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BACKGROUND: Bortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials. AIM: We compared the outcomes of 1216 patients treated with VCd (N = 690) or VRd (N = 526) in a real-world setting. RESULTS: Patients treated with VCd had more often severe renal dysfunction, ISS-3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar. VRd was associated with substantially higher overall response and CR/VGPR rates to induction(P < .001) and improved PFS and OS in univariate analysis, especially among patients with standard risk disease, without renal dysfunction and in the elderly; however, in multivariate analysis there was no significant difference in either PFS or OS. In patients strictly matched 1:1 for major prognostic variables (188 in each group, total N = 376), the superiority of VRd in terms of responses rates and depth of response was confirmed, but without significant PFS or OS difference. CONCLUSION: VRd is a more active induction regimen than VCd, although use of maintenance with lenalidomide may dilute the PFS or OS benefit. VCd induction remains an option in special circumstances. With the implementation of monoclonal antibodies, VCd backbone can be considered for patients without access to or who do not tolerate VRd.
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The treatment paradigm of multiple myeloma (MM) has shifted in the past years, as continuous therapy is becoming the standard of care for both newly diagnosed and relapsed patients. Although it is indisputable that continuous therapy has added a great benefit on the progression-free as well as overall survival, it is still unclear what the patients' perspective is on this therapeutic approach. METHODS: This study included 155 adult MM patients from Fundeni Clinical Institute in Romania, receiving continuous therapy with daratumumab, proteasome inhibitors, immunomodulators, or bi-specific antibodies. The patients had varied economic, social, and educational backgrounds. We developed a questionnaire to interrogate the quantitative and qualitative effect of the therapy on the patients' personal and professional life and to identify the side effects that had the strongest impact on their quality of life. RESULTS: 74.83% of the patients reported that the treatment they received negatively impacted their quality of life. Among them, 40% considered that the most detrimental aspects of the therapy are the financial burden and the negative impact on their professional life. One-third of the patients reported that the therapy negatively impacted their personal life and that it had a deleterious effect on their relationship with their partner and family members. In terms of the side effects experienced, patients considered that tiredness was the main factor causing a decrease in their quality of life, followed by insomnia and bone pain. Despite this, almost none of the patients considered dropping the therapy, and almost half of the patients considered that the frequent visits to the hospital offered them psychological comfort. In addition, more than 70% of the patients declared that they were afraid to stop the therapy if given the choice, with the main concerns being the fear of an early relapse. CONCLUSIONS: Although continuous therapy is associated with a high financial burden and a negative impact on both professional and personal life, the frequent visits to the hospital appear to be reassuring. Moreover, the patients would not opt for treatment discontinuation and felt safer when monitored frequently.
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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.
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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.
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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.
