ABSTRACT
Introduction: Despite several studies, the impact of coronavirus disease 2019 on patients with multiple myeloma remains uncertain. Material(s) and Method(s): We performed a survey that covered the period of the first and second waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in 23 centers inseven countries. Out of 352 patients with myeloma and SARS-CoV-2, 23% died. Results/Conclusions: Logistic regression showed a lower risk of death among patients treated with proteasome inhibitor and a higher risk of death for those who had a severe or a very severe course of disease.Copyright © 2023 Sciendo. All rights reserved.
ABSTRACT
Background: Venetoclax, a selective bcl-2 inhibitor first approved for CLL has been investigated for the treatment of relapsed myeloma patients, and although it failed to show benefit for myeloma patients as a whole, t(11;14) patients demonstrated exceptional responses in the Bellini trial (Lancet Oncol 2020;21:1630), thus paving the way towards the first genetically targeted treatment in myeloma. Aims: Off label use of venetoclax is on the rise, even though clinicians have to face unanswered questions regarding the right dosage and length of therapy, as well as the potential for adverse events (AEs), especially infections. Real world data could help to elucidate its optimal use, but is very limited as of yet. Methods: We addressed all Hungarian centers treating myeloma to evaluate the efficacy and safety of venetoclax in their practice treating t(11;14) myeloma, collecting data about the treatment duration, AEs, dose modifications and treatment discontinuations, and analyzed response rates as well as progression free and overall survivals (PFS, OS). Results: 50 patients were reported from 7 Hungarian sites. 33 patients were relapsed and heavily pretreated with an average of 4.8 prior lines, whereas 17 patients received venetoclax after a suboptimal initial response to their first line treatment (8 PR, 7 SD, 2 PD) as planned pre-transplantation salvage. Most patients had venetoclax in combination with a proteasome inhibitor and dexamethasone. The response rate was remarkably high given the refractoriness of this cohort: all but two patients responded, with 28% CRs, 38% VGPRs and 30% PRs. The median PFS and OS calculated from initiation of venetoclax dosing were 15.5 and 24 months, respectively, Figure 1. shows the PFS and OS curves of the 2nd line and late line cohorts. The most common AEs were cytopenias, gastrointestinal toxicities and infections, reported in 8, 9 and 10 patients with 1 fatal infection. Two patients had COVID-19 related hospitalization, both recovered. An important point to emphasize is the very high risk nature of this cohort. 13 out of the 47 patients had deletion 17p before venetoclax dosing was initiated, explaining their refractoriness to standard treatments. Notably, of these patients 2 reached CR, 9 VGPR, 1 PR, and only one progressed while on venetoclax treatment. The median PFS and OS were 9.6 and 10 months, respectively. Five patients had plasma cell leukaemia and 1 CNS involvement, the PFS and OS of these ultra-high risk patients were 10 and 12 months. Another important aspect of our analysis was the question of venetoclax dosing, as the appropriate dose in this indication is not yet clear. Reflecting this uncertainty, as well as funding difficulties with this off-label drug, only 2 patients received the 800 mg dose as seen in the Bellini trial;one received 600 mg daily, with all others taking 400 mg or less. To counteract this many centers employed a combination with either clarithromycin or fluconazole, CYP3A inhibitors known to increase venetoclax serum levels two- to threefold. Where available, serum venetoclax levels were monitored to ensure serum levels comparable to regular dosing.Summary/Conclusion: Our results highlight the importance of targeted treatments in multiple myeloma. We experienced lasting responses in quadruple-refractory patients, many with other high risk features. In the newly diagnosed group, where the depth of pre-ASCT response has great impact on PFS, venetoclax may have a role converting suboptimal responses into CRs by eliminating residual disease.
ABSTRACT
The novel SARS-CoV-2 corona virus is a risk factor for worse outcome in patients with haematological tumors. As haematological diseases with paraproteinemia affect a wide range of the population, we aimed to examine how COVID-19 infection affects disease outcome. We also aimed to present a few instructive case reports. We enrolled 24 patients to the study (newly diagnosed or undergoing therapy or directly after stem cell transplantation or prepared for future stem cell transplantation). We compared their paraprotein and free light chain concentrations, IL-6, procalcitonin, CRP and D-dimer results. For patients who were not hospitalized (42% of all examined patients) the median data were: age: 60 years, paraprotein: 1.05 g/L, lambda: 8.02 mg/L, kappa: 9.7 mg/L. For hospitalized patients (the remaining 58%): median age: 66 years, paraprotein: 4.9 g/L, lambda: 18.8 mg/L, kappa: 48.85 mg/L. 42% of the latter group were administered to intensive care (paraprotein: 4.65 g/L, lambda: 16.85 mg/L, kappa: 48.85 mg/L). 16% of all patients died because of a relapse or their disease transformed to leukaemia or they were directly after transplantation. Conclusion: The severity and outcome of COVID-19 is affected by a number of factors associated with paraproteinemia. Namely, the stage of the disease, whether the treatment had already been started or not, whether the patient is in remission or in a relapse or whether the patient needed any additional treatment or not.