The Results of the Russian Registry of Primary Immune Thrombocytopenia (ITP) in Adults

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4642-4642
Author(s):  
Igor Lisukov ◽  
Alexey Maschan ◽  
Anastasia Shamardina ◽  
Tatyana Chagorova ◽  
Igor Davydkin ◽  
...  
Keyword(s):  
Partial Response ◽  
Conflicts Of Interest ◽  
Disease Onset ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Chronic Itp ◽  
Best Response ◽  
History Of ◽  
Clinically Significant ◽  
Observation Period

Abstract Study objectives The aim of the study was to evaluate disease characteristics and treatment practices of ITP in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. The observation period for each patient in the Registry was not less than 12 months. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient. Exclusion criteria: secondary thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics was used. Patients were registered since June 2011 till June 2014. Results Five hundred and seven adult 394female (77.7%)/113 male(22.3%) pts from 26 hematology centers in various regions of the Russian Federation were included. Observation period ranged from 1.4 to 29.8 months with an average of 18.6 ± 6.2 mo. Median age was 50.2 years (range 18.6-89.1). Median disease duration was 1.83 years (range 0-56.07). History of ITP of lasting < 1 year was reported in 186 (36.7%) pts, 1-5 years - in 142 (28%), 5-10 years - in 56 (11%), over 10 years - in 87 (17.2%), and was considered as unknown - in 36 (7.1%). Newly diagnosed ITP was reported in 19.5% of adult pts; persistent - in 16.6% and chronic ITP - in 63.9% of pts, respectively. Median platelets count was 14,0 x 109/L (range 0.0- 119.0 x 109/L). Hemorrhagic manifestations in the history of ITP were reported in 92.5% of pts: skin hemorrhages - in 89.5% of pts, oral bleeding - in 50.3% , epistaxis - in 37.3% , gastrointestinal bleeding - in 7.7%, intracranial bleeding - in 0.4%, hematuria - in 4.5%, and other hemorrhages - in 20.9% of pts. Severe ITP at the time of enrollment was observed in 158 (31.2%) pts (104 pts (20.5%) had a clinically significant bleeding at the disease onset, and 54 (10.7%) pts developed new clinically significant hemorrhages during the treatment. Refractory ITP at the time of enrollment was reported in 100 (19.7%) pts (resistance to the first, second and subsequent lines of therapy in 62 (12.2%) pts); 38 (7.5%) pts did not respond to splenectomy. At the time of enrollment, 250 (49.3%) pts received medical treatment for ITP. Severe ITP after enrollment was observed in 124 (24.8%) adult pts. Throughout the study, various hemorrhagic manifestations of ITP were reported in 48.0% of pts, severe hemorrhagic syndrome was reported in 10.0% of pts; Before enrollment, splenectomy was reported in 94 pts (18.5%); complete response (CR) was maintained in 34 (36.2%) pts, partial response - in 20 (21.3%), and no response - in 7 (7.4%). Thirty-two (34.0%) pts had lost the response after initial success. During the study, splenectomy was performed in 44 (10.8%) pts, of those - in 7 pts (15.9%) with newly diagnosed ITP; in 6 pts (13.6%) - with persistent ITP, and in 31 pts (70.5%) - with chronic ITP. The duration of the disease at the time of splenectomy varied from 0 to 21 yrs; with a median of 1.03 year. CR to splenectomy was observed in 31 (70.5%) pts, partial response - in 10 (22.7%), and no response in 1 (2.3%), while 2 (4.5%) pts lost response. Since the response to splenectomy might change during the observation in the study, the best response was registered. Table 1. Distribution of the best response to splenectomy variable (before study entry and in the course of the study). Number of Pts (n) % Best response to splenectomy Missing data 1 0.7% Complete response 65 47.1% A response 30 21.7% No response 8 5.8% Loss of response 34 24.6% Total 138 100% Two hundred and forty-three (47.9%) pts received their first-line treatment during the study; glucocorticosteroids (GCS) - 222 (91.3%) pts, immunoglobulins (IVIG) - 2 pts (0.8%), other drugs - 26 (10.7 %) pts. A second-line therapy was administered to 133 pts (26.23%), of which 27 (20.3%) received GCS, IVIG - 23 (17.3%), alfa-interferons - 6 (4.5%), immunosuppressants - 8 (6%), rituximab - 18 (13.53%), romiplostim - 39 (29.3%), eltrombopag - 37 (27.8%), other drugs - 2 (1.5%) pts. Conclusion For the first time in Russia, information regarding the clinical presentation and the "real life" management practice of adults with primary ITP was obtained in a large cohort of pts in a prospective study. The Registry showed a variability of ITP clinical course. One fifth of pts were refractory to therapy. The main therapy options for the ≥ 2nd line in a cohort of adult pts were splenectomy and TPO receptor agonists. However, large proportion of pts still received GCSs in the 2nd and even 3rd line of therapy. Disclosures No relevant conflicts of interest to declare.

Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5036-5036 ◽  
Author(s):  
Beihui Huang ◽  
Juan Li ◽  
Junru Liu ◽  
Dong Zheng ◽  
Mei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematologic Response ◽  
Best Response ◽  
Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

Results of the Russian Registry of Primary Immune Thrombocytopenia in Pediatric Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4643-4643
Author(s):  
Anastasia Shamardina ◽  
Inna Markova ◽  
Tatyana Sycheva ◽  
Elena Volodicheva ◽  
Alexander Rumyantsev ◽  
...  
Keyword(s):  
Platelet Count ◽  
Immune Thrombocytopenia ◽  
Disease Onset ◽  
Specific Treatment ◽  
Complete Response ◽  
Second Line ◽  
Second Line Therapy ◽  
Chronic Itp ◽  
Line Therapy ◽  
Clinically Significant

Abstract Study objectives We aim to evaluate disease characteristics and treatment practices of pediatric pts. with Immune thrombocytopenia (ITP) in Russia. Materials and methods The ITP Registry was a multicenter, prospective, observational cohort study. Inclusion criteria: diagnosis of primary ITP, informed consent of the patient/guardians. Exclusion criteria: secondary or congenital thrombocytopenia. Data from medical records were registered in the e-CRF in average every 3 months. Descriptive statistics were used. Patients were registered since June 2011 till June 2014. Results Ninety-three pediatric pts, 46 male (49.5%) and 47 female (50.5%) with a median age 8.4 yrs (range 0.5-17.8) from 5 centers in various regions of Russia were included. The mean observation period reached 17.1 ± 6.5 mo (range1.4 to 28.6 months). Seventy (75.3%) pts had acute and 24.7% pts had insidious disease onset. The presence of trigger factors for ITP development was found in more than half of the cases (in 61.3% of patients), they are listed in Table 1. Table 1. Triggers N % No triggers 36 38.7% Infection 46 49.5% Vaccination 8 8.6% Other 3 3.2% Total 93 100% Median disease duration at enrollment was 1.07 years (range 0 to 16.7 yrs). ITP duration shorter than 5 years at the enrollment was reported in 89.2% pts, up to 1 year - in 43 (46.2%), 1- 5 years - in 40 (43%), 5-10 years - in 8 (8.6%), >10 years - in 2 (2.2%) pts. Newly diagnosed ITP was reported in 35 (37.6 %) pts, persistent ITP - in 12 (12.9 %), chronic ITP - in 46 (49.5 %) pts.Median platelets count was 12,0 x 109/L (range 0.0 - 72.0 109/L). Ninety-two (98%) pts experienced hemorrhagic manifestations during the course of ITP: skin hemorrhages - in 98.9%, oral bleeding - in 15.1%, epistaxis - in 36.6%, gastrointestinal bleeding - in 1.1%, intracranial bleeding - in 1.1%, hematuria - in 1.1%, and other hemorrhages - in 9.7% of pts. Relationship between hemorrhagic syndrome and platelet count at the enrollment is provided in table 2. Table 2. Relationship between hemorrhagic syndrome and platelet count (at enrollment) Hemorrhage highest grade according to WHO Platelet count (visit 1) Total pts / % < 30,000 30,000 -50,000 >50,000 0 3 5.5% 3 5.5% 49 89.1% 55 100% 1 11 40.7% 5 18.5% 11 40.7% 27 100% 2 5 62.5% 0 0% 3 37.5% 8 100% 3 2 66.7% 1 33.3% 0 0% 3 100% Total 21 22,6% 9 9.7% 63 67.7% 93 100% Severe course of ITP after enrollment was observed in 12 (13%) pts (of whose 6 (6.5%) had clinically significant hemorrhage at the disease onset and 6 (6.5%) had new clinically significant hemorrhages during follow-up period. Refractory ITP at enrollment was reported in 9 (9.7%) pts and was associated with the resistance to the first-, second- and subsequent lines of therapy. At enrollment 42 (45.2%) pts received specific treatment for ITP. Before enrollment, splenectomy was reported in only 1 (1.1%) 14-years old patient who had a complete response. During the study, splenectomy was performed in 6 (6.6%) pts with chronic ITP; the duration of the disease at the time of splenectomy varied from 2 to 10 years, with average duration of 4.69 years (median - 4.5 years). Complete response to splenectomy was observed in 3 (50%) pts, a partial response - in 2 (33.3%), no response - in 1 (16.7%) patient. Loss of response to splenectomy was not reported. During the study, severe ITP was reported in 8 (8.7%) pts, 41 (44.6%) pt had various hemorrhagic manifestations of ITP at least at 1 visit, grade IV hemorrhagic syndrome was not reported. Thirty-eight (41%) pts received 1-st line treatment: glucocorticosteroids (GCS) - 23 (60.5%) pts, IVIG - 5 (13.2%), alfa-interferons -16 pts (42.1%). Twenty-three pts (24.7%) received second-line therapy: GCS - 1 (4.3%), IVIG -1 (4.3%), immunosupression - 1 (4.3%), rituximab - 2 (8.7%), romiplostim - 11 (47.8%), eltrombopag - 14 (60.9%). Conclusion For the first time new information on the features of the disease and patterns of management of pediatric pts with primary ITP in Russia was obtained in a prospective study. Interestingly, the preferred therapy for the 2nd or subsequent lines are TPO receptor agonists used outside the approved indications in research institutions, based on published clinical trial data. Splenectomy rate before and during the study was only 7.5% (7 pts) with chronic ITP; in 1 child (14.3%) splenectomy was ineffective. Low acceptance of splenectomy suggests TPO-mimetics as potential second-line therapy. In total, good disease control is achievable in the majority of pediatric pts with ITP. Disclosures Off Label Use: use of TPO-mimetics in children.

