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Early access to the drug: the role of the pharmacist in the management of CNN drugs in oncology

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European Statement

Introductory Statements and Governance

Author(s)

Aldo De Luca, Andrea Ghiori, Cecilia Orsi, Michele Cecchi

Why was it done?

CNN drugs are drugs that have obtained authorisation from EMA and AIFA (Italian drugs authority) but that have not been negotiated for the purposes of the reimbursement of the National Health System. These drugs are often clinical innovations that fill therapeutic gaps. In our Region, access to these therapies is allowed only on a special request made by the clinicians at the Pharmacy that is evaluated positively, presents it to the Regional Authority. The regional assessment is also implied by the presence of specific contractual agreements with the pharmaceutical companies. Requests have been considered for enfortumab vedotin (EV), indicated for urothelial carcinoma, and trastuzumab deruxtecan (T-DXd), indicated for breast cancer. The objective of this article is to highlight the activity of the pharmacist in the management of drugs in the CNN range.

What was done?

A pathway has been developed at regional level to promote early access to new drugs and further therapeutic possibilities.

How was it done?

All requests for CNN drugs received in the semester November 2022 to May 2023 to our Operations Unit and subsequently included in the regional portal were analysed on the basis of approved indications, bibliography, clinical reports, and eligibility card (for T-DXd only) validated by the medical division of the pharmaceutical company.

What has been achieved?

During the period analysed, 25 applications were made (11 for EV, 14 for T-DXd) for a total of 30 treatments (11 for EV, 19 for T-DXd). Of the 25 requests received by the Pharmacy, 24 (96%) were sent to the region for treatment authorisation; one was not submitted because the patient did not comply with the approved indication. We obtained 100% of the required treatment approvals.

What next?

The hospital pharmacist is configured as a collector of clinical requests with an important function as a filter of prescriptive appropriateness in requesting regional authorisation for the treatment of drugs in the CNN range; moreover, the pharmacist is a necessary reference figure between the need for clinical innovation and the need to guarantee sustainability of the system in order to ensure early access to innovative therapeutic opportunities. This model could be exported to other regions at national and European level.

Implementation of a multidisciplinary circuit for the management of haematologic patients under treatment with bispecific antibodies

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European Statement

Patient Safety and Quality Assurance

Author(s)

Carla Noguera-Jurado, Alba Manzaneque, Gloria Molas, Genis Castells, Sandra Jara, Bernat Tenas, Jordi Nicolas

Why was it done?

Bispecific antibodies (BA) have the ability to specifically bind two different antigens, thereby presenting specificity for two different cells. Among the toxicities associated with these drugs are cytokine release syndrome (CRS) and immunoeffector cell-associated neurotoxicity syndrome (ICANS), the management of which requires multidisciplinary action. The purpose of this circuit is to ensure adequate management of these toxicities to guarantee patient safety.

What was done?

Creation of an action plan for haematological patients treated with bispecific antibodies for the detection and proper management of their toxicities.

How was it done?

A multidisciplinary team formed by Pharmacy, Haematology, Nursing, Intensive Care Medicine and Neurology was created and the healthcare professionals involved were specifically instructed. Moreover, an action circuit was implemented for the detection and management of these toxicities, and a specific protocol was created for the preparation and dispensing of tocilizumab. The protocol contemplated: centralisation of the preparation in the pharmacy department (within the pharmacy hours) or preparation in the hospitalisation ward by trained professionals using a kit previously prepared by the pharmacist (containing drug, serum and closed system dispositive for the preparation and administration of tocilizumab outside pharmacy hours).

What has been achieved?

From July 2022 to August 2023, a total of five patients have been treated with BA in our institution (elranatamab (4/5), and teclistamab (1/5)), including clinical trials and compassionate use, for Multiple Myeloma.
Three patients presented grade 1 CRS in the first cycle of treatment, which was resolved with symptomatic therapy, with no need for tocilizumab administration in any case. In addition, one also presented grade 1 ICANS, which only required monitoring without treatment.
The availability of the toxicity management circuit, in addition to staff training, allowed toxicities to be detected and resolved early and, if tocilizumab had been needed, the circuit would have ensured its immediate availability.

What next?

