Karen Sweiss, PharmD: Winner of HOPA’s 2017 Oncology Pharmacy Practice Literature Award
Danielle Schlafer, PharmD BCOP
Clinical Pharmacy Specialist, Hematology/Oncology
Emory University Hospital/Winship Cancer Institute
Karen Sweiss, PharmD, was awarded HOPA’s 2017 Oncology Pharmacy Practice Literature Award at the 13th Annual HOPA Conference in Anaheim, CA. This award recognizes an author who has written an article, other than scientific research, that contributes significantly to the betterment of the hematology/oncology pharmacy profession and describes innovations in community, hospital, or healthcare system hematology/oncology pharmacy practice that are applicable beyond the practice site where they were developed or evaluated.
Dr. Sweiss is a clinical assistant professor at the University of Illinois at Chicago (UIC) College of Pharmacy and a clinical pharmacist specializing in hematology and bone marrow transplant (BMT) at UI Health. In addition to having rounding responsibilities with the medical team, she is actively involved with protocol writing, nursing and physician in-services, and the Foundation for the Accreditation of Cellular Therapy (FACT) accreditation process, and she has also helped to establish a collaborative MD-PharmD multiple myeloma clinic. She gives didactic lectures at the UIC College of Pharmacy and precepts students and residents. Throughout her career, Dr. Sweiss has done research in collaboration with BMT physicians and pharmacists, and she has published both retrospective and prospective studies. She was recognized for her lead authorship of a May 2016 article in Bone Marrow Transplantation: “Melphalan 200 mg/m2 in Patients with Renal Impairment Is Associated with Increased Short-Term Toxicity but Improved Response and Longer Treatment-Free Survival.”1
High-dose melphalan with autologous stem cell transplant (ASCT) is considered a standard-of-care approach for treating patients with multiple myeloma. Although renal impairment is a common complication of multiple myeloma, most studies evaluating pretransplant conditioning with melphalan 200 mg/m2 (Mel200) have excluded patients with renal impairment. The rationale for this exclusion is related to concern for increased treatment-related morbidity and nonrelapse mortality, although pharmacokinetic studies of melphalan clearance are conflicting with regard to renal function. Despite conflicting data, major working groups, including the International Myeloma Working Group (IMWG) and the American Society for Blood and Marrow Transplantation (ASBMT), recommend a dose reduction to 140 mg/m2 for patients with creatinine clearance (CrCl) less than 60 ml/min.
The objective of Dr. Sweiss’s study was to evaluate the clinical outcomes and tolerability of melphalan 200 mg/m2 in patients with normal and impaired renal function. This retrospective single-center study included patients with multiple myeloma who received ASCT with melphalan 200 mg/m2; it excluded those who received melphalan 140 mg/m2, were receiving hemodialysis, had had a previous allogeneic stem cell transplant, or had received a second autologous transplant within 6 months of the first transplant. Renal impairment was defined as CrCl less than 60 ml/min on admission, calculated using the Cockcroft-Gault equation. Median CrCl in the renal impairment group (n = 46) was 50 ml/min (range 20–59), compared to 83 ml/min (range 60–128) in patients with normal renal function (n = 103).
Patients with renal impairment had longer time to neutrophil engraftment (median 10 days vs. 9 days, p = .008) and platelet engraftment (median 12 days vs. 10 days, p < .001). Duration of hospitalization was also significantly longer in the renal impairment group (16 days vs. 14 days, p = .02). Grade 4 mucositis, grade 2–4 diarrhea, and documented infections occurred more frequently in the renal impairment group. Duration of use of total parenteral nutrition and duration of diarrhea were both significantly longer in patients with renal impairment (10 days vs. 6 days and 8 days vs. 5 days, respectively). However, renal function in patients with CrCl less than 60 ml/min was not negatively affected by Mel200. Although pre- and posttransplant disease response data were not available for all patients, a statistically significant increase of 20% in rate of complete response (CR) was observed in the renal impairment group. A nonsignificant increase of 14% in CR rate was observed in patients with normal renal function. No significant difference in overall survival was seen, but treatment-free survival was significantly longer in the renal impairment group (37 months vs. 17 months, p = .0025).
Sweiss and colleagues concluded that patients with CrCl less than 60 ml/min experienced increased toxicities following high-dose melphalan compared to patients with normal renal function. Despite the expected, reversible toxicities, patients with impaired renal function had improved outcomes. This research makes an important contribution to the understanding of approaches to drug dosing in transplant conditioning regimens and provides supporting literature to tailor treatment options for this patient population.
Dr. Sweiss explains, “The idea of ‘one size fits all’ does not apply in this setting.Our BMT team assesses each multiple myeloma patient individually (based on renal function, age, and performance status) and subsequently determines the appropriateness of dose reduction in those patients with renal impairment. We have given Mel200 to patients with moderate renal impairment despite IMWG recommendations recommending reduced dose in patients with a creatinine clearance less than 60 mL/min. Based on our data, we favor giving Mel200 to these patients despite these recommendations as long as we have also weighed the risks and benefits against each other.”
Her future research objectives include identifying ways to further improve and individualize dosing of high-dose melphalan. When asked to comment on the significance of the HOPA Oncology Pharmacy Practice Literature Award for her personally, Dr. Sweiss responded, “It was a great honor to be recognized for my research by my colleagues and by HOPA. Although we are not trained as basic scientists or full-time researchers, as clinical pharmacists, we have clinical experience that is so valuable and that nobody else has, and I think this experience allows us to contribute uniquely to research in hematology/oncology. This award has motivated me to continue to conduct research and contribute ideas that will impact the care of oncology patients, especially in BMT, in order to optimize efficacy and minimize toxicity from drug therapy.”
- Sweiss K, Patel S, Culos K, Oh A, Rondelli D, Patel P. Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival. Bone Marrow Transplant. 2016;51(10):1337-1341.