Purpose: IgM MGUS and Waldenstrom Macroglobulinemia (WM) represent a disease spectrum with highly... more Purpose: IgM MGUS and Waldenstrom Macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences. Experimental Design: We used bone marrow (BM) clonal CD19+ and CD138+ sorted cells, matched BM supernatant and peripheral blood serum from 32 patients (7MGUS, 25 WM) to perform the first multi-omics approach including whole exam sequencing, RNA-sequencing, proteomics, metabolomics and mass cytometry. Results: We identified three clusters with distinct pathway activation, immune continent, metabolic and clinical features. Cluster 1 (C1) included only WM patients and was characterized by transcriptional silencing of genes involved in cell cycle and immune resp...
Previous studies have found that the prevalence of subtypes of T cells may be associated with pat... more Previous studies have found that the prevalence of subtypes of T cells may be associated with patient outcomes, but a comprehensive analysis of the immune profile in the TM of FL has not been done. In the present study, we identified groups of FL patients with discretely unique TMEs and determined whether the T-cell phenotypes in the TME differed among groups. Using a cohort of 82 FL patients with biopsy specimens collected before treatment, we defined the type of TME based on the content of major lineages (T, B, monocytes/macrophages and NK cells) determined by CyTOF analysis. Hierarchical clustering of this cohort stratified patients into 4 groups with different TME: group 1 (G1) included patients with a high percentage of monocyte/macrophages/NK cells; patients from G2 and G3 were enriched for intratumoral T and B cells, respectively. Patients with intermediate numbers of T and B cells were included in G4. CITRUS analysis revealed that T-cell clusters with phenotypes expressing K...
Background: With the incorporation of positron emission tomography (PET) imaging as part of the s... more Background: With the incorporation of positron emission tomography (PET) imaging as part of the standard staging evaluation of follicular lymphoma (FL), it is generally recommended to obtain the diagnostic biopsy from a lesion with the highest standardized uptake value (SUV) to rule out de novo histologic transformation (HT). In some cases such an approach might be impractical, while in other cases a biopsy from a diseased area with a high SUV may still demonstrate an indolent histology. To date, there is no data to guide treatment choices in patients (pts) with FL with high SUVmax but with no documented evidence of HT. Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, provide a better outcome than R-Bendamustine (BR). Furthermore, it is unknown whether rituximab (R) maintenance is beneficial in this setting. Therefore, we aimed to compare the efficacy of R-CHOP vs BR in newly diagnosed FL pts with high SUVmax at baseline PET and to clarify ...
Context Tafasitamab+LEN, a chemotherapy-free, novel treatment for R/R DLBCL, demonstrated efficac... more Context Tafasitamab+LEN, a chemotherapy-free, novel treatment for R/R DLBCL, demonstrated efficacy in ASCT-ineligible patients in the single-arm Phase II L-MIND study (NCT02399085). Objective To compare outcomes in patients treated with tafasitamab+LEN in the L-MIND study with matched patient populations treated with commonly administered NCCN-/ESMO-recommended therapies for non-transplant-eligible patients with R/R DLBCL in routine clinical practice. Design RE-MIND2 (NCT04150328) is an observational, retrospective cohort study. The L-MIND tafasitamab+LEN cohort was matched with RE-MIND2 patients using estimated propensity score-based 1:1 nearest neighbor matching balanced for nine patient and disease baseline characteristics: age ( 9 /L), anemia (cut-off upper limit of normal). Setting Academic, public, and private hospitals in Europe, North America, and Asia-Pacific. Patients Age: ≥18 years old with histologically confirmed DLBCL. Prior systemic therapy for DLBCL: ≥1, including ≥1 anti-CD20 therapy. Interventions Data are presented for tafasitamab+LEN vs all (pooled) systemic therapies, tafasitamab+LEN vs bendamustine+rituximab (BR), and tafasitamab+LEN vs rituximab+gemcitabine+oxaliplatin (R-GemOx). Main Outcome Measures The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate, complete response rate, progression-free survival, event-free survival, duration of response, and time to next treatment. Results In RE-MIND2, 3,454 patients were enrolled from 200 centers. For the comparative analysis, 76 patients from the L-MIND tafasitamab+LEN study were included in the full analysis set. Strictly matched pairs of patients (standardized mean difference ≤0.2) included: tafasitamab+LEN vs pooled therapies, n=76 pairs; tafasitamab+LEN vs BR, n=75 pairs; and tafasitamab+LEN vs R-GemOx, n=74 pairs. Tafasitamab+LEN was associated with longer OS compared with pooled therapies (HR: 0.55; p=0.0076), BR (HR: 0.42; p Conclusions Results of this analysis suggest that tafasitamab+LEN has improved OS vs commonly used regimens. Funding This study was funded by MorphoSys AG.
