Thalidomide in Multiple Myeloma - A Community Hospital Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5140-5140 ◽  
Author(s):  
Homayoun Leon Daneschvar ◽  
Hamed Daw ◽  
Asif Chaudhry ◽  
Harris Taylor ◽  
Manmeet Ahluwalia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Partial Response ◽  
Community Hospital ◽  
Response Rate ◽  
Complete Response ◽  
M Protein ◽  
Newly Diagnosed ◽  
Number Of Patients

Abstract Multiple Myeloma accounts for 10% of malignant hematologic neoplasms. For the past 30 years, a combination of melphalan and prednisone has been the standard treatment for this disease. Nonetheless, it remains an incurable malignancy with a median survival that does not exceed three years. Recent evidence suggests that angiogenesis is increased in multiple myeloma and has prognostic value. Because of its anti-angiogenic properties, thalidomide has been employed as therapy and several trials show that thalidomide alone is active in 25% to 35% of patients with relapsed and refractory myeloma. Among previously untreated patients with more advanced and symptomatic disease, the combination of thalidomide-dexamethasone doubled the response rate to 72 % (in comparison to thalidomide alone) and induced remissions more rapidly. Objectives: To evaluate the efficacy and side effects of thalidomide in combination with glucocorticoid in previously untreated (newly diagnosed) and treated (refractory to other chemotherapies) multiple myeloma patients in a community hospital setting. Patients and Methods: We retrospectively identified eighty-four consecutive patients with multiple myeloma treated between September 1999 and October 2004 at the Cleveland Clinic Center at Fairview Hospital. The sixteen of eighty-four patients (Table 1) who had received thalidomide were selected for further study. The median starting dose was 150 mg/d. The maintenance dosage was 50–100 mg/d in accordance with tolerability. In addition to thalidomide all sixteen patients were receiving dexamethasone. All provided written informed consent prior to receiving treatment. The primary end point of the study was response rate, defined as complete (undetectable monoclonal M protein in the serum) or partial (greater than 50% reduction in serum monoclonal M protein level) Results: Three patients achieved a partial response in the refractory group and 2 in the newly diagnosed group. One patient achieved a complete response in the refractory group and four in newly diagnosed patients. Sixty percent of the patients in the refractory group and 100% of the newly diagnosed patients survived the follow up time (Table 2). Major side effects included sedation in four (25%), deep venous thrombosis in three (18.7%), neuropathy in three (18.7%) and constipation in two (12.5 %) of the patients. Conclusion: The combination of thalidomide and dexamethasone appears to show promising activity in patients with newly diagnosed and possibly with refractory MM. The combination induced a high frequency of response, rapid onset of remission, and low incidence of serious irreversible toxicity. However, ongoing randomized trials are still needed to define further the role of thalidomide with dexamethasone in the treatment of multiple myeloma. Table 1 Patients Characteristics Refractory patients Newly diagnosed patients Number of patients 10 6 Age (years) 66.3 60.5 Sex 7 male, 3 female 1 male, 5 female IgA type 3 3 IgG type 6 2 Biclonal 1 1 Table 2 Refractory patients Newly diagnosed patients Partial response 3 2 Complete response 1 4 No response 6 0 Median follow up (months) 25.2 11.3 Median progression free survival (months) 7.5 10 Diagnosis to start of thalidomide (months) 18.7 2.5 Time on thalidomide (months) 14.2 11.2 Number of deaths (during follow up time) 4 0

Utility of Serum Free Light Chain Measurements in Multiple Myeloma Patients Not Achieving Complete Response

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3427-3427
Author(s):  
Muhamad Alhaj Moustafa ◽  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Francis K Buadi ◽  
Morie A Gertz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Complete Response ◽  
M Protein ◽  
P Value ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Best Response ◽  
First Response

