Sutimlimab: A Complement C1s Inhibitor for the Management of Cold Agglutinin Disease-Associated Hemolysis.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of sutimlimab for the management of cold agglutinin disease (CAD)-associated hemolysis. DATA SOURCES: A literature search of PubMed (1966-October 2022) was conducted using the keywords sutimlimab, BIVV009, and cold agglutinin. Data were also obtained from prescribing information, meeting abstracts, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: All published prospective clinical trials, prescribing information, and meeting abstracts on sutimlimab for the treatment of CAD were reviewed. DATA SYNTHESIS: Sutimlimab is a first-in-class complement C1s inhibitor indicated for the treatment of CAD-associated hemolysis. This approval was based on the phase III CARDINAL trial, which evaluated sutimlimab in patients with CAD-associated hemolysis. The primary endpoint of achieving a hemoglobin of ≥12 g/dL or increase of ≥2 above baseline was achieved by 54% of patients with sutimlimab in the 26-week trial. The phase III CADENZA trial was a placebo-controlled trial in which sutimlimab has demonstrated a significant improvement in the composite endpoint of hemoglobin increase of ≥1.5 g/dL, avoidance of transfusion, and avoidance of additional CAD therapies (73% sutimlimab vs 15% placebo). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS: Sutimlimab rapidly halts hemolysis, improves hemoglobin, and improves quality-of-life in patients with CAD. Safety issues with sutimlimab include infusion-related reactions and risk of serious infections with encapsulated bacteria. CONCLUSIONS: Sutimlimab provides an additional therapeutic option in the treatment of CAD-associated hemolysis that can lead to rapid improvement in hemoglobin and anemia-related symptoms.

Real-world Experience of Caplacizumab for Adolescents in the First-line Setting: Case Reports.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a thrombotic microangiopathy resulting in high mortality. Caplacizumab is approved for treatment of adults with acquired thrombotic thrombocytopenic purpura that has shown faster platelet normalization, clinical improvement, and reduced risk of recurrent/refractory disease. We report 2 cases of adolescents treated off-label with caplacizumab who were able to stop before 30 days from end of plasma exchange after platelets normalized and ADAMTS13 activity recovered to >20% to 30%. Our results show similar efficacy to other reports of patients under 18 receiving caplacizumab in first line, regardless of plasma exchange strategy, and may offer insight into early cessation criteria.

Measuring the Impact of a Pharmacist-Driven Blood Factor Education Program: A Prospective, Single-Center Observational Study.

Introduction: Patients with bleeding disorders are best served by multidisciplinary teams. Pharmacists can play a critical role in the optimal management of patients with bleeding disorders through blood factor stewardship strategies and programs. An educational program was developed and implemented wherein a hematology pharmacist provided brief recorded lectures to an entire department of pharmacists in a multi-site health-system with the goal to improve the knowledge base and confidence among this population of general practitioners. Methods: The primary objective of this study was to evaluate the educational outcomes of a blood factor education program for pharmacists. The impact of the educational program was determined by measuring the difference in mean test scores between the pre- and post-program surveys. Results: The final analysis included 214 participants. The primary endpoint of mean competency test score was significantly improved in the post-test compared to pre-test (78.33% vs 52.83%; P < .0001). Any degree of test score improvement was observed in 99% (n = 212) of participants. Pharmacist confidence was significantly improved in all 20 domains of bleeding disorders and blood factor product verification and management. Conclusion: This program identified that most pharmacists in a large multi-site health-system were not familiar with bleeding disorders to a satisfactory degree, commonly because of the relative rare encounters with bleeding disorder-related orders, and that despite systems-based support there was an opportunity to improve practice through education. Such educational programming could be beneficial for the development of pharmacist-provided care and is a measure that could be implemented as part of blood factor stewardship initiatives.

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations.

