25 results on '"Zannetti BA"'
Search Results
2. High CNA level and over-expression of genes involved in response mechanisms to genotoxic stress characterize newly diagnosed Multiple Myeloma (MM) patients carrying amplified MDM4 and/or deleted TP53
- Author
-
CAROLINA TERRAGNA, MARINA MARTELLO, LUCIA PANTANI, Patriarca, F., Elena Zamagni, Galli, M., PAOLA TACCHETTI, Petrucci, Mt, Crippa, C., Bringhen, S., Brioli, Annamaria, Offidani, M., Perrone, Giulia, Zannetti, Ba, Enrica Borsi, NICOLETTA TESTONI, GIULIA MARZOCCHI, Baccarani, Michele, GIOVANNI MARTINELLI, MICHELE CAVO, Terragna C, Martello M, Pantani L, Patriarca F, Zamagni E, Galli M, Tacchetti P, Petrucci MT, Crippa C, Bringhen S, Brioli A, Offidani M, Perrone G, Zannetti BA, Borsi E, Testoni N, Marzocchi G, Baccarani M, Martinelli G, and Cavo M.
- Subjects
MULTIPLE MYELOMA - Published
- 2012
3. Gene expression analysis of newly diagnosed Multiple Myeloma (MM) patients carrying amplified MDM4 and/or deleted p5
- Author
-
CAROLINA TERRAGNA, MARINA MARTELLO, GIOVANNI MARTINELLI, Sandra Durante, LUCIA PANTANI, Elena Zamagni, PAOLA TACCHETTI, Brioli, Annamaria, Perrone, Giulia, Zannetti, Ba, Enrica Borsi, GUIDO BIASCO, Baccarani, Michele, MICHELE CAVO, Terragna, C, Martello, M, Martinelli, G, Durante, S, Pantani, L, Zamagni, E, Tacchetti, P, Brioli, A, Perrone, G, Zannetti, Ba, Borsi, E, Biasco, G, Baccarani, M, and Cavo, M.
- Subjects
GENE EXPRESSION ,MULTIPLE MYELOMA
4. Role of Consolidation Therapy in Transplant Eligible Multiple Myeloma Patients
- Author
-
Michele Cavo, Annamaria Brioli, Ba Zannetti, Katia Mancuso, Elena Zamagni, Paola Tacchetti, Cavo M, Brioli A, Tacchetti P, Zannetti BA, Mancuso K, and Zamagni E.
- Subjects
Oncology ,medicine.medical_specialty ,Transplantation, Autologous ,Bortezomib ,Consolidation therapy ,Maintenance therapy ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lenalidomide ,Multiple myeloma ,CONSOLIDATION ,Clinical Trials as Topic ,business.industry ,Consolidation Chemotherapy ,Hematology ,medicine.disease ,Boronic Acids ,Thalidomide ,Surgery ,Transplantation ,Treatment Outcome ,Pyrazines ,Multiple Myeloma ,business ,Stem Cell Transplantation ,medicine.drug - Abstract
The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients.
- Published
- 2013
5. Peripheral neuropathy induced by subcutaneous bortezomib-based induction therapy for newly diagnosed multiple myeloma
- Author
-
Elena Zamagni, Paola Tacchetti, Serena Rocchi, Beatrice Anna Zannetti, Katia Mancuso, Lucia Pantani, Annalisa Pezzi, Michele Cavo, Annamaria Brioli, Brioli, A, Zannetti, Ba, Zamagni, E, Tacchetti, P, Pantani, L, Mancuso, K, Pezzi, A, Rocchi, Serena, and Cavo, M
- Subjects
Oncology ,medicine.medical_specialty ,subcutaneous bortezomib ,peripheral neuropathy ,Cyclophosphamide ,Bortezomib ,business.industry ,Hematology ,medicine.disease ,Surgery ,Transplantation ,Thalidomide ,multiple myeloma ,Peripheral neuropathy ,Refractory ,Internal medicine ,medicine ,business ,Dexamethasone ,Multiple myeloma ,medicine.drug - Abstract
Lok et al.1 recently reported in this Journal on the efficacy and toxicity of subcutaneous (sc) bortezomib given at a reduced dose in combination with thalidomide and dexamethasone (sc vTD) as induction therapy before, and as consolidation after, autologous stem-cell transplantation (ASCT) in 31 patients with newly diagnosed multiple myeloma (MM). The treatment plan included four cycles of induction therapy and two cycles of consolidation, both comprising sc bortezomib (1.0 mg/m2 twice weekly), thalidomide (100 mg per day) and dexamethasone (total dose 320 mg per cycle on the first two cycles and 160 mg per cycle on the subsequent two cycles of the induction phase). The rate of at least very good partial response (VGPR) after induction therapy was 52% for all patients and increased up to 73% among patients who actually received consolidation therapy. The incidence of treatment-emergent peripheral neuropathy (PN) after the induction phase (16% grade 1–2, including 3% grade 2) was lower than that previously reported by the same group after four cycles of either vTD at the same doses but using intravenous (iv) bortezomib (53% all grades, including 14% grade 2 or higher) or iv standard dose bortezomib (1.3 mg/m2) and dexamethasone (VD) (70% all grades, 34% >grade 2, 11% grade 3–4).2 We report, herein, on the outcomes of 22 newly diagnosed, ASCT-eligible, MM patients who were programmed to receive at our center four 21-day cycles of sc bortezomib (1.3 mg/m2 twice weekly) plus dexamethasone (total dose 320 mg per cycle) and either thalidomide (100 mg per day) (sc VTD: 13 patients) or cyclophosphamide (500 mg/m2 on Days 1 and 8 per cycle) (sc VCD: 9 patients). All patients were prospectively evaluated for efficacy and toxicity of sc bortezomib-based induction therapy. Presence of higher than grade 1 PN at diagnosis was an exclusion criterion for enrollment. Symptoms and signs of PN were carefully assessed at every programmed clinical appointment and were graded according to National Cancer Institute’s Common Toxicity Criteria (NCI CTCAE) v.3.0. No electrophysiological study was performed. Base-line patients’ characteristics and treatment response are summarized in Tables 1 and and2.2. A median of four cycles was administered. The overall response rate among all patients was 95%, including 27% stringent complete response (sCR) and 77% VGPR or better. Treatment-emergent grade 1–3 PN was observed in 14 patients (64%), including 18% (4 patients: 2 treated with VCD and 2 with VTD) grade 2 and 14% (3 patients: 2 receiving VTD and one VCD) grade 3. In one of these 3 patients, treatment was discontinued after the third cycle. Among the 7 patients with grade 2–3 PN, the median time from start of induction therapy to the first onset of PN was 72 days (range 48–109). In 3 patients, symptoms and signs of PN (grade 2 in 2 cases and grade 3 in the remaining one) emerged after the induction phase was completed, more specifically 103, 106 and 109 days after starting induction therapy. With appropriate treatment modifications,3,4 symptoms and signs of PN resolved or improved to grade 1 in 9 out of 14 (64%) patients within a median time of 94 days. Table 1. Base-line patients’ characteristics. Table 2. Efficacy and neurological toxicity of sc VTD or VCD induction therapy. Data reported here raise several considerations, but should be interpreted with caution due to the limited number of patients. The high overall response rate of 95%, including 27% sCR and 77% VGPR or better, further supports the conclusion that the efficacy of sc bortezomib reported in the relapsed/refractory setting5 is retained when the