Determining diagnostic delays in Romanian multiple myeloma patients using the Aarhus statement.

Introduction: Multiple Myeloma (MM) is classified as one of the most challenging cancers to diagnose, and the hematological malignancy is associated with prolonged diagnostic delays. Although major steps have been made in the improvement of MM patient diagnosis and care, Romanian patients still face long diagnostic delays. Thus far, there have been no studies evaluating the factors associated with diagnostic errors in Romanian MM patients. Methods: Using the Aarhus statement, we prospectively determined the diagnostic intervals for 103 patients diagnosed with MM at Fundeni Clinical Institute, between January 2022 and March 2023. Results: Our data revealed that the main diagnostic delays are experienced during the "patient interval." Patients spend a median of 162 days from the first symptom onset until the first doctor appointment. Bone pain is the most frequently reported symptom by patients (78.64%), but it leads to a medical-seeking behavior in only half of the reporting patients and results in a median delay of 191 days. The changes in routine lab tests are considered most worrisome for patients, leading to a medical appointment after a median of only 25 days. The median primary care interval was 70 days, with patients having an average of 3.7 medical visits until MM suspicion was first raised. The secondary care interval did not contribute to the diagnostic delays. Discussion: Overall, the median diagnostic path for MM patients in Romania was more than 6 months, leading to a higher number of emergency presentations and myeloma-related end-organ damage.

The Efficacy of Carfilzomib Treatment in Bortezomib-Refractory Patients-Real Life Experience in a Tertiary Romanian Hospital.

Background: Proteasome inhibitors (PIs) represent one of the most effective classes of therapy for patients with multiple myeloma (MM) and are incorporated in many of the current treatment regimens. The first-generation PI, bortezomib, has shown impressive results in patients with either newly diagnosed or relapsed/refractory MM, but once patients become resistant, treatment is increasingly challenging. Although the existing data show that the second-generation PI, carfilzomib, is highly efficient, there is still limited knowledge regarding the response to carfilzomib-based therapy in bortezomib-resistant patients. The aim of this study was to evaluate carfilzomib treatment performance in bortezomib-sensitive versus -refractory patients, in a real-life eastern European country setting. Methods: We retrospectively evaluated 127 adult patients exposed to bortezomib with relapsed or refractory MM, that subsequently received a carfilzomib-based therapy. We investigated the differences in the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) after carfilzomib-based therapy between the two patient groups. Results: The ORR in the bortezomib-sensitive group was significantly higher than that in the refractory group, leading to a superior PFS in this category of patients. For patients presenting with a high cytogenetic risk, we observed a significant difference in PFS between the bortezomib-sensitive and -refractory group, while standard cytogenetic risk patients presented a similar PFS regardless of the bortezomib sensitivity status. In addition, in patients with ISS (International Staging System) stage I or II, the previous sensitivity to bortezomib correlated with an improved PFS, while for patients with ISS stage III, both groups had a comparable PFS. No significant differences in OS were observed between the two groups. Conclusions: In countries where novel or experimental therapies are not readily available, carfilzomib-based therapy can still be a viable therapy option for patients presenting with bortezomib-refractory status, an ISS stage III, and standard cytogenetic risk.

Evans Syndrome as a Possible Complication of Brentuximab Vedotin Therapy for Peripheral T Cell Lymphoma.

Recently, Brentuximab Vedotin (BV) has emerged as an important therapy not only for Hodgkin's Lymphoma, but also for CD30-positive T cell lymphomas. Although anemia and thrombocytopenia are common myelosuppressive side effects, to our knowledge, this is the first described case of Evans Syndrome associated with BV therapy. We present the case of a 64-year-old female, diagnosed with relapsed Peripheral T Cell Lymphoma Not Otherwise Specified (PTCL-NOS), who, after receiving six cycles of BV, developed authentic severe autoimmune hemolytic anemia with strong positive direct anti-globulin (Coombs) test, simultaneously associated with severe immune thrombocytopenia. The patient was unresponsive to systemic corticotherapy, but fully recovered after a course of IV immunoglobulin.