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Background: Patients (pts) with multiple myeloma (MM) often relapse and become refractory to successive lines of therapy, warranting better treatment options. The Phase 3 IKEMA ...study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in pts with relapsed MM (RMM) (HR 0.53; 99% CI 0.32–0.89; P= 0.0007). We evaluated the efficacy and/or safety of Isa-Kd by number of prior lines of therapy (1 vs > 1) and refractoriness to lenalidomide (Len) or bortezomib (Bor). Methods: Pts were randomized (3:2) to Isa-Kd (n = 179) or Kd (n = 123). Isa (10 mg/kg IV) was given weekly for 4 weeks, then every 2 weeks. K (20 mg/m² days 1-2, then 56 mg/m²) was given twice-weekly 3 of 4 weeks, and d (20 mg) twice-weekly. The primary endpoint was PFS; key secondary endpoints were very good partial response or better (≥VGPR), minimal residual disease negativity (MRD-), and complete response (CR) rates. Results: Of the 302 randomized pts, 44.7% had 1 prior line, 55.3% had > 1 prior line, 32.8% were Len-refractory, and 30.1% were Bor-refractory. PFS was improved with Isa-Kd vs Kd in pts who received 1 prior line and > 1 prior line, as well as in pts refractory to Len, Len at last regimen, Bor, or Bor at last regimen (Table). The addition of Isa to Kd improved depth of response (≥VGPR, MRD-, and CR rates) in all subpopulations analyzed by prior treatment. Grade ≥3 treatment-emergent adverse events (TEAEs) were generally similar between the prior line subgroups (77.2% Isa-Kd vs 64.8% Kd, 1 prior line; 76.5% Isa-Kd vs 69.1% Kd, > 1 prior line) and the overall safety population (76.8% Isa-Kd vs 67.2% Kd). Serious AEs were 62.0% vs 48.1% in the 1 prior line subgroup, and 57.1% vs 64.7% in the > 1 prior line subgroup; TEAEs leading to discontinuations were 8.9% vs 11.1%, 1 prior line and 8.2% vs 16.2%, > 1 prior line. Conclusions: The addition of Isa to Kd improved PFS and depth of response, irrespective of prior lines of therapy or refractory status, consistent with the benefit observed in the overall IKEMA study population. Isa-Kd had a manageable safety profile regardless of number of prior lines. Isa-Kd is a potential new treatment option for pretreated pts with RMM. Clinical trial information: NCT03275285. Table: see text
Background: Outcomes reported in real-world practice versus controlled clinical trials show markedly shorter treatment durations, progression free survival (PFS) and overall survival (OS). ...Understanding effectiveness of therapeutic regimens in routine practice is critical for treating physicians as well as for regulatory and reimbursement authorities. We have performed a real-world comparison of two regimens, ixazomib, lenalidomide and dexamethasone (IRD) triplet and lenalidomide and dexamethasone (Rd) doublet in patients with relapsed and/or refractory multiple myeloma (RRMM) treated in seven Czech and one Slovak hematology-oncology centers.
Patients and methods: Between 3/2015 and 5/2017, 344 patients with RRMM were treated with either IRD (N=127) or RD (N=217). Patients selected for both cohorts had the same inclusion and exclusion criteria. Patient baseline characteristics were well balanced. The data were collected through the Czech Registry of Monoclonal Gammopathies (RMG), which is an international database gathering data from patients with monoclonal gammopathies within Central Europe.
Results: The median follow-up in the IRD vs RD arm was 20.8 vs 15.5 months, respectively. Median PFS in pts with 1-3 prior lines for the IRD cohort was 23.1 months (95% CI 11.8-34.5 months) and 11.6 months (95% CI 8.4-11.8 months) for the RD cohort favoring the all-oral triplet (p=0.001). The median PFS for all patients including 4+ line of therapy was 17.5 months (95% CI 10.3-24.7) in the IRD cohort versus 11.5 months (95% CI 8.6-14.3) in the RD group (p=0.005).
Median OS for pts with 1-3 prior lines for IRD cohort was not reached, and was 27.1 months (95% CI 23.1-31.1 months) in the RD cohort (p=0.002). Median OS for all patients, including 4+ lines of treatment was 36.6 months in the IRD vs 26.0 months in the RD cohort (p=0.008).
