Reduced-Dosage of Three Drugs Combination of Cyclophosphamide, Bortezomib and Dexamethasone (reduced-CyBorD) Retains High Response Rate with Less Toxicities in Elderly Patients with Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1865-1865 ◽  
Author(s):  
Hideo Yagi ◽  
Ryosuke Fujiwara ◽  
Keigo Sano ◽  
Fujita Mariko ◽  
Takashi Iizuka ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Elderly Patients ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
High Response Rate ◽  
High Response ◽  
High Dose ◽  
Weekly Schedule ◽  
High Dose Dexamethasone

Abstract Abstract 1865 Background: The three drugs combination of cyclophosphamide, bortezomib and dexamethasone (CyBorD) has been proven to be a powerful regimen for the treatment of the patients with multiple myeloma (MM). However, twice-weekly schedule of bortezomib and high dose dexamethasone has been shown to cause significant toxicities, including severe peripheral neuropathy (PN). Recently, once-weekly bortezomib induction therapy with CyBorD (modified-CyBorD) has shown less toxicity with high response rate equal to original regimen (Reeder, CB et al. Leukemia 2009). However, more than half of the patients developed bortezomib induced PN (BiPN) in modified-CyBorD. Thus it was still concerned adverse event for the transplant ineligible patients, especially frail elderly patients because it often caused interruption or withdrawal of the treatments, resulting in fewer efficacies. Under these circumstances, we introduced the reduced-dosage of CyBorD regimen (reduced-CyBorD) in the transplant ineligible patients with multiple myeloma for continuation of the treatment. Methods: The protocol consisted of bortezomib given intravenously at a dose of 1.3 mg/m2once a week on days 1, 8, 15, cyclophosphamide orally at a dose of 50 mg daily on days 1–21, and dexamethasone orally or intravenously at a dose of 20 mg daily on days 1,2,8,9,15,16 in 4-week cycles. Total of 20 patients, including 12 newly diagnosed and 8 refractory, were treated with reduced-CyBorD and evaluated its efficacy and safety. Results: The median age was 72 years (range from 62 to 81). 14 patients were more than 70 year-old (70%). A half of the patients were female. According ISS, 3 patients were classified in stage I, 6 were in II, and 11 were in III. The overall response was 86.6 % with 26.7 % CR/nCR (1 CR, 3 nCR, 5 VGPR and 4 PR). Hematological adverse events were neutropenia (35%; G1/2 n=7), lymphocytopenia (35%; G1/2 n=1, G3/4, n=1), thrombocytopenia (10%; G1/2 n=2). Non-hematological adverse events were pneumonia (20%; G2 n=2, G3 n=2), VZV infection (15%; G2 n=3), cerebral infarction (5%; G2 n=1). Importantly, only three patients (15%) developed grade 1 PN, and no patient reduced or discontinued bortezomib due to PN. Conclusions: Reduced-CyBorD with three times once-weekly bortezomib retained high efficacy seen in standard and modified CyBorD (4 times bortezomib administration). Furthermore, it was found that this regimen obviously revealed less toxicity, especially BiPN compared with those previous regimens (See Table). Our results suggested that reduced-CyBorD might be safe and effective approach to the transplant ineligible patients, especially elderly frail patients with MM. Disclosures: No relevant conflicts of interest to declare.

Reduced-Dosage Of Three Drugs Combination Of Cyclophosphamide, Bortezomib and Dexamethasone (reduced-CyBorD) Is Suitable For Elderly Frail Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1963-1963 ◽  
Author(s):  
Hideo Yagi ◽  
Ryosuke Fujiwara ◽  
Keigo Sano ◽  
Keiko Yamazaki ◽  
Hitoshi Hanamoto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
High Response Rate ◽  
High Dose ◽  
Weekly Schedule ◽  
Old Patients ◽  
High Dose Dexamethasone ◽  
Highly Active ◽  
Frail Patients

