Efficacy Of Lenalidomide Treatment In Multiple Myeloma (MM) Patients – a Report of Polish Myeloma Group

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3236-3236
Author(s):  
Lidia Usnarska-Zubkiewicz ◽  
Jakub Debski ◽  
Aleksandra K. Butrym ◽  
Wojciech Legiec ◽  
Marek Hus ◽  
...  
Keyword(s):  
Renal Failure ◽  
Disease Progression ◽  
Light Chain ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Staging System ◽  
Total N ◽  
Light Chain Disease ◽  
Disease Stabilization ◽  
Beta 2

Abstract The aim of the multi-centre observational study was to evaluate the efficacy of lenalidomide (len) therapy in patients (pts) with resistant or relapsed MM as well in pts who continued treatment with len due to complications from the earlier lines of the therapy. The study involved 306 pts, 153 women and 153 men, aged 26-89 years (mean 60,5); on the onset of lenalidomide therapy 115 pts (38,8 %, Cohort 1, C1) were diagnosed with resistant MM, 135 pts (44,1%, Cohort 2, C2) had relapse of the disease, and 56 (18,3 %, Cohort 3, C3 ) len was instituted as continuation therapy due to polyneuropathy. In Stage I, II and III according to Durie - Salmon staging system there were 36, 88 and 182 pts respectively; 23 pts developed renal failure. 179 pts had IgG myeloma, 78 – IgA, 31pts were diagnosed with light chain disease, 13 – with non-secretory myeloma, 3- IgM, 2 -IgD and 196 with kappa light chain disease. Prior to len therapy the pts received 1-9 treatment lines (mean:3); 83 pts underwent megachemiotherapy. Average time from diagnosis to start of len treatment was 47 months (1-230). In 284 (92,8%) pts, len was administered at the dose of 25mg p.o , on days 1-21, in the remaining 22 (7,2%) pts (14, 3, 5 pts respectively) at the dose of 15mg, 10mg or 5 mg for 21 days, and dexamethasone (dx) at the dose of 20 mg on days 1-4, 8-11. 28 pts received only len at the dose of 25 mg for 21 days; individual pts were administered len with bortezomib or bendamustin and dexamethasone. The cycles were repeated every 28 days. All the pts were administered aspirin 75mg as the prophylaxis of deep vein thrombosis. Therapeutic response was evaluated on the basis of modified criteria of the European Group for Blood and Marrow Transplantation in all pts. At the time of the assessment 32 (10,45% ) pts have completed 1-2 cycles, 48 (15,7%) 3-4 cycles, the others 6 and more. The response rate was highest in pts continuing treatment, significantly higher than in resistant and relapsed myeloma. The response rate in group 1 and 2 was comparable 68,7% i 85,7%.(tabl ) respectively.ResponseResistant MM n=115 (C1);Relapsed MM n=135 (C2);Treatment continuation n=56 (C3);Total (n=306)CR/sCR10 (8,7 %)13 (9,6 %)15 (26,8 %)38VGPR11 (9,6 %)19 (14,1%)19 (33,9 %)49PR58 (50,4%)70 (51,9 %)16 (28,6 %)144SD29 (25,2 %)21 (15,6 %)3 (5,3 %)53PD7 (6,1 %)12 (8,9 %)3 (5,3 %)22Response:79 (68,7%)102 (85,7%)50 (89,2%)No response:36 (31,3%)33 (27,7%)6 (10,%)PC1:C2 =0,2266PC1:C3=0,0033PC2:C3=0,0321 The percentage of all responses was significantly higher in pts without renal insufficiency compared to those with renal failure (224/283 vs. 11/23) p= 0,0006, and in the group of pts whose serum beta-2-microglobulin was <3.5 mg/L compared to those with beta-2-m > 3.5 mg/L 89/112 vs 45/68 p=0,0316. There were no significant differences in response to len, depending on the number of previous lines of treatment 1 vs.> 1, stage ISS, and underwent or no megachemotherapy. The median TTP was 14.0 months in pts who responded to treatment with len and dx (CR, nCR, VGPR, PR). The TTP in pts with disease stabilization, or disease progression was significantly shorter (p = 0.0000), median 5.0 months. The median TTP was 9.0 months in pts with resistant MM, 8.0 months in pts with relapsed MM, and was significantly shorter (p = 0.00007) compared with median TTP in pts continuing treatment (16.50 months). The median OS was 15.0 months in pts who responded to treatment with len and dx (CR, nCR, VGPR, PR), and it was significantly longer (p = 0.00000) than the median OS in pts with disease stabilization, or disease progression (median 8.0 months). In pts with resistant MM median OS was 10.50 months, in pts with relapsed MM -11.0 months, and were significantly shorter (p = 0.00077) comparing to pts continuing treatment (18.0 months). Summary Lenalidomide with dexamethasone is an orally administrated and effective both in resistant and relapsed patients as well as maintenance therapy. Disclosures: No relevant conflicts of interest to declare.

Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma (MM) Patients: a Preliminary Report of Polish Myeloma Group

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5125-5125
Author(s):  
Lidia Usnarska-Zubkiewicz ◽  
Jakub Debski ◽  
Aleksandra Butrym ◽  
Wojciech Legiec ◽  
Anna Dmoszynska ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Disease Progression ◽  
Light Chain ◽  
Therapeutic Response ◽  
Conflicts Of Interest ◽  
Staging System ◽  
Efficacy And Safety ◽  
Vein Thrombosis ◽  
Light Chain Disease

Abstract Abstract 5125 The aim of the multi-centre observational study was to evaluate the efficacy and safety of lenalidomide therapy in patients with resistant or relapsed multiple myeloma as well in maintenance treatment. The study involved 84 patients, 47 women and 37 men, aged 38–84, mean age 57.8 years; in Stage I, II and III according to Durie - Salmon staging system there were 6, 28 and 50 patients respectively; 12 patients developed renal failure. Fourty-eight patients had IgG myeloma, 26 – IgA, 6 patients were diagnosed with light chain disease, 2 – with non-secretory myeloma and 56 with kappa light chain disease. Prior to lenalidomide therapy the patients had received 1–8 treatment lines (mean:3). In 19 patients (22.6%), who were in disease remission (including CR 2, VGPR 6 and PR 11) lenalidomide was instituted due to polyneuropathy (Cohort 1, C1), among the remaining patients, on the onset of lenalidomide therapy 27 patients (32.1%, Cohort 2, C2) were diagnosed with resistant multiple myeloma and 38 patients (45.3%, Cohort 3, C3) had relapse of the disease. Lenalidomide was administered at the dose of 25mg p.o, on days 1–21 (15 pts in C1 and 54 in C2 and C3), at the dose of 15mg, 10mg or 5 mg for 21 days (1 and 2 patients in C2 and 1, 2 and 1 patient in C3 respectively) and dexamethasone at the dose of 20 mg on days 1–4, 8–11 and 17–20. Four patients with C1 and 2 with C2 received only lenalidomide at the dose of 25 mg for 21 days; individual patients from group C2 were administered lenalidomide with bortezomib or bendamustin and dexamethasone. The cycles were repeated every 28 days. All the patients were administered aspirin 75mg in the prophylaxis of deep vein thrombosis. Therapeutic response was evaluated on the basis of modified criteria of the European Group for Blood and Marrow Transplantation (EPMT) in patients who had completed at least 3 therapeutic cycles. In patients who were administered lenalidomide as a maintenance therapy, there were no cases of disease progression, and the percentage of CR and VGPR increased (from 42% to 68.4%), in the group of resistant patients the percentage of therapeutic response was 44.4% and in the group of relapsed myeloma it was 44.7%. The analysis of response rates in patients with maintenance therapy, resistant and relapsed MM is shown in Table 1.Table 1.Response rate analyzed by disease status.C1 n=19 maintenance therapyC2, n=27 resistantC3, n=38 relapsedCR3 (15.7%)1 (2.6%)VGPR10 (52.6%)2 (7.4%)3 (7.8%)PR6 (31.5%)10 (37.0%)13 (34,2%)SD12 (44.4%)13 (34.2%)PD3 (11.1%)8 (20.9%) During the observation period there were three deaths: 2 patients died due to disease progression, 1 patient due to pulmonary thrombosis. Other undesired effects included neutropenia and thrombocytopenia (II and III grade), and infections. Summary: Lenalidomide with dexamethasone is an effective and well tolerated both in maintenance therapy as well as in resistant and relapsed patients. Disclosures: No relevant conflicts of interest to declare.