drug is administered in patients with newly diagnosed MM.1 Although cross-trial comparison is inadequate due to heterogeneities in the design of the studies and patients’ characteristics, it is likely that the discrepancy in the rates of high-quality responses between our series and that reported by Lok et al.1 reflects the lower activity of reduced-dose bortezomib used in the French study, with the possible contribution of the lower total dose of dexamethasone given in the third and fourth cycles of the induction phase. Differences between the two studies with respect to the doses of sc bortezomib incorporated into induction therapy may only explain in part the controversies about the frequency and severity of treatment-induced PN. Additional factors potentially compromising a meaningful interpretation of our data, as well as of those reported by others,1,6,7 include: i) the retrospective nature of several analyses which were performed either on patients who, due to their age, were eligible or ineligible to receive ASCT or on patients who had plasma cell dyscrasias other than MM, such as systemic amyloidosis;6,7 ii) the possible different methodological approaches used to assess PN. In our study, clinical evaluation of PN was performed at baseline, at the beginning of each cycle of induction therapy, before each dose of bortezomib, and every 21–28 days after the last dose of bortezomib was given. Neurological monitoring was continued until ASCT was received and allowed us to register 3 patients who suffered from late emergence of neurological toxicity, after induction therapy was completed. Although worsening of taxane-induced neurotoxicity was observed even after treatment was stopped,8 to the best of our knowledge, a similar phenomenon has not been reported for bortezomib. As far as this last issue is concerned, it is important to highlight that all the patients described here had a late emergence of previously undetected, typical bortezomib-induced PN (BiPN) and that in each of them any additional cause potentially contributing to the development of neurotoxicity was excluded. With the limits of the small sample size of patients analyzed, the 32% rate of grade 2 or higher PN is very similar to values previously reported after four cycles of iv VD or VTD incorporating standard-dose bortezomib.2,9,10 Knowledge of the mechanisms underlying BiPN has remained limited for many years.11 Recently, new insights into a better understanding of the pathogenesis of BiPN have been provided by analyses of gene expression profiles and single nucleotide polymorphisms of MM plasma cells.12–14 Results of these studies, performed in patients treated in Western countries but whose ethnicity was not detailed, showed that differently expressed genes involved in drug-induced apoptosis, DNA repair, inflammatory pathways, and development and function of nervous system are related to a different risk for, and time to onset of, BiPN. In addition, the patient’s inherited genetic background might also contribute to the individual risk for neurological toxicity.12,13 The possibility that patient- and disease-related genetic profiles might have been differently expressed in our series of patients compared to those reported by Lok et al.,1 thus partly contributing to the controversies observed in terms of frequency, severity and time to onset of PN, cannot be confirmed or ruled out. In conclusion, our data support the efficacy of sc bortezomib when incorporated into induction therapy for newly diagnosed, ASCT-eligible, MM patients. On the other hand, no conclusions about the different rate and severity of sc versus iv BiPN can be drawn. The possibility of late emergence of PN, even after an uneventful induction phase, should be taken into consideration and alert the physician to the need to continue close neurological monitoring after sc bortezomib-based induction therapy has been discontinued. Results of ongoing studies that aim to prospectively evaluate the efficacy and toxicity of sc bortezomib as part of first-line therapy will hopefully clarify the controversies discussed here.
- Published
- 2014
6. Long-term follow-up after autologous stem cell transplantation for light- and heavy-chain deposition disease
- Author
-
Patrizia Tosi, Alessandro Petrucci, Lucia Pantani, Paola Tacchetti, Giulia Perrone, Beatrice Anna Zannetti, Michele Baccarani, Elena Zamagni, Sonia Pasquali, Michele Cavo, Annamaria Brioli, Brioli A, Zamagni E, Pasquali S, Tosi P, Tacchetti P, Perrone G, Pantani L, Petrucci A, Zannetti BA, Baccarani M, and Cavo M
- Subjects
Adult ,Male ,medicine.medical_specialty ,Long term follow up ,Paraproteinemias ,Transplantation, Autologous ,Autologous stem-cell transplantation ,medicine ,Humans ,Aged ,Retrospective Studies ,Transplantation ,STEM CELL TRANSPLANTATION ,business.industry ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,long term follow up ,Surgery ,Female ,Immunoglobulin Light Chains ,Heavy Chain Deposition Disease ,business ,Immunoglobulin Heavy Chains ,Deposition (chemistry) ,Follow-Up Studies ,Heavy Chain Disease - Abstract
Monoclonal Ig deposition disease (MIDD) is a broad and uncommon entity, including light chain deposition disease (LCDD), light- and heavy-chain deposition disease and heavy-chain deposition disease.1 Overall, the kidney is the major target organ, the clinical picture being most frequently characterised by nephrotic syndrome, hypertension and renal failure.2 Light-chain Fanconi syndrome due to proximal tubular involvement may also occur, and typically manifests with type II renal tubular acidosis, hypophosphatemia, glycosuria and hypouricemia. Heart, liver and other organs are less frequently involved.3, 4 In approximately one-third of patients with MIDD the underlying clone of monoclonal plasma cells cannot be routinely detected.2 However, recent availability of serum free light chain (FLC) assay has allowed to demonstration of the presence of increased monoclonal FLC in virtually all patients.5 Treatment strategies in these patients have been highly variable, ranging from steroids with or without chemotherapy2 to high-dose therapy followed by autologous stem-cell transplantation (ASCT).5, 6 We retrospectively analyzed the outcomes of 8 consecutive patients who were admitted to our Institute from 1993 to 2006 and received a diagnosis of MIDD, as confirmed by kidney biopsy. Additional investigations to confirm the diagnosis included light microscopy, congo red staining, immunofluorescence with anti-κ and anti-λ antibodies and EM; immunohistochemistry with antibodies directed against plasma cell-associated Ags was performed, when appropriate.
