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Daratumumab and Darbepoetin for Refractory Warm Autoimmune Hemolytic Anemia: A Novel Duo for a Tough Case
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.
How to Make Keeping Up With the Drugs as Easy as Keeping Up With the Kardashians: Implementing a Local Oncology Drug Review Committee
Background
From 2000-2022 there were over 200 new drug and over 500 indication approvals specific to oncology. The rate of approvals has increased exponentially, making it difficult to maintain an up-to-date, standardized practice. Nationally, Veterans Affairs (VA) formulary decisions can take time given a lengthy approval process. Locally, the need was identified to incorporate new drugs and data into practice more rapidly. When bringing requests to the facility Pharmacy and Therapeutics (P&T) Committee, it was recognized that the membership consisting of non-oncology practitioners did not allow for meaningful discussion of utilization. In 2017, a dedicated oncology drug review committee (DRC) comprised of oncology practitioners and a facility formulary representative was created as a P&T workgroup. Purpose: Evaluate and describe the utility of forming a local oncology DRC to incorporate new drugs and data into practice.
Methods
DRC minutes from December 2017 to May 2023 were reviewed. Discussion items were categorized into type of review. Date of local review was compared to national formulary criteria for use publication dates, and date of FDA approval for new drugs or publication date for new data, where applicable. Items were excluded if crucial information was missing from minutes. Descriptive statistics were used.
Results
Over 65 months, 38 meetings were held. Thirty total members include: pharmacists, physicians, fellows, and advanced practice providers. Items reviewed included: 36 new drugs (ND), 36 new indications/data (NI), 14 institutional preferences, 10 new dosage form/biosimilars, 4 drug shortages and 2 others. The median time from ND approval to discussion was 3 months (n= 36, IQR 3-6) and NI from publication was 3 months (n=30, IQR 1-8). Nearly all (34/36, 94%) ND were reviewed prior to national review. Local review was a median of 7 months before national, with 11 drugs currently having no published national criteria for use (n=25, IQR 2-12).
Conclusions
DRC formation has enabled faster incorporation of new drugs/indications into practice. It has also created an appropriate forum for in-depth utilization discussions, pharmacoeconomic stewardship, and sharing of formulary and medication related information. VA Health Systems could consider implementing similar committees to review and implement up-to-date oncology practices.
Background
From 2000-2022 there were over 200 new drug and over 500 indication approvals specific to oncology. The rate of approvals has increased exponentially, making it difficult to maintain an up-to-date, standardized practice. Nationally, Veterans Affairs (VA) formulary decisions can take time given a lengthy approval process. Locally, the need was identified to incorporate new drugs and data into practice more rapidly. When bringing requests to the facility Pharmacy and Therapeutics (P&T) Committee, it was recognized that the membership consisting of non-oncology practitioners did not allow for meaningful discussion of utilization. In 2017, a dedicated oncology drug review committee (DRC) comprised of oncology practitioners and a facility formulary representative was created as a P&T workgroup. Purpose: Evaluate and describe the utility of forming a local oncology DRC to incorporate new drugs and data into practice.
Methods
DRC minutes from December 2017 to May 2023 were reviewed. Discussion items were categorized into type of review. Date of local review was compared to national formulary criteria for use publication dates, and date of FDA approval for new drugs or publication date for new data, where applicable. Items were excluded if crucial information was missing from minutes. Descriptive statistics were used.
Results
Over 65 months, 38 meetings were held. Thirty total members include: pharmacists, physicians, fellows, and advanced practice providers. Items reviewed included: 36 new drugs (ND), 36 new indications/data (NI), 14 institutional preferences, 10 new dosage form/biosimilars, 4 drug shortages and 2 others. The median time from ND approval to discussion was 3 months (n= 36, IQR 3-6) and NI from publication was 3 months (n=30, IQR 1-8). Nearly all (34/36, 94%) ND were reviewed prior to national review. Local review was a median of 7 months before national, with 11 drugs currently having no published national criteria for use (n=25, IQR 2-12).
Conclusions
DRC formation has enabled faster incorporation of new drugs/indications into practice. It has also created an appropriate forum for in-depth utilization discussions, pharmacoeconomic stewardship, and sharing of formulary and medication related information. VA Health Systems could consider implementing similar committees to review and implement up-to-date oncology practices.
