Practical Considerations for the Daratumumab Management in Portuguese Routine Clinical Practice: Recommendations From an Expert Panel of Hematologists.

The recent therapeutic progress in multiple myeloma (MM) has led to the introduction of novel and highly potent drug classes. Daratumumab was the first CD38-targeting antibody showing to be effective and safe in MM patients as monotherapy and in combination regimens, which led to its rapid implementation in clinical practice. Considering that treatment discontinuation for drug-related adverse events can impact patients' quality of life and outcomes, the treatment decision should consider different factors and be weighted for each patient individually. Here, we aimed to guide clinicians using daratumumab treatment for MM by addressing practical real-world considerations based on an expert panel of Portuguese hematologists. Carefully following the recommendations mentioned in daratumumab's SmPC, and of those from other drugs used in combination regimens, along with ensuring a good communication with all healthcare professionals involved, is critical to prevent any complications arising from treatment. The risk of infection should be assessed for all patients under treatment with daratumumab and patients should be educated on the potential adverse events. Recommendations on prophylaxis and vaccination should be considered to avoid infections, and delays in the planned therapeutic schedule may be required to prevent adverse consequences of hematological toxicity. Daratumumab treatment is effective and feasible in patients with renal impairment, although careful patient monitoring and a frequent communication with the Nephrology department are of the utmost importance. Sharing clinical practice plays an important role in medical education by allowing to maximize treatment efficacy and minimize its safety risks.

Non-biological Complex Drugs (NBCDs): Complex Pharmaceuticals in Need of Individual Robust Clinical Assessment Before Any Therapeutic Equivalence Decision.

Non-Biological Complex Drugs (NBCDs) are complex non-biological drugs comprised of large high molecular weight molecules and, often, nanoparticular structures (including liposomes and block-copolymer micelles). In the case of NBCDs, the entire complex is the active pharmaceutical ingredient and its properties cannot be fully characterized by physicochemical analysis. Moreover, the manufacturing process is fundamental in creating the correct originator product. The same is true for generic versions of the product. A recent appraisal of approval procedures for NBCDs "follow-on products" approved in Europe shows a diversity of regulatory pathways. In fact, three different abridged application procedures, under European legislation, were used: the generic application procedure of Article 10(1), the hybrid application procedure of Article 10(3), and the biosimilar application procedure of Article 10(4). Three informed consent applications via Article 10(c) from innovator companies of glatiramer acetate and sevelamer carbonate were submitted shortly after the approval of the first follow-on products. Furthermore, a number of "well-established use" applications [via Article 10(a)] were approved for iron sucrose and iron dextran complexes. In order to protect patients from the increased risks of NBCD products and NBCD follow-on products, two complementary approaches should be considered: (i) improving the regulatory procedures and their guidance documents within the pre-registration phase, and (ii) not considering interchangeability whenever clinical data is not available. With regards to the latter, the need for adequate safety and efficacy data might also include risk management programmes within post-approval pharmacovigilance actions. This, however, would depend on a risk appraisal that must be considered for individual medicinal products, based on the nature of the submitted relevant set of safety/efficacy data.

Role of 18F-FDG PET/CT in the diagnosis and management of multiple myeloma and other plasma cell disorders: a consensus statement by the International Myeloma Working Group.

The International Myeloma Working Group consensus aimed to provide recommendations for the optimal use of 18fluorodeoxyglucose (18F-FDG) PET/CT in patients with multiple myeloma and other plasma cell disorders, including smouldering multiple myeloma and solitary plasmacytoma. 18F-FDG PET/CT can be considered a valuable tool for the work-up of patients with both newly diagnosed and relapsed or refractory multiple myeloma because it assesses bone damage with relatively high sensitivity and specificity, and detects extramedullary sites of proliferating clonal plasma cells while providing important prognostic information. The use of 18F-FDG PET/CT is mandatory to confirm a suspected diagnosis of solitary plasmacytoma, provided that whole-body MRI is unable to be performed, and to distinguish between smouldering and active multiple myeloma, if whole-body X-ray (WBXR) is negative and whole-body MRI is unavailable. Based on the ability of 18F-FDG PET/CT to distinguish between metabolically active and inactive disease, this technique is now the preferred functional imaging modality to evaluate and to monitor the effect of therapy on myeloma-cell metabolism. Changes in FDG avidity can provide an earlier evaluation of response to therapy compared to MRI scans, and can predict outcomes, particularly for patients who are eligible to receive autologous stem-cell transplantation. 18F-FDG PET/CT can be coupled with sensitive bone marrow-based techniques to detect minimal residual disease (MRD) inside and outside the bone marrow, helping to identify those patients who are defined as having imaging MRD negativity.

[High-dose chemotherapy and stem-cell in patients with breast cancer]. / Quimioterapia intensiva comsuporte hematopoiético autólogoem doentes com carcinoma da mama.

BACKGROUND: The treatment of breast cancer patients with high-dose chemotherapy and stem-cell support is still highly controversial. The elucidation of its clinical benefit awaits the maturation of on-going clinical trials. METHODS: Patients with chemotherapy-sensitive metastatic or locally advanced disease and patients with stage II/III disease and at least four positive axillary lymph nodes in the initial surgical specimen were eligible for transplantation. RESULTS: Fifty-five women underwent transplantation between 1994 and 2000. For the 19 women with metastatic disease, the median time to progression was seven month and survival 28 months. Only two patients are progression-free, at 48 and 77 months, both with supraclavicular and/or cervical lymph node-only disease. For the 36 women with stage II/III disease, the median time to progression and survival were both 65 months -19 are alive, 18 disease-free. Among the subgroup of 23 patients with 10 or more positive axillary nodes, the five-year event-free survival was 57%. CONCLUSION: The clinical benefit of stem-cell transplantation for metastatic breast cancer is limited since the time to progression and survival after transplantation is similar to those reported in patients with newly diagnosed metastases and treated with conventional-dose chemotherapy. However, in patients with high-risk stage II/III disease the time to progression is longer than that reported for similar patients treated with conventional systemic treatment. These results are similar to previous reports in the literature.