Abstract Background The three drugs combination of cyclophosphamide, bortezomib and dexamethasone (CyBorD) is highly active regimen for the treatment of the patients with multiple myeloma (MM). However, twice-weekly schedule of bortezomib and high dose dexamethasone has been shown to cause significant toxicities, including peripheral neuropathy (PN) and thrombotic events. Once-weekly bortezomib induction therapy with reduced dosage of dexamethasone (modified-CyBorD) has shown less toxicity with high response rate equal to original regimen (Reeder, CB et al. Leukemia 2009). However, it was found more than half of the patients still developed bortezomib induced PN (BiPN) in this modification. Thus it was still concerned adverse event for the transplant ineligible patients, especially frail elderly patients because it often caused interruption or withdrawal of the treatments, resulting in fewer efficacies. Under these circumstances, we have studied the reduced-dosage of CyBorD regimen (reduced-CyBorD) in the treatment of transplant ineligible patients with MM to assess response and toxicity. Methods The protocol consisted of bortezomib given intravenously at a dose of 1.3 mg/m2 once a week on days 1, 8, 15, cyclophosphamide orally at a dose of 50 mg daily on days 1-21, and dexamethasone orally or intravenously at a dose of 20 mg daily on days 1,2,8,9,15,16 in 4-week cycles. Total of 32 patients, including 20 newly diagnosed and 12 refractory, were treated with reduced-CyBorD and evaluated its efficacy and safety. Results The median age was 72 years (range from 62 to 88). 14 patients were more than 75 year-old (44 %). 15 patients were female. According ISS, 4 patients were classified in stage I, 10 were in II, and 18 were in III. The overall response (ORR) was 90.6 % with 43.8 % of CR/nCR (6 CR, 8 nCR, 7 VGPR and 8 PR). Hematological adverse events were anemia (18.8%; G1/2 n=7), neutropenia (37.5%; G1/2 n=10, G3/4 n=2), lymphocytopenia (43.8%; G1/2 n=10, G3/4 n=4), thrombocytopenia (12.5%; G1/2 n=1, G3/4 n=3). Non-hematological adverse events were pneumonia (12.5%; G2 n=2, G3 n=2), VZV infection (15.6%; G1/2 n=5), cerebral infarction (3.1%; G2 n=1). Importantly, only 6 patients (18.8%) developed grade 1 PN, and no patient reduced or discontinued bortezomib due to PN. The overall survival (OS) at 1, 2, and 3 years were 81, 63.1, and 45.9 %, respectively. In this study, neither inferior response nor poor survivals were significantly observed between over 75 year-old patients group (n=14) and under 75 year-old group (n=18) (ORR; 100 vs 83.4 %, CR/nCR; 42.9 vs 44.4 %, 1-year PFS 54.6 vs 50 %, and 3-year OS 29.8 vs 55 %). Conclusions Reduced-CyBorD with three times once-weekly bortezomib retained high efficacy seen in standard and modified CyBorD previously reported (ORR; 90.6 vs 88 and 93 %, CR/nCR; 43.8 vs 39 and 43 %). These results showed that our regimen has less toxicity, especially BiPN (18.8 %) compared with those previous regimens (64 % and 57 %), resulting in no discontinuation nor reduction of bortezomib. Furthermore, over 75 year-old patients group did not showed inferior outcomes in comparison with under 75 year-old patients group. Our results suggested that reduced-CyBorD might be suitable for the transplant ineligible patients, especially elderly frail patients (over 75 year-old) with MM. Disclosures: No relevant conflicts of interest to declare.