Improving Outcomes in Patients with Renal Failure Secondary to Multiple Myeloma: Results From ChAR2M2.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1875-1875
Author(s):  
Colin Hutchison ◽  
Parisa Airia ◽  
Mark Cook ◽  
Daniel Grima
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Side Effects ◽  
Light Chain ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Treatment Patterns ◽  
Free Light Chain ◽  
High Rate ◽  
Sustained Reduction

Abstract Abstract 1875 Poster Board I-900 Study purpose: To explore how free light chain (FLC) removal by high cut-off haemodialysis (HCO-HD) has been adopted into clinical practice for the management of renal failure secondary to multiple myeloma. Describing treatment patterns and the laboratory and clinical outcomes associated with its use. Methods: A chart audit of patients treated with FLC removal by HCO-HD, using the Gambro HCO 1100 dialyser, was performed in 16 dialysis centers across 9 countries. Patient demographics, treatment patterns and dialysis side-effects were recorded. In addition, the following outcomes were measured: dialysis independence and reductions in serum FLCs concentrations at 12 and 21 days. Results: Data for 66 patients was entered. Patients had an average age of 65.1 (SD×10.1); 42 of them (63.64%) were male and 24 (36.36%) were female. Sixteen (24%) presented with relapsing myeloma and 50 (76%) had de novo disease. On average, each patient received 13 HCO-HD sessions (SD×8). Forty-one patients became dialysis independent (62.12%), after an average of 12 sessions. Dialysis related side-effects were reported in 6% of all patients. Forty patients (60.61%) were reported to have a sustained reduction in serum FLC concentrations by day 12. By day 21 this had increased to forty-one (62.12%). Among the patients who achieved a sustained reduction in serum FLC concentrations, 28 (70%) had a decline in FLC levels of more than 50% by day 12 and 34 (82.93%) by day 21. Among patients who achieved sustained reduction of more than 50% in serum FLC concentrations by day 12, 75% became dialysis independent. In comparison only 53% of those with a reduction of less than 50% became dialysis independent (p×0.007). Furthermore, among patients who achieved sustained FLC reduction of greater than 75%, 81% became dialysis independent. The rate of dialysis independence was also significantly higher in patients with de novo disease compared with those with relapsing myeloma (64% versus 56%, p×0.04). Conclusion: Free light chain removal by HCO-HD was well tolerated and associated with a very high rate of dialysis independence in patients with renal failure secondary to multiple myeloma. Rates of renal recovery were greater in patients with de novo myeloma and those who achieved an early reduction in serum FLC concentrations. Disclosures: No relevant conflicts of interest to declare.

Outcomes of Patients with Myelodysplastic Syndromes/Myeloproliferative Neoplasms with Emphasis On MDS/MPN-Unclassified

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5025-5025
Author(s):  
Charikleia Kelaidi ◽  
Varnavas Constantinou ◽  
George Papaioannou ◽  
Niki Stavroyianni ◽  
Chrysanthi Vadikoliou ◽  
...  
Keyword(s):  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Systemic Mastocytosis ◽  
Myeloproliferative Neoplasms ◽  
Univariate Analysis ◽  
Jak2 V617f ◽  
Female Ratio ◽  
Wbc Count