- Published
- 2012
7. High Number of Copy Number Alterations and Over-Expression of Genes Involved in the Response Mechanisms to Genotoxic Stress Both Characterize Newly Diagnosed Multiple Myeloma (MM) Patients Carrying Amplified MDM4 and/or Deleted p53
- Author
-
Enrica Borsi, Paola Tacchetti, Carolina Terragna, Lucia Pantani, Marina Martello, Michele Cavo, Annamaria Brioli, Giovanni Martinelli, Elena Zamagni, Giulia Perrone, Sandra Durante, Beatrice Anna Zannetti, Michele Baccarani, TERRAGNA C, MARTELLO M, DURANTE S, PANTANI L, ZAMAGNI E, TACCHETTI P, BRIOLI A, PERRONE G, ZANNETTI BA, BORSI E, BACCARANI M, MARTINELLI G, and CAVO M
- Subjects
WWOX ,Immunology ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Group A ,Molecular biology ,medicine.anatomical_structure ,Autologous stem-cell transplantation ,H2AFX ,MULTIPLE MYELOMA ,Cancer cell ,medicine ,Bone marrow ,Multiple myeloma ,SNP array - Abstract
Abstract 3935 Background The p53 tumor suppressor pathway is tightly kept in check, or completely silenced in cancer cells. A potent inhibitor of p53 is represented by MDM4, which is critical for the control of p53 activity during the response to stress and is often amplified in several types of cancer. TP53 mutations are rare in newly diagnosed MM, while occur more frequently as late event in the course of the disease and are related to survival. Recently, the adverse prognostic impact of chr. 1q amplification, described in almost 40% of newly diagnosed MM pts, has been reported. The minimal amplified region on chr. 1q harbors MDM4. Since both del(17p) and amp(1q) identify a subgroup of high-risk MM pts, even when the novel agents are part of up-front treatment strategy, we molecularly analyzed a subgroup of MM patients treated with bortezomib-thalidomide-dexamethasone (VTD) incorporated into autologous stem cell transplantation, in order to investigate mechanisms which might be activated in myeloma plasma cells to direct and/or indirect limit the p53 function. Methods Thirty eight pts treated with VTD incorporated into autologous stem cell transplantation were analysed by means of gene expression profile (Affymetrix U133 Plus2.0 array) and unpaired analysis of copy number alterations (CNA) (Affymetrix 6.0 SNP array). Both GEP and SNP arrays experiments were performed on highly purified CD138+ bone marrow plasma cells obtained at diagnosis from each pts. The presence of CNAs in chr.1 and 17 was evaluated to identify pts carrying amp(1q) and del(17p). Results Eighteen out of 38 pts (42%) carried a minimal amplification region of 1,1 Mb on chr.1q, which harbors MDM4. Five out of 38 pts (13%) carried a minimal deletion region of 482 Kb on chr.17, which harbors TP53. To explore the involvement of the p53 pathway in MM, pts were stratified according to the presence of amplified MDM4 and/or deleted p53 (group A, 18 pts) or the absence of both these abnormalities (group B, 20 pts). Baseline clinical characteristics were homogeneous, except for a higher rate of ≥ 3 bone lesions in pts carrying amplified MDM4 and/or deleted p53. The rate of best complete or near complete response was 89% in group A and 75% in group B. With a median follow-up of 36 months, the risk of relapse or progression was 50% for pts in group A and 25% for those in group B. The average number of aberrations per group was overall higher in group A as compared to group B (165 vs. 103 CNAs, p =0.03); indeed, the presence of amplified MDM4 and/or deleted p53 was significantly associated with a list of 95 CNAs (clustered on chr. 1, 2, 6, 8, 11, 13, 16 and 18), which included del16q (with a minimal area of deletion including WWOX), observed in 39% vs. 5% cases from group A and B, respectively (p Conclusions Pts carrying amplified MDM4 and/or deleted p53 showed a significantly higher number of CNAs and the significant over-expression of genes involved in the response mechanisms to genotoxic stress, as compared to pts lacking these chromosomal aberrations. This might account for the worse outcome of patients harboring del(17p) and/or amp(1q). The amplification of MDM4 locus and the over-expression of YY1 might contribute to maintain p53 in an OFF state by an indirect mechanism. Additional data on the role of both direct and indirect control of p53 pathway on VTD-treated MM pts prognosis, extended to an higher number of pts, will be presented during the meeting. Supported by: Fondazione Del Monte di Bo e Ra, Ateneo RFO grants (M.C.) BolognAIL. Disclosures: Cavo: Genzyme: Honoraria.