OBJECTIVE: To review the available data for the efficacy and safety of daratumumab in the treatment of multiple myeloma (MM), both in the newly diagnosed and relapsed/refractory settings, as well as provide additional guidance to clinicians on operational, safety, and supportive care considerations. DATA SOURCES: A literature search of PubMed (1966 to October 2021) was conducted using the keywords daratumumab, Darzalex, and myeloma. Data were also obtained from prescribing information and unpublished abstracts from meetings. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles, prescribing information, and unpublished meeting abstracts on daratumumab for the treatment of MM were reviewed. DATA SYNTHESIS: Daratumumab is an anti-CD38 monoclonal antibody indicated for the treatment of MM. The addition of daratumumab to proteasome inhibitor and immunomodulatory drug-based regimens has led to a consistent improvement in progression-free survival and response rates in relapsed/refractory MM as per the POLLUX, CASTOR, APOLLO, and CANDOR trials. The ALCYONE and MAIA phase III trials have demonstrated an overall survival benefit when adding daratumumab to frontline regimens for transplant-ineligible patients with newly diagnosed MM. In transplant-eligible patients, daratumumab-based quadruplet regimens have improved depth of response in the CASSIOPIEA and GRIFFIN trials. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Operational and safety considerations that clinicians need to account for do exist, including different administration and infusion strategies, infusion-related reactions, increased risk for infectious complications, and interference with blood transfusion management. CONCLUSIONS: Daratumumab has led to a shift in the treatment paradigm of both newly diagnosed and relapsed/refractory MM, leading to improvements in outcomes such as response rates, depth of response, and progression-free survival.

Comparative Utilization and Efficacy of Thrombopoietin Receptor Agonists in Relapsed/Refractory Immune Thrombocytopenia.

BACKGROUND: The thrombopoietin (TPO) agonists, eltrombopag and romiplostim, stimulate the production of platelets and offer an effective treatment option in relapsed/refractory immune thrombocytopenia (ITP). Recently published 2019 ITP guidelines recommend the TPO agonists as second-line therapy following corticosteroids; however, little data offer insights into comparative efficacy and tolerability. STUDY QUESTION: Is there a difference in the efficacy between romiplostim and eltrombopag in relapsed/refractory ITP? STUDY DESIGN: We conducted a single-center, retrospective chart review of patients with ITP treated with romiplostim or eltrombopag. MEASURES AND OUTCOMES: The primary objective was a sustained platelet response, defined as platelets greater than 50,000/µL in more than 66% of clinic visits over a 6-month period. Secondary objectives sought to evaluate response to and tolerability of TPO agonists. RESULTS: The study included 107 consecutive patients, 67 (63%) on romiplostim and 40 (37%) on eltrombopag. Previous corticosteroids and rituximab were used in 95% and 50% of patients, respectively. There was no difference identified in platelet responses between the TPO-RAs, 72% romiplostim versus 65% eltrombopag (P = 0.520). In addition, no differences were identified in secondary measures of response. CONCLUSIONS: In our experience with romiplostim and eltrombopag for ITP, we did not identify a difference in the efficacy of these agents. Further larger and prospective evaluations should be considered.

Ibrutinib treatment via alternative administration in a patient with chronic lymphocytic leukemia and dysphagia.

INTRODUCTION: Ibrutinib is a small molecule inhibitor of Bruton's tyrosine kinase indicated for the treatment of a variety of B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenstrom's macroglobulinemia. These indolent hematologic malignancies are considered diseases of the elderly, a population that may have dysphagia leading to difficulty swallowing tablets and capsules. Ibrutinib is currently not available in a liquid oral dosage form. We report the utilization and clinical outcomes associated with alternative administration of ibrutinib capsules in a patient with chronic lymphocytic leukemia and significant dysphagia. CASE REPORT: An 86-year old female requiring chronic lymphocytic leukemia-directed therapy due to a rising absolute lymphocyte count and worsening, transfusion-dependent anemia with a past medical history of dementia and dysphagia, was initiated on ibrutinib. MANAGEMENT & OUTCOME: Due to the patient's significant inability to swallow, ibrutinib capsules were administered via an alternative method by opening them and sprinkling onto soft food or applesauce. With ibrutinib therapy, the patient has had a significant clinical response in her chronic lymphocytic leukemia as evidenced by her decreased absolute lymphocyte count and achieving transfusion independence with improvements in hemoglobin. DISCUSSION: Ibrutinib administration via this alternative method resulted in an initial clinical response in the treatment of our patient's chronic lymphocytic leukemia as evidenced by a decreasing absolute lymphocyte count and improved anemia that achieved transfusion independence. The patient has maintained this response to therapy after approximately 1 year at the time of manuscript preparation.

Publication rates of hematology/oncology abstracts presented at major pharmacy association meetings.