Abstract Background: Normalization of serum free light chain ratio (FLCr) following achievement of a complete response (CR) to therapy denotes a stringent CR in multiple myeloma, and is associated with improved overall survival (OS). However, its value in patients achieving less than a CR is not clear. We hypothesized that patients in whom FLCr normalizes with the initial anti-myeloma therapy will have an improved outcome, even in the absence of a CR. Methods: We analyzed the medical records of patients with MM who were evaluated at Mayo Clinic, Rochester, MN between January 2004 and December 2011, seen within 90 days of diagnosis. We selected patients with measurable disease on serum protein electrophoresis, defined as a serum M-spike ≥1 g/dl at the time of diagnosis. Then, we excluded all patients with negative immunofixation for monoclonal M-protein in serum and urine at their first response as well as those who did not have serum FLC results available from the time of their first best response. M protein measurements were collected serially from the time of diagnosis until the time of the first relapse or last follow up date if no relapse was recorded. Progression-free survival (PFS) and OS were analyzed using the Kaplan-Meier method. Results: Out of the 1354 MM patients seen at our institution during this period, a total of 453 patients were included in our study. The median age of the cohort at the time of diagnosis was 65 (range, 29-91); 49% were older than 65 years and 284 (63%) were male. The estimated median follow up for the whole cohort was 66 months (95% CI; 61, 71); 241 patients were alive with a median follow up of 4.7 years (range, 0.4 to 10). Three hundred and seventy three (82%) patients had relapsed following the initial therapy with a median time to progression (TTP) of 19.5 months (95% CI; 18, 22) and PFS of 19 months (95% CI; 17, 20). The median OS for the entire cohort is 67 months (95% CI; 59, 73). The median time to the best first response was 6.9 months (range: 0.3-83 months). At the time of the best first response 154 patients (34%) had normal FLCr. Patients with normal FLCr had a longer PFS (29 vs. 16 months, P< .0001) and OS (91 vs. 58 months, P= .0002). We then examined the impact of FLCr normalization on survival outcomes according to their IMWG response categories. We found that FLCr normalization had a favorable impact on PFS in each of the three groups [very good partial response (VGPR), Partial response (PR), and Stable disease (SD)], However, when looking at the OS, only patients with PR had a better OS associated with a normal sFLC κ/λ ratio (Table 1). Conclusions: Obtaining a normal sFLC ratio appears to confer a more favorable prognosis irrespective of the depth of the response, suggesting an important role for serial-sFLC measurements in disease monitoring even in patients who achieve only a PR to therapy as their best response. This supports the inclusion of sFLC at all levels of response included in the current International Myeloma Working Group (IMWG) criteria. Abstract 3427. Table 1 Effect of FLCr normalization according to IMWG response categories SD PR VGPR Normal FLCr Abnormal FLCr p-value Normal FLCr Abnormal FLCr p-value Normal FLCr Abnormal FLCr p-value Number of patients 7 70 62 157 85 60 PFS, month, median (95% CI) 27 (14, 36) 7 (5, 12) < .02 26 (20, 36) 17 (13, 20) .0005 29 (23, 32) 21 (18, 26) .03 OS, months, median (95% CI) 68 (49, 68) 41 (31, 61) > .1 NR (65, NR) 61 (50, NR) .004 74 (67, 107) 73 (59, NR) > .9 • Abbreviations: NR; statistically not reached •• Progressive disease (PD) was not included because none of the 12 patients achieved a normal FLCr. Disclosures No relevant conflicts of interest to declare.

Daratumumab (DARA) in combination with carfilzomib, lenalidomide, and dexamethasone (KRd) in patients (pts) with newly diagnosed multiple myeloma (MMY1001): An open-label, phase 1b study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8000-8000 ◽  
Author(s):  
Andrzej J. Jakubowiak ◽  
Ajai Chari ◽  
Sagar Lonial ◽  
Brendan M. Weiss ◽  
Raymond L. Comenzo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Safety Profile ◽  
Standard Of Care ◽  
Complete Response ◽  
Newly Diagnosed ◽  
Open Label ◽  
Frontline Treatment ◽  
Grade 3