The implementation of a multidisciplinary care circuit led by pharmacy and haematology guarantees the adequate management of toxicities associated with the treatment, ensuring the best quality of care for the patients and their safety.

DEVELOPMENT OF A PROTOCOL TO STANDARDISE CELL-BASED MEDICINAL PRODUCTS HANDLING IN AN ONCO-HAEMATOLOGY CLINICAL TRIALS UNIT

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European Statement

Patient Safety and Quality Assurance

Author(s)

JOSE MANUEL DEL RIO GUTIERREZ, EUGENIA SERRAMONTMANY MORANTE, SARA GIMENEZ GINER, PILAR ROVIRA TORRES, PATRICIA GARCIA ORTEGA, CARLOTA VARON GALCERA, ISABEL CIDONCHA MUÑOZ, MARIA QUERALT GORGAS TORNER

Why was it done?

One of the most important challenges we currently face is the increase of clinical trials (CTs) including CBMPs. These drugs require special storage, preparation, delivery and administration; so developing standard operating procedures (SOPs) and ensuring proper coordination between all professionals involved, including pharmacists, is essential.

What was done?

Management of cell-based medicinal products (CBMPs) was protocolised in an onco-haematology clinical trials unit.

How was it done?

Pharmacists, doctors and nurses participate in a multidisciplinary team to standardise CBMPs handling. The following protocol was agreed:
1.The entire multidisciplinary team is notified when a CBMP prescription is planned to ensure proper coordination.
2.The CBMP is manufactured by the CT sponsor. Then, it is transferred to the blood bank for cryopreservation. CBMPs usually require a temperature between -80ºC and -200ºC and expire in some weeks.
3.Before CBMP administration, patients undergo lymphodepletion. The lymphodepletion regimen is performed according to the CT protocol or arranged between medical and pharmacy teams. Chemotherapy, serum therapy and antiemetic regimen are discussed and specified.
4.Once the treatment is prescribed, it is verified by a pharmacist who ensures its suitability.
5.On the infusion day, the blood bank delivers the CBMP. Then, a pharmacist checks if it arrives in proper condition and it is defrosted. The pharmacy department reconditions the CBMP in another infusion bag or syringe if required. This is the most critical point because CBMP expires after some minutes of defrosting, requiring extensive coordination.
6.CBMP is administered according to the CT protocol.

What has been achieved?

72 patients were recruited in 15 CT. 8 of them use as CBMP Chimeric Antigen Receptor T-Cells (CAR-T-CELLS), 4 Specific Peptide-Enhanced Affinity Receptor T-Cells (SPEAR-T-CELLS), 2 Tumour-Infiltrating Lymphocytes (TILs) and one cytokine-stimulated Natural-Killer-Cells (CS-NK-CELLS). Seven assays are intended for haematological neoplasms and eight for solid malignant neoplasms. One assay requires CBMP syringe reconditioning in the pharmacy department.
The described process optimises CBMPs handling, avoids delays in administration and reduces the risk of misuse.

What next?

CBMPs represent a novel therapy, and pharmacists have an essential role in developing new procedures to incorporate them into clinical practice. This protocol may be helpful for other centres to implement guidelines to work with CBMPs.

Medication reconciliation : a pharmaceutical teleconsultation for patients followed in hematology in a French Comprehensive Cancer Center

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European Statement

Clinical Pharmacy Services

Why was it done?

Oncology patients are often elderly and multi-medicated, with many physicians involved in their management. Their treatments can therefore often be changed while chemotherapy have a high risk of drug’s interactions. However, in our center, the length of patient stays and pharmaceutical resources are incompatible with the systematic achievement of reconciliation during hospitalization. In addition, more and more patients are benefiting from oral chemotherapy, outside any hospitalization. Besides, hematologists already offered teleconsultations to some patients, for their comfort and because of the COVID-19 pandemic.

What was done?

A pharmaceutical teleconsultation is now offered to our hematology patients in order to make the comprehensive list of medications taken, including self-medication, herbal medicines and food supplements. The comparison with the usual treatment in the medical record allows to update the patient file and prepares a proactive reconciliation.

How was it done?

A comparison and tests of the different reconciliation tools were carried out. The Hospiville® platform was chosen, also allowing remote and secure communication with retail pharmacies. Moreover, communication devices have been installed, such as webcams, headphones and microphones. This equipment was financed by our Regional Health Agency.