Epigenetic reprogramming is a hallmark of lymphomagenesis, however its role in reshaping the tumo... more Epigenetic reprogramming is a hallmark of lymphomagenesis, however its role in reshaping the tumor microenvironment is still not well understood. Here we review the most common chromatin modifier mutations in B cell lymphoma and their effect on B cells as well as on T cell landscape. We will also discuss precision therapy strategies to reverse their aberrant signaling by targeting mutated proteins or counterbalance epigenetic mechanisms.
Background The importance of the immune system in modulating the trajectory of lymphoma outcomes ... more Background The importance of the immune system in modulating the trajectory of lymphoma outcomes has been increasingly recognized. We recently showed that CD4+ cells are associated with clinical outcomes in a prospective cohort of almost 500 patients with follicular lymphoma (FL). Specifically, we showed that the absence of CD4+ cells inside follicles was independently associated with increased risk of early clinical failure. These data suggest that the composition, as well as the spatial distribution of immune cells within the tumor microenvironment (TME), play an important role in FL. To further define the architecture of the TME in FL we analyzed a FL tumor section using the Co-Detection by Indexing (CODEX) multiplex immunofluorescence system. Methods An 8-micron section from a formalin-fixed paraffin-embedded block containing a lymph node specimen from a patient with FL was stained with a cocktail of 15 CODEX antibodies. Five regions of interest (ROIs) were imaged using a 20X ai...
Background Several therapies are recommended by NCCN/ESMO guidelines for autologous stem cell tra... more Background Several therapies are recommended by NCCN/ESMO guidelines for autologous stem cell transplant (ASCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In the single-arm, Phase II L-MIND study (NCT02399085), the chemotherapy-free regimen tafasitamab + lenalidomide (LEN) demonstrated efficacy for this patient population. In the absence of randomized clinical trial data, RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared patient outcomes from L-MIND with matched patient populations treated with NCCN/ESMO recommended therapies for ASCT-ineligible patients with R/R DLBCL. Methods Data were retrospectively collected between 1 April and 13 November 2020 from academic and public hospitals, as well as private practices in North America, Europe and Asia Pacific. To ensure consistency with L-MIND I/E criteria, patients aged ≥18 years with histologically confirmed DLBCL and who had received ≥2 systemic therapies for ...
Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prop... more Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermo...
The PIM kinases are highly expressed in activated B-cell (ABC) diffuse large B-cell lymphoma (DLB... more The PIM kinases are highly expressed in activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL). Oncogenic cooperation between PIMs and MYC has been demonstrated. Transgenic mice co-expressing Eμ-PIM and Eμ-MYC showed accelerated lymphomagenesis. Conversely, knockdown of PIMs dramatically decreased cMYC levels and lowered tumor incidence. Based on these preclinical data, a treatment strategy aiming at disrupting the oncogenic cooperation between PIMs and MYC may improve the outcome of DLBCL. Therefore, we treated a panel of DLBCL cell lines with increasing dose of the clinically relevant pan-PIM inhibitor (PIMi) AZD1208 (from 0.1 to 10μM) for 48 hours (Hrs), which resulted in a dose-dependent growth inhibition with a stronger efficacy in ABC DLBCL cell lines. The analysis of a CRISPR loss-of-function screening in three ABC (LY3, TMD8, HBL1) and three GCB (SUDHL-4, Pfeiffer, BJAB) DLBCL cell lines (Reddy et al, 2017) showed that PIM2 silencing led to significantly decreased viab...
Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma. While immunochemothe... more Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma. While immunochemotherapy (IC) treated FL patients who achieve event-free status at 24 months after diagnosis (EFS24) have the subsequent life expectancy of the general population, those who fail to achieve EFS24 have aggressive disease with poor outcomes. Similarly, in FL patients initially observed or treated with rituximab monotherapy, EFS at 12 months (EFS12) is a strong predictor of subsequent outcome. Thus, an unmet patient need is to predict at diagnosis those at greatest risk of early failure in order to identify better treatments. The lymphoma microenvironment may be a key determinant of early failure. Therefore, we aimed to improve risk stratification of newly diagnosed FL patients by using a discovery and validation study design to identify microenvironment determinants of early failure and then integrate them into the Follicular Lymphoma International Prognostic Index (FLIPI). Patients and Method...
MYC overexpression is a poor prognostic predictor in Diffuse Large B-Cell Lymphoma (DLBCL). MYC-t... more MYC overexpression is a poor prognostic predictor in Diffuse Large B-Cell Lymphoma (DLBCL). MYC-targeting with bromodomain and extraterminal protein family (BET) inhibitors is a promising strategy for the treatment of MYC-driven cancers, including lymphomas. However, preclinical and emerging data from early clinical trials demonstrated a modest antiproliferative activity in vitro and in vivo. We hypothesized that BET inhibition may induce feedback survival mechanisms preventing or attenuating cell death that could be exploited for designing future, more effective, combination strategies. In a high-throughput combinatorial drug screening experiment, we found that phosphatidylinositol 3-kinase (PI3K) pathway inhibitors enhanced the antiproliferative effects of BET inhibitors (JQ1, I-BET 151, CPI-203) with a strong class effect. JQ1 upregulated the mRNA expression of several upstream components of the PI3K pathway, including PIK3CA, PIK3R1, PDK1 in a large panel of DLBCL and Burkitt ly...
Background Biosimilar drugs, including erythropoirtin zed, have a similar, but usually not inferi... more Background Biosimilar drugs, including erythropoirtin zed, have a similar, but usually not inferior although not hidentical effects of originator drugs. Safety is hidentical to originator drugs. Aims Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha and erythropoietin zed, are not inferior to erythropoietin alpha in terms of safety, efficacy and costs. Methods This study is a retrospective study.Between july 2008 and december 2013, 101 patients affected by refractory anemia were studied.Median follow-up was 16 months (R10-28). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In group C patient received biosimilar erythropoietin zed 40000 IU sc/weekly. In all three arms patients received liposomial iron (Sideral®) 14 mg 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median a...
Background Biosimilar drugs have a similar, but usually not inferior although not hidentical effe... more Background Biosimilar drugs have a similar, but usually not inferior although not hidentical effects of old registred drugs. Safety is hidentical to old registred drug. Aims Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha is not inferior to erythropoietin alpha in terms of safety, efficacy and costs. Methods This study is a dicentric, nonrandomized, retrospective study. Between july 2008 and june 2012, 92 patients affected by refractory anemia were studied. Median follow-up was 22 months (R3-34). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In both groups patients received liposomal iron (Sideral®) 14 mg, 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median age was 70 years (R63-75), M/F: 18/28; in group B median age was 64 years (R60-70), M/F: 25/21. IPSS was low in...
e19517 Background: Approximately one third of Diffuse Large B-cell Lymphoma (DLBCL) arise in tiss... more e19517 Background: Approximately one third of Diffuse Large B-cell Lymphoma (DLBCL) arise in tissue different from the lymph node and they are usually termed as extranodal DLBCL. Patients (pts.) wi...
Purpose: IgM MGUS and Waldenstrom Macroglobulinemia (WM) represent a disease spectrum with highly... more Purpose: IgM MGUS and Waldenstrom Macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences. Experimental Design: We used bone marrow (BM) clonal CD19+ and CD138+ sorted cells, matched BM supernatant and peripheral blood serum from 32 patients (7MGUS, 25 WM) to perform the first multi-omics approach including whole exam sequencing, RNA-sequencing, proteomics, metabolomics and mass cytometry. Results: We identified three clusters with distinct pathway activation, immune continent, metabolic and clinical features. Cluster 1 (C1) included only WM patients and was characterized by transcriptional silencing of genes involved in cell cycle and immune resp...