8000 Background: DARA in combination with established standard of care regimens prolongs PFS, deepens responses, and demonstrates a favorable safety profile in relapsed or refractory multiple myeloma (MM). The tolerability and efficacy of DARA-KRd in newly diagnosed MM pts was examined. Methods: Newly diagnosed pts regardless of transplantation eligibility were enrolled. Pts received DARA 16 mg/kg QW for Cycles 1-2, Q2W for Cycles 3-6, and Q4W thereafter. All pts received the 1st dose of DARA split over 2 days. Carfilzomib (K) was administered on Days 1, 8 and 15 of each 28-day cycle (20 mg/m2 on C1D1, 36 or 70 mg/m2 subsequently based on tolerability of first dose) for ≤13 cycles or elective discontinuation for ASCT. Lenalidomide 25 mg was given on Days 1-21 and dexamethasone 20-40 mg per week. The primary endpoint was tolerability. Results: Twenty-two pts (median [range] age, 60 [34-74] y) were enrolled and received a median of 8 (1-10) treatment cycles. Nineteen pts escalated K dose to 70 mg/m2 by C1D15. Median (range) duration of follow-up was 7.4 (4.0-9.3) months. Six (27%) pts discontinued treatment (1 AE [pulmonary embolism]; 1 PD; 4 other [ASCT]). Serious AEs occurred in 46% of pts, and 14% were possibly related to DARA; 18 (82%) experienced a grade 3/4 TEAE. The most common grade 3/4 TEAEs (>10%) were lymphopenia (50%) and neutropenia (23%); 1 (5%) cardiac grade 3 TEAE was observed (congestive heart failure) which resolved; pt quickly resumed study treatment with reduced K dose. No grade 5 TEAE was reported. All DARA-associated infusion reactions (27% of pts) were grade ≤2. Treatment with DARA-KRd yielded an ORR (≥partial response) of 100% (5% complete response, 86% ≥very good partial response) in 21 response-evaluable pts. The 6-month PFS rate was 100%. Conclusions: The addition of DARA to KRd was well tolerated; the overall safety profile was consistent with that previously reported for KRd, with no additional toxicity observed with the addition of DARA. Deep and durable responses were observed. These data support further investigation of DARA-KRd as a frontline treatment regimen. Updated data will be presented based on longer follow up. Clinical trial information: NCT01998971.

Updated Follow-up and Results of Subsequent Therapy in the Phase III VISTA Trial: Bortezomib Plus Melphalan–Prednisone Versus Melphalan–Prednisone in Newly Diagnosed Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 650-650 ◽  
Author(s):  
Jesus F San Miguel ◽  
Rudolf Schlag ◽  
Nuriet K Khuageva ◽  
Meletios A Dimopoulos ◽  
Ofer Shpilberg ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Interim Analysis ◽  
Response Rates ◽  
Complete Response ◽  
Phase Iii ◽  
High Dose ◽  
End Point ◽  
Number Of Patients

Abstract Based on the results of the large, international, phase III VISTA trial in previously untreated MM patients ineligible for high-dose therapy with stem cell transplantation (HDT-SCT), bortezomib (VELCADE®) was approved by the US FDA for the initial treatment of multiple myeloma (MM). Data from VISTA showed that bortezomib plus melphalan–prednisone (VMP) was superior to melphalan–prednisone (MP) across all efficacy end points, including response rates (overall and complete response [CR] rates), time to progression (TTP), time to subsequent therapy (TTNT), and overall survival (OS). Patients (N=682) from 151 centers in 22 countries in Europe, North and South America, and Asia were randomized (1:1) to 54 weeks treatment with VMP (N=344) or MP (N=338). Patients received nine 6-week cycles of bortezomib 1.3 mg/m2 (days 1, 4, 8, 11, 22, 25, 29, 32 in cycles 1–4 and days 1, 8, 22, 29 in cycles 5–9) with melphalan 9 mg/m2 and prednisone 60 mg/m2 (days 1–4 in cycles 1–9), or melphalan plus prednisone, per the dose and schedule described above. The primary end point was TTP, with progression determined using European Group for Blood and Marrow Transplantation (EBMT) criteria. Median age was 71 years; 30% of patients were aged ≥75 years. At baseline, 34% of patients had Karnofsky Performance Status (KPS) ≤70%, 33% had β2-microglobulin >5.5 mg/L, and 34% had International Staging System (ISS) Stage III disease. An Independent Data Monitoring Committee recommended the trial be stopped based on a protocol-specified interim analysis as the statistical boundary for the primary end point had been crossed. VMP was well tolerated, with patients remaining on VMP therapy for a median of 46 weeks (8 cycles) versus 39 weeks (7 cycles) with MP; median total dose of bortezomib received was 38.5 mg/m2. Collection of tumor assessment data was stopped after presentation of the positive interim analysis. Collection of survival data, subsequent therapy data and safety/recovery data continued. Updated follow-up through April 25, 2008 confirms a statistically significant survival benefit for VMP versus MP (HR=0.64, P=0.0032) after a median follow-up of 25.9 months. Three-year survival rates were 72% versus 59%, respectively. TTNT and treatment-free interval (TFI) were also significantly longer in the VMP arm (TTNT 28.1 vs 19.2 months, HR=0.53, P<0.000001; TFI 16.6 vs 8.4 months, HR=0.54, P<0.00001). Fewer patients in the VMP versus MP arm (38% vs 57%, respectively) required subsequent therapy. Of the patients receiving subsequent therapy in the VMP and MP arms, 16% and 43% received bortezomib, 49% and 44% received thalidomide, and 19% and 6% received lenalidomide, respectively. Re-treatment with bortezomib was effective in the VMP arm (6% CR) (Table); a 10% CR rate was reported in the MP arm after bortezomib-based therapy. Peripheral neuropathy (PN) in the VMP treatment arm improved or resolved in 79% of events (median 1.9 months), with 60% of PN events resolving completely (median 5.7 months). VMP is an active and well-tolerated treatment option for previously untreated MM patients and significantly prolongs survival and time to subsequent therapy. Patients can be successfully treated with subsequent immunomodulatory-based combination therapy and can also be retreated with bortezomib, achieving high response rates with manageable toxicity. Table. Investigator-reported best responses with subsequent therapies per treatment arm VMP arm (n=129)* MP arm (n=194) Subsequent therapy and number of patients who received therapy* Complete response (%) Partial response (%) Complete response (%) Partial response (%) * Other agents were used as subsequent therapy including dexamethasone; patients could receive multiple-agent regimens Bortezomib or bortezomib combination (n=105) 6 33 10 45 Thalidomide combination (n=149) 4 44 3 52 Lenalidomide Combination (n=37) 4 52 0 55

