scholarly journals Clinical profile of multiple myeloma in Asia: An Asian Myeloma Network (AMN) study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8097-8097 ◽  
Author(s):  
Jae Hoon Lee ◽  
Kihyun Kim ◽  
Jin Seok Kim ◽  
Chang Ki Min ◽  
Kazuyuki Shimizu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Clinical Characteristics ◽  
Overall Response Rate ◽  
Response Rate ◽  
New Drugs ◽  
Asian Countries ◽  
Asian Patients ◽  
The Difference ◽  
Few Data

8097 Background: The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However the difference of clinical characteristics between ethnic groups is not well-defined. In Asian countries the incidence of MM has been lower compared with Western countries. However, there are growing evidences that MM is increasing very rapidly in this region. Until now, only few data of Asian patients has been reported. Asian myeloma network (AMN) decided to analyze the first multinational project to explore clinical characteristics of Asian MM patients and clinical practice performed in Asian countries. Methods: Data were collected from 21 centers from 7 countries and regions were collected retrospectively. Clinical characteristics of 2969 symptomatic MM patients at diagnosis were described. Overall survival (OS) and prognostic factors were analyzed for 2273 patients who have survival data. Results: Median OS was 54 months (95% CI 48.0-60.0). Patients who were diagnosed before 2000 were shorter survival. Transplantation was performed to 513 patients with better survival (84 vs. 45 months, p<0.001). First line treatment of 2339 evaluable patients was analyzed. Overall response rate was 71% with 30%, VGPR or better. New drugs including bortezomib, thalidomide or lenalidomide were combined for 32.5% of all 2339 patients without difference in response rate or OS according to combination. Conclusions: We successfully described clinical characteristics of Asian MM patients and this project will be the base for future studies or clinical trials for Asian MM patients. Updated analyses and comparison with Western data will be presented. AMN, supported by the International Myeloma Foundation (IMF) IMWG initiative.

scholarly journals Clinical Profile of Multiple Myeloma in Asia - an Asian Myeloma Network (AMN) Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5035-5035
Author(s):  
Jae Hoon Lee ◽  
Kihyun Kim ◽  
Jin Seok Kim ◽  
Chang Ki Min ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Survival Data ◽  
Clinical Characteristics ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Asian Countries ◽  
Genetic Characteristics ◽  
Asian Patients ◽  
The Difference ◽  
Few Data

Abstract Abstract 5035 Background: The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However the difference of clinical characteristics between ethnic groups is not well-defined. In Asian countries the incidence of MM has been lower compared with Western countries. However, there are growing evidences that MM is increasing very rapidly in this region. Until now, only few data of Asian patients has been reported. Asian myeloma network (AMN) decided to analyze the first multinational project to explore clinical characteristics of Asian MM patients and clinical practice performed in Asian countries. Methods: Data were collected from 22 centers from 7 countries and regions were collected retrospectively. Clinical characteristics of 3377 symptomatic MM patients at diagnosis were described. Overall survival (OS) and prognostic factors were analyzed for 3324 patients who have survival data. Results: Clinical and genetic characteristics were summarized at table 1. Median OS was 47 months (95% CI 48. 0–60. 0). Patients who were diagnosed before 2000 were shorter survival. Transplantation was performed to 607 patients with better survival (84 vs 40 months, p<0. 001). First line treatment of 2906 evaluable patients was analyzed. Overall response rate was 71% including VGPR or better 31%. Novel drug-based regimens including bortezomib, thalidomide or lenalidomide were used for 32. 5% of all 2906 patients without difference in response rate or OS. Conclusions: We successfully described clinical characteristics of Asian MM patients and this project will be the base for future studies or clinical trials for Asian MM patients. Updated analyses and comparison with Western data will be presented. AMN, supported by the International Myeloma Foundation (IMF) IMWG initiative. Disclosures: No relevant conflicts of interest to declare.

Induction with New Drugs and Planned Autologous Followed by Non-Myeloablative Allogeneic Transplantation in Newly Diagnosed Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4330-4330
Author(s):  
Luisa Giaccone ◽  
Moreno Festuccia ◽  
Roberto Sorasio ◽  
Nicola Mordini ◽  
Fabrizio Carnevale Schianca ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
New Drugs ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Post Transplant ◽  
The Impact