Abstract Abstract 5025 Background: Data on outcomes of patients (pts) with myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), especially MDS/MPN-unclassified (MDS/MPN-U), are scarce. Patients/methods: We retrospectively studied pts followed in our center, with MDS/MPN according to WHO 2008 criteria. Because of overlap characteristics of MPN and MDS, pts with systemic mastocytosis associated with MDS (SM/MDS) were also included. Pts with previous MDS or MPN were excluded. Response and disease progression were defined according to IWG 2006 criteria. Results: Twenty-five pts with MDS/MPN were included. Median age was 70 y (range 19–79). Male/female ratio was 1.77/1. Diagnosis was CMML-1 N=7, CMML-2 N=7, JMML N=1, MDS/MPN-U N=8, systemic mastocytosis (SM)/MDS N=2, with one additional pt with CMML subsequently developing SM. At diagnosis, median WBC count was 18.8 G/L (range 3–120), ANC 15.5 G/L (0.6–70), monocytes 1.9 G/L (0.1–16), left shift 16% (0–28), Hb 11.2 g/dL (6–17), platelets 99 G/L (10–680), peripheral and bone marrow (BM) blasts 5% (0–17) and 7% (2–19), respectively (resp.). 25% of pts had platelets count ≥400 G/L. Splenomegaly, B-symptoms and BM fibrosis were present in 23%, 57% and 27% of pts, resp. Karyotype was fav, int and unfav in 55%, 36% and 9% of pts, with −7, +8, del(12)(p11), del(12)(q14;q21), +10, +21, and previously unreported t(9;12)(q13;q13) in 3, 6, and 1 pt each, resp., while +21 and i(17)(q10) appeared during disease progression other than AML transformation. IPSS was low/int-1 and int-2/high in 50% and 50% of pts, resp. JAK2 V617F and CKIT D816V mutations were detected in 2/6 pts and 2/2 SM/MDS pts, resp. 70% and 29% of pts were transfused at diagnosis with PRBC and platelets, resp. Treatment included erythropoiesis stimulating agents (ESAs), low dose chemotherapy, intensive chemotherapy (IC) and azacitidine (AZA) in 40%, 36%, 16% and 48% of pts resp. Response rate to ESAs, IC and AZA was 60%, 14% and 14% resp. Response rate to AZA in CMML-1 pts was 33%. Dasatinib yielded no response in 1 SM/MDS pt with CKIT D816V. 3-year cumulative incidence of AML and median overall survival (OS) in pts with CMML-1, CMML-2 and MDS/MPN-U were 20%, 40% and 0 (P=0.059) and 39, 8, and 20 mo (P=0.50), resp. The pt with JMML died from AML transformation 3 months after diagnosis. 2/3 pts with SM/MDS died from disease progression w/o AML at a median of 10 mo after diagnosis. Median survival after disease progression other than AML transformation was 35, 15 and 14 mo in pts with CMML-1, CMML-2 and MDS/MPN-U, resp. (P=0.88). Cause of death was disease progression other than AML, AML transformation and unrelated to disease in 50%, 50%, and 0 and 80%, 0 and 20% of cases in CMML and MDS/MPN-U, resp. (P=0.10). Percentage of circulating blasts ≥5% was the only independent factor affecting risk of AML transformation in the overall population (P=0.0004). Diagnosis other than CMML-1, WBC ≥30 G/L, % of circulating blasts ≥5% and IPSS high/int-2 were associated with worse survival in univariate analysis (P=0.06, 0.03, 0.04 and 0.08, resp.). No predictive factor of OS was found in multivariate analysis. Conclusion: MDS/MPN are heterogeneous disorders with respect to disease progression and AML transformation. MDS/MPN-U tended to differ from CMML-1 by shorter survival after disease progression other than AML, and from CMML-2 by lower risk of AML transformation. Mortality of pts with MDS/MPN-U was mainly attributed to disease progression without AML transformation. Alternatively to hypomethylating agents, therapeutic options in pts with MDS/MPN-U could include JAK2 inhibitors. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Renal involvement as the first symptom of multiple myeloma

2019 ◽  
Author(s):  
Yongjing Du ◽  
Ping Zhang ◽  
Xiang Zhong ◽  
Shasha Chen ◽  
Guisen Li ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Light Chain ◽  
Clinical Laboratory ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Renal Amyloidosis ◽  
Cast Nephropathy ◽  
Light Chain Disease ◽  
Immunofixation Electrophoresis