scholarly journals Efficacy of Bortezomib plus dexamethasone as a first line treatment in newly diagnosed cases of Multiple Myeloma: A Single Centre Study in a Tertiary Care Hospital

2020 ◽  
Vol 28 (1) ◽  
pp. 34-41
Author(s):  
Mahbuba Sharmin ◽  
Mohammad Manirul Islam ◽  
Abdul Aziz ◽  
Salauddin Shah ◽  
Md Jalilur Rahman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Intracranial Haemorrhage ◽  
Response Rate ◽  
Malignant Tumors ◽  
Tertiary Care ◽  
Care Hospital ◽  
Newly Diagnosed ◽  
Overall Response ◽  
Highly Effective

Background: Multiple Myeloma (MM) accounts for 1% of malignant tumors and 10%–15% of hematopoietic neoplasms. Bortezomib, a first in class proteasome inhibitor, induces apoptosis and growth arrest and reverse chemoresistence in Myeloma cell and has demonstrated no irreversible adverse effect on haemopoietic stem cell. Dexamethasone increases the response rate. Thus, Bortezomib plus dexamethasone represent highly effective regimen for previously untreated Multiple Myeloma cases and significantly higher response rates approximately 70%– 90% have been observed.This combination thus may serve the basis of future strands of care in Multiple Myeloma patients. Objective: The aim of the study was to assess the efficacy , safety and tolerability of Bortezomib in newly diagnosed cases of Multiple Myeloma patients in Bangladesh. Materials & Methods: This prospective observational study was carried out in the Haematology department of BSMMU from June 2017 to December 2018. Patients received inj. Bortezomib (1.3mg/m2 ) 4 cycles as an intravenous bolus on days 1,4,8,11 in a three week cycle (twice weekly administration) in indoor and same patients as day care basis in outpatients department. Dexamethasone at 40 mg was given intravenously or orally on the day of and day after inj Bortezomib.A self administered questionnaire containing different set of questions regarding Multiple Myeloma were used for data collection. Results: Among the study population, 93% of patients had anaemia followed by bone pain (86%) and renal impairment (39%). Out of 25 patients,complete response achieved in 13 patients (52%), where 4 patients(16%) showed partial response,6 (24%) showed very good partial response and 2 (8%) patients showed no response. The overall response rate was 92% belonged to partial,very goofd partial and no respone respectively. Death occurred in 3 cases (12%). 5 patients (20%) developed Bortezomib induced peripheral neuropathy.Life threatening intracranial haemorrhage occurred in two patients (8%). Death occurred in 3 cases (12%),2 patients due to intracranial haemorrhage and another from cardiac arrest. In this study,S. creatinine, â2 microglobulin and bony lesion variables showed significant association with treatment response. Conclusion: Bortezomib plus dexamethasone is a highly effective and safe regimen for previously untreated multiple myeloma patients. This novel therapy in myeloma represent a new trearment paradigm targeting both tumor and microenvironment which has markedly improve overall response(OR), long progression free survival (PFS) and overall survival (OS)across in all risk groups. Moreover,it can be administered safely in the outpatient setting provided by clinicians. J Dhaka Medical College, Vol. 28, No.1, April, 2019, Page 34-41