8. HIF 1 Alpha: A Suitable Target for Multiple Myeloma
- Author
-
Carolina Terragna, Marina Martello, Enrica Borsi, Giulia Perrone, Paola Tacchetti, Manuela Mancini, Michele Baccarani, Elena Zamagni, Giovanni Martinelli, Michele Cavo, Annamaria Brioli, Maria Alessandra Santucci, Sandra Durante, Beatrice Anna Zannetti, Michela Aluigi, Lucia Pantani, PERRONE G, BORSI E, TERRAGNA C, DURANTE S, MARTELLO M, ALUIGI M, MANCINI M, ZAMAGNI E, TACCHETTI P, BRIOLI A, PANTANI L, ZANNETTI BA, MARTINELLI G, SANTUCCI MA, BACCARANI M, and CAVO M
- Subjects
education.field_of_study ,Membrane permeability ,Angiogenesis ,Growth factor ,medicine.medical_treatment ,Immunology ,Population ,Cell Biology ,Hematology ,Biology ,Biochemistry ,Molecular biology ,HIF1A ,MULTIPLE MYELOMA ,Gentamicin protection assay ,Cell culture ,medicine ,Viability assay ,education - Abstract
Abstract 2901 Hypoxia-inducible factor-1 alpha (HIF1 α) is a transcription factor that plays a critical role in survival and angiogenesis. In solid tumors, elevated expression of HIF-1 α, in response to hypoxia or activation of growth factor pathways, is associated with tumor proliferation, metastasis, and drug resistance and correlated with poor prognosis. In contrast to solid tumors, the role of HIF1 α in hematological malignancies is not completely known. In particular in multiple myeloma (MM) HIF1 α has been suggested to be constitutively expressed and HIF1 α knockdown cell lines have shown higher sensitivity to standard chemotherapy, suggesting a role in the pathophysiology of MM. In the present study, we explored the effect of EZN2968, an antisense oligonucleotide against HIF1 α, as a molecular target in MM. We showed, using real time PCR, and Western blotting analysis, that the expression of HIF1 α in several MM cell lines (MM1S, U266, OPM2, RPMI8226) is detectable under conditions of normoxia or hypoxia and is increased in the presence of growth stimuli (IL-6 and stroma cells). The immunofluorescence analysis suggested that the protein is ubiquitously present in both the cytosol and nucleus. To evaluate the specificity of the oligonucleotide for the target, we tested whether EZN2968 was able to induce a selective and stable down-modulation of HIF1 α mRNA and protein expression. We confirmed that the downmodulation was lasting in a long term culture experiment (up to 96 hours) either in normoxic or hypoxic conditions, and did not affect the expression of other family members of hypoxia inducible transcription factors (HIF2 α). We next explored the effects of EZN-2968 on the growth and survival of MM cells. Using an MTT colorimetric survival assay, we showed that, after 48 hours of culture in the presence of the HIF1 α inhibitor (20μM), MM1.S and U266 cell lines exhibited a reduction of 30% of viability compared to untreated cells, while RPMI8226 of 15%. AnnexinV/PI staining revealed that EZN-2968 (20μM) increased, after 48 hours of culture, the percentage of PI+ cells compared to the control, suggesting a disruption on membrane permeability. In addition, immunoblotting revealed PARP cleavage as early as 24 hours. Evaluation of cell cycle profile, by flow cytometric analysis, showed an increase of the sub-G0/G1 population from 3.5% to 30 %, after 48 hour of exposure to EZN-2968. To evaluate if the impact on cell viability was irreversible, we performed a cell death commitment assays. MM1S cells were incubated with EZN2968 (20 μM) for 24 to 96 hours, following incubation in drug-free medium for additional 24 to 72 hours. MTT colorimetric survival assay showed that EZN-2968 treatment for as early as 24h resulted in commitment to death in all cell lines tested. To evaluate the effect of microenvironment, MM cells treated with EZN2968 were exposed to IL-6 and stroma cells for additional 24 hours. EZN2968 overcame the proliferative effect induced by cytokines. We next evaluated the impact of EZN-2968 on purified CD138+ cells from MM patients with advanced MM. MTT colorimetric survival assay showed a reduction of cells viability of 30% after 24 hours of incubation. In addition we observed a low sensitivity of PBMCs and CD34+cells, derived from healthy donors, to EZN-2968 treatment suggesting that EZN-2968 has selective in vitro activity against MM cells. Evaluation of gene expression profiling modulation induced by EZN 2968 is on going. In summary, our results suggests that the inhibition of HIF1 α activity can be used as an attractive therapeutic target for MM patients and provide the rationale for clinical evaluation of HIF inhibitors. Disclosures: No relevant conflicts of interest to declare.
9. Novel insights and therapeutic approaches in secondary AML.
- Author
-
Marconi G, Rondoni M, Zannetti BA, Zacheo I, Nappi D, Mattei A, Rocchi S, and Lanza F
- Abstract
Secondary acute myeloid leukemia (sAML) presents as a complex and multifaceted ensemble of disorders, positioning itself as both a challenge and an intriguing frontier within hematologic oncology. Its origins are diverse, stemming from antecedent hematologic conditions, germline predisposing mutations, or the sequelae of cytotoxic therapies, and its development is driven by intricate genetic and epigenetic modifications. This complexity necessitates a diverse array of therapeutic strategies, each meticulously tailored to address the distinctive challenges sAML introduces. Such strategies require a personalized approach, considering the variegated clinical backgrounds of patients and the inherent intricacies of the disease. Allogeneic stem cell transplantation stands as a cornerstone, offering the potential for curative outcomes. This is complemented by the emergence of innovative treatments such as CPX-351, venetoclax, and glasdegib, which have demonstrated promising results in enhancing prognosis. The evolving landscape of sAML treatment underscores the importance of continued research and innovation in the field, aiming not only to improve patient outcomes but also to deepen our understanding of the disease's biological underpinnings, thereby illuminating pathways toward more effective and individualized therapies., Competing Interests: GM received research funds from AbbVie, Astellas, AstraZeneca, Daiichi Sankyo, Pfizer, and Syros and was a consultant or was included in the speakers bureau for AbbVie, Astellas, AstraZeneca, Immunogen, Janssen, Menarini/Stemline, Pfizer, Ryvu, Servier, Syros, and Takeda. MR was a consultant or was included in the speakers bureau for Novartis, Gentili, Blueprint, and Jazz. FL received research funds from Pfizer and Alexion and is a consultant from Sobi, Roche, AbbVie, Amgen, and Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Marconi, Rondoni, Zannetti, Zacheo, Nappi, Mattei, Rocchi and Lanza.)