Abstract Background Renal involvement is a common complication of multiple myeloma (MM). However, most studies have focused on renal failure in MM, and little information is available about the other renal manifestations in MM and their association with immunophenotypes and renal pathology. Methods We retrospectively analyzed the clinical, laboratory and pathology data of 283 MM patients treated in Sichuan Provincial People’s Hospital, West China, between January 1990 and May 2017. The patients were divided into a renal involvement group (n = 200) and a non-renal involvement group (n = 83). Results In the renal involvement group, 90 (45.0%) patients were diagnosed with MM in the Nephrology department, and isolated proteinuria, renal failure and nephrotic syndrome were detected in 90(45.0%), 94 (47.0%) and 53 (27.0%) patients, respectively. 135 patients with renal involvement underwent immunofixation electrophoresis, and IgG, IgA, IgD, IgE, pure light chain and nonsecretory MM were detected in 52 (38.5%), 32 (23.7%), 1 (0.7%), 1 (0.7%), 45(33.3%) and 4 (3.0%) patients, respectively. 47 patients without renal involvement also underwent immunofixation electrophoresis, and IgG and IgA MM were found in 24 (51.0%) and 18 (38.3%) patients, respectively. Severe anemia and hypertension, hypercalcemia and pure light chain disease were more frequent in patients with renal involvement (P < 0.05). 9 patients with renal involvement were performed renal biopsy, and cast nephropathy and renal amyloidosis were proved in 5(55.6%) and 4(44.4%) patients, respectively. Conclusions Renal involvement was common at MM diagnosis and had diverse clinical manifestations. Nephrologists should rule out MM in patients presenting with renal involvement.

Light chain disease and massive proteinuria.

1985 ◽  
Vol 31 (3) ◽  
pp. 475-477 ◽  
Author(s):  
F Lessard ◽  
P Bannon ◽  
R Lepage ◽  
J G Joly
Keyword(s):  
Renal Failure ◽  
Light Chain ◽  
Light Chains ◽  
Light Chain Disease ◽  
Bence Jones Proteinuria

Abstract We describe the case of a 64-year-old man with lambda type light chain disease, in whom panhypogammaglobulinemia was associated with anemia, massive Bence Jones proteinuria (24.6 g/L), and renal failure. Lambda type light chains were present in the serum.

HORIZON (OP-106): An exploratory analysis of time-to-next treatment (TTNT) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) who received melflufen plus dexamethasone (dex).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20570-e20570
Author(s):  
Maria-Victoria Mateos ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Blade ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Progression Free Survival ◽  
Staging System ◽  
Median Number ◽  
Ocean Study ◽  
Disease Stabilization ◽  
Heavily Pretreated ◽  
Secondary Endpoints ◽  
International Staging System

e20570 Background: Melflufen is a novel peptide-drug conjugate that rapidly delivers a cytotoxic payload into tumor cells. Melflufen + dex showed efficacy and a manageable safety profile in pts with poor-risk, heavily pretreated RRMM in the phase 2 HORIZON study (Mateos et al. ASH 2019. Abs. 1883). For pts with RRMM, longer TTNT is indicative of disease stabilization and clinical benefit and is associated with lower costs (Chen et al. J Manag Care Spec Pharm. 2017). This report of TTNT after melflufen + dex from HORIZON is, to our knowledge, the first report from a trial population with such advanced RRMM. Methods: Pts with RRMM who had received ≥2 prior lines of therapy, including an IMiD and a proteasome inhibitor (PI), and were refractory to pomalidomide and/or an anti-CD38 monoclonal antibody (mAb), received melflufen 40 mg (IV on d1 of each 28-d cycle) + dex 40 mg/wk until disease progression or unacceptable toxicity. The primary endpoint was overall response rate. Secondary endpoints included progression-free survival (PFS) and safety. TTNT was defined as the time from start of melflufen + dex to first subsequent therapy. Results: Overall, 154 pts were treated (data cutoff, Oct 1, 2019); median age was 64.5 y (range, 35-86), 32% had International Staging System stage 3 disease, 38% had high-risk cytogenetics, 32% had extramedullary disease (EMD), the median number of prior therapies was 5 (range, 2-12), and 71% had triple-class refractory MM (IMiD + PI + anti-CD38 mAb). Treatment discontinuation occurred in 108 pts (70%), most commonly due to disease progression (47%) and adverse events (14%). Among 125 pts evaluable for response, with a median follow up of 15.3 mo, the median TTNT was 8.0 mo (95% CI, 7.2-8.9) and the median PFS was 4.2 mo (95% CI, 3.7-4.9). TTNT and PFS were similar in subgroups of pts with triple-class refractory MM and EMD (Table). Subsequent therapies after melflufen + dex will be presented. Conclusions: TTNT in HORIZON (median 5 prior lines) was consistent with previous reports of TTNT in pts with RRMM who received melflufen + dex or other therapies (median 2-4 prior lines) (Bringhen et al. J Clin Oncol. 2019. Abs. 8043). Melflufen + dex is being further evaluated in the phase 3 OCEAN study (NCT03151811) in pts with RRMM who are refractory to lenalidomide. Clinical trial information: NCT02963493. [Table: see text]

