Establishment of a clinical pharmacist-led multiple myeloma clinic with collaborative prescribing model at the national center for cancer care and research in Qatar.

BACKGROUND: Multiple myeloma (MM) is a chronic and incurable hematologic malignancy that is prevalent among the elderly. Interprofessional patient care showed superiority over physician-only care in multiple settings, including MM. OBJECTIVE: The primary objective of this study was to evaluate the impact of clinical pharmacist (CP)-led clinic and CPs interventions on MM patient care. PRACTICE DESCRIPTION: Real-world analysis of ambulatory patients with MM showed that CPs were central to the optimization of therapy and adherence to treatment schedules and supportive medications. PRACTICE INNOVATION: The CP-led MM Clinic was established with a collaborative prescribing agreement (CPA) in 2022 at the National Center for Cancer Care and Research in Qatar and was the first of its kind in the Middle East and North Africa region. This CPA allowed CPs to issue refills for supportive medications and order required laboratory tests. EVALUATION METHODS: Data collected included the number of CP interventions, refills ordered by CPs, documentation of patient education, and medication reconciliations. The data were retrospectively collected and analyzed comparing ambulatory patients with MM treated before (2021) to those treated after the clinic implementation in 2022. RESULTS: The study population comprised 22 patients. A higher number of CPs interventions were documented post-clinic than preclinic (343 vs. 76, P = 0.004), with earlier initiation of bisphosphonate post-clinic (25 vs. 206 days, P = 0.008). There were also significant improvements in the introduction of risk appropriate venous thromboembolism prophylaxis (43% vs. 6%, P = 0.001) as well as vitamin D and calcium supplementation (100% vs. 68%, P = 0.02) post-clinic. Twenty-two medication refills for supportive medications and eight prechemotherapy laboratory investigations were ordered by CPs. CONCLUSION: The CP-led clinic provided a timely link to care optimization for ambulatory MM patients. This innovative CPA model implemented in the clinic could potentially be applied to different cancer settings to optimize safe and effective patient care.

Carfilzomib-induced life-threatening lung injury in refractory multiple myeloma.

INTRODUCTION: Carfilzomib is a second-generation selective proteasome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib is associated with respiratory side effects, such as cough, dyspnea, and upper respiratory tract infection. However, severe pulmonary toxicity is rare and is only reported in a few case reports. CASE REPORT: Here, we present a case of a 65-year-old male with refractory multiple myeloma who developed a life-threatening lung injury during his third cycle of carfilzomib. The patient presented with a decreased level of consciousness and was found to have Type I respiratory failure. He was admitted to the intensive care unit, where he was intubated. Blood cultures and viral panel were negative. The patient received a prolonged course of antibiotics with 2 days of hydrocortisone. MANAGEMENT AND OUTCOMES: After discharge, repeated myeloma workup showed disease progression and carfilzomib was reintroduced. The next day, he presented with fever, vomiting, and hypoxia. Chest x-ray showed congestive lung changes with patchy airspace opacities. Repeated echocardiography showed normal ejection fraction with moderate pulmonary hypertension (RVSP 46 mm Hg). The patient was transferred again to the ICU and kept on continuous positive airway pressure. Antibiotics were started, and blood cultures and respiratory viral panels were negative for any infectious organism. The patient improved in terms of inflammatory markers and oxygen requirements. Treatment with carfilzomib was stopped permanently. DISCUSSION: Pulmonary toxicity associated with carfilzomib in patients with multiple myeloma can be potentially life-threatening. The mechanism with which carfilzomib induces lung-related AEs is still not fully understood. In our patient, carfilzomib-induced lung injury was evident after rechallenging the patient with carfilzomib, in the radiographic x-ray changes and the new onset moderate pulmonary hypertension. Healthcare providers should be encouraged to report rare adverse events in order to identify the risk factors that can predispose patients to the development of these adverse events.

Effects of Intermittent Fasting on Response to Tyrosine Kinase Inhibitors (TKIs) in Patients With Chronic Myeloid Leukemia: An Outcome of European LeukemiaNet Project.