What has been achieved?

An appointment is offered to the patients listed on the weekly hematology teleconsultation schedule. Their usual pharmacy’s contact details are then requested.
Information collected from the medical file and from the pharmacy are provided on Hospiville®, then completed during the interview by Teams®. The pharmacist lists the prescribed medications, assesses the patient’s compliance and analyzes the interactions between drugs or complementary medicines. If necessary, the referring hematologist is contacted to adjust the drug’s management. Afterwards, the report of the teleconsultation is added to the medical file (Elios®).

What next?

By carrying out the consultation from home, patients report being more exhaustive in the information they provide. They also appreciate the short time needed and the easiness of speaking in familiar surroundings.
Thanks to scheduled teleconsultation, pharmacists further secure the patient’s medication path without disrupting the pharmacy’s activity. This experience will be used for the experiment “ORAL THERAPIES – home monitoring of patients on oral cancer drugs” in the French context of Article 51.

Critical points in the management of intratumoral treatments in oncology clinical trials

European Statement

Clinical Pharmacy Services

Author(s)

Lorena Garcia Basas, Pablo Latorre Garcia, Eugenia Serramontmany Morante, Patricia Garcia Ortega, Pilar Rovira Torres, Laura Maños Pujol, Isabel Cidoncha Muñoz, Maria Queralt Gorgas Torner

Why was it done?

Increasing number of CT with IT, in different pathologies, with different tumor locations, contributes an increase in the complexity of drug compounding and procedures. Their preparation, administration and handling requirements differ from current therapies.

What was done?

Identification of critical points concerning intratumoral treatments (IT) preparation in patients with cancer included in clinical trials (CT).

How was it done?

Ongoing CT with IT in our unit were reviewed to identify critical points regarding prescription and preparation process. 14 trials with IT, 8 (57%) of which have ongoing patients were identified. Two of these trials are “first in human”. The critical points were:

  • Nature of the IT: virus (4, 29%), nanoparticles (3, 21%), ribonucleic acid (2, 14%), cyclic dinucleotides (2, 14%), monosaccharides (1, 7%), phospholipids (1, 7%) and proteins (1,7%).Particularly, virus have special safety measures and transport conditions
  • Dosing units: mcg (4, 29%), plaque-forming unit/mL (PFU/mL)(3, 21%), mL (3, 21%), mg (2 14%), ng (1, 7%), 50% Tissue Culture Infectious Dose (TCID50)(1, 7%).
  •  Prior dilution before filling the syringe: 8 (57%) of our preparations require at least one prior dilution.
  •  Drug volume to prepare according to the tumor size: 8 (57%) IT preparations depend on the tumor size.
  •  Depending on the depth of the target tumor lesion (visceral or superficial), different size of needle is required. This is important because different priming volumes of the needles are necessary.

 

What has been achieved?

The whole information necessary for a complete prescription, validation and correct preparation goes further than information usually needed for current therapies such as chemotherapy. The results of the study of the critical points allow us to elaborate the standardized operational procedures (SOP) for each CT and IT.  These SOPs include the necessary information for a correct preparation for each IT, reducing risk of mistakes and achieving uniformity in the process.

What next?

These types of therapies represent a challenge, and pharmacists have an important role in developing new procedures. Communication between radiology, oncology and pharmacy departments in a multidisciplinary teamwork is essential. This information may be useful to other centers due to the lack of experience and SOPs to work with this type of therapy.

Distribution optimization of oral oncology therapy in the treatment of advanced renal cell carcinoma: between environmental impact and indirect costs

European Statement

Introductory Statements and Governance

Author(s)

Nicola Nigri, Maria Antonietta Calzola, Silvia Di Marco, Elisa Di Maio, Benedetta Fagotti, Martina Savoia, Luciana Negroni, Fausto Bartolini

Why was it done?

The 1st line treatment in RCC provides Pembrolizumab 200mg IV/21 days plus Axitinib (56cps/pack) P.O./BIS meaning two journeys. The PT and or CG have to come back to the hospital at different moments from the infusion date for 9 times/year, affecting negatively: the compliance, the IC, the patient’s follow-up and, the environmental impact.

What was done?

