Cancer patients treated with PARP inhibitors need monitoring for pancytopenia

Reuters Health - 02/11/2021 - Cancer patients treated with poly(adenosine diphosphate-ribose) inhibitors (PARPis) appear to be at high risk of developing pancytopenia, so doctors need to closely monitor them, a new study suggests.

"To our knowledge, this work is the first to highlight a substantial association between PARPi class and an increased risk of reported pancytopenia," researchers write in JAMA Oncology. "Our results indicate that half of the patients in this study had an early onset of pancytopenia within the first 2 months after the initiation of PARPi treatment for cancer, suggesting the need for enhanced blood surveillance."

The authors advise clinicians to "consider careful monthly blood monitoring for patients with PARPi-treated cancer to check for early pancytopenia onset. This surveillance should be followed by a dose interruption as soon as possible to avoid the permanent discontinuation of these drugs, which could lead to a cancer relapse."

Dr. Joachim Alexandre of Caen University Hospital, in France, and his colleagues examined more than 20 years' worth of individual case safety reports from the World Health Organization (WHO) pharmacovigilance database VigiBase.

They explain that they "performed a case-noncase study using the reporting odds ratio (ROR) to compare observed and expected drug-AE (adverse event) associations when using the full database as the comparator." The five examined PARPis were niraparib, olaparib, rucaparib, talazoparib and veliparib.

Of the more than 23,000 AEs for the five drugs, pancytopenia was significantly linked with the PARPi class, with 201 reports (ROR, 5.5). This link was significant for each PARPi studied, with 102 reports for niraparib (ROR, 6.8), 57 for olaparib (ROR, 5.3), 21 for rucaparib (ROR, 2.2), 16 for talazoparib (ROR, 17.4), and five for veliparib (ROR, 8.2).

Serious pancytopenia was documented in 194 reports, and the median latency period - the interval between first PARPi treatment and pancytopenia diagnosis - was 1.6 months. Frequently reported AEs included myelodysplastic syndrome and acute myeloid leukemia.

The authors acknowledged limitations to this study, including the inability to form causal associations for individual cases and to compute the incidence of PARPi-related pancytopenia.

"It is well established that treatment with PARP inhibitors is associated with an increased risk of hematologic toxicities in cancer patients," said Dr. Timothy Yap, an associate professor of investigational cancer therapeutics and medical director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center in Houston.

"The findings from this study should not discourage the use of PARP inhibitors in multiple (Food and Drug Administration)-approved indications where they have been shown to improve cancer patient outcomes," he told Reuters Health by email.

"However," added Dr. Yap, who was not involved in the study, "this study does demonstrate that a subset of patients will develop pancytopenia, which may be clinically significant. These findings indicate that treating physicians should regularly implement prospective monitoring of patients and lab counts - especially hemoglobin, platelets, and neutrophil counts - during therapy with PARP inhibitors."

Doctors should advise patients about their risk of developing pancytopenia and their need for regular clinical and lab monitoring, he said. "They should also have clear management plans for drug interruptions and dose reductions as indicated."

Dr. Yap noted that the "study does not consider other baseline factors that may increase patients' susceptibility to pancytopenia on PARP inhibitors, including previous anticancer therapies such as cytotoxic chemotherapy, the burden and location of cancer, and baseline lab values such as hemoglobin levels."

"In the future," he added, "the development of next-generation PARP1-selective inhibitors may potentially lead to improved toxicity profiles for patients."

Dr. Alexandre did not respond to requests for comment.

The authors report no conflicts of interest. Dr. Yap disclosed financial ties to makers of PARPis.

SOURCE: https://bit.ly/3EujMLC JAMA Oncology, online October 14, 2021.

By Lorraine L. Janeczko



Posted on 2 November 20219 November 2021