The overall survival of patients with Chronic Myeloid Leukemia (CML) treated by using tyrosine kinase inhibitors (TKIs) is very close to that of the healthy population. However, little is known about the effect of specific measures such as intermittent fasting, especially during Ramadan period. A 3-year retrospective study was conducted to evaluate the effect of fasting on patients with CML receiving TKIs by evaluating certain clinical, hematological, and molecular parameters. A total of 49 patients were eligible, with a median age of 46 years (range: 22-86), of these 36 (73.5%) were males and 13 (26.5%) were females. Twenty-seven (55%) patients are Middle Eastern, while 16 (32.7%) from the Indian subcontinent, and 6 (12.3%) Africans. Imatinib was the most common TKI; used in 25 patients (51%). The mean White blood cells (WBCs), neutrophils, and BCR-ABL were found to be reduced after fasting compared to before and during with statistical difference. The use of TKIs while fasting did not result in significant changes in hematological nor BCR-ABL levels in our study. Patients who wish to practice intermittent fasting may be reassured in this regard, yet physicians can adopt the safe trial approach, where they allow the patients to fast, but with instructions such as when to break fasting.

Perceptions and expectations of health care providers towards clinical pharmacy services at a tertiary cancer centre in Qatar.

BACKGROUND: Clinical pharmacy services started in 2009 at the National Center for Cancer Care and Research, Qatar. Clinical pharmacy services was established to provide comprehensive prescription of drug management and support, and consulting services to build clinically efficient and cost-effective pharmacy program. AIM: To determine perceptions and expectations of healthcare providers toward the clinical pharmacy services at the National Center for Cancer Care and Research. METHODS: A cross-sectional survey of healthcare providers was conducted from January to May 2018. A self-administered electronic/paper survey containing four domains assessing healthcare providers' perceptions and expectations towards clinical pharmacy services, perceived barriers to clinical pharmacist role and suggested area for improvement was sent to 375 healthcare providers including physicians, operational pharmacists, nurses and dietitians. RESULTS: The response rate was 112/375. Most of the healthcare providers (74%) perceived the increasing interest in clinical pharmacy services. Also, they expected (1) providing consultations regarding appropriate medication choices (82%); (2) providing information about medication availability and shortages (82%); (3) assisting in the prescribing of cost-effective drugs by providing pharmacogenomics information routinely (75%) and (4) Participating actively in research activities (74%). Overall, healthcare providers have a high level of trust in the clinical pharmacists' abilities (P < 0.01). Nurses were less appreciative (P < 0.002) of the positive role of clinical pharmacists in direct patient care as compared to both physicians and pharmacists (64.2%, 90% and 95.7%, respectively). CONCLUSION: This study revealed a positive attitude towards the role of clinical pharmacists by healthcare providers at National Center for Cancer Care and Research. However, there is an area of improvement by empowering with privilege and staffing, elevating the awareness and expansion in the ambulatory care settings.

Nurses' perceptions of and satisfaction with the use of automated dispensing cabinets at the Heart and Cancer Centers in Qatar: a cross-sectional study.

BACKGROUND: Automated dispensing cabinets (ADCs) were introduced in 2010 and 2012 at the Heart Hospital (HH) and National Center for Cancer Care and Research (NCCCR), both run by Hamad Medical Corporation in Qatar. These medication distribution systems provide computer-controlled storage, dispensing, and tracking of drugs at the point of care in patient care units. The purpose of this study was to assess nurses' perceptions of and satisfaction with the use of ADCs at HH and NCCCR. METHODS: A cross-sectional study was conducted in the two institutions in May and November 2012 using a piloted, validated, online, and anonymous questionnaire. The questionnaire consisted of four parts: nurses' sociodemographic and practice characteristics, 21 questions about their perceptions, one question about their overall satisfaction, and one about the system's ease of use. The self-administered survey was distributed to 503 nurses working at HH and NCCCR over three weeks using Survey Monkey®. RESULTS: The survey response rate was 80 % (n = 403). No significant difference was found in perception scores between the two institutions (p = 0.06). Ninety-four percent (n = 378) of nurses agreed that the medication delivery system allowed them to do their job more safely, and 90 % (n = 363) nurses agreed that they now spent less time waiting for medication from the pharmacy than they did before the ADC system was introduced. Eighty seven percent (n = 349) nurses agreed that they were able to administer medication more efficiently with the ADC system. The overall satisfaction rate (either "very satisfied" or "satisfied") for the two hospitals was 91 %. CONCLUSIONS: The nurses' perceptions of and levels of satisfaction with the ADC system were very good over the 6 months after complete implementation and integration at HH and NCCCR. ADCs appear to increase efficiency in the medication process and should therefore improve the quality of care.