Previous studies have found that the prevalence of subtypes of T cells may be associated with pat... more Previous studies have found that the prevalence of subtypes of T cells may be associated with patient outcomes, but a comprehensive analysis of the immune profile in the TM of FL has not been done. In the present study, we identified groups of FL patients with discretely unique TMEs and determined whether the T-cell phenotypes in the TME differed among groups. Using a cohort of 82 FL patients with biopsy specimens collected before treatment, we defined the type of TME based on the content of major lineages (T, B, monocytes/macrophages and NK cells) determined by CyTOF analysis. Hierarchical clustering of this cohort stratified patients into 4 groups with different TME: group 1 (G1) included patients with a high percentage of monocyte/macrophages/NK cells; patients from G2 and G3 were enriched for intratumoral T and B cells, respectively. Patients with intermediate numbers of T and B cells were included in G4. CITRUS analysis revealed that T-cell clusters with phenotypes expressing K...
Background: With the incorporation of positron emission tomography (PET) imaging as part of the s... more Background: With the incorporation of positron emission tomography (PET) imaging as part of the standard staging evaluation of follicular lymphoma (FL), it is generally recommended to obtain the diagnostic biopsy from a lesion with the highest standardized uptake value (SUV) to rule out de novo histologic transformation (HT). In some cases such an approach might be impractical, while in other cases a biopsy from a diseased area with a high SUV may still demonstrate an indolent histology. To date, there is no data to guide treatment choices in patients (pts) with FL with high SUVmax but with no documented evidence of HT. Specifically, it remains unclear whether anthracycline-containing regimens, such as R-CHOP, provide a better outcome than R-Bendamustine (BR). Furthermore, it is unknown whether rituximab (R) maintenance is beneficial in this setting. Therefore, we aimed to compare the efficacy of R-CHOP vs BR in newly diagnosed FL pts with high SUVmax at baseline PET and to clarify ...
Context Tafasitamab+LEN, a chemotherapy-free, novel treatment for R/R DLBCL, demonstrated efficac... more Context Tafasitamab+LEN, a chemotherapy-free, novel treatment for R/R DLBCL, demonstrated efficacy in ASCT-ineligible patients in the single-arm Phase II L-MIND study (NCT02399085). Objective To compare outcomes in patients treated with tafasitamab+LEN in the L-MIND study with matched patient populations treated with commonly administered NCCN-/ESMO-recommended therapies for non-transplant-eligible patients with R/R DLBCL in routine clinical practice. Design RE-MIND2 (NCT04150328) is an observational, retrospective cohort study. The L-MIND tafasitamab+LEN cohort was matched with RE-MIND2 patients using estimated propensity score-based 1:1 nearest neighbor matching balanced for nine patient and disease baseline characteristics: age ( 9 /L), anemia (cut-off upper limit of normal). Setting Academic, public, and private hospitals in Europe, North America, and Asia-Pacific. Patients Age: ≥18 years old with histologically confirmed DLBCL. Prior systemic therapy for DLBCL: ≥1, including ≥1 anti-CD20 therapy. Interventions Data are presented for tafasitamab+LEN vs all (pooled) systemic therapies, tafasitamab+LEN vs bendamustine+rituximab (BR), and tafasitamab+LEN vs rituximab+gemcitabine+oxaliplatin (R-GemOx). Main Outcome Measures The primary endpoint was overall survival (OS). Secondary endpoints included objective response rate, complete response rate, progression-free survival, event-free survival, duration of response, and time to next treatment. Results In RE-MIND2, 3,454 patients were enrolled from 200 centers. For the comparative analysis, 76 patients from the L-MIND tafasitamab+LEN study were included in the full analysis set. Strictly matched pairs of patients (standardized mean difference ≤0.2) included: tafasitamab+LEN vs pooled therapies, n=76 pairs; tafasitamab+LEN vs BR, n=75 pairs; and tafasitamab+LEN vs R-GemOx, n=74 pairs. Tafasitamab+LEN was associated with longer OS compared with pooled therapies (HR: 0.55; p=0.0076), BR (HR: 0.42; p Conclusions Results of this analysis suggest that tafasitamab+LEN has improved OS vs commonly used regimens. Funding This study was funded by MorphoSys AG.