High response rate to low-dose rituximab plus high-dose dexamethasone as frontline therapy in adult patients with primary immune thrombocytopenia

2013 ◽  
Vol 90 (6) ◽  
pp. 494-500 ◽  
Author(s):  
David Gómez-Almaguer ◽  
Luz Tarín-Arzaga ◽  
Brizio Moreno-Jaime ◽  
José Carlos Jaime-Pérez ◽  
Adrián Alejandro Ceballos-López ◽  
...  
Keyword(s):  
Immune Thrombocytopenia ◽  
Low Dose ◽  
Response Rate ◽  
High Response Rate ◽  
High Response ◽  
Adult Patients ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Primary Immune Thrombocytopenia ◽  
Frontline Therapy

Lenalidomide plus high-dose dexamethasone provides improved overall survival compared to high-dose dexamethasone alone for relapsed or refractory multiple myeloma (MM): Results of a North American phase III study (MM-009)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
D. M. Weber ◽  
C. Chen ◽  
R. Niesvizky ◽  
M. Wang ◽  
A. Belch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Response Rate ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Time To Progression ◽  
Prognostic Features ◽  
High Dose Dexamethasone ◽  
Grade 3

7521 Background: Lenalidomide is a novel, orally administered, immunomodulatory drug (IMiD) that has single-agent activity against MM and additive effects when combined with dexamethasone (Dex). Methods: In this phase 3, multicenter, double-blind trial, 354 patients (pts)with relapsed or refractory MM were treated with Dex 40 mg daily on days 1–4, 9–12, 17–20 every 28 days and were randomized to receive either lenalidomide (Len) 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning with cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were stratified with respect to B2M (≤ 2.5 vs. > 2.5 mg/mL), prior stem cell transplant (none vs. ≥ 1), and number of prior regimens (1 vs > 1). The treatment arms were well balanced for prognostic features. Results: The overall response rate was greater with Len-Dex than with Dex-placebo (59.4% vs. 21.1%; p < 0.001). Complete responses were achieved in 12.9% of pts treated with Len-Dex and 0.6% of pts treated with Dex-placebo. The median time to progression (TTP) for pts treated with Len-Dex was 11.1 months compared to 4.7 months for pts treated with Dex-placebo (p < 0.000001). Median overall survival was higher with Len-Dex (not reached) compared to Dex-placebo (24 months) (hazard ratio 1.76, p = .0125). Grade 3–4 neutropenia was more frequent with combination therapy than with Dex-placebo (24% vs. 3.5%), however ≥ grade 3 infections were similar in both groups. Thromboembolic events occurred in 15% of pts treated with Len-Dex and in 3.5% of pts treated with Dex-placebo. Atrial fibrillation occurred in 8 pts and CHF developed in 4 pts treated with Len-Dex. Conclusions: Considering the ease of oral administration, higher response rate, longer time to progression and overall survival benefit, the combination of lenalidomide-dexamethasone may very well represent the treatment of choice for early refractory or relapsing multiple myeloma. The relatively infrequent side effects should not detract from these improvements, but the use of prophylactic antithrombotic therapy should be considered for patients treated with the combination of lenalidomide and dexamethasone. [Table: see text]

Doxil (D), Vincristine (V), Reduced Frequency Dexamethasone (d) and Revlimid(R) (DVd-R) Results in a High Response Rate in Patients with Refractory Multiple Myeloma (RMM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2559-2559 ◽  
Author(s):  
Rachid Baz ◽  
Toni K. Choueiri ◽  
Rony Abou Jawde ◽  
Bridget McGowan ◽  
Yvette Ellis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Median Time ◽  
Progressive Disease ◽  
Response Rate ◽  
Median Number ◽  
High Response Rate ◽  
High Response ◽  
Chemotherapeutic Regimen ◽  
Best Response ◽  
Grade 3