A Phase II Study of PS-341 for Patients with High Risk, Newly Diagnosed Multiple Myeloma: A Trial of the Eastern Cooperative Oncology Group (E2A02).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2546-2546 ◽  
Author(s):  
Angela Dispenzieri ◽  
Emily Blood ◽  
David Vesole ◽  
Rafael Fonseca ◽  
Natalie Callander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
High Risk ◽  
Partial Response ◽  
Progressive Disease ◽  
Response Rate ◽  
Cell Labeling ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Background: Multiple myeloma (MM) is an incurable disease with a anticipated overall survival (OS) ranging from months to decades. Modest improvements in OS have been made with high-dose chemotherapy with peripheral blood stem cell transplant (PBSCT), but to date prognostic factors have a greater impact on OS than do individual therapies. Patients with adverse risk factors such as elevated beta-2 microglobulin (B2M), plasma cell labeling index, deletions of the long arm of chromosome 13 by metaphase cytogenetics (del 13q) require innovative new treatment strategies. Bortezomib has significant activity in patients with both newly diagnosed and relapsed/refractory MM, but its specific role in patients with adverse features has not yet been defined. Methods: Patients with newly diagnosed “high-risk” myeloma (B2M ≥ 5.5., PCLI ≥ 1, or del 13q) and adequate organ and functional status were eligible. Patients were treated with bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 every 21 days for 8 cycles as induction. After induction, patients were scheduled to receive bortezomib 1.3 mg/m2 every other week indefinitely. Elective peripheral stem cell mobilization (growth factor alone) was allowed after 4 cycles of bortezomib. Patients relapsing on maintenance schedule were to have the full induction schedule resumed. Responses were by the EBMT criteria but a very good partial response category was included. The primary end-point was the response rate in these high-risk patients (90% power to detect a response rate of 50% or higher). The study decision rule requires that 16 or more responses, among 39 eligible patients, are seen in order to declare this treatment effective. Results: Between March 15, 2004 and March 10, 2005, 44 patients enrolled on study. Among the 43 eligible patients, median age was 63; 51% were male. All patients had high risk disease: del 13q (6/41); plasma cell labeling index ≥1% (16/34); and B2M≥5.5 (34/43). Preliminary response data are available for 18 of the 44 cases enrolled, of which 7 had partial response, 1 had minimal response, 1 had no response, 2 had progressive disease, and 5 were unevaluable. Among those patients completing induction therapy and with response information, the median number of cycles of therapy administered is 5, range (0,8). The most common non-hematologic adverse events (AEs) of grade 3 or higher included hyponatremia (9 patients) and diarrhea (6 patients). Mild sensory peripheral neuropathy was common: grade 1, 16 patients; grade 2, 2 patients. Only 1 patient had grade 3 peripheral neuropathy. One patient died after receiving 2 doses bortezomib due to heart block and asystole. Two patients had a grade 4, 25 patients had grade 3, and 13 had grade 1 or 2 as the worst grade non-hematologic adverse event. Based on data received by August 1, 2005, 18 patients have gone off study: AEs (2); death (1); progressive disease (9); and other reasons (6). Updated results on the full study population along with FISH data for IgH translocations and deletions of 13q and 17p will be presented at the meeting. Conclusions: Preliminary results suggest that upfront bortezomib has activity in patients with high-risk MM, but further follow-up is required.

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.

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.