- Published
- 2024
- Full Text
- View/download PDF
10. Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy.
- Author
-
Rocchi S, Zannetti BA, Marconi G, and Lanza F
- Subjects
- Humans, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma therapy, Multiple Myeloma immunology, Transplantation, Autologous, Immunotherapy methods
- Abstract
Upfront high-dose therapy with melphalan (HDM) followed by autologous stem cell transplantation (ASCT) has established itself as a core treatment for newly diagnosed multiple myeloma (NDMM) patients in the past 30 years. Induction therapy, HDM-ASCT, and subsequent consolidation and maintenance therapy comprise the current fundamental framework for MM treatment. The introduction of anti-CD38 monoclonal antibodies such as daratumumab and isatuximab has changed the treatment paradigm for transplant-eligible NDMM patients in that quadruplets have become the new standard induction therapy. The treatment landscape of MM is undergoing a transformative shift with the introduction of potent new immunotherapies, such as chimeric antigen receptor (CAR)-T cells and bispecific antibodies (BsAbs), which are currently used in the relapsed/refractory setting (RRMM) and are already being tested in the NDMM. This review will focus on the incorporation of immunotherapy in the treatment scenario of NDMM patients eligible for ASCT.
- Published
- 2024
- Full Text
- View/download PDF
11. New Horizons in Immunology and Immunotherapy of Acute Leukemias and Related Disorders.
- Author
-
Lanza F, Rondoni M, and Zannetti BA
- Abstract
Accumulating data have shown that molecular aberrations have the potential to trigger the development of acute leukemia, and that the routine application of novel molecular biology technologies has facilitated the development of investigational drugs which target driver genetic mutations [...].
- Published
- 2023
- Full Text
- View/download PDF
12. Low-Dose Cyclophosphamide versus Intermediate-High-Dose Cyclophosphamide versus Granulocyte Colony-Stimulating Factor Alone for Stem Cell Mobilization in Multiple Myeloma in the Era of Novel Agents: A Multicenter Retrospective Study.
- Author
-
Zannetti BA, Saraceni F, Cellini C, Fabbri E, Monaco F, Guarini A, Laszlo D, Martino M, Olivieri A, Imola M, Tosi P, Chiarucci M, Zuffa E, and Lanza F
- Subjects
- Antigens, CD34, Cyclophosphamide adverse effects, Granulocyte Colony-Stimulating Factor therapeutic use, Hematopoietic Stem Cell Mobilization, Humans, Retrospective Studies, Heterocyclic Compounds, Multiple Myeloma drug therapy
- Abstract
The optimal stem cell (SC) mobilization strategy for patients with multiple myeloma (MM) remains a matter of debate. Possible approaches include low or high doses of cyclophosphamide (Cy), other chemotherapeutic agents, or granulocyte colony-stimulating factor (G-CSF) alone. The scope of the study was to compare low-dose Cy plus G-CSF versus intermediate-high-dose Cy plus G-CSF versus G-CSF alone for SC mobilization in MM, in terms of efficacy and safety. We retrospectively analyzed 422 MM patients undergoing SC mobilization in 6 Italian centers, including 188 patients who received low-dose Cy (LD-Cy group, defined as 2 g/m
2 ), 163 patients who received intermediate-high-dose Cy (HD-Cy group, defined as ≥ 3 g/m2 ), and 71 patients who received G-CSF alone (G-CSF group). The median peak of circulating CD34+ cells was 77/µL in the LD-Cy group, 92/µL in the HD-Cy group, and 55/µL in the G-CSF group (P = .0001). The median amount of SCs collected was 9.1 × 106 /kg, 9.7 × 106 /kg, and 5.6 × 106 /kg in the 3 groups, respectively (P = .0001). The rate of mobilization failure (defined as failure to collect ≥2 × 106 /kg) was 3.7% in the LD-Cy group, 3.4% in the HD-Cy group, and 4.3% in the G-CSF group (P = .9). The target SC dose of at least 4 × 106 /kg was reached in 90.4%, 91.1%, and 78.6% of the patients in these 3 groups, respectively (P = .014). The "on demand" use of plerixafor was higher in the G-CSF group (76%) compared with the LD-Cy group (19%) and the HD-Cy group (6%). In multivariate analysis, G-CSF mobilization and previous use of melphalan or radiotherapy were independently associated with failure to collect the target SC dose of ≥4 × 106 /kg. No impacts of age, blood counts, or previous treatment with lenalidomide, bortezomib, or carfilzomib were observed. Our results suggest that LD-Cy may be considered for successful SC mobilization in patients with MM., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
- Full Text
- View/download PDF
13. Novel Insights in Anti-CD38 Therapy Based on CD38-Receptor Expression and Function: The Multiple Myeloma Model.
- Author
-
Zannetti BA, Faini AC, Massari E, Geuna M, Maffini E, Poletti G, Cerchione C, Martinelli G, Malavasi F, and Lanza F
- Subjects
- ADP-ribosyl Cyclase 1 immunology, Antibodies, Monoclonal immunology, Antibodies, Monoclonal, Humanized therapeutic use, Antibody-Dependent Cell Cytotoxicity, Humans, Multiple Myeloma pathology, Tumor Microenvironment, ADP-ribosyl Cyclase 1 metabolism, Antibodies, Monoclonal therapeutic use, Multiple Myeloma therapy
- Abstract
Multiple myeloma (MM) is a hematological disease characterized by the proliferation and accumulation of malignant plasmacells (PCs) in the bone marrow (BM). Despite widespread use of high-dose chemotherapy in combination with autologous stem cell transplantation (ASCT) and the introduction of novel agents (immunomodulatory drugs, IMiDs, and proteasome inhibitors, PIs), the prognosis of MM patients is still poor. CD38 is a multifunctional cell-surface glycoprotein with receptor and ectoenzymatic activities. The very high and homogeneous expression of CD38 on myeloma PCs makes it an attractive target for novel therapeutic strategies. Several anti-CD38 monoclonal antibodies have been, or are being, developed for the treatment of MM, including daratumumab and isatuximab. Here we provide an in-depth look atCD38 biology, the role of CD38 in MM progression and its complex interactions with the BM microenvironment, the importance of anti-CD38 monoclonal antibodies, and the main mechanisms of antibody resistance. We then review a number of multiparametric flow cytometry techniques exploiting CD38 antigen expression on PCs to diagnose and monitor the response to treatment in MM patients.