Abstract Background: The combination of DVd with Thalidomide (T) results in a high response rate (greater than 80% with about 50% of patients achieving a CR or NCR) in multiple myeloma. Revlimid, an immunomodulatory drug (IMiD) is active in patients with MM. We previously reported on a phase I trial of DVd-R in patients with MM, in which the maximum tolerated dose of R was 10mg daily. Methods: The DVd-R regimen was given as follows: on day 1 D was given at 40 mg/m2 IVPB; V at 2 mg IVP; d at 40 mg PO daily for 4 days, R was started at 10mg daily. R was given for 21 days consecutively. For the first cycle R was started 7 days prior to chemotherapy, while it was started on day 1 on subsequent cycles (cycle 1 was 35 days). DVd was planned every 28 days for 2 cycles after best response or a minimum of 4 cycles. Maintenance therapy consisted of R +/− Prednisone 50 mg Qod. All patients received amoxicillin, acyclovir and aspirin 81mg prophylactically. Responses were assessed based on the criteria set forth by SWOG. Patients: The study accrued 58 patients to date (36 refractory and 22 relapsed patients), 45 are evaluable for response. The median patient age at the start of the study is 62 years and 74% are males. The median number of prior chemotherapeutic regimen is 3 (range 1–7), 67% of patients had progressed after a Thalidomide containing regimen, 70% had received a VAD like regimen and 17% had received a prior autologous stem cell transplant. The median time from diagnosis to study entry is 39 month (range 5–182). Eighty six percent had Durie Salomon stage III. The mean serum B2microglobin was 6.6mg/dL (s.d.4.2). Results: The median number of cycles of DVd-R delivered was 4. Of evaluable patients, 6 patients had a CR (13%), 5 had a NCR (11%), 16 had a PR (35%), 11 had stable disease (24%), and 7 had progressive disease (15%) as their best response. The median time to best response was 38 days. After a median follow up of 7.3 month (range 0–24 months), 23 patients had progressive disease and 16 patients had died. Fifty two percent of refractory patients (19/36) had a response on DVd-R. Grade 3 and 4 leukopenia occurred in 24% and 15% respectively, however febrile neutropenia occurred in only 1 patient. Grade 3 and 4 infections occurred in 26% and 3% respectively (all but one were pneumonia). Grade 3 thrombocytopenia occurred in 20%. Venous thromboembolic events occurred in 5 patients (9%) (2 patients with pulmonary embolus and 4 with deep venous thrombosis). Grade 3 neuropathy occurred in 3 patients (no patients had grade 4 neuropathy). Two patients developed grade 3 tumor lysis syndrome. Conclusion: DVd-R is an effective chemotherapeutic regimen in patients with RMM who progressed or did not respond to VAD like regimens or to Thalidomide containing regimens, produces a high response rate among chemotherapy resistant patients, and has a manageable toxicity profile. The results will be updated at the time of the meeting.

Lenalidomide/Dexamethasone Improves Response and Prolongs Time to Progression, Even in Patients with IgA Multiple Myeloma: A Sub-Analysis of the MM-009/010 Studies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4839-4839 ◽  
Author(s):  
Robert Foa ◽  
Donna Weber ◽  
Meletios Dimopoulos ◽  
Marta Olesnyckyj ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response ◽  
High Response Rate ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Phase Iii Trials ◽  
The Impact