Combination Therapy Based on Bortezomib for Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5048-5048
Author(s):  
Jingsong He ◽  
Li Yang ◽  
Dian Jin ◽  
Xuanru Lin ◽  
Qianqian Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Combination Therapy ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Serious Adverse Events ◽  
Novel Drugs ◽  
Grade 3

Abstract Abstract 5048 Introduction: Novel drugs, such as bortezomib, have significantly improved the response rates in multiple myeloma (MM), but little has been reported on bortezomib-based therapies in Chinese patients. Methods: In the initial eight 28-day cycles, newly diagnosed ymptomatic patients were treated with combination therapy including bortezomib plus dexamethasone (PD) and the triplet combinations of PD with adriamycin (PAD), cyclophosphamide (PCD), thalidomide (PDT) between February 1, 2006 and May 31, 2012. Among the above regimens, bortezomib (1. 3 mg/m2) was given intravenously on days 1, 4, 8, 11, while dexamethasone (20 mg/m2/day) was given intravenously on days 1–2, 4–5, 8–9, 11–12, adriamycin (10 mg/m2) was given intravenously on days 1–4, cyclophosphamide (200 mg/m2) was given intravenously on days 1–4 and thalidomide (100 mg) was administered orally each day. Results: The overall response rate (¡Ý partial response, PR) of all the 151 eligible patients was 88. 7% (including 29. 8% very good partial response (VGPR) and 25. 8% complete response/near complete response (CR/nCR). The responses per IMWG criteria for patients are shown in Table 2. The median PFS was 20. 3 months (95% CI: 14. 8–25. 8 months) in the patients who received PDT, 24. 8 months (95% CI: 20. 0–30. 0 months) in the patients who received PCD, 22. 9 months (95% CI: 17. 6–28. 2 months) in patients who received PAD and 21. 8 months (95% CI: 15. 3–28. 3 months) in the patients who received PD with no significant differences between the groups. The median OS for PD arm was 42. 0(95% CI: 20. 1–63. 9 months) months while other arms were not reached, but the median OS for PDT, PCD and PAD was significant longer than PD (P=0. 042, 0. 039, 0. 010). PFS and OS for patients with favorable cytogenetics were significantly longer than those with unfavorable cytogenetics by FISH. The frequently observed hematologic toxicities (Grade 3/4) were: thrombocytopenia (17. 00%), neutropenia (15. 00%) and anemia (8. 61%). The most common non-hematologic toxicities included (all Grades) peripheral neuropathy(57. 61%), fatigue(27. 15%), infection(23. 84%), constipation(22. 52%), herpes zoster(17. 22%) and diarrhea(15. 23%). Conclusions: Our experience indicated that bortezomib-based regimens were active and well-tolerated for MM patients, and triplet combinations were superior to PD. Serious Adverse events were rare in the Chinese patients with MM who received bortezomib-based chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Rituximab in the Treatment of Adults with Chronic Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3930-3930 ◽  
Author(s):  
Ghassan Zalzaleh ◽  
Ahmad Jajeh ◽  
Diemante Tamoseviciene
Keyword(s):  
Partial Response ◽  
Hemolytic Anemia ◽  
Complete Response ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Overall Response ◽  
Medical Centers ◽  
History Of ◽  
Refractory Itp