INTRODUCTION: Professional conferences are where research findings are initially presented. Studies suggest many research ideas presented at conferences are never published. Previous studies have demonstrated that the full publication rate of abstracts presented at pharmacy meetings is approximately 20%. The objective of this study was to determine the full publication rate of hematology/oncology abstracts presented at major pharmacy organization annual meetings. METHODS: A systematic search of PubMed and Google Scholar was performed. Publication status was evaluated for hematology/oncology abstracts presented at annual meetings for the following organizations: American College of Clinical Pharmacy Annual Meeting, American Society of Health-System Pharmacists Midyear Clinical Meeting, Hematology/Oncology Pharmacy Association Annual Meeting, and International Society of Oncology Pharmacy Practitioners Annual Meeting. Data collected included the meeting of abstract presentation, number of authors, abstract study type, country of origin, journal of publication, and type of publication. Abstracts presented as trainee research were excluded. RESULTS: Of 451 oncology abstracts evaluated, the most common topic categories included pharmacotherapy (n = 244; 54.1%), clinical pharmacy practice (n = 84; 18.6%), and operational/compounding (n = 69; 15.3%). The overall publication rate was 17.5% (n = 79). Abstracts were published as full manuscripts over a spread of 48 different journals. Factors associated with full publication included abstracts with more than 5 authors (OR 3.86, 95% CI 2.32-6.43; p < 0.0001) and abstracts presented at oncology-focused pharmacy meetings (OR 2.92, 95% CI 1.49-5.72; p = 0.0018). CONCLUSION: This study showed an overall publication rate of 17.5% for abstracts presented at pharmacy meetings, consistent with prior studies.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis.

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Retrospective Analysis of Clinical Outcomes Associated With the Use of Pegfilgrastim On-body Injector in Patients Receiving Chemotherapy Requiring Granulocyte Colony-Stimulating Factor Support.

Objectives: Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) used as primary prophylaxis in patients receiving myelosuppressive chemotherapy regimens that have greater than 20% risk of developing febrile neutropenia (FN). Historically, pegfilgrastim has been administered 24 to 72 hours after chemotherapy, necessitating a return to clinic to receive the provider-administered injection. An alternative option is the pegfilgrastim on-body injector (OBI). With the OBI device, patients have their pegfilgrastim administered 27 hours after receiving chemotherapy while remaining at home, avoiding an additional clinic appointment. Concerns with pegfilgrastim OBI include lack of experience with the device in both the patient and provider, device-related failures, and the success of delivery. This study evaluates pegfilgrastim OBI failure rates through associated patient outcomes among cancer patients receiving chemotherapy requiring G-CSF. Methods: A retrospective electronic chart review was conducted of adult patients with cancer who received chemotherapy and pegfilgrastim OBI from July 1, 2016, to July 31, 2018. The primary objective of this study was the incidence of FN in patients receiving pegfilgrastim OBI. Results: There were no reported cases of hospitalization due to FN in patients who received pegfilgrastim OBI. Dose delays and dosage modifications were not observed in our review. The OBI device failure rate was found to be low (1.92%). Conclusion: The low device failure rate from this study suggests that the OBI is a viable option for administration of pegfilgrastim in patients receiving chemotherapy requiring G-CSF.

A Review of Growth Factor Support in Bloodless Autologous Hematopoietic Stem Cell Transplant.

Bloodless autologous hematopoietic cell transplantation is associated with risks of severe bleeding and profound anemia. RBC or platelet transfusions are often used to prevent these hematologic complications. However, in patients such as Jehovah's Witnesses who refuse major blood components, the lack of transfusion support is not an absolute contraindication to an autologous hematopoietic cell transplant. Pennsylvania Hospital performed the world's first bloodless hematopoietic cell transplant more than 15 years ago and has gradually improved its technique with a sizable patient population. Erythropoiesis-stimulating agents were successfully employed as part of their pretransplant regimen to prevent severe anemia. Thrombopoietin agonists' potential role in bloodless transplant is also currently being explored. Although there is limited literature, available reports in combination with physiologic reasoning may support the use of these growth factors to promote transplant success. These agents offer potential benefit and may be of utility in minimizing complications of a bloodless transplant. In this review, we summarize the available literature and offer insight into how we may incorporate growth factors to allow bloodless autologous hematopoietic cell transplantation to be an available option to patients who may otherwise be denied.