Abstract Background: Historically, patients with IgA multiple myeloma (MM) respond poorly to treatment. In 2 recent phase III trials, Lenalidomide (Len) in combination with Dexamethasone (Dex) led to an overall response (OR) rate of approximately 60% (61% in MM-009 and 60% in MM-010), a complete response (CR) rate of about 15% (14% and 16%, respectively), an overall survival (OS) of at least 29.5 months (29.5 and not yet reached), and a median time to progression (TTP) of at least 11.1 months (11.1 months and 11.3 months, respectively) in patients with relapsed/refractory MM. In both studies, OR, CR, OS and TTP were significantly better with Len/Dex than with Dex alone. Here, we assess the impact of IgA disease on the efficacy and tolerability of treatment with Len/Dex versus Dex alone. Methods: Data were pooled from the MM-009 and MM-010 studies. Patients were randomized to receive Len (25 mg/day on days 1–21 of each 28-day cycle) or placebo. Both groups received Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After four cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, and adverse events were assessed. Response rate and TTP were based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: Of 154 patients with IgA at baseline, 72 were treated with Len/Dex and 82 with Dex alone. Among those without IgA, 281 received Len/Dex and 269 received Dex alone. Baseline characteristics were balanced between treatment groups. Len/Dex was associated with a significantly higher OR and longer median TTP than Dex alone in patients with and without IgA (Table). In the non-IgA group, patients treated with Len/Dex had a significantly longer OS than those treated with Dex alone. Response, TTP and OS were comparable between IgA and non-IgA patient groups. There was no difference in the incidence of adverse events between patients with and without IgA. Among those with IgA, the most common grade 3–4 adverse events with Len/Dex and Dex alone were neutropenia (37.5% and 2.4%), thrombocytopenia (16.7% and 8.5%), and anemia (11.1% and 7.3%). The respective rates for patients without IgA were 46.5% and 14.5%, 12.1% and 5.7%, and 11.0% and 5.7%. Conclusion: In patients with and in those without IgA MM, Len/Dex treatment induces a high response rate and a prolonged TTP compared with Dex. IgA non-IgA Clinical response, % Len/Dex (n=72) Dex alone (n=82) P Len/Dex (n=281) Dex alone (n=269) P OR 68.1 18.3 <0.001 57.7 23.0 <0.001 CR 18.1 0 NS 14.2 2.6 NS PR 38.9 15.9 NS 35.6 19.3 NS Median TTP, wks 44.3 16.4 <0.001 52.1 20.1 <0.001 Median OS, wks 130.4 102.4 NS 156.0 136.1 <0.05

scholarly journals Bortezomib-Melphalan-Prednisone (VMP) Versus MP As Initial Treatment for Patients Older Than 75 Years with Newly Diagnosed Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5683-5683
Author(s):  
Min Kyoung Kim ◽  
Kihyun Kim ◽  
Dok Hyun Yoon ◽  
Cheolwon Suh ◽  
Jae Hoon Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Response Rate ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
Newly Diagnosed ◽  
Very Elderly ◽  
Age Related

Abstract Although bortezomib-melphalan-prednisone (VMP) therapy is a well-established standard treatment for patients with multiple myeloma (MM) who are ineligible for high-dose therapy, it is not clear whether very elderly patients should be treated with VMP, considering the toxicities. The purpose of this case-control study was to compare the efficacy of VMP versus melphalan-prednisone or cyclophosphamide-prednisone (MP/CP) as initial therapy for very elderly patients. We retrospectively studied 202 patients aged 75 years or older with newly diagnosed multiple myeloma between March 2007 and February 2015. One-hundred twenty two patients received VMP and eighty patients received MP/CP regimen were enrolled from 13 institutions throughout Korea. Patient characteristics were comparable in these two groups. Overall response rate was 69.7% in VMP patients and 47.5% in MP/CP patients (P=0.002). Complete response rate was 24.6% in VMP patients and 10% in MP/CP patients (P=0.005). After a median follow-up for survivors of 28.4 months, progression-free survival was significantly different between the two groups (median 21.0 vs. 11.9 months in VMP and MP/CP group, respectively, P=0.037). Overall survival was also significantly different between the two groups (median 34.6 vs. 27.8 months in VMP and MP/CP group, respectively, P= 0.023). Hematologic grade 3-4 toxicities were more common with VMP (anemia: 29.1% vs 15.3%, P=0.077; thrombocytopenia: 39.3% vs. 15.3%, P < 0.001). Grade 2-4 diarrhea (22.5% vs. 2.8%, P = 0.001), vomiting (13.7% vs. 1.4%, P = 0.011), and peripheral sensory neuropathy (35.3% vs. 4.2%, P <0.001) were also more common with VMP. Despite the presence of age-related comorbidities, VMP therapy was associated with modest toxicity, a better response rate and prolonged survival, supporting the use of this effective combination as frontline therapy for very elderly patients with MM. Disclosures Lee: Amgen: Membership on an entity's Board of Directors or advisory committees. Kim:Celltrion, Inc.: Research Funding.

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