The PFS benefit of IRD over RD was observed in most of the assessed subgroups; in younger pts ≤65 years with hazard ratio (HR) 0.58, in pts 66-75 years HR 0.64. There was a trend towards better PFS in patients with lower ISS stage; ISS1 HR 0.53, ISS2 HR 0.58 and ISS3 the HR was 0.87. Patients in the 1st relapse (HR 0.53) benefited most from the IRD, followed by the 2nd relapse (HR 0.58), 3rd relapse (HR 0.90) and pts relapsing after 4+ therapies (HR 0.88). The PFS benefit of IRD regimen was observed in pts regardless of previous stem cell transplantation; transplant-eligible patients HR 0.51 and transplant-ineligible HR 0.71. Patients who did not benefit from the triplet regimen were those over 75 years of age and pts with the presence of extramedullary disease.
The IRD treatment was well tolerated. The safety profile was concordant with previously reported data.
Conclusions: This RMG comparative cohort analysis shows PFS benefit of all-oral IRD regimen over RD in the real world setting, and confirms growing evidence that long term outcomes with IRD triplet are comparable with phase 3 TOURMALINE-MM1 trial. Our analysis also shows an overall survival benefit of IRD over RD treatment. Patients older than 75 years, with 4+ lines of therapy and presence of extramedullary disease did not profit from addition of ixazomib to RD doublet.Additional data with larger patient populations confirming RWE effectiveness are warranted.
With support of AZV 17-29343A, NV18-03-00500, FNOl 00098892, IGA-LF-2019-001, PROGRES Q40/08, MH CZ-DRO (UHHK, 00179906)
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Minarik:Celgene: Consultancy, Honoraria, Research Funding; Amgen, BMS, Janssen-Cilag, Takeda: Consultancy, Honoraria. Straub:Amgen, Takeda, Celgene: Consultancy. Spicka:Celgene: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Sanofi: Consultancy. Skacel:Millennium Pharmaceuticals, Inc., subsidiary of Takeda Pharmaceutical Company Limited: Employment. Maisnar:Janssen, Amgen, Celgene, Takeda, BMS: Consultancy, Honoraria.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We have performed a head to head comparison of all-oral triplet combination of ixazomib, lenalidomide and dexamethasone (IRD) versus lenalidomide and dexamethasone (RD) in patients with relapsed and ...refractory multiple myeloma (RRMM) in the routine clinical practice. A total of 344 patients treated with IRD (N = 127) or RD (N = 217) were selected for analysis from the Czech Registry of Monoclonal Gammopathies (RMG). Descriptive statistics were used to assess patient's characteristics associated with the respective therapy. The primary endpoint was progression free survival (PFS), secondary end points included response rates and overall survival (OS). Survival endpoints were plotted using Kaplan-Meier methodology at 95% Greenwood confidence interval. Univariable and multivariable Cox proportional hazards models were used to evaluate the effect of treatment regimens and the significance of uneven variables. Statistical tests were performed at significance level 0.05. In the whole cohort, median PFS for IRD was 17.5 and for RD was 11.5 months favoring the all-oral triplet, p = 0.005; in patients within relapse 1-3, the median PFS was 23.1 vs 11.6 months, p = 0.001. The hazard ratio for PFS was 0.67 (95% confidence interval CI 0.51-0.89, p = 0.006). The PFS advantage translated into improved OS for patients treated with IRD, median 36.6 months vs 26.0 months (p = 0.008). The overall response rate (ORR) was 73.0% in the IRD group vs 66.2% in the RD group with a complete response rate (CR) of 11.1% vs 8.8%, and very good partial response (VGPR) 22.2% vs 13.9%, IRD vs RD respectively. The IRD regimen was most beneficial in patients less than or equai to75 years with ISS I, II, and in the first and second relapse. Patients with the presence of extramedullary disease did not benefit from IRD treatment (median PFS 6.5 months). Both regimens were well tolerated, and the incidence of total as well as grade 3/4 toxicities was comparable. Our analysis confirms the results of the TOURMALINE-MM1 study and shows benefit of all-oral triplet IRD treatment versus RD doublet. It demonstrates that the addition of ixazomib to RD improves key survival endpoints in patients with RRMM in a routine clinical setting.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction: Multiple myeloma patients over the age of 65 represent the majority of myeloma population. The main goal was to evaluate treatment outcomes in terms of overall survival for elderly ...patients based on initial choice of anti-myeloma drugs, and to find potential factors affecting survival.
Patients and Methods: This is a retrospective registry based analysis from the Registry of monoclonal gammopathies of the Czech Myeloma Group. Patients with multiple myeloma diagnosed between 2007-2016 over the age of 65 with symptomatic myeloma were included in the analysis. Basic demographic data and disease characteristics were obtained. The Kaplan-Meier estimates were completed by the Greenwood confidence interval. The log-rank test was used to estimate the statistical significance of the difference between the curves. The Cox proportional hazards model was performed to explore the univariate significance of risk factors.