Abstract Corticosteroids have been the first line of treatment of ITP since 1950, however some patients do not respond to this treatment (refractory) and some will relapse after its discontinuation. For such patients second line treatments were introduced. Some patients will continue to be refractory to this treatment and need other therapy modality. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen exposing B Lymphocytes, causing its depletion. This could alter the production of auto-antibodies in some Auto-Immune diseases and thus could be used in their treatment. Few medical centers had reported using Rituximab in the treatment of refractory (ITP) and (AIHA), yet its definite role could not be determined, and here we share our experience. Patients with documented diagnosis of ITP or AIHA who were refractory to at least two lines of therapy including steroids were offered to receive Rituximab (375mg/m2 weekly for 4 weeks). 15 patients were enrolled, 10 with ITP, 4 with AIHA, 1 with Coombs negative Hemolytic anemia, and 1 with pure red cell aplasia. One had both ITP and AIHA. 10 were females and 5 males. 5 were >60 years old and 10 were < 60 years old. 2 out of the 10 patients with ITP had also Chronic Lymphocytic Leukemia (CLL). Duration of follow up ranged from 2 months to 17 months (average 7 mos). Of the 10 patients with refractory ITP treated with Rituximab overall response was 60%. 4 were NR (no response), 2 were MR (minimal response: Platelets increased to <50000), 2 were PR (Partial response: Platelets increased to <100000) and 2 were complete response (Platelets became normal). 3 patients of 6 with Hemolytic anemia or PRC aplasia had NR, 1 had MR (Hct <30), and 2 had partial response (Hct 30–35). No complete response was observed in this group. In 3 patients with hemolytic anemia and CLL 1 had MR, 1 had PR and 1 had NR. 2 patients with hemolytic anemia who had NR died as a complication of their disease (one with septic shock and one with severe autoimmune flare up). Only one patient with refractory ITP had mild allergic side effects and did not complete 4 doses. No Rituximab related mortality was observed. CONCLUSION: Rituximab therapy had a variable but valuable effect in the treatment of patients with chronic refractory ITP and refractory/ relapsed AIHA. Overall response in our group reached 60%. No clinical or laboratory parameters were found to predict response, although there was a suggestion that males, younger age, and no history of splenectomy have a better chance of response. As we lack an effective alternative treatment in chronic refractory ITP and AIHA, Rituximab use could be a valid option in view of its mild toxicity. Further follow up of our patients and input from other institutions in this regard are needed.

First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4940-4940
Author(s):  
Gerrard Teoh ◽  
Kihyun Kim ◽  
Alok Srivastava ◽  
Vasant Pai ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Osteonecrosis Of The Jaw ◽  
High Rate ◽  
Asia Pacific ◽  
Hematopoietic Stem ◽  
Asian Patients ◽  
Tract Infections

Abstract Abstract 4940 Introduction Many physicians have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently unable to tolerate full doses of dexamethasone (Dex) and/or thalidomide (Thal). Unfortunately, co-operative clinical studies from the Asia-Pacific countries are presently lacking and the effective dose of the Dex/Thal combination in Asians is unknown. Since higher doses of zoledronic acid (Zol) have been shown to exert an anti-MM effect in pre-clinical models of MM, we investigated whether higher frequency dosing of Zol combined with lower doses of Dex/Thal could be an effective and better tolerated regimen in Asian patients. Moreover, since attainment of very good partial response (VGPR), near complete response (nCR) or complete response (CR) prior to autologous hematopoietic stem cell transplantation (AHSCT) correlates with good outcome in MM, we wanted to determine if this lower-dose Dex/Thal with higher-frequency dosing Zol regimen could be a good preparative regimen in transplant-eligible patients. Patients and Methods In this international co-operative multicenter phase II non-randomized single arm study in previously untreated patients with MM (n=44), all patients received up to 6 cycles of three-weekly Dex/Thal/Zol (or “dtZ”). Doses of Dex ranged from 20 mg weekly to 20 mg four times a week; and doses of Thal ranged from 50 mg weekly to 100 mg every night. Zol 4 mg was given three-weekly. Response was graded using Blade's criteria. Results The study population included 67.3% Oriental (Korean and Chinese), 30.8% Indian and 1.9% Malay patients. 15.4% of patients were ISS stage I, 61.5% stage II and 23.1% stage III prior to treatment. 39 (88.6%) patients demonstrated at least a partial response (PR); and 23 (52.3%) of patients achieved VGPR (18.2%), near nCR (15.9%) or CR (18.2%). The fastest time to VGPR/nCR/CR was 1 cycle. Most patients tolerated treatment very well and were managed in the outpatient clinic. Sepsis was the most frequently reported grade 3 or 4 toxicity – 8 (18.2%) patients developed bronchopneumonia, and 3 (6.8%) gastrointestinal or urinary tract infections. 1 (2.3%) patient was suspected of having pulmonary embolism. There were 4 (9.1%) deaths – 3 from severe sepsis and 1 from an unknown cause. Importantly, there were no reports of peripheral neuropathy, osteonecrosis of the jaw (ONJ) or end stage renal failure. In fact, there was an overall 2.4% improvement in the median creatinine clearance time (CCT). Finally, the percentage of CD34 stem cells was not adversely affected by treatment with dtZ. Conclusions The dtZ regimen appears to be an effective and well-tolerated treatment regimen for Asian patients with newly-diagnosed MM. The high rate of VGPR/nCR/CR will greatly facilitate AHSCT in transplant-eligible patients. Judicious use of low-dose Thal has abrogated the numerous side-effects associated with Thal and greatly improved patient tolerance. Even though Zol is administered at a higher frequency, it is not associated with worsening of renal function or ONJ. Infections are the most frequent and worrisome complications of treatment. These are likely to be related to the dose of Dex. Accordingly, it is probably wise to further lower the dose of Dex in future studies. (This study is registered with NIH PRS # 00263484.) Disclosures No relevant conflicts of interest to declare.