- Published
- 2020
- Full Text
- View/download PDF
14. Novel agent-based salvage autologous stem cell transplantation for relapsed multiple myeloma.
- Author
-
Zannetti BA, Tacchetti P, Pantani L, Gamberi B, Tosi P, Rocchi S, Cellini C, Ronconi S, Pezzi A, Mancuso K, Rizzello I, Caratozzolo I, Martello M, Dozza L, Cavo M, and Zamagni E
- Subjects
- Aged, Autografts, Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Myeloma mortality, Recurrence, Survival Rate, Time Factors, Bortezomib administration & dosage, Multiple Myeloma therapy, Secondary Prevention, Stem Cell Transplantation
- Abstract
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard frontline therapy for multiple myeloma (MM). Therapeutic options for patients with relapsed MM after ASCT include novel agents in different combos, salvage ASCT (sASCT), and allogeneic transplant, with no unique standard of care. We retrospectively analyzed 66 MM patients who relapsed after up-front single or double ASCT(s) and received novel agent-based sASCT at five Italian centers. Median event-free survival from up-front ASCT(s) to first relapse (EFS1) was 44 months. Seventy-three percent of patients received sASCT at first disease progression. Re-induction regimens were bortezomib based in 87% of patients. Response to re-induction therapy included complete response (CR) 18%, ≥ very good partial response (VGPR) 48%, and overall response rate (ORR) 83%. Response to sASCT included CR 44%, ≥ VGPR 77%, and ORR 94%. With a median follow-up of 24 months after sASCT, 39 patients experienced disease progression. Median EFS from sASCT (EFS2) was 17 months. Median overall survival from ASCT (OS1) and sASCT (OS2) was 166 and 43 months, respectively. EFS2 and OS2 were significantly shorter in patients with EFS1 ≤ 24 months, in patients who did not receive sASCT at first disease progression and in patients with extramedullary disease (EMD). In multivariate analysis, EFS1 ≤ 24 months was associated with shorter EFS2 and OS2, EMD was associated with shorter EFS2, and < CR after sASCT was associated with shorter OS2. Novel agent-based sASCT is a safe and effective procedure for relapsed MM.
- Published
- 2017
- Full Text
- View/download PDF
15. Role of serum free light chain assay in the detection of early relapse and prediction of prognosis after relapse in multiple myeloma patients treated upfront with novel agents.
- Author
-
Tacchetti P, Pezzi A, Zamagni E, Pantani L, Rocchi S, Zannetti BA, Mancuso K, Rizzello I, and Cavo M
- Subjects
- Biomarkers, Tumor blood, Bortezomib therapeutic use, Disease Progression, Gene Expression, Humans, Immunoglobulin Light Chains blood, Immunoglobulin M blood, Immunoglobulins blood, Lenalidomide, Multiple Myeloma genetics, Multiple Myeloma mortality, Multiple Myeloma therapy, Prognosis, Recurrence, Stem Cell Transplantation, Survival Analysis, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Antineoplastic Agents therapeutic use, Biomarkers, Tumor genetics, Immunoglobulin Light Chains genetics, Immunoglobulin M genetics, Immunoglobulins genetics, Multiple Myeloma diagnosis
- Published
- 2017
- Full Text
- View/download PDF
16. Opposite activation of the Hedgehog pathway in CD138+ plasma cells and CD138-CD19+ B cells identifies two subgroups of patients with multiple myeloma and different prognosis.
- Author
-
Martello M, Remondini D, Borsi E, Santacroce B, Procacci M, Pezzi A, Dico FA, Martinelli G, Zamagni E, Tacchetti P, Pantani L, Testoni N, Marzocchi G, Rocchi S, Zannetti BA, Mancuso K, Cavo M, and Terragna C
- Subjects
- Animals, Antigens, CD19, B-Lymphocytes immunology, B-Lymphocytes metabolism, Cell Line, Tumor, Heterografts, Humans, Mice, SCID, Multiple Myeloma immunology, Multiple Myeloma metabolism, Plasma Cells immunology, Plasma Cells metabolism, Prognosis, Signal Transduction, Syndecan-1, Tumor Cells, Cultured, B-Lymphocytes pathology, Hedgehog Proteins metabolism, Multiple Myeloma diagnosis, Plasma Cells pathology
- Abstract
Hyperactivation of the Hedgehog (Hh) pathway, which controls refueling of multiple myeloma (MM) clones, might be critical to disease recurrence. Although several studies suggest the Hh pathway is activated in CD138- immature cells, differentiated CD138+ plasma cells might also be able to self-renew by producing themselves the Hh ligands. We studied the gene expression profiles of 126 newly diagnosed MM patients analyzed in both the CD138+ plasma cell fraction and CD138-CD19+ B-cell compartment. Results demonstrated that an Hh-gene signature was able to cluster patients in two subgroups characterized by the opposite Hh pathway expression in mature plasma cells and their precursors. Strikingly, patients characterized by Hh hyperactivation in plasma cells, but not in their B cells, displayed high genomic instability and an unfavorable outcome in terms of shorter progression-free survival (hazard ratio: 1.92; 95% confidence interval: 1.19-3.07) and overall survival (hazard ratio: 2.61; 95% confidence interval: 1.26-5.38). These results suggest that the mechanisms triggered by the Hh pathway ultimately led to identify a more indolent vs a more aggressive biological and clinical subtype of MM. Therefore, patient stratification according to their molecular background might help the fine-tuning of future clinical and therapeutic studies.
- Published
- 2016
- Full Text
- View/download PDF
17. Prognostic impact of serial measurements of serum-free light chain assay throughout the course of newly diagnosed multiple myeloma treated with bortezomib-based regimens.