Background
From 2000-2022 there were over 200 new drug and over 500 indication approvals specific to oncology. The rate of approvals has increased exponentially, making it difficult to maintain an up-to-date, standardized practice. Nationally, Veterans Affairs (VA) formulary decisions can take time given a lengthy approval process. Locally, the need was identified to incorporate new drugs and data into practice more rapidly. When bringing requests to the facility Pharmacy and Therapeutics (P&T) Committee, it was recognized that the membership consisting of non-oncology practitioners did not allow for meaningful discussion of utilization. In 2017, a dedicated oncology drug review committee (DRC) comprised of oncology practitioners and a facility formulary representative was created as a P&T workgroup. Purpose: Evaluate and describe the utility of forming a local oncology DRC to incorporate new drugs and data into practice.
Methods
DRC minutes from December 2017 to May 2023 were reviewed. Discussion items were categorized into type of review. Date of local review was compared to national formulary criteria for use publication dates, and date of FDA approval for new drugs or publication date for new data, where applicable. Items were excluded if crucial information was missing from minutes. Descriptive statistics were used.
Results
Over 65 months, 38 meetings were held. Thirty total members include: pharmacists, physicians, fellows, and advanced practice providers. Items reviewed included: 36 new drugs (ND), 36 new indications/data (NI), 14 institutional preferences, 10 new dosage form/biosimilars, 4 drug shortages and 2 others. The median time from ND approval to discussion was 3 months (n= 36, IQR 3-6) and NI from publication was 3 months (n=30, IQR 1-8). Nearly all (34/36, 94%) ND were reviewed prior to national review. Local review was a median of 7 months before national, with 11 drugs currently having no published national criteria for use (n=25, IQR 2-12).
Conclusions
DRC formation has enabled faster incorporation of new drugs/indications into practice. It has also created an appropriate forum for in-depth utilization discussions, pharmacoeconomic stewardship, and sharing of formulary and medication related information. VA Health Systems could consider implementing similar committees to review and implement up-to-date oncology practices.
Implementation of Electronic Antineoplastic Ordering Templates in a Veterans Health System
BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.
PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.
METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.
RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).
IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.
BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.
PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.
METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.
RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).
IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.
BACKGROUND: Antineoplastic ordering is high in both complexity and risk for medication errors. Joint Commission and institutional policy recommends computerized prescriber order entry and verification by a pharmacist as a best practice for patient safety. The use of ordering templates minimizes the risk of errors and ensures appropriate supportive care is being provided. The Veterans Affairs electronic medical record does not feature an antineoplastic ordering component; historically, templates have been on paper. The oncology, pharmacy, and clinical informatics departments in our health system formed a team to create electronic antineoplastic ordering templates.
PURPOSE: To evaluate the impact of electronic antineoplastic ordering templates on pharmacy and infusion clinic efficiency and pharmacist interventions.
METHODS: Ordering templates, which included standard dosing and supportive care medications, were developed and activated for prescribers in phases over the course of two years. Immunotherapy and oral oncolytic templates were activated initially, followed by full implementation of the majority of intravenous (IV) ordering templates. Percent of electronic antineoplastic orders, pharmacy processing time, time to first drug delivery, and number of pharmacist encounters and interventions were documented daily for four weeks after initial implementation and for ten weeks after full implementation. Means were compared using unpaired t tests.
RESULTS: After initial implementation, the percentage of electronic antineoplastic orders increased from 0% to 100% for oral antineoplastics and from 0% to 39% for IV orders. After full implementation, IV orders increased to 69% in weeks 1-5 and 96% in weeks 6-10. Mean pharmacy processing time for supportive care medications was 35 minutes initially. This increased briefly after full implementation (weeks 1-5), then decreased to 17 minutes in weeks 6-10 (p<0.01). Delivery of the first medication to the infusion center decreased by 31 minutes at week ten (<0.01). Mean daily pharmacist encounters increased by 28%(<0.01) and documented interventions increased by 22% (<0.01).
IMPLICATIONS: Implementation of electronic antineoplastic ordering templates increased provider order entry, pharmacy and infusion clinic efficiency and pharmacist interventions. These outcomes may translate to improved patient safety and patient access to quality care. Templates developed can serve as a model for other health systems to implement electronic antineoplastic ordering.