Achievement of Complete Response Is a Strong Prognostic Factor In Elderly Newly Diagnosed Myeloma: Retrospective Analysis of 1175 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1949-1949
Author(s):  
Francesca Gay ◽  
Alessandra Larocca ◽  
P.W. Wijermans ◽  
Sara Bringhen ◽  
Tommasina Guglielmelli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Complete Response ◽  
New Drugs ◽  
Response To Treatment ◽  
Maximal Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Best Response ◽  
The Impact

Abstract Abstract 1949 Introduction: There is extensive evidence from numerous studies in the transplant setting that achievement of complete response (CR) or at least very good partial response (VGPR) is significantly associated with prolonged progression-free survival (PFS) and overall survival (OS). In elderly myeloma patients CR was a rare event since new drugs has been added to standard melphalan-prednisone (MP). After the introduction of novel agents, CR represents an achievable goal, also outside of the transplant setting. Aims: to assess the impact of response to treatment on time-to-event parameters (PFS and OS) in elderly myeloma patients. Methods: We retrospectively analysed newly diagnosed myeloma patients, older than 65 years old, or younger but not eligible for high-dose chemotherapy and transplant. Patients were enrolled in 3 multicentre randomized European trials of the GIMEMA and Hovon groups, and were treated with MP (n=332), MP plus thalidomide (MPT, n=332), MP plus bortezomib (VMP, n=257) or MP plus bortezomib-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT, n=254). PFS, OS and duration of CR were analysed by the Cox proportional hazards model, comparing the two arms by the Wald test and calculating 95% confidence interval (CI). Univariate and multivariate analyses were performed for the following variables: age at diagnosis (>75 vs. ≤75 yrs), International Staging System (ISS) stages, type of chemotherapy and best response achieved. Best response was treated as a time-dependent variable. Results: A total of 1,175 patients, enrolled from November, 2001 to January, 2009, were retrospectively analysed. The best response to treatment was available in 1,136 patients: CR was reported in 195, VGPR in 212, PR in 397. Baseline characteristics according to best response achieved in patients who obtained CR, VGPR or PR were similar. Since response rates vary according to treatment regimens the proportion of patients who received MP, MPT, VMP, and VMPT-VT was different in the different response categories. After a median follow-up of 29 months, PFS was significantly higher in patients who achieved CR compared to those who obtained VGPR (HR 0.16; 95% CI 0.10–0.24; p<0.001) or PR (HR 0.07; 95% CI 0.04–0.13; p<0.001). The advantage in PFS translated into an advantage in OS: patients obtaining CR have a significantly prolonged OS than patients who achieved VGPR (HR 0.15; 95% CI 0.08–0.28; p<0.001) or PR (HR 0.08; 95% CI 0.04–0.16, p<0.001), (table). In multivariate analysis CR achievement was as an independent predictor of longer PFS and OS, regardless of age, ISS stage, and treatment administered. In patients > 75 years, both PFS and OS were shorter as compared to younger patients. Despite these differences, the impact of CR on outcome was identical. In the subgroup of patients > 75 years, PFS was significantly prolonged in patients who achieved CR, compared with those who obtained VGPR (HR 0.26; 95% CI 0.12–0.58, p = 0.001) or PR (HR 0.20; 95% CI 0.10–0.41, p < 0.001). Accordingly, OS was significantly higher in patients who achieved CR, compared with those who obtained VGPR (HR 0.13; 95% IC 0.03–0.58; p = 0.007), or PR (HR 0.12; 95% IC 0.03–0.51, p = 0.004), (table). No significant PFS differences between patients obtaining CR during the first 6 months of treatment or later were seen (HR 1.06; 95% IC 0.49–2.27; p=0.878). Similarly, no OS differences between these two groups were detected (p = 0.676). Duration of CR was comparable in patients who obtained CR during or after the first 6 months of treatment (HR 0.66; 95% CI 0.30–1.45; p = 0.305). Patients whose CR lasted more than 18 months have a significant OS benefit compared to patients who did not (p=0.006). Conclusions: These finding highlight the importance of CR, also outside of the transplant setting, regardless of age, ISS and treatment administered, and support the use of new drugs, also in patients older than 75 years, to achieve and maintain maximal response. Disclosures: Gay: Celgene: Honoraria. Bringhen:Calgene: Honoraria; Janssen-Cilag: Honoraria. Guglielmelli:Celgene: Honoraria; Janssen Cilag: Honoraria. Boccadoro:Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees. Sonneveld:Celgene: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson : Membership on an entity's Board of Directors or advisory committees. Palumbo:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Family History Of Hematologic Malignancies and Disorders In a Population Based Study Of Myelodysplastic Syndromes (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1541-1541
Author(s):  
Angela R. Smith ◽  
Erica D. Warlick ◽  
Rachel K. Fonstad ◽  
Michelle A. Roesler ◽  
Jenny N. Poynter ◽  
...  
Keyword(s):  
Family History ◽  
Conflicts Of Interest ◽  
Positive Family History ◽  
Hematologic Malignancies ◽  
Population Based ◽  
Newly Diagnosed ◽  
Population Based Study ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
History Of