Azacitidine (AZA) Combined with Idarubicin in Untreated Patients with High Risk MDS – Results of a Phase I/II Study of the Groupe Francophone Des Myelodysplasies

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1720-1720 ◽  
Author(s):  
Lionel Ades ◽  
Benoit de Renzis ◽  
Ramzi Jeddi ◽  
Jacques Delaunay ◽  
Thorsten Braun ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Disease Progression ◽  
Stable Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Single Agent ◽  
Overall Response

Abstract Abstract 1720 Background: hypomethylating agents, especially AZA, have become the reference treatment of higher risk MDS, but the median survival of about 2 years obtained with AZA remains modest, and must be further improved. In addition, if it is able to increase overall survival in MDS, AZA yields only about 30% of marrow response (including CR+PR+ mCR), Idarubicin given at conventional dose (12 mg/m2/d during 3 days) is the anthracycline of choice in the intensive chemotherapy given with cytarabine in patients with high risk MDS and, given as a single agent, induces up to 30% of complete remission (CR) in elderly AML patients. Thus, we designed a phase I/II study evaluating the safety and efficacy of 2 doses of Idarubicin combined with Azacitidine in high risk MDS patients (clinical trial NCT01305135). Methods: For this trial Azacitidine was combined with increasing doses of Idarubicin. Main Inclusion criteria were: (1) IPSS int 2 or high MDS, or CMML with WBC < 13,000/mm3 and marrow blasts > 10% or AML with 20–30% marrow blasts (corresponding to EU label for AZA) (2) Age 3 18 years (3) Performance Status (PS) <=2 (4) no prior treatment except ESAs. Patients received Azacytidine 75 mg/m2/d SC during 7 days every 4 weeks combined on day 8 of each cycle to Idarubicin 5 mg/m2 (administered by 1 hour IV infusion) in the first cohort of 10 patients, escalated to Idarubicin 10 mg/m2 IV in the second cohort of 10 patients after review of toxicity (especially hematological) of the 1st cohort by the independent DSMB r. The primary endpoint of the study was response after 6 cycles according to IWG criteria. Data were analyzed at the reference date of June, 1St 2012. Results: The 20 study patients (from 8 centers) were enrolled between Dec 2010 and Feb 2012, including 7 women and 13 men with a median age of 75 years. At inclusion, WHO classification was RCMD in 1 pt, CMML in 1 pt, RAEB-1 in 6 pts, RAEB-2 in 7 pts, AML in 3 pts and unclassified in 2 pt. Median marrow blasts were 6.5% (0–26) Karyotype (IPSS) was favorable in 7 pts, int in 3 pts and unfav in 8 pts (2 pts had cytogenetic failure). IPSS was high in all patients. PS was 0 in 28% pts, 1 in 50% and 2 in 22%. A total of 92 cycles of treatment had been administrated with a median number of 5 cycles/patient and 10 pts had received 6 or more cycles. 14 patients had terminated the study due to side effects (severe febrile pancytopenia, n=2), disease progression (n=5, after 2–10 cycles), death (disease progression, severe septic shock after Cycle 2, and unrelated coma), stable disease after 6 cycles (n=3), and patient decision (n=1). Overall 7 pt had died. 18 SAEs were reported observed in 9 patients, including 10 episodes of febrile neutropenia, 3 episodes of bleeding and 5 unrelated SAE. Of the 20 patients enrolled in the study, 19 were evaluable for response after 3 cycles, including 10/10 in the First cohort and 9/10 in the second cohort. One patient achieved CR, 2 PR, 1 mCR and 2 additional patients achieved stable disease with HI, leading to an Overall response rate of 6/19 (32%). Two patients were still on study but did not reached cycle 6. Thus, after 6 cycles, 17 patients, only could be evaluated. Among them 9/17 (53%) patients were still on study, 2 pts had died, 3 progressed, 2 had experienced sides effects and had terminated the study and 1 pt had withdrawn consent. Two patients achieved CR (including 1 already in CR at cycle 3), 2 PR and 2 additional patients achieved stable disease with HI leading to an Overall response rate of 6/17 (35%). At the time of the present analysis, none of the responder had relapsed. Conclusion: The phase I/II results presented here show that Idarubicin can be combined to Azacitidine with acceptable toxicity. Whether the azacitidine- Idarubicin combination can improve the outcome of higher risk MDS patients will be evaluated in a phase II randomized trial comparing this combination (and other combinations of azacitidine with other drugs) to azacitdine alone alone. Data of the present phase I/II trial will be updated at the meeting. Disclosures: No relevant conflicts of interest to declare.