Epigenetic reprogramming is a hallmark of lymphomagenesis, however its role in reshaping the tumo... more Epigenetic reprogramming is a hallmark of lymphomagenesis, however its role in reshaping the tumor microenvironment is still not well understood. Here we review the most common chromatin modifier mutations in B cell lymphoma and their effect on B cells as well as on T cell landscape. We will also discuss precision therapy strategies to reverse their aberrant signaling by targeting mutated proteins or counterbalance epigenetic mechanisms.
Background The importance of the immune system in modulating the trajectory of lymphoma outcomes ... more Background The importance of the immune system in modulating the trajectory of lymphoma outcomes has been increasingly recognized. We recently showed that CD4+ cells are associated with clinical outcomes in a prospective cohort of almost 500 patients with follicular lymphoma (FL). Specifically, we showed that the absence of CD4+ cells inside follicles was independently associated with increased risk of early clinical failure. These data suggest that the composition, as well as the spatial distribution of immune cells within the tumor microenvironment (TME), play an important role in FL. To further define the architecture of the TME in FL we analyzed a FL tumor section using the Co-Detection by Indexing (CODEX) multiplex immunofluorescence system. Methods An 8-micron section from a formalin-fixed paraffin-embedded block containing a lymph node specimen from a patient with FL was stained with a cocktail of 15 CODEX antibodies. Five regions of interest (ROIs) were imaged using a 20X ai...
Background Several therapies are recommended by NCCN/ESMO guidelines for autologous stem cell tra... more Background Several therapies are recommended by NCCN/ESMO guidelines for autologous stem cell transplant (ASCT)-ineligible patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In the single-arm, Phase II L-MIND study (NCT02399085), the chemotherapy-free regimen tafasitamab + lenalidomide (LEN) demonstrated efficacy for this patient population. In the absence of randomized clinical trial data, RE-MIND2 (NCT04697160), an observational, retrospective cohort study, compared patient outcomes from L-MIND with matched patient populations treated with NCCN/ESMO recommended therapies for ASCT-ineligible patients with R/R DLBCL. Methods Data were retrospectively collected between 1 April and 13 November 2020 from academic and public hospitals, as well as private practices in North America, Europe and Asia Pacific. To ensure consistency with L-MIND I/E criteria, patients aged ≥18 years with histologically confirmed DLBCL and who had received ≥2 systemic therapies for ...
Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prop... more Although methotrexate (MTX) is the most widely used therapy for central nervous system (CNS) prophylaxis in patients with diffuse large B-cell lymphoma (DLBCL), the optimal regimen remains unclear. We examined the efficacy of different prophylactic regimens in 585 patients with newly diagnosed DLBCL and high-risk for CNS relapse, treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or R-CHOP-like regimens from 2001 to 2017, of whom 295 (50%) received prophylaxis. Intrathecal (IT) MTX was given to 253 (86%) and high-dose MTX (HD-MTX) to 42 (14%). After a median follow-up of 6.8 years, 36 of 585 patients relapsed in the CNS, of whom 14 had received prophylaxis. The CNS relapse risk at 1 year was lower for patients who received prophylaxis than patients who did not: 2% vs. 7.1%. However, the difference became less significant over time (5-year risk 5.6% vs. 7.5%), indicating prophylaxis tended to delay CNS relapse rather than prevent it. Furthermo...
The PIM kinases are highly expressed in activated B-cell (ABC) diffuse large B-cell lymphoma (DLB... more The PIM kinases are highly expressed in activated B-cell (ABC) diffuse large B-cell lymphoma (DLBCL). Oncogenic cooperation between PIMs and MYC has been demonstrated. Transgenic mice co-expressing Eμ-PIM and Eμ-MYC showed accelerated lymphomagenesis. Conversely, knockdown of PIMs dramatically decreased cMYC levels and lowered tumor incidence. Based on these preclinical data, a treatment strategy aiming at disrupting the oncogenic cooperation between PIMs and MYC may improve the outcome of DLBCL. Therefore, we treated a panel of DLBCL cell lines with increasing dose of the clinically relevant pan-PIM inhibitor (PIMi) AZD1208 (from 0.1 to 10μM) for 48 hours (Hrs), which resulted in a dose-dependent growth inhibition with a stronger efficacy in ABC DLBCL cell lines. The analysis of a CRISPR loss-of-function screening in three ABC (LY3, TMD8, HBL1) and three GCB (SUDHL-4, Pfeiffer, BJAB) DLBCL cell lines (Reddy et al, 2017) showed that PIM2 silencing led to significantly decreased viab...
Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma. While immunochemothe... more Background: Follicular lymphoma (FL) is the most frequent indolent lymphoma. While immunochemotherapy (IC) treated FL patients who achieve event-free status at 24 months after diagnosis (EFS24) have the subsequent life expectancy of the general population, those who fail to achieve EFS24 have aggressive disease with poor outcomes. Similarly, in FL patients initially observed or treated with rituximab monotherapy, EFS at 12 months (EFS12) is a strong predictor of subsequent outcome. Thus, an unmet patient need is to predict at diagnosis those at greatest risk of early failure in order to identify better treatments. The lymphoma microenvironment may be a key determinant of early failure. Therefore, we aimed to improve risk stratification of newly diagnosed FL patients by using a discovery and validation study design to identify microenvironment determinants of early failure and then integrate them into the Follicular Lymphoma International Prognostic Index (FLIPI). Patients and Method...
MYC overexpression is a poor prognostic predictor in Diffuse Large B-Cell Lymphoma (DLBCL). MYC-t... more MYC overexpression is a poor prognostic predictor in Diffuse Large B-Cell Lymphoma (DLBCL). MYC-targeting with bromodomain and extraterminal protein family (BET) inhibitors is a promising strategy for the treatment of MYC-driven cancers, including lymphomas. However, preclinical and emerging data from early clinical trials demonstrated a modest antiproliferative activity in vitro and in vivo. We hypothesized that BET inhibition may induce feedback survival mechanisms preventing or attenuating cell death that could be exploited for designing future, more effective, combination strategies. In a high-throughput combinatorial drug screening experiment, we found that phosphatidylinositol 3-kinase (PI3K) pathway inhibitors enhanced the antiproliferative effects of BET inhibitors (JQ1, I-BET 151, CPI-203) with a strong class effect. JQ1 upregulated the mRNA expression of several upstream components of the PI3K pathway, including PIK3CA, PIK3R1, PDK1 in a large panel of DLBCL and Burkitt ly...
Background Biosimilar drugs, including erythropoirtin zed, have a similar, but usually not inferi... more Background Biosimilar drugs, including erythropoirtin zed, have a similar, but usually not inferior although not hidentical effects of originator drugs. Safety is hidentical to originator drugs. Aims Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha and erythropoietin zed, are not inferior to erythropoietin alpha in terms of safety, efficacy and costs. Methods This study is a retrospective study.Between july 2008 and december 2013, 101 patients affected by refractory anemia were studied.Median follow-up was 16 months (R10-28). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In group C patient received biosimilar erythropoietin zed 40000 IU sc/weekly. In all three arms patients received liposomial iron (Sideral®) 14 mg 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median a...
Background Biosimilar drugs have a similar, but usually not inferior although not hidentical effe... more Background Biosimilar drugs have a similar, but usually not inferior although not hidentical effects of old registred drugs. Safety is hidentical to old registred drug. Aims Aim of this study is to verify if in MDS patient with refractory anemia biosimilar erythropoietin alpha is not inferior to erythropoietin alpha in terms of safety, efficacy and costs. Methods This study is a dicentric, nonrandomized, retrospective study. Between july 2008 and june 2012, 92 patients affected by refractory anemia were studied. Median follow-up was 22 months (R3-34). Patients received in group A erythropoietin alpha 40000 IU sc/weekly. In group B patient received biosimilar erythropoietin alpha 40000 IU sc/weekly. In both groups patients received liposomal iron (Sideral®) 14 mg, 2 tablets orally/day calcium levofolinate 7.5 mg/day orally + Vitamin B12: 400 mg/day orally. In group A median age was 70 years (R63-75), M/F: 18/28; in group B median age was 64 years (R60-70), M/F: 25/21. IPSS was low in...
e19517 Background: Approximately one third of Diffuse Large B-cell Lymphoma (DLBCL) arise in tiss... more e19517 Background: Approximately one third of Diffuse Large B-cell Lymphoma (DLBCL) arise in tissue different from the lymph node and they are usually termed as extranodal DLBCL. Patients (pts.) wi...
Uploads
Papers by Patrizia Mondello