Dissecting bloodstream infections in febrile neutropenic patients with hematological malignancies, a decade-long single center retrospective observational study (2009-2019).

BACKGROUND: The use of ill-suited antibiotics is a significant risk factor behind the increase in the mortality, morbidity, and economic burden for patients who are under treatment for hematological malignancy (HM) and bloodstream infections (BSI). Such unfitting treatment choices intensify the evolution of resistant variants which is a public health concern due to possible healthcare-associated infection spread to the general population. Hence, this study aims to evaluate antibiograms of patients with BSI and risk factors associated with septicemia. METHODS: A total of 1166 febrile neutropenia episodes (FNE) among 513 patients with HM from the National Center for Cancer Care and Research (NCCCR), Qatar, during 2009-2019 were used for this study. The socio-demographic, clinical, microbial, and anti-microbial data retrieved from the patient's health records were used. RESULTS: We analyzed the sensitivity of gram-negative and gram-positive bacilli reported in HM-FN-BSI patients. Out of the total 512 microorganisms isolated, 416 (81%) were gram-negative bacteria (GNB), 76 (15%) were gram-positive bacteria (GPB) and 20 (4%) were fungi. Furthermore, in 416 GNB, 298 (71.6%) were Enterobacteriaceae sp. among which 121 (41%) were ESBL (Extended Spectrum Beta-Lactamase) resistant to Cephalosporine third generation and Piperacillin-Tazobactam, 54 (18%) were Carbapenem-resistant or multidrug-resistant organism (MDRO). It's noteworthy that the predominant infectious agents in our hospital include E. coli, Klebsiella species, and P. aeruginosa. Throughout the study period, the mortality rate due to BSI was 23%. Risk factors that show a significant correlation with death are age, disease status, mono or polymicrobial BSI and septic shock. CONCLUSION: Decision pertaining to the usage of antimicrobials for HM-FN-BSI patients is a critical task that relies on the latest pattern of prevalence, treatment resistance, and clinical outcomes. Analysis of the antibiogram of HM-FN-BSI patients in Qatar calls for a reconsideration of currently followed empirical antibiotic therapy towards better infection control and antimicrobial stewardship.

Real world evidence of epidemiological trends, clinical presentation, and prognostic outcomes of multiple myeloma (2007-2021).

Background: Multiple myeloma (MM) is one of the most common hematological malignancies globally, and it is projected to increase in the coming years. It occurs more frequently in males and affects older individuals. Presenting symptoms can range from being asymptomatic to severely debilitating. The objective of this study was to determine the epidemiology, clinical features, and prognostic outcomes of patients with MM in the only tertiary cancer hospital in Qatar. Methods: Patients with symptomatic myeloma diagnosed at the National Center for Cancer Care and Research in Qatar between 2007 and 2021 were included. Data on demographics, laboratory work, bone marrow analysis, radiology, and given treatment were collected. Descriptive statistics, survival curves, and multivariable cox regression were used to identify independent mortality risk factors. Results: During the study period of 15 years, a total of 192 patients were diagnosed with MM. The incident rate of myeloma cases in 2021 was 8 patients per million. The median age of patients was 57 years [range 22-88], with 68% being above the age of 50 years at diagnosis. The majority of patients were male (71%) and (85%) were expats. At the time of diagnosis, most patients [n = 169 (88%)] had bone lesions, and 27% had extramedullary plasmacytoma. Anemia, hypercalcemia, and spinal cord compression were reported in 53%, 28%, and 7% of patients, respectively, at presentation. The monoclonal immunoglobulin subtypes were IgG, IgA, and free light chain in 52%, 16%, and 26% of patients, respectively. The overall median survival was 103 months (95% CI 71-135 months). In a multivariate cox-regression analysis for risk factors, only high serum calcium (≥ 2.7 mmol/L) was associated with increased mortality (HR: 2.54, 95% C.I.: 1.40-4.63, p = 0.002). Patients who received an autologous stem cell transplant (ASCT) had significantly better overall survival. Conclusion: In this comprehensive study of patients with MM treated in a country with a small and young general population, centralized hematology care, and free cancer care, we found a low but increasing incidence of MM and a good overall survival. Hypercalcemia was confirmed as a negative risk factor. ASCT had a significant positive impact on survival and should be provided to all patients eligible for this treatment, even in the era of novel agents.