Results: Data from 1410 MM patients were obtained. Gender HR 1.316 (1.124-1.541), p=0.001, age above 75 vs. 66-75, HR 1.437 (1.221-1.692), p< 0.001, creatinine levels at cutoff 152 µmol/L, HR 1.613 (1.365-1.905), p< 0.001 and ECOG performance status 0-1 vs. 2-4, 1.869 (1.594-2.191), p< 0.001 were found to significantly affect overall survival. Moreover these risk factors have cumulative effect on overall survival of the patients. Overall survival of patients regardless to above mentioned risk factors treated with upfront bortezomib (N = 880) was median OS 40.4 months (CI: 36.1-44.7), patients treated with upfront thalidomide (N = 370) had median OS 48.1 months (CI: 41.0-55.2), for lenalidomide (N = 64) median overall survival was 53.2 months (CI: 44.6-61.8) and for combination of bortezomib and thalidomide (N = 46) 32.2 months (CI: 26.6-37.8). When any of these risk factors was present the OS in each group shortened. In the group of patients with no risk factors (N = 255) the median OS for bortezomib (N = 126) was not reached, for thalidomide (N = 96) the median OS was 66.3 months (CI: 43.1-89.6), for lenalidomide (N = 17) 71.1 months (CI: 44.8-97.4) and for combination of bortezomib and thalidomide (N=8) was not reached. In the group of patients with 1 risk factor (N = 514) the median OS for bortezomib (N = 303) was 46.1 months (CI: 36.2-56.1), for thalidomide (N = 141) 56.2 months (CI: 47.5-64.9), for lenalidomide (N = 29) 49.0 months (CI: 9.7-88.2) and for combination of bortezomib and thalidomide (N=20) was not reached. In the group of patients with 2 risk factors (N = 420) the median OS for bortezomib (N = 288) was 34.0 months (CI: 24.7-43.4), for thalidomide (N = 87) 31.9 months (CI: 22.8-40.9), for lenalidomide (N = 14) 33.2 months (CI: 0.0-67.6) and for combination of bortezomib and thalidomide (N=20) 29.4 months (CI: 7.6-51.1). In the group of patients with 3-4 risk factors (N = 221) the median OS for bortezomib (N = 163) was 19.2 months (CI: 14.9-23.5), for thalidomide (N = 46) 18.9 months (CI: 13.0-24.7), for lenalidomide (N = 4) 6.1 months (CI: 0.0-63.0) and for combination of bortezomib and thalidomide (N=3) 14.3 months (CI:-).
Conclusion: The overall survival of patients above the age of 65 shows promising results with the use of novel agents. The treatment outcomes seem to be generally affected by overall condition, age and gender of the patient rather than treatment modality used upfront.
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Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding. Maisnar:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims: Treatment of multiple myeloma (MM) in relapsed and refractory setting (RRMM) has been a challenge. The best outcomes have been observed in triplet combination of novel drugs. However, most ...combinations require weekly parenteral administration thus degrading patients´adherence to therapy, especially when treatment is scheduled “until progression”. The introduction of fully oral triplet combination ixazomib, lenalidomide and dexamethasone (IRD) showed an outstanding efficacy in the Tourmaline-MM1 trial. Our aim is to determine the efficacy and safety of IRD regimen outside clinical trials.
Patients and methods: A cohort of 127 RRMM patients from the Czech and Slovak Republic were treated with IRD regimen within a Named Patient Program between 2016 and 2018. The M/F ratio was 1.2:1 with median age 66 years (41-84). The representation of M-protein and light chain types as well as ISS stage was standard. The data for cytogenetics were recorded only at the time of diagnosis in 71% of patients with 15 patients having high-risk features - t(4;14), t(14;16) and del17, and 41 patients having standard risk features. In 34 patients we were not able to determine the risk status as at least one abnormality was missing and none was positive. The presence of extramedullary plasmocytoma was recorded in 15% of patients.
Most patients received IRD for their 1st relapse (58.5%), followed by 2nd (23.7%) and 3rd relapse (7.6%) with significant portion of patients being treated in ≥4th relapse (10.1%). The pretreatment with individual drugs was as follows: bortezomib (BTZ) 94.5%, thalidomide (THAL) 40.9%, lenalidomide (LEN) 18.9% and carfilzomib 5.5%. 62.2% of patients underwent previous autologous stem cell transplant. Altogether 25.2% of patients were refractory to at least 1 drug with 18.9% being BTZ refractory and 7.9% LEN refractory.