Abstract Abstract 4330 Introduction Immunomodulatory drugs have recently changed the treatment options in multiple myeloma. Moreover, thalidomide, bortezomib and lenalidomide have also been used in the setting of allografting as post-transplant salvage therapy or as maintenance. We are currently evaluating the impact of new drugs as induction therapy in newly diagnosed multiple myeloma before a planned standard autograft followed by a non-myeloablative allograft (Tandem auto-allo). Patients and methods Twenty-five newly diagnosed patients (median age 55 years old, range 26-65) entered a recently designed prospective phase II program of tandem auto-allo which included the use of so-called new drugs during induction. Here, we report data on the first 11 evaluable patients with a follow up of at least 1 month after the allograft. Induction consisted of lenalidomide and dexamethasone (n=5), thalidomide and dexamethasone (n=4), or bortemomib-containing regimens (n=2), followed by G-CSF mobilized peripheral blood stem cell harvest. A standard autograft after melphalan 200 mg/m2 was planned 2-4 months before a low-dose (2 Gy) TBI-based allograft from an HLA-identical sibling. GVHD prophylaxis consisted of cyclosporin and mycophenolate mofetil. Disease status at allografting and post-transplant outcomes were compared to those of 22 patients pair-matched for beta2microglobulin and age, who underwent tandem auto-allo after induction with VAD-based regimens without new drugs (Blood, 2009). Results At the time of allografting after induction with new drugs and the autograft overall response rate was 81% (9/11), including a immunofixation-negative complete remission (CR). Following allografting, all patients promptly achieved donor engraftment. After a median follow-up of 11 months (2-26), all patients are alive and the overall response rate was 91% (10/11). Incidence of grade II-IV GVHD was 34% (4/11), including 1 patient with grade III GVHD. Chronic GVHD was observed in 40% (4/10) of patients with at least 3 months of follow-up. The induction with new drugs did not increase allotransplant-related toxicity or incidence of acute GVHD (Table 1). We observed a higher response disease before allografting in patients treated with new drugs. Conclusions Induction with lenalidomide, thalidomide or bortezomib does not impact feasibility and safety of tandem auto-allo. Longer follow up and a larger cohort of patients are necessary to evaluate the impact of new drugs in improving disease control post-tandem auto-allo. Disclosures: Patriarca: Janssen Cilag: Honoraria; Celgene: Honoraria. Boccadoro:Celgene: Consultancy, advisory committees, Research Funding; Pharmion: Consultancy, advisory committees, Research Funding; Janssen Cilag: Consultancy, advisory committees, Research Funding.

Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4445-4451 ◽  
Author(s):  
Michael Wang ◽  
Meletios A. Dimopoulos ◽  
Christine Chen ◽  
M. Teresa Cibeira ◽  
Michel Attal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Time To Progression ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Previously Treated ◽  
Survival Studies

AbstractThis analysis assessed the efficacy and safety of lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma (MM) previously treated with thalidomide. Of 704 patients, 39% were thalidomide exposed. Thalidomide-exposed patients had more prior lines of therapy and longer duration of myeloma than thalidomide-naive patients. Lenalidomide + dexamethasone led to higher overall response rate (ORR), longer time to progression (TTP), and progression-free survival (PFS) versus placebo + dexamethasone despite prior thalidomide exposure. Among lenalidomide + dexamethasone-treated patients, ORR was higher in thalidomide-naive versus thalidomide-exposed patients (P = .04), with longer median TTP (P = .04) and PFS (P = .02). Likewise for dexamethasone alone-treated patients (P = .03 for ORR, P = .03 for TTP, P = .06 for PFS). Prior thalidomide did not affect survival in lenalidomide + dexamethasone-treated patients (36.1 vs 33.3 months, P > .05). Thalidomide-naive and thalidomide-exposed patients had similar toxicities. Lenalidomide + dexamethasone resulted in higher rates of venous thromboembolism, myelosuppression, and infections versus placebo + dexamethasone, independent of prior thalidomide exposure. Lenalido-mide + dexamethasone was superior to placebo + dexamethasone, independent of prior thalidomide exposure. Although prior thalidomide may have contributed to inferior TTP and PFS compared with thalidomide-naive patients, these parameters remained superior compared with placebo + dexamethasone; similar benefits compared with placebo + dexamethasone were not evident for thalidomide-exposed patients in terms of overall survival. Studies were registered at http://www.clinicaltrials.gov under NCT00056160 and NCT00424047.

scholarly journals Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

2020 ◽  
pp. JCO.20.02259
Author(s):  
Paul G. Richardson ◽  
Albert Oriol ◽  
Alessandra Larocca ◽  
Joan Bladé ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Duration Of Response ◽  
Heavily Pretreated ◽  
Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