Erythema nodosum following treatment with dasatinib plus chemotherapy in a patient with myeloid blast phase of chronic myeloid leukemia.

Erythema nodosum (EN) is a type of panniculitis occurring due to various conditions. It can be associated with certain malignancies or manifest as a side effect of drugs. This article presents a unique case of EN in a patient with chronic myeloid leukemia (CML-blast phase) following dasatinib and chemotherapy. Timely recognition and appropriate management are crucial to alleviate symptoms and consider potential drug-induced etiology.

Tyrosine Kinase Inhibitors in pediatric chronic myeloid leukemia: a focused review of clinical trials.

Tyrosine Kinase Inhibitors (TKIs) is revolutionizing the management of pediatric Chronic Myeloid Leukemia (CML), offering alternatives to Allogeneic Hematopoietic Stem Cell Transplantation (AHSCT). We conducted a comprehensive review of 16 Randomized Controlled Trials (RCTs) encompassing 887 pediatric CML patients treated with TKIs including Imatinib, Dasatinib, and Nilotinib. The median patient age ranged from 6.5 to 14 years, with a median white blood cell count of 234 x 10^9/uL, median hemoglobin level of 9.05 g/dL, and median platelet count of 431.5 x 10^9/µL. Imatinib seems to be predominant first line TKI, with the most extensive safety and efficacy data. BCR::ABL response rates below 10% ranged from 60% to 78%, CCyR at 24 months ranged from 62% to 94%, and PFS showed variability from 56.8% to 100%, albeit with differing analysis timepoints. The Safety profile of TKIs was consistent with the known safety profile in adults. With the availability of three TKIs as first line options, multiple factors should be considered when selecting first line TKI, including drug formulation, administration, comorbidities, and financial issues. Careful monitoring of adverse events, especially in growing children, should be considered in long term follow-up clinical trials.

How I treat obesity and obesity related surgery in patients with chronic myeloid leukemia: An outcome of an ELN project.

Obesity may affect treatment outcome in CML patients, therefore the treatment of this cohort of patients need careful monitoring, TKIs dose adjustment may be required for certain patients. Further studies are needed to determine the proper TKIs doses.

Outcome of Pregnancy in the Era of PEGylated Interferon-α2a in Females with Chronic Myeloid Leukemia: An Experience from Qatar.

Chronic myelogenous leukemia (CML), also known as chronic myeloid leukemia, is a myeloproliferative neoplasm characterized by increased proliferation of the granulocytic cell line without loss of its capacity to differentiate. It accounts for 20% of all adults affected by leukemia. Tyrosine kinase inhibitors revolutionized the treatment for CML and improved quality of life. Fertility is an important issue for both males and females. Here, we report our experience with a pregnant female with CML, and shed light on safety and efficacy of PEGylated interferon-αa in pregnant women with CML and its outcome.

Outcome of Pregnancy in the Era of Pegylated Interferon Alpha 2a in Females with Essential Thrombocythemia: An Experience from Qatar.

Myeloproliferative neoplasms are a diversified group of diseases of the hematopoietic stem cell, such as essential thrombocythemia (ET) and polycythemia vera. They are mainly caused by mutations in the following genes: JAK2, CALR, and MPL. All carry an increased risk to transform into acute leukemia or chronic myelogenous leukemia along with thrombosis and hemorrhagic complications. Treatment of such disorders during pregnancy is a challenging footstep, given the high risk of complications for both the mother and the fetus. Here, we report about two pregnant females with ET that has been treated with pegylated interferon alpha with safe and effective outcome.

Denosumab versus zoledronic acid for patients with beta-thalassemia major-induced osteoporosis.