- Author
-
Tacchetti P, Cavo M, Rocchi S, Pezzi A, Pantani L, Brioli A, Testoni N, Terragna C, Zannetti BA, Mancuso K, Marzocchi G, Borsi E, Martello M, Rizzello I, and Zamagni E
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib administration & dosage, Female, Humans, Male, Middle Aged, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Neoplasm Staging, Prognosis, Proportional Hazards Models, Treatment Outcome, Biomarkers, Tumor, Immunoglobulin Light Chains blood, Multiple Myeloma blood, Multiple Myeloma mortality
- Abstract
We retrospectively investigated the role of serial serum-free light chain (sFLC) evaluations in 150 multiple myeloma (MM) patients treated with first-line bortezomib-based regimens. Baseline sFLC ratio (sFLCR) identified three groups of patients - normal, lightly abnormal (<100), and highly abnormal (≥100) - with different progression-free survival (PFS: 3-year estimate 72% versus 61% versus 44%, respectively, p = 0.03). Moreover, the achievement of a normal sFLCR correlated with extended PFS (49 versus 17 months, p < 0.0001) and overall survival (75 versus 43 months, p < 0.0001) as compared with abnormal sFLCR, a gain maintained in a multivariate analysis for PFS. At relapse, a high sFLCR was associated with earlier start of salvage therapy compared with sFLCR <100 (3-month probability: 89% versus 64%, p = 0.0426). In 20% of patients, sFLC escape preceded the conventional relapse by a median of 3.8 months. Our results highlight the role of sFLC assay in the prognosis and follow-up of MM.
- Published
- 2016
- Full Text
- View/download PDF
18. Current and emerging triplet combination therapies for relapsed and refractory multiple myeloma.
- Author
-
Pantani L, Brioli A, Tacchetti P, Zannetti BA, Mancuso K, Rocchi S, Martello M, Rizzello I, Terragna C, Zamagni E, and Cavo M
- Subjects
- Antibodies, Monoclonal therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib therapeutic use, Histone Deacetylase Inhibitors therapeutic use, Humans, Immunologic Factors therapeutic use, Lenalidomide, Multiple Myeloma pathology, Multiple Myeloma therapy, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local therapy, Proteasome Inhibitors therapeutic use, Salvage Therapy, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Antineoplastic Agents therapeutic use, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy
- Abstract
Despite significant improvement in outcomes have been observed for multiple myeloma (MM) patients over the past 10-15 years, mainly due to the introduction of novel agents targeting the tumor clone and the bone marrow microenvironment, treatment of refractory and/or relapsed (RR) disease remains a challenge, particularly for patients who have failed prior bortezomib- and lenalidomide-based therapies. More recently, new drugs with different mechanisms of action, including second generation proteasome inhibitors, third generation immunomodulatory drugs, histone deacetylase inhibitors and monoclonal antibodies, have been developed and are under investigation, further increasing treatment options for RRMM patients. Overall, novel agent-based triplet combinations demonstrated superior response rates and prolonged disease control when compared with two-drug regimens in several randomized clinical trials, without adding any relevant additional toxicity. Salvage triplet therapies are likely to play a key role in overcoming drug-resistance and hold promise to further improve long-term outcomes of RRMM patients.
- Published
- 2016
- Full Text
- View/download PDF
19. Bortezomib-based therapy combined with high cut-off hemodialysis is highly effective in newly diagnosed multiple myeloma patients with severe renal impairment.
- Author
-
Zannetti BA, Zamagni E, Santostefano M, De Sanctis LB, Tacchetti P, Mancini E, Pantani L, Brioli A, Rizzo R, Mancuso K, Rocchi S, Pezzi A, Borsi E, Terragna C, Marzocchi G, Santoro A, and Cavo M
- Subjects
- Adult, Aged, Aged, 80 and over, Bortezomib, Creatinine blood, Female, Glomerular Filtration Rate, Humans, Immunoglobulin Light Chains blood, Induction Chemotherapy, Kidney immunology, Kidney pathology, Kidney physiopathology, Male, Middle Aged, Multiple Myeloma complications, Multiple Myeloma immunology, Multiple Myeloma physiopathology, Remission Induction, Renal Insufficiency, Chronic complications, Renal Insufficiency, Chronic immunology, Renal Insufficiency, Chronic physiopathology, Survival Analysis, Antineoplastic Agents therapeutic use, Boronic Acids therapeutic use, Kidney drug effects, Multiple Myeloma drug therapy, Pyrazines therapeutic use, Renal Dialysis methods, Renal Insufficiency, Chronic drug therapy
- Abstract
Multiple myeloma (MM) is often associated with renal insufficiency (RI) which adversely influences the prognosis. Several studies demonstrated that bortezomib can improve both renal function and outcome. We prospectively evaluated 21 newly diagnosed MM patients with severe renal impairment secondary to tubular-interstitial damage, most of them due to myeloma kidney, who were primarily treated with bortezomib-based therapy combined with high cut-off hemodialysis (HCOD). The median serum creatinine level at baseline was 6.44 mg dL(-1) and calculated median estimated glomerular filtration rate (eGFR), according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, was 8 mL/min/1.73 m(2) . Serum free light chain (sFLC) median concentration was 6,040 mg L(-1) . Post induction and best stringent complete response rates were 19 and 38%, respectively. Responses were fast, occurring within a median of 1.4 months. The combination of bortezomib and HCOD led to a prompt and remarkable (>90%) decrease in sFLC levels. Sixteen patients (76%) became dialysis independent within a median of 32 days. With a median follow up of 17.2 months, the 3-year PFS and OS were 76 and 67%, respectively. No early deaths were observed. This study demonstrates that incorporation of bortezomib into induction therapy combined with HCOD is a highly effective strategy in rescuing renal function and improving outcomes in patients with MM and RI., (© 2015 Wiley Periodicals, Inc.)
- Published
- 2015
- Full Text
- View/download PDF
20. Successful mobilization of PBSCs predicts favorable outcomes in multiple myeloma patients treated with novel agents and autologous transplantation.