Data were analyzed from the Czech Registry of Monoclonal Gammopathies. Data were described by absolute and relative frequencies of categorical variables and mean (standard deviation), median (minimum-maximum) of quantitative variables. Survival measures were plotted using Kaplan-Meier methodology at 95% confidence interval, log-rank test was used to estimate the statistical significance at P<0.05.
Results: The overall response rate to IRD regimen (≥ partial response, PR) was 67.1% with clinical benefit rate (≥ minimal response, MR) of 77.2%. The rate of individual responses was as follows: complete response (CR) in 11.4%, very good partial response (VGPR) in 16.5%, PR in 39.2%, MR in 10.1%, stable disease (SD) in 13.9% and progressive disease (PG) in 8.9%. The median overall survival was not reached after median follow up of 9.4 months. Median progression free survival (PFS) was 23.1 months. PFS was significantly decreasing with number of previous lines (not reached after 1 previous lines, 23.1 after 2 lines, 8.7 after 3 lines and 4.6 after ≥4 lines, p = 0,006). As expected, the best PFS increased with deeper therapeutic response (SD+PD = 4.1 months, MR = 9.0 months, PR = 15.1 months, VGPR = 13.2 months, and CR = median PFS not reached).
There were limited information regarding the high risk features. Still, we confirmed adverse impact of the presence of extramedullary disease (PFS 5.5 vs 23.1 months, p = 0.001). Similarly, patients did worse when being pretreated by both proteasome inibitor and an IMiD versus solely proteasome inhibitor (PFS 10.0 vs 23.1 months, p = 0.001). The outcomes of high-risk cytogenetics were beyond statistical significance.
Most toxicities were grade ≤2. Only hematological toxicity and infection reached grade 3 or higher, as follows: neutropenia in 35.1%, thrombocytopenia in 22.8%, anemia in 12.3% and infection in 19.3%.
Conclusions: IRD regimen is very effective in RRMM. We confirmed its efficacy even in highly pretreated population (≥4 prior regimens) and in patients refractory to BTZ or LEN, which were exclusion criteria for the Tourmaline trial. The fully oral combination is well tolerated, with manageable side effects and easy management of dose modifications. Unlike the original trial our data show better results in patients with less pretreatment. The presence of extramedullary plasmocytoma deteriorates the prognosis of patients on IRD regimen.
We thank to Takeda for enabling the Named Patient Program. With support of AZV 17-29343A, MH CZ - DRO (FNOl, 00098892)
Maisnar:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective: Neoplastic milieu is an integral part of all malignant diseases including multiple myeloma and plays variable role in their development, retention/adhesivity, resistency or sensitivity to ...therapeutic approach, homing and also paraneoplastic manifestations. Relatively genetically stable milieu may play an important role in new specific molecular therapeutic approaches and therefore should be contextually studied with neoplastic cells as complex neoplastic tissues. The expressions of 15 proteins with close relation to the development of myeloma bone disease (MBD) were analysed in consecutive multiple myeloma specimens.
Methods: Bone marrow trephine biopsy specimens (n=57) with multiple myeloma were included in our prospective study. FFPE tissues were processed in app. 5microm sections and placed on charged slides. The indirect immunohistochemical staining was applicated after antigen retrieval and commercial primary antibodies were used for the detection of observed proteins. Standard secondary antibody and ABC method were included in visualisation. We analysed the expressions of MIP1alfa, Annexin A2, TRAP, DKK-1, RANK, RANKL, OPG, Sclerostin, Activin A, NFkappaB proteins (p50, p52, p65), p62 (sequestosome 1), MMP9 and RUNX2.
Results: Bone marrow multiple myeloma specimens showed variable positivity of MIP1alfa in 60% (cut-off point 20%), Annexin A2 in 42% (myeloma cells, cut-off point 30%) and in 74% (stromal cells, cut-off point 5%), TRAP in 28% (cut-off point 5%), DKK-1 in 23% (cut-off point 30%), RANK in 53% (cut-off point 30%), RANKL in 70%, OPG in 39% (cut-off point 5%), Sclerostin in 95% (cut-off point 90%), Activin A in 35% (cut-off point 30%), cytoplasmic positivity of p50 in 5% (cut-off point 10%), p52 in 86% (cut-off point 10%), p62 in 91% (cut-off point 10%), p65 in 89% (cut-off point 10%), positivity of MMP9 in 22% (cut-off point 30%) and positivity of RUNX2 in 56% (cut-off point 30%).