Abstract Background MDS is a clonal hematopoietic stem cell disorder characterized by dysplastic changes in the bone marrow, ineffective hematopoiesis and an increased risk for developing acute myeloid leukemia (AML). The majority of MDS cases are sporadic, but rare familial cases have been described and are often ascertained through clinic-based referrals. To our knowledge, no population based study of MDS has examined the frequency of family history of hematologic malignancies and disorders in patients, nor associations with disease characteristics and outcomes. Methods Newly diagnosed MDS cases are being identified by rapid case ascertainment by the Minnesota Cancer Surveillance System (MCSS), a population-based cancer registry in Minnesota. Eligibility criteria include all newly diagnosed cases of MDS during the period April 1, 2010-October 31, 2014, between 20-85 years, Minnesota resident, and ability to understand English or Spanish. Proxy interviews are not being conducted. Medical records and biologic samples are obtained and questionnaires are filled out by participants. Centralized pathology and cytogenetics review confirm diagnosis and classify by subtype and risk score including the Revised International Prognostic Scoring System (IPSS-R). Since 2010, information on family history has been obtained through questionnaire responses and/or medical record review on 353 MDS patients. Cases were considered to have a positive family history if they reported a first degree relative with MDS, leukemia, lymphoma or other hematologic condition (multiple myeloma [n=4], Waldenstrom’s macroglobulinemia [n=1] and idiopathic thrombocytopenic purpura [n=1]). Treatment related MDS cases were excluded leaving 330 MDS patients for analysis. Unconditional logistic regression was used to calculate crude odds ratios (ORs) and 95% confidence intervals (CI) overall and by sex. Results A total of 61/330 (18.5%) cases reported a family history of a hematologic condition. The mean age at diagnosis was 71.3 years in those with a family history compared to 72.2 years in those without a family history (p=0.53). There was no difference in the sex distribution between the two groups. Though not statistically significant, the odds of having abnormal cytogenetics or an IPSS-R of High/Very High was lower for those having a positive family history (OR 0.57 [CI 0.25-1.33, p=0.19 and 0.67 [CI 0.24-1.84, p=0.29], respectively). The odds of survival at one year after diagnosis was significantly higher in those with a family history (OR 2.79 [CI 1.04-7.51, p=0.04]) compared to those without (Table). Further stratification by sex revealed that this association was strongest for males (OR=4.23, [CI 0.94-19.0, p=0.06] compared to females (OR=1.84 [CI=0.47-7.19, p=0.38]). Discussion In this population based study of adults with MDS, the prevalence of MDS cases having a positive family history was higher than previous reports. Additionally, cases reporting a family history of hematologic malignancies and disorders appear to experience lower risk disease and have significantly improved overall survival, especially males. It is possible that patients with a family history of hematologic conditions are diagnosed earlier in the course of their disease secondary to increased awareness about blood disorders and/or more active screening within the family. Our analysis is limited by relatively small numbers, but enrollment is ongoing so subsequent analyses with larger numbers of subjects may be more revealing. Additionally, a prospective study to examine these families further, including detailed medical histories and collection of biospecimens (saliva, blood, skin) for genetic analyses is underway in order to identify potential mechanisms and mutations involved in the development of MDS and progression to AML. Disclosures: No relevant conflicts of interest to declare.