Targeting Complete Response with Upfront Bortezomib Followed By Autologous Transplantation and Consolidation Therapy for Untreated Multiple Myeloma (TUBA study)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3463-3463
Author(s):  
Hideki Nakasone ◽  
Kiriko Terasako-Saito ◽  
Teiichi Hirano ◽  
Atsushi Wake ◽  
Seiichi Shimizu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Induction Treatment ◽  
High Dose ◽  
Induction Phase ◽  
Consolidation Therapy ◽  
Newly Diagnosed ◽  
Free Survival

Abstract [Background] Multiple myeloma (MM) is generally considered incurable. Recently, novel drugs, including bortezomib, have demonstrated a survival benefit for newly diagnosed MM patients compared with classical treatments. Complete response (CR) after treatment is known to be associated with superior progression-free survival. Thus, we prospectively evaluated the efficacy and safety of boretezomib + dexamethasone (BD) for patients with newly diagnosed MM, followed by autologous hematopoietic stem cell transplantation (ASCT). We added BD consolidation therapy to aim CR if CR was not achieved after ASCT. [Patients and methods] This clinical study prospectively recruited newly diagnosed MM patients eligible for ASCT between 2010 and 2012. Due to health insurance issues in Japan, two courses of high-dose dexamethasone (HD-DX) had been administrated prior to BD induction treatment until Nov. 2011, while BD was administrated as an initial induction treatment since Dec. 2011. BD induction treatment included 1.3 mg/m2 of bortezomib on days 1, 4, 8, and 11 with 20mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11, and 12. This BD induction cycle was repeated every 3 weeks for 4 courses. Thereafter, filgrastim-based mobilization and ASCT following high-dose melphalan administration was performed. If patients did not achieve CR after ASCT, BD consolidation therapy (bortezomib: 1.3 mg/m2 on days 1, 8, and 15; dexamethasone 20 mg/day on days 1-2, 8-9, and 15-16) every 4 weeks was added to target CR (Figure 1) (UMIN-CTR: UMIN000002442). [Results] The median observational duration among survivors was 1536 days (range: 464-2023) at this analysis. Of the 47 enrolled MM patients, 46 (male 27; female 19) were eligible for BD induction treatment, while the remaining one achieved CR before BD induction. The median age of the patients was 59 (range: 35-67) years. Of the 44 patients whose karyotype analyses were available, normal karyotype was observed in 35. Abnormal karyotype included complex type in 4, diploid in 1, and other abnormalities in 4. FISH revealed deletion of p53 in 5 of 39 patients whose information was available; deletion of 13-chromosome in 16 of 42, IgH-MAF fusion in 1 of 40; IgH-FGFR3 fusion in 5 of 41; IgH-BCL1 fusion in 9 of 39. Of the 46 MM patients, 19 received HD-DX prior to BD induction, and 34 received ASCT after BD induction treatment (Figure 1). During the BD induction phase, 3 patients experienced disease progression, and BD treatment was discontinued in 9 patients because of their consent withdrawal (n=2) and adverse events (n=7) including interstitial pneumonia in 2, persistent neuropathy in 1, CMV enterocolitis in 1, heart failure in 1, diabetes mellitus in 1, and liver dysfunction in 1. After BD induction phase (n=46), their response was >= CR in 4 (8%), very good partial response (VGPR) in 10 (22%), partial response (PR) in 18 (39%), stable disease (SD) in 2 (4%), and progression or withdrawal in 12 (26%). After ASCT, their response was >=CR in 9 (20%), VGPR in 11 (24%), PR in 12 (26%), SD in 1 (2%), and additional progression or withdrawal in 1 (2%). Of the 24 patients who received ASCT and whose response was less than CR, 21 received BD consolidation therapy for a median of 4 courses (range: 1- 8). BD consolidation was discontinued in 4 patients due to persistent neuropathy or cytopenia. Finally, maximum response after ASCT with or without BD consolidation was >= CR in 19 (41%), VGPR in 7 (15%), PR in 6 (13%), < SD in 2 (2%, Figure 2). Through BD consolidation, CR was achieved in 8 of 11 patients with post-ASCT VGPR and 2 of 12 patients with post-ASCT PR. In total, 4-year progression-free survival (PFS) and overall survival (OS) was 43% (95%CI: 28-57%) and 80 % (95%CI: 64-90%), respectively. Focusing on CR patients after ASCT and those who actually received BD consolidation, PFS adjusted for karyotype and age were not different between CR patients after ASCT and after BD consolidation, while patients with VGPR or less after consolidation had significantly lower PFS (Figure 3). [Conclusion] BD induction and ASCT provided CR rate of 27% among ASCT patients, although BD induction may expectedly cause adverse events including persistent neuropathy and viral infections. Patients who achieved CR after ASCT showed good PFS, and targeting CR through BD consolidation might improve CR rate. It is worthwhile to prospectively compare the efficacy of BD consolidation only for patients who failed to achieve CR or universal consolidation strategy. Disclosures Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding.

Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

2014 ◽  
Vol 32 (7) ◽  
pp. 634-640 ◽  
Author(s):  
Antonio Palumbo ◽  
Sara Bringhen ◽  
Alessandra Larocca ◽  
Davide Rossi ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Complete Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Grade 3 ◽  
To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

scholarly journals Survival Analysis of Newly Diagnosed Transplant-Eligible Multiple Myeloma Patients in Czech Republic

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4894-4894
Author(s):  
Tereza Popkova ◽  
Ludek Pour ◽  
Ivan Spicka ◽  
Jakub Radocha ◽  
Alexandra Jungova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Survival Analysis ◽  
Czech Republic ◽  
Partial Response ◽  
Complete Response ◽  
High Dose ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
First Line Treatment

Abstract Introduction: Although highly effective agents and novel therapeutic strategies are being developed, high-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) has not been overcome in the first-line treatment for fit patients (pts) with multiple myeloma. The objective of this work is to retrospectively analyze the use of this procedure in newly diagnosed Czech patients. Methods: Data were derived using the Czech Myeloma Group Registry of Monoclonal Gammopathies. By February 2 nd 2021, a total of 2154 newly diagnosed multiple myeloma patients who underwent HDT/ASCT were identified. Results: At the time of multiple myeloma diagnosis, the median age was 59 years; 24%/56%/14%/5%/1% pts were ECOG 0/1/2/3/4; 44%/32%/24% pts were ISS stage I/II/III; 14.5%/17.5%/68% and 84%/16% pts were Durie-Salmon stage I/II/III and subclassification A/B, respectively. The combinations of agents used in the induction regimen were proteasome inhibitor (PI), immunomodulatory drug (IMiD) and glucocorticoid (GC) in 28.5% (613/2154) pts; PI, GC and chemotherapy (CHT) in 24.8% (534/2154) pts; GC and CHT in 22,5% and IMiD, GC and CHT in 16.1% (346/2154). Other combination of drugs was used in 8.2% (177/2154) pts. It was registered that 3.7% (79/2154) induction regimens were switched to a different combination because of toxicity, patient's choice, poor peripheral venous access or other reasons. Single HDT/ASCT was performed in 77.3% (1665/2154) cases whereas tandem HDT/ASCT was given to 11.8% (254/2154) patients. In 10% (215/2154) cases, the transplantation technique was not specified. Nine percent (193/2154) patients were treated within a clinical study. The median progression free survival (mPFS) and the median overall survival (mOS) of the whole cohort was 28.9 and 92.1 months, respectively. Information about response to treatment before and after the high-dose therapy were available for 75.7% (1627/2154) and 92.2% (1987/2154) patients, respectively. Disease status at the time of HDT/ASCT was defined as stringent complete response (sCR) at 2.2% (36/1627), complete response (CR) at 11.9% (194/1627), very good partial response (VGPR) at 38.2% (621/1627), partial response (PR) at 40.9% (666/1627), minimal response (MR) at 3.6%, (58/1627), stable disease (SD) at 2.2% (36/1627), progressive disease (PD) at 1% (16/1627) patients. The overall response rate (ORR) on day 100 was 92.8% (sCR: 10.5% [209/1987], CR: 22.4% [446/1987], VGPR: 35% [696/1987], PR: 24.8% [493/1987], MR: 2.7% [54/1987], SD: 1.4% [27/1987], PD: 3.1% [62/1987]). We also performed a survival analysis of patients progressing up to 18 months after HDT/ASCT (n=1219) versus patients progressing in more than 18 months (n=935). The median OS was 41.5 versus 124.9 months, respectively. An analysis of the role of tandem HDT/ASCT in this real-world cohort will be presented at the conference. Conclusion: Globally as well as in the Czech Republic, HDT/ASCT is an important therapeutic approach in the first-line treatment of multiple myeloma. Our analysis of 2154 newly diagnosed transplant-eligible patients confirms high effectiveness - ORR of 92.8%, mPFS of 28.9 months, and long-term survival reaching mOS of 92.1 months. Disclosures Minarik: Amgen: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria.

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