In Italy, the 1st line treatment of advanced renal cell carcinoma (RCC) involves 4791 new diagnoses/year. The most innovative therapies imply the association of intravenous therapy (IV) and oral chemotherapy.
In this case, the Hospital Pharmacist (HP) can assist the compliance and help to minimize the impact linked to indirect costs (IC), often unconsidered, through the reduction of the patient (PT) and or caregiver (CG) trips, improving also their quality of life. The HP can participate in decreasing the CO2 emissions that, in 70% of the cases, are generated by road transportations.

How was it done?

On the IV therapy day, is given to the patient, the oral treatment too (42cps), provided with the necessary documents.
To measure the IC has been considered the organizational costs to the PT and or CG. The time commitment was estimated, in the worst case, in a 2h return journey (150km) between the PT/CG location and the dispensation point. It has been considered 30min as the estimated time to park, arrival, waiting time in pharmacy, drug pick-up and back.
The average hourly earnings considered has been 13,6 €/h. The average diesel-engined utility car emits 95g/km of CO2 emissions.

What has been achieved?

Each avoided trip is 2h x 13,6€ = 34€ for missing productivity or 68€ if both are involved. The total IC avoided/year/PT is the number of avoided journeys/year x 34 = 306€ (612€ if both are involved).
The CO2 emissions are equal to 95g x 150km =14,25kg/distribution/PT, 128,25 kg/year/PT, equal almost to 2,3% of CO2 emission perceived in Italy, that, in the worst case, times the incident PTs/year that will become 614.000tonnes/year.

What next?

The HP shows, even more, its influence on more layers: clinic, economic, and environmental to benefit the patient, our NHS, and our planet, hoping in this approach in more combined therapies.

OUTPATIENT ADMINISTRATION OF BLINATUMOMAB FOR ACUTE LYMPHOCYTYC LEUKEMIA

European Statement

Clinical Pharmacy Services

Author(s)

MV VILLACAÑAS PALOMARES, CM VALENCIA SOTO, A GARCIA-AVELLO FERNANDEZ-CUETO, M MARTIN LOPEZ, S BARBADILLO VILLANUEVA, M OCHAGAVIA SUFRATEGUI, V MARTINEZ CALLEJO, M RIOJA CARRERA, P DEL RIO ORTEGA, M VALERO DOMINGUEZ

Why was it done?

This drug is administered continuously during a 28 days infusion. Due to the risk of cytokine release syndrome (CRS) it is initially administered in the inpatient setting and then transitioned to the outpatient, requiring an important interdisciplinary coordination to optimize the process.
Home-based chemotherapy offers several potential benefits: reduced exposure to hospital infections, less disruption of routine and family life, lower health care cost, …

What was done?

Pharmacy and haematology services designed a workflow for the outpatient administration of blinatumomab, a bispecific T-cell engager approved for relapsed ALL.
Here, we describe our experience transitioning from inpatient to outpatient setting.

How was it done?

First step was to review blinatumomab stability, as well as material compatibility and transfer set necessaries for both hospital and domiciliary administration.
Reconstituted blinatumomab may be stored at refrigerated (2-8°C) for up to 24 hours. Prepared infusion bag (with preservative) may be stored at room temperature (up to 27°C) for up to 96 h and for up to 10 days refrigerated (2-8ºC).
Second step was to establish with the haematology service the patient´s scheduled visits to the hospital to ensure maximum stability of the blinatumomab preparation.
We decided to prepare the blinatumomab infusion bag every three- or four-days beginning on Monday, Thursday or Friday avoiding visits on weekends.
In order to take advantage of the rest of the vial, we diluted itn a new bag with stabilizer solution but without in-line filter for the next preparation. We noted the date of elaboration and the amount of medication remaining.
We used this preparation initial in each new visit add the dose necessary and an in-line filter. We primed the filter with the prepared solution for infusion

What has been achieved?

Out of the four patients who have received blinatumomab in our hospital(May 2020 – September 2021), three have benefited from this circuit.18 doses were administered at home, avoiding 68 days of hospital admission.

What next?

Outpatient administration could reduce health expenditure, therefore allowing for additional investments in new therapies.
Since the use of blinatumomab is not very common and there is not much evidence at this respect, our experience can help other Pharmacy Services to implement this circuit.

