66 research outputs found
Novel Approaches Outside the Setting of Immunotherapy for the Treatment of Multiple Myeloma: The Case of Melflufen, Venetoclax, and Selinexor
Although the survival rate of patients with multiple myeloma has significantly improved in the
last years thanks to the introduction of various classes of new drugs, such as proteasome
inhibitors, immunomodulatory agents, and monoclonal antibodies, the vast majority of these
subjects relapse with a more aggressive disease due to the acquisition of further genetic
alterations that may cause resistance to current salvage therapies. The treatment of these
often âtripleâ (or even more) refractory patients remains challenging, and alternative
approaches are required to overcome the onset of that resistance. Immunotherapies with
novel monoclonal, drug-conjugated, or bi-specific antibodies, as well as the use of chimeric
antigen receptor T cells, have been recently developed and are currently investigated.
However, other non-immunologic therapeutic regimens based on melfluflen, venetoclax, or
selinexor, three molecules with new mechanisms of action, have also shown promising
results in the setting of relapsed/refractory myeloma. Here we report themost recent literature
data regarding these three drugs, focusing on their efficacy and safety in multiple myelom
SARS-CoV-2 infection in fully vaccinated patients with multiple myeloma
No abstract availabl
What Is New in the Treatment of Smoldering Multiple Myeloma?
Smoldering multiple myeloma (SMM), an asymptomatic plasma cell neoplasm, is currently
diagnosed according to the updated IMWG criteria, which reflect an intermediate tumor mass
between monoclonal gammopathy of undetermined significance (MGUS) and active MM. However,
SMM is a heterogeneous entity and individual case may go from an âMGUS-likeâ behavior to âearly
MMâ with rapid transformation into symptomatic disease. This wide range of clinical outcomes
poses challenges for prognostication and management of individual patients. However, initial studies
showed a benefit in terms of progression or even survival for early treatment of high-risk SMM
patients. While outside of clinical trials the conventional approach to SMM generally remains that of
close observation, these studies raised the question of whether early treatment should be offered in
high-risk patients, prompting evaluation of several different therapeutic approaches with different
goals. While delay of progression to MM with a non-toxic treatment is clearly achievable by early
treatment, a convincing survival benefit still needs to be proven by independent studies. Furthermore,
if SMM is to be considered less biologically complex than MM, early treatment may offer the chance
of cure that is currently not within reach of any active MM treatment. In this paper, we present
updated results of completed or ongoing clinical trials in SMM treatment, highlighting areas of
uncertainty and critical issues that will need to be addressed in the near future before the âwatch and
waitâ paradigm in SMM is abandoned in favor of early treatmen
Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the epicovideha registry
Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 Ă 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic
Residual peripheral blood CD26+leukemic stem cells in chronic myeloid leukemia patients during TKI therapy and during treatment-free remission
Chronic myeloid leukemia (CML) patients in sustained âdeep molecular responseâ may stop TKI treatment without disease recurrence; however, half of them lose molecular response shortly after TKI withdrawing. Well-defined eligibility criteria to predict a safe discontinuation up-front are still missing. Relapse is probably due to residual quiescent TKI-resistant leukemic stem cells (LSCs) supposedly transcriptionally low/silent and not easily detectable by BCR-ABL1 qRT-PCR. Bone marrow Ph+âCML CD34+/CD38â LSCs were found to specifically co-express CD26 (dipeptidylpeptidase-IV). We explored feasibility of detecting and quantifying CD26+ LSCs by flow cytometry in peripheral blood (PB). Over 400 CML patients (at diagnosis and during/after therapy) entered this cross-sectional study in which CD26 expression was evaluated by a standardized multiparametric flow cytometry analysis on PB CD45+/CD34+/CD38â stem cell population. All 120 CP-CML patients at diagnosis showed measurable PB CD26+ LSCs (median 19.20/ÎŒL, range 0.27â698.6). PB CD26+ LSCs were also detectable in 169/236 (71.6%) CP-CML patients in first-line TKI treatment (median 0.014âcells/ÎŒL; range 0.0012â0.66) and in 74/112 (66%), additional patients studied on treatment-free remission (TFR) (median 0.015/ÎŒL; range 0.006â0.76). Notably, no correlation between BCR-ABL/ABLIS ratio and number of residual LSCs was found both in patients on or off TKIs. This is the first evidence that âcirculatingâ CML LSCs persist in the majority of CML patients in molecular response while on TKI treatment and even after TKI discontinuation. Prospective studies evaluating the dynamics of PB CD26+ LSCs during TKI treatment and the role of a âstem cell responseâ threshold to achieve and maintain TFR are ongoing
Elotuzumab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: a multicenter, retrospective real-world experience with 200 cases outside of controlled clinical trials
In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone
(EloPd) proved a superior clinical benefit over Pd with a manageable toxicity profile, leading to its
approval in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior
therapies, including lenalidomide and a proteasome inhibitor (PI).
We report here a real-world experience of 200 RRMMs treated with EloPd in 35 Italian centers
outside of clinical trials. In our dataset, the median number of prior lines of therapy was 2, with
51% of cases undergoing autologous stem cell transplant (ASCT) and 73% exposed to
daratumumab.
After a median follow-up of 9 months, 126 patients stopped EloPd, most of them (88.9%) because
of disease progression. The overall response rate (ORR) was 55.4%, in line with the pivotal trial
results. Regarding adverse events, our cohort experienced a toxicity profile similar to the
ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older
patients. The median progression-free survival (PFS) was 7 months, shorter than that observed in
the ELOQUENT-3, probably due to the different clinical characteristics of the two cohorts.
Interestingly, the ISS stage III (HR:2.55) was associated with worse PFS. Finally, our series's
median overall survival (OS) was shorter than that observed in the ELOQUENT-3 trial (17.5 versus
29.8 months). In conclusion, our real-world study confirms EloPd as a safe and possible therapeutic
choice for RRMM who received at least two prior therapies, including lenalidomide and a PI
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