ABSTRACT: The main aim of this study is to compare the 2 medications denosumab and zoledronic acid for patients with beta-thalassemia major induced osteoporosis. Patients with B-thalassemia major induced osteoporosis will undergo baseline assessment of the bone densitometry by bone density(DEXA) scan as a standard of care by the radiology department, then a blood test for bone-specific alkaline phosphatase and type-1 collagen telopeptide will be measured by the chemistry laboratory.Patients with B-thalassemia major induced osteoporosis, who are 18 years of age or more and willing to participate in the study will be enrolled after consenting by the primary investigator in hematology outpatient clinics. Patients with osteoporosis will receive 1 of the 2 medications; at the end of the year, DEXA scan will be done to compare the response of the 2 medications. The potential risks include drug-related side effects.The outcome will be measured biochemically by measuring bone-specific alkaline phosphatase and type 1 collagen carboxy telopeptide and radiologically by DEXA scan at baseline and 1 year using Z score.

Thrombocytosis in a male patient with acute promyelocytic leukaemia during all-trans retinoic (ATRA) acid treatment.

We present a rather uncommon side effect observed in a 20-year-old man with acute promyelocytic leukemia during treatment with ATRA. He developed a high platelet counts reaching up to 1655×109/L on day 29 of ATRA treatment, and started to recover spontaneously on day 33 of treatment, without any change in ATRA, or adding any cytoreduction therapy. No complications associated with thrombocytosis were observed. IL-6 seems to play an important role in the pathogenesis of the thrombocytosis induced by ATRA. However, it is unclear what are the precipitating factors for this rare phenomenon and whether it is caused by certain predisposing factors that might be related to patient's, disease pathogenesis or other unknown factors.

Jadenu® Substituting Exjade® in Iron Overloaded ß-Thalassemia Major (BTM) Patients: A Preliminary Report of the Effects on the Tolerability, Serum Ferritin Level, Liver Iron Concentration and Biochemical Profiles.

INTRODUCTION: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with ß-thalassemia major (BMT). The aim of this study was to evaluate the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. PATIENTS AND METHODS: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. RESULTS: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. CONCLUSIONS: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.

Nilotinib Induced Recurrent Gastric Polyps: Case Report and Review of Literature.

BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment. We excluded common causes of gastric polyps and therefore considered nilotinib as a probable cause of recurrent gastric polyps. CONCLUSIONS Recurrent gastric polyps could be a potential side effect of nilotinib treatment. Careful long-term monitoring of patients on TKI therapy is necessary and further long-term studies of TKI side effects are needed.

Population Pharmacokinetics of Intravenous Methotrexate in Patients with Hematological Malignancies: Utilization of Routine Clinical Monitoring Parameters.

BACKGROUND AND OBJECTIVE: Clinical response to methotrexate in cancer is variable and depends on several factors including serum drug exposure. This study aimed to develop a population pharmacokinetic model describing methotrexate disposition in cancer patients using retrospective chart review data available from routine clinical practice. METHODS: A retrospective review of medical records was conducted for cancer patients in Qatar. Relevant data (methotrexate dosing/concentrations from multiple occasions, patient history, and laboratory values) were extracted and analyzed using NONMEM VII®. A population pharmacokinetic model was developed and used to estimate inter-individual and inter-occasion variability terms on methotrexate pharmacokinetic parameters, as well as patient factors affecting methotrexate pharmacokinetics. RESULTS: Methotrexate disposition was described by a two-compartment model with clearance (CL) of 15.7 L/h and central volume of distribution (V c) of 79.2 L. Patient weight and hematocrit levels were significant covariates on methotrexate V c and CL, respectively. Methotrexate CL changed by 50 % with changes in hematocrit levels from 23 to 50 %. Inter-occasion variability in methotrexate CL was estimated for patients administered the drug on multiple occasions (48 and 31 % for 2nd and 3rd visits, respectively). CONCLUSION: Therapeutic drug monitoring data collected during routine clinical practice can provide a useful tool for understanding factors affecting methotrexate pharmacokinetics. Patient weight and hematocrit levels may play a clinically important role in determining methotrexate serum exposure and dosing requirements. Future prospective studies are needed to validate results of the developed model and evaluate its usefulness to predict methotrexate exposure and optimize dosing regimens.