer therapies to date. “However, dose-limiting toxicities and unwanted side effects have been a challenge from the beginning and it has been difficult to pinpoint the actual reasons for these side effects. This study brings new knowhow on this topic by identifying folate deficiencies as a reason for treatment-associated anemia conditions. This finding could have widespread clinical and health economic implications,” Daugaard told the Medical Post. He said the number of patients receiving PARP inhibitors worldwide has not been well documented. However, it is estimated in the tens of thousands annually worldwide. “Around 30% of patients experience various degrees of anemia as a side effect, so the impact could be significant,” said Daugaard. “Also, PARP inhibitors are currently being tested outside the BRCA-mutated space in combination with other treatments, which could potentially increase the number of patients receiving PARP inhibitors in the future.”Reference:N. Rippel, D. I. Nathan, W. Fu, J. M. Liu, I. Shapira, P. Klein; PARP inhibitor–associated folate deficiency anemia. Blood Red Cells & Iron 2026; 2 (2): 100052.

A simple change may help prevent anemia associated with PARP inhibitors for some patients

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