A Phase I/II Study of Bortezomib and Low Dose Intravenous Melphalan (BM) for Relapsed Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2555-2555 ◽  
Author(s):  
Rakesh Popat ◽  
Heather E. Oakervee ◽  
Nicola Foot ◽  
Samir Agrawal ◽  
Patricia Smith ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Progressive Disease ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Median Number ◽  
Overall Response ◽  
Grade 3 ◽  
Number Of Cycles

Abstract Background: Bortezomib as a single agent has known efficacy in the treatment of relapsed multiple myeloma. The overall response rate (CR+PR+MR) was 35% in the SUMMIT study and 46% in the APEX study. In-vitro studies including our own have demonstrated potent synergy with other chemotherapeutic agents such as melphalan. It therefore follows that responses to bortezomib may be further improved by the combination of such drugs. Aims: The primary objectives of this Phase I/II study was to assess the safety, tolerability and response rates in patients with relapsed multiple myeloma; secondary objectives being time to progression (TTP) and overall surival (OS). Methods: This was a multi-centre, non-randomised trial for patients with relapsed myeloma. Patients received bortezomib 1.3mg/m2 on days 1,4,8 and 11 of each 28 day cycle with melphalan on day 2 at increasing dose levels. This was initially at 10mg/m2, but due to cytopenias subsequently at 2.5 and 5mg/m2 (levels 1a, 1 and 2) and we plan to escalate to 7.5mg/m2. Up to 8 cycles were given with dexamethasone added for stable or progressive disease after 4 or 2 cycles respectively. Responses were determined by EBMT criteria. Results: To date, 18 patients have been enrolled (12 male 6 female; median age 60 [range 44–73]; median number of prior therapies 3 [range 1–5] of which 17 have had at least one autologous stem cell procedure with high dose melphalan; 10 prior thalidomide and 2 prior bortezomib). 12 patients received melphalan at 10mg/m2 but due to unacceptable delays predominantly due to thrombocytopaenia, subsequent treatment levels commenced at 2.5mg/m2. The median number of cycles completed thus far is 4 (range 0–8) and of the 16 evaluable, the overall response rate (CR+PR+MR) across all treatment levels was 50% rising to 75% following the addition of dexamethasone as per protocol. At level 1a (melphalan 10mg/m2 ,N=12, median number of cycles completed =5) the best responses (with dexamethasone as indicated) were: 1CR, 1 VGPR, 5 PR, 2 MR; at level 1 (melphalan 2.5mg/m2, N=4) 1 PR, 2 MR (after 2 cycles only). The median time to any response was 1 cycle (range 1–3 ). Three patients have progressive disease, but the median TTP and OS have not yet been reached (median follow-up 3 months). Non-haematological toxicities have been modest with 7 SAEs reported of which only 1 was possibly drug related (myocardial infarction), and 4 episodes of Grade 3 neuropathy (2 resulting in study withdrawal). The commonest grade 3–4 haematological toxicity was thrombocytopaenia (N=10) complicated by bleeding in one patient, followed by neutropenia (N=6). Summary: The combination of bortezomib and intravenous melphalan can be given safely to patients with relapsed multiple myeloma and dose escalation is ongoing. Myelosupression was the commonest grade 3–4 adverse event. A response rate of 50% was seen, which was further improved to 75% with the addition of dexamethasone. This combination may therefore result in higher responses than single agent bortezomib in heavily pretreated patients.

Thalidomide-Dexamethasone Versus Melphalan-Prednisolone as First Line Treatment in Elderly Patients with Multiple Myeloma: An Interim Analysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 782-782 ◽  
Author(s):  
Heinz Ludwig ◽  
Johannes Drach ◽  
Elena Tóthová ◽  
Heinz Gisslinger ◽  
Werner Linkesch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Interferon Alpha ◽  
Survival Data ◽  
Response Rate ◽  
Skin Toxicity ◽  
Thromboembolic Complications ◽  
Interferon Alpha 2B ◽  
Best Response ◽  
Present Trial