DEVELOPMENT OF GUIDELINES FOR SAFE HANDLING OF ONCOLYTIC VIRUSES (submitted in 2019)

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European Statement

Clinical Pharmacy Services

Author(s)

Faten Ahmad Díaz, Eugenia Serramontmany Morante, Carla Esteban Sánchez, Pablo Latorre García, Montserrat Carreres-Prieto, Javier Martínez Casanova

Why was it done?

Different critical points were detected: 1) some OV dose prescription depends on tumor size, 2) special storage conditions, 3) special safety measures related to preparation to prevent cross-contamination and technician exposure, 4) special transport conditions in a safety container, and 5) safe administration. The increasing number of clinical trials with OV combined with the identified critical points implies a better coordination between the different departments involved.

What was done?

Development of a standardised working procedure for the safe handling considerations, storage requirements, and modes of administration of oncolytic viruses (OV) in patients with cancer.

How was it done?

Different meetings were arranged with a multidisciplinary team to standardise procedures, in order to avoid errors: 1. The pharmacist validates the prescription volume reflected on the certified sheet according to the tumour size. Then, a pharmacy technician is authorised to remove the vials from the freezer to start the preparation. 2. Special −80ºC freezer is needed to preserve the OV. 3. According to the preventive medicine service, OV must be prepared in biological safety cabinet class II (BSC) with personal protective equipment. At the end of preparation, the BSC must be cleaned with the OV appropriate disinfectant and ventilated for 1 hour before restarting to work again. So, the OV preparation was established at 7 a.m. in order to avoid cross-contamination with the chemotherapy (first preparation in the day). 4. Safety transport must be considered, so OV is packaged in a special hermetic box. 5. The majority of the OV preparations are administered intralesionally at the radiology room so safe administration is needed to avoid the room contamination.

What has been achieved?

By using these procedures, it is possible to work with a single BSC, avoiding delays in the administration of other therapies while reducing the risk of mistakes.

What next?

These types of therapies represent a novel therapeutic modality: their preparation, administration and handling requirements differ from current therapies; pharmacists have an important role in developing new procedures to incorporate them into clinical practice. This protocol may be useful to other centres due to the lack of experience and standardised guidelines to work with this type of therapy.

OPTIMISATION OF CANCER CARE PATHWAY OF SCHEDULED PATIENTS WHEN OUTSOURCING CHEMO SUPPLY (submitted in 2019)

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European Statement

Introductory Statements and Governance

Author(s)

Charlotte Chatain, Orane Gleizes, Séverine Barbault-Foucher, Sophie Barthier, André Rieutord, Niccolo Curatolo

Why was it done?

The production of chemotherapy of our hospital will be outsourced by September 2019. This is going to lead to new constraints including anticipated production before patients are admitted to the clinical ward.

What was done?

The clinical pathway of scheduled patients receiving chemotherapy in the main full hospitalization unit of the hospital was optimised.

How was it done?

The clinical pathway of scheduled patients was mapped to describe each step and validated by all the concerned health professionals. Data were collected between October and December 2017 to monitor the percentage of anticipated orders by physicians for chemotherapy production (also called “OK production”). Critical steps and/or bottlenecks were identified. Brainstorming workshops were set to identify areas of improvement with pharmacists, physicians, nurses and secretaries. Finally, the proposals made were implemented.

What has been achieved?

Two critical steps have been identified in this pathway: the receipt of the biological test results by the secretary and the “OK production” given by the physician. It has been decided for the secretary to call patients 72 hours (instead of 24 hours) before to remind them to do their biological test in the medical laboratory. An electronic and standardised prescription with the specific date for the biological test has also been created. In addition, a follow-up form was completed by pharmacists to secure all the critical steps and remind secretaries when they had to call patients and remind physicians when they had to give the “OK production”. Over a two months period, “OK production” given 24−48 hours before the admission increased from 18% to 40% (n= 15 patients).

What next?

These clinical pathway improvements allowed a better anticipation. The process-oriented approach used to identify solutions was very fruitful and led to collaborative solutions likely to be applied and accepted by both clinical ward and pharmacy. This method could be applied to improve other types of processes in our hospital.

Safe and integrated onco-hematology workflow

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European Statement

Production and Compounding

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