Weekly Carfilzomib, Cyclophosphamide and Dexamethasone (wCCyd) in Elderly Newly Diagnosed Multiple Myeloma Patients: Results of a Phase 2 Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1828-1828 ◽  
Author(s):  
Sara Bringhen ◽  
Davide Rossi ◽  
Alessandra Larocca ◽  
Paolo Corradini ◽  
Piero Galieni ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
Board Of Directors ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Background Carfilzomib is a novel second generation proteasome-inhibitor with significant anti-MM activity and favorable toxicity profile. In a recent phase 1/2 study in relapsed/refractory patients (pts) a weekly schedule of carfilzomib in combination with dexamethasone showed to be effective (overall response rate of 77%) and safe (ASCO 2015). The ongoing phase 3 ARROW study is comparing once- with twice-weekly carfilzomib. In the newly diagnosed setting, no data are available on weekly carfilzomib. We designed a phase 1/2 study of weekly carfilzomib in combination with cyclophosphamide and dexamethasone (wCCyd) for newly diagnosed MM pts. Results of the dose-escalation phase 1 portion of study were previously reported (Palumbo A et al, Blood 2014), the maximum tolerated dose of weekly carfilzomib was established as 70 mg/m2. Here we report efficacy and safety results of the phase 2 portion of the study. Methods Newly diagnosed pts ineligible for autologous stem-cell transplantation due to age or co-morbidities were enrolled in the phase 2 portion of the study. Pts received IV carfilzomib at the maximum tolerated dose 70 mg/m2 on days 1, 8, 15 combined with oral cyclophosphamide at 300 mg/m2 on days 1, 8, 15 and oral dexamethasone at 40 mg on days 1, 8, 15, 22, in 28-daycycles. After the completionof 9 cycles, pts received 28-day maintenance cycles with carfilzomib at 70 mg/m2 on days 1, 8, 15 until disease progression or intolerance. The primary objectives were to determine the efficacy and safety of wCCyd. The secondary objectives included the evaluation of time to progression, progression-free survival, time to next therapy and overall survival. Response was assessed according to the modified International Uniform Response Criteria. Adverse events (AEs) were graded following NCI-CTCAE v4. Results As of July 15, 2015, 47 newly diagnosed MM pts were enrolled in the phase 2 portion of the study. Median age was 72 years, 23% of pts were older than 75 years, 30% had ISS stage III, 34% had unfavorable FISH profile [t(4;14) or t (14;16) or del17p or amp1]. Toxicityand response data were available in 40 pts, who completed atleast the first cycle; 7 pts were still receiving their first cycle of treatment. Pts received a median of 6 cycles (range 1-9). Overall, 80% of pts achieved at least a partial response, 60% at least a very good partial response, and 28% a near complete response. Responses improved over time (Table 1). During the study, 9 pts progressed or died, the progression-free survival at 1 year was 75%. Grade (G) 3-4 drug-related adverse events included neutropenia (22%, 9 pts), thrombocytopenia (7%, 3 pts), infection (10%, 4 pts), acute pulmonary edema (5%, 2 pts), creatinine increase (5%, 2 pts), fever (2.5%, 1 pt), fatigue (2.5%, 1 pt) and headache (2.5%, 1 pt). G1-2 hypertension was reported in 6 pts (15%). No peripheral neuropathy was reported. Overall, the wCCyd regimen was well tolerated, 4 pts (10%) required carfilzomib dose-reduction (G3 hematologic toxicities [2 pts], G3 headache [1 pt] and G2 fatigue [1 pt]) and 9 pts (22%) required treatment discontinuation due to adverse events (2 infections, 1 acute pulmonary edema, 1 creatinine increase, 1 fever, 1 pt condition, 1 second tumor, 1 pericardial effusion, 1 sudden death). Conclusions This is the first prospective study evaluating once-weekly carfilzomib in treatment-naïve MM. wCCyd therapy appears safe and effective in newly diagnosed MM pts. Responses became deeper with subsequent cycles and toxicities were manageable. The response rate observed with weekly carfilzomib compares favorably with similar studies with standard twice-weekly carfilzomib infusion. Updated results will be presented at the meeting. Table 1. 2nd cycle 6th cycle 9th cycle Complete Response 17% 26% 33% At least near Complete Response 29% 39% 40% At least Very Good Partial Response 66% 82% 87% At least Partial Response 86% 87% 87% Disclosures Bringhen: Janssen-Cilag, Celgene, Novartis: Honoraria; Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Use off-label of drugs for the dose and/or schedule and/or association. Larocca:Janssen-Cilag, Celgene: Honoraria. Offidani:Janssen-Cilag, Celgene, Sanofi, Amgen, Mundipharma: Honoraria. Gaidano:Celgene, Onyx: Membership on an entity's Board of Directors or advisory committees. Boccadoro:Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees. Sonneveld:Janssen-Cilag, Celgene, Onyx, Karyopharm: Honoraria, Research Funding; novartis: Honoraria. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria.

Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4210-4210
Author(s):  
Luiza soares Vieira ◽  
Edvan de queiroz Crusoe ◽  
Manuella de S. Sampaio Almeida ◽  
Lais Sousa ◽  
ana Lucia Perez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Oligoclonal Bands ◽  
High Dose ◽  
Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Phase 2 Trial of Concurrent Monosialotetrahexosylganglioside in the Prophylactic Treatment of Bortezomib-Induced Peripheral Neuropathy in Patients of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5399-5399
Author(s):  
Liang Wang ◽  
Zhongjun Xia ◽  
Xiaoqin Chen
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Partial Response ◽  
Subcutaneous Injection ◽  
Complete Response ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Female Ratio ◽  
Phase 2 Trial

Abstract Backgrounds Bortezomib is an important drug in the treatment of multiple myeloma (MM), and peripheral neuropathy (PN) is a significant dose-limiting toxicity of bortezomib. No effective prophylaxis has been defined for PN. Monosialotetrahexosylganglioside (GM), a nerve-protecting drug, is often used to promote growth of nerve and function restoration of damaged nerve. The role of GM in the prophylaxis of bortezomib-induced PN in MM patients has never been investigated. Methods A phase 2 clinical trial was conducted in newly diagnosed MM patients to evaluate the value of GM in the prophylaxis of bortezomib-induced PN. All eligible patients were treated with VD (bortezomib 1.3mg/㎡,subcutaneous injection, d1 ,8,15,22, and dexamethasone 40mg, po,d1 ,8,15,22, 4 weeks a cycle) or CyBorD (cyclophosphamide 300mg/㎡,po,d1 ,8,15, bortezomib 1.3mg/㎡,subcutaneous injection, d1 ,8,1 5,22, and dexamethasone 40mg, po,d1 ,8,15,22, 4 weeks a cycle) for at least 4 cycles. GM was used at a dosage of 100mg/day intravenously at d1 -2, 8-9, 15-16, 22-23. No other nerve-protective drugs or thalidomide-containing regimens were allowed. The primary endpoint was overall incidence rate of PN (the grade of PN was recorded according to CTCAE v3.0). The secondary endpoints included duration of PN, complete response rate after 4 cycles of treatment, 1-year PFS and OS rate. (This trial was registered in ClinicalTrial.gov, NCT02093910). Results From February 2014 to February 2015, 25 patients of newly diagnosed MM were enrolled. The median age was 55 years old (37-75), and male to female ratio was 19:6. 5 patients had ISS stage I disease, 6 patients with stage II, and the remaining 14 patients with stage III. All patients received a median of 4 cycles (range 2-9) of Bortezomibcontaining regimens. At the time of data analysis, 84% of patients had at least partial response, 48% had at least very good partial response, and 24% had complete response. 7 patients experienced PN after a median of 2 cycles (range 1-4) of treatment, resulting in the overall PN rate of 28%. Among these 7 patients, only 1 patient (4%) had grade 2 PN, leading to dose reduction of bortezomib, and all other patients had grade 1 PN. During treatment, 1 patient (4%) had grade 2 diarrhea, and another 1 patient (4%) had herpes zoster infection. The concurrent use of GM did not introduce new side effects and seemed not compromise the efficacy of bortezomib. At a median follow up time of 8 months, 1-year PFS rate and OS rate were speculated to be 69.8% and 100%, respectively. Conclusions The early-term analysis of this phase 2 trial found it feasible to concurrently use GM and bortezomib-containing regimens, and GM had the potential role of reducing bortezomib-induced PN rate and severity without compromising efficacy. This needs to be validated in future phase 3 randomized clinical trials. Disclosures No relevant conflicts of interest to declare.

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