Refinement in Patient Selection to Reduce Treatment-Related Mortality From Stem Cell Transplantation in Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 599-599
Author(s):  
Morie A Gertz ◽  
Martha Q Lacy ◽  
Angela Dispenzieri ◽  
Shaji K. Kumar ◽  
David Dingli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Troponin T ◽  
Early Death ◽  
Staging System ◽  
Transplant Recipients ◽  
Light Chain Amyloidosis

Abstract Abstract 599 Purpose: This study was undertaken to develop selection guidelines for transplant centers to determine eligibility for stem cell transplantation in patients with light chain amyloidosis. Patients and Methods: Patients with biopsy-confirmed immunoglobulin light chain amyloidosis who underwent stem cell transplantation between March 8, 1996, and December 31, 2011, were reviewed in 2 cohorts: those who underwent transplantation between March 8, 1996, and June 30, 2009, and those who underwent transplantation between July 1, 2009, and December 31, 2011 (table 1). A second comparison was undertaken among patients who died before posttransplant day 100 to determine features predictive of early death (table 2). Results: A total of 499 patients were identified, 410 in the earlier group and 89 in the later group. After July 1, 2009, significantly fewer transplant recipients had Mayo stage III cardiac involvement. Mortality before posttransplant day 100 was 10.5% (43/410) in the earlier group and 1.1% (1/89) in the later group. In the earlier group, one-quarter of transplant recipients with N-terminal pro-brain natriuretic peptide (NT-proBNP) levels higher than 5,000 pg/mL died by 10.3 months (fig 1, left). When the serum troponin T level was > 0.06 ng/mL, 25% died at 3.7 months (fig 2, right). Conclusion: The Mayo staging system is highly predictive for overall survival but not useful for selecting transplant recipients. Patients with serum troponin T levels higher than 0.06 ng/mL or NT-proBNP levels >5,000 pg/mL (not on dialysis) should not be considered acceptable candidates for stem cell transplantation because of unacceptable early mortality. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Kidney failure as an unusual initial presentation of biclonal gammopathy (IgD multiple myeloma associated with light chain disease): A case report

2015 ◽  
Vol 72 (2) ◽  
pp. 196-199
Author(s):  
Violeta Rabrenovic ◽  
Zoran Mijuskovic ◽  
Slobodan Marjanovic ◽  
Milorad Rabrenovic ◽  
Dragan Jovanovic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Case Report ◽  
Light Chain ◽  
Bone Biopsy ◽  
Autologous Bone Marrow Transplantation ◽  
Laboratory Analysis ◽  
Team Work ◽  
Light Chain Disease ◽  
Biclonal Gammopathy

Introduction. Immunoglobulin D (IgD) myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy - associated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. Case report. 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg). Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L) and renal failure dialysis rank: creatinine 1,408 ?mol/L, urea31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2 M components - massive in ? 2 fraction of 71%; 7% in the discrete ? fraction, beta 2M /serum 110 mg/L, in urine 1.8 mg/L - extremely high; IgL kappa / lambda index 1 : 13 (reference value ratio 2 : 1). The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, ? - light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission. Conclusion. The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and team-work that can alter the course of this serious disease.

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