- Author
-
Brioli A, Perrone G, Patriarca F, Pezzi A, Nobile F, Ballerini F, Motta MR, Ronconi S, Tacchetti P, Catalano L, Zannetti BA, Rizzi S, Volpe S, Zamagni E, Liberati AM, Mancuso K, Boccadoro M, Davies FE, Morgan GJ, Palumbo A, and Cavo M
- Subjects
- Autografts, Female, Humans, Induction Chemotherapy methods, Male, Middle Aged, Bortezomib administration & dosage, Dexamethasone administration & dosage, Hematopoietic Stem Cell Mobilization methods, Multiple Myeloma therapy, Peripheral Blood Stem Cell Transplantation, Thalidomide administration & dosage
- Abstract
Incorporation of novel agents into auto-SCT for patients with multiple myeloma has led to improvement in their outcomes. However, the effects of new drugs, either single or combined, on PBSC mobilization have not been fully evaluated, particularly in phase 3 clinical studies. We analyzed the impact of two novel agent-based induction treatments in patients enrolled in the GIMEMA MMY-3006 study comparing bortezomib, thalidomide and dexamethasone (VTD) versus thalidomide and dexamethasone (TD) in preparation for double auto-SCT. Results showed that a short-term induction therapy with VTD did not adversely affect CD34(+) cell yields as compared with TD (9.75 vs 10.76 × 10(6) CD34(+) cells/kg, P=0.220). For poor mobilizers (<4 × 10(6) CD34(+) cells/kg), 5-year rates of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were significantly shorter than for successful mobilizers (TTP:17 vs 48%, P<0.0001; PFS: 16 vs 46%, P<0.0001; OS: 50 vs 80%, P<0.0001). These differences were retained across patients randomized to the TD arm; conversely, no differences in outcomes were seen in patients treated with VTD, irrespective of the number of harvested CD34(+) cells. The number of collected PBSCs predicted better outcomes after auto-SCT and VTD overcame the negative impact of a poor stem cell mobilization.
- Published
- 2015
- Full Text
- View/download PDF
21. Peripheral neuropathy induced by subcutaneous bortezomib-based induction therapy for newly diagnosed multiple myeloma.
- Author
-
Brioli A, Zannetti BA, Zamagni E, Tacchetti P, Pantani L, Mancuso K, Pezzi A, Rocchi S, and Cavo M
- Subjects
- Female, Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation, Multiple Myeloma therapy
- Published
- 2014
- Full Text
- View/download PDF
22. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment.
- Author
-
Borsi E, Perrone G, Terragna C, Martello M, Zamagni E, Tacchetti P, Pantani L, Brioli A, Dico AF, Zannetti BA, Rocchi S, and Cavo M
- Subjects
- Bone Marrow Cells drug effects, Bone Marrow Cells metabolism, Cell Adhesion drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Coculture Techniques, Humans, Interleukin-6 metabolism, Oligonucleotides pharmacology, Oligonucleotides, Antisense pharmacology, Plasma Cells metabolism, Signal Transduction drug effects, Hypoxia-Inducible Factor 1, alpha Subunit antagonists & inhibitors, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Multiple Myeloma metabolism, Plasma Cells drug effects, Tumor Microenvironment drug effects
- Abstract
Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma., (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
23. Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes.
- Author
-
Pantani L, Zamagni E, Zannetti BA, Pezzi A, Tacchetti P, Brioli A, Mancuso K, Perrone G, Rocchi S, Tosi P, and Cavo M
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Boronic Acids administration & dosage, Boronic Acids adverse effects, Bortezomib, Combined Modality Therapy, Dexamethasone administration & dosage, Dexamethasone adverse effects, Drug Evaluation, Female, Follow-Up Studies, Gastrointestinal Diseases chemically induced, Humans, Immunologic Factors administration & dosage, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma surgery, Peripheral Nervous System Diseases chemically induced, Proteasome Inhibitors administration & dosage, Proteasome Inhibitors adverse effects, Pyrazines administration & dosage, Pyrazines adverse effects, Recurrence, Remission Induction, Retrospective Studies, Salvage Therapy, Thrombocytopenia chemically induced, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse.
- Published
- 2014
- Full Text
- View/download PDF
24. Role of consolidation therapy in transplant eligible multiple myeloma patients.
- Author
-
Cavo M, Brioli A, Tacchetti P, Zannetti BA, Mancuso K, and Zamagni E
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boronic Acids administration & dosage, Bortezomib, Clinical Trials as Topic, Humans, Lenalidomide, Pyrazines administration & dosage, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Transplantation, Autologous methods, Treatment Outcome, Consolidation Chemotherapy, Multiple Myeloma therapy, Stem Cell Transplantation methods
- Abstract
The role of high-dose therapy and autologous stem-cell transplantation (ASCT) in the treatment of multiple myeloma (MM) has continued to evolve in recent years. The novel agents thalidomide, bortezomib, and lenalidomide have been successfully incorporated into induction therapy in preparation for ASCT and are currently being investigated also as post-ASCT consolidation and maintenance therapy. Consolidation treatment is generally short term and aims to increase the frequency and depth of response obtained with the previous treatment phases, including novel agent-based induction therapy and ASCT. This review will focus on recent trials of novel agents as post-ASCT consolidation therapy, offering an overview of pros and cons of this new treatment strategy in the ASCT sequence for MM patients., (© 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
25. Long-term follow-up after autologous stem cell transplantation for light- and heavy-chain deposition disease.
- Author
-
Brioli A, Zamagni E, Pasquali S, Tosi P, Tacchetti P, Perrone G, Pantani L, Petrucci A, Zannetti BA, Baccarani M, and Cavo M
- Subjects
- Adult, Aged, Female, Follow-Up Studies, Heavy Chain Disease metabolism, Heavy Chain Disease pathology, Humans, Male, Middle Aged, Paraproteinemias metabolism, Paraproteinemias pathology, Retrospective Studies, Transplantation, Autologous, Heavy Chain Disease surgery, Hematopoietic Stem Cell Transplantation methods, Immunoglobulin Heavy Chains metabolism, Immunoglobulin Light Chains metabolism, Paraproteinemias surgery
- Published
- 2012
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.