Conclusion: Our study showed variable expression of proteins related to MBD in multiple myeloma and its bone marrow microenvironment that imply biological heterogeneity, different development and stromal plasticity in this complex hemato-oncological disease. The exact and contextual knowledge of the engaged signaling pathways may suggest more specific or tailored therapeutic approaches (e.g. anti-RANKL, anti-DKK-1, anti-Sclerostin, anti-Activin A).
Supported by the grant NT 14393.
No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aims: The aim of our study was to assess the prognostic potential of parameters reflecting myeloma bone disease (MBD) assessed at the time of multiple myeloma (MM) diagnosis with respect to the ...extent of the disease, treatment approach and response to treatment.
Patients and methods: We assessed prospectively a cohort of 52 patients with newly diagnosed multiple myeloma indicated for treatment initiation. The median age was 68 years (40-88) with M/F ratio 1:1,3. All patients were treated initially using proteasome inhibitor (PI) based regimen - either bortezomib based (N=48) or carfilzomib based (N=4). 15 patients (29%) underwent autologous stem cell transplant (ASCT). 3 patients only continued with lenalidomide based maintenance.
We evaluated parameters reflecting the extent of the disease and bone involvement, presence of extramedullary masses, and activation of MBD signaling pathways with respect to treatment response and progression free survival (PFS). For the assessment of the extent of bone involvement we used whole-body techniques, either low-dose computed tomography scan (LD-CT) or magnetic resonance imaging (WB-MRI) or both. Following parameters reflecting MBD signaling were assessed from peripheral blood: hepatocyte growth factor (HGF, Human HGF Quantine ELISA), macrophage inflammatory factor alpha (MIP-1 α,Human CCL3/MIP-1a Quantikine ELISA), Syndecan-1 (Human Syndecan-1 (CD138) ELISA), osteoprotegerin (OPG, Human Osteoprotegerin ELISA), Activin A (Human Activin A Quantikine ELISA), Dickkopf-related protein-1 (DKK1, Human DKK-1 Quantikine ELISA), Annexin A2 (Human Annexin A2 ELISA kit), nuclear factor-kappa B (NF-κB, Human Nuclear factor-kappa B),Sclerostin (Sclerostin ELISA kit, Biomedica), matrix metalloproteinase 9 (MMP9, BlueGene Biotech ELISA kit).
For statistical estimation we used Kaplan-Meier analysis, Chi-square test, with log rank test (Mantel-Cox) at p < 0,05. To construct the PFS curves for each serum parameter we used median levels as cut-off for even distribution.
Results: PFS of the whole cohort was 21months. Overall survival did not reach median (M) yet, with 36-month survival of 79,6%. Despite low patient count there were significant differences between patients reaching complete remission (CR), very good partial remission (VGPR) and partial remission (PR) with PFS medians 36 vs 23 vs 17 months (p = 0,039, RR 3,189). The curves reflecting relationship of PFS and Durie-Salmon staging system showed better course with lower stages, still, the limited number of patients with stage I (N=3) precluded valid statistical estimation. Similarly, we could trace differences between ISS stages (M not reached vs 20 vs 17 months), the difference was, however, not statistically significant.
Out of the whole cohort, 16 patients were found to have an extramedullary myeloma. Interestingly, there was no significant difference in PFS based on the presence of extramedullary disease. Similarly, we did not find significant difference with respect to skeletal involvement based on LD-CT or WB-MRI.
From the selected parameters of MBD signaling, we found significant correlation to PFS in the case of HGF and MIP-1α. Patients with HGF≤ 3048pg/mL had significantly better PFS than patients with HGF>3048pg/mL (M 36 vs 17 months, p = 0,001, RR 3,835), and patients with MIP-1α≤25,5pg/mL had sigificantly better PFS than patients with MIP-1α>25,5pg/mL (29 vs 17 months, p = 0,025, RR 2,361).
With regard to treatment apporach, patients undergoing ASCT had significantly better PFS than patients with standard treatment only (M not reached vs 17months, p = 0,0005).
Conclusions: We found statistically significant prognostic value of HGF and MIP-1α in patients with newly diagnosed MM treated using PI based induction treatment. Despite limited number of patients, our cohort confirmed the significance of the depth of treatment response and ASCT on PFS. Interestingly, patients with extramedullary disease treated with PI based regimen did not have adverse PFS with respect to patients without the presence of extramedullary massess.
With support of the grant IGA_LF_2016_001.
No relevant conflicts of interest to declare.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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