Abstract Thalidomide-Dexamethasone (TD) is an active regimen in patients with relapsing/refractory multiple myeloma (MM). Recent phase II and III studies revealed an even higher response rate in previously untreated patients. In the present trial we compare TD with standard Melphalan-Prednisone (MP) in previously untreated elderly patients with multiple myeloma. The trial is designed to include 350 pts with MM, 190 patients have been enrolled so far (median age: 72 years, stage I: 9 (5%), stage II: 61 (32%), stage III: 120 (63%). Patients are randomized to Thalidomide 200mg/day and Dexamethasone 40mg, days 1–4 and 15–18 (on odd cycles) and days 1–4 (on even cycles) or Melphalan 2.5mg/kg day 1–4 and Prednisone 2mg/kg days 1–4, q 4–6 weeks. Thalidomide should be dosed up to 400mg/day, if feasible. Patients achieving response or stabilization are randomized to maintenance treatment either with Thalidomide (maximal dose 200mg/day)-Interferon alpha-2b (3Mega U, TIW) or Interferon alpha-2b (3Mega U/TIW). All patients are scheduled for monthly Zometa (4mg) during the entire period. Response is defined according Blade’s criteria, statistical results are given by intend to treat analysis. 125 patients are evaluable for response as yet. Best response to TD was: CR 6 (10%), NCR 7 (12%), and VGPR 9 (15%) PR 9 (15%), MR 10 (16%) yielding an ORR of 67%. Four pts had SD (7%) and 16 PD or failure (26%). The respective results in pts on MP were: CR 2 (3%), NCR 4 (6%), VGPR 5 (8%), PR 13 (20%), MR 7 (11%), ORR 48% (p&lt;0.05). Analysis per protocol revealed an ORR of 89% in the TD and 66% in the MP group (p&lt;0.02). Time to response and time to best response was significantly shorter in the TD (8, 11 weeks, respectively) compared to the MP group (10, 39 weeks, respectively; p&lt;0.01, p&lt;0.0047, respectively). Due to the interim nature of the analysis, survival data will be presented only for both groups combined at the meeting. Grade III-IV thrombocytopenia was more frequent and leucopoenia was statistically significant more common in pts on MP (4 (7%) vs. 1 (2%); ns. and (8 (13%) vs. 1 (2%); p&lt; 0.05, respectively). Patients on TD had more grade II-III neuropathy 15 (25%), psychological toxicity 12 (20%) and, skin toxicity 7 (12%) compared to those on MP (5 (8%), 5 (8%), 3 (3%), respectively). Thromboembolic complications were seen in 5 (8%) pts on TD and in 2 (3%) on MP. In conclusion, time to response and time to best response was significantly shorter in pts on TD. Both, the intend to treat and per protocol analysis showed a higher response rate in TD treated pts (67% vs. 48%, p&lt;0.05 and 89% vs. 66%, p&lt;0.02, respectively). Leucopoenia was more frequent in pts on MP and neuropathy more common in TD treated pts. There was a tendency for increased incidence of thromboembolic complications, psychological disturbances and skin toxicity in pts on TD. In relation to the high median age (72 years) of pts studied, TD was well tolerated.

A Phase I/II Trial of Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3542-3542 ◽  
Author(s):  
Rakesh Popat ◽  
Catherine Williams ◽  
Mark Cook ◽  
Charles Craddock ◽  
Supratik Basu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Median Time ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Chemotherapeutic Agents ◽  
Time To Progression ◽  
Overall Response ◽  
Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (MR+PR+CR) of 46% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were classified by EBMT criteria. Results: To date 39 patients have been enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. 36 have now completed at least 1 cycle and are therefore evaluable for response. The overall response rate (CR+PR+MR) across all treatment levels was 75% rising to 81% (CR 11%; nCR 3%; VGPR 8%; PR 39%; MR 19%) with the addition of dexamethasone in 13 cases for suboptimal response. Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression is 10.1 months and the median overall survival has not yet been reached at a median follow-up of 7.4 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 13 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma where a response rate of 81% is seen with 14% achieving nCR/CR. The toxicity profile associated is predictable, manageable and predominantly haematological. Recruitment is ongoing to a total of 53 patients.

Bortezomib, Low Dose Intravenous Melphalan and Dexamethasone for Patients with Relapsed Multiple Myeloma: Final Results of a Phase I/II Clinical Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2713-2713
Author(s):  
Rakesh Popat ◽  
Catherine Williams ◽  
Mark Cook ◽  
Charles Craddock ◽  
Supratik Basu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Phase I ◽  
Median Time ◽  
Low Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Time To Progression ◽  
Overall Response ◽  
Grade 3

Abstract Background: Bortezomib is an effective treatment for patients with relapsed multiple myeloma with an overall response rate (≥PR) of 43% and time to progression of 6.2 months (APEX study). We and others have previously demonstrated potent in-vitro synergy with chemotherapeutic agents such as melphalan and it is likely that this will translate into improved responses in the clinical setting. Methods: This was a multi-centre, non-randomised Phase I/II clinical trial for patients with relapsed multiple myeloma. Bortezomib 1.3mg/m2 was given on Days 1,4,8 and 11 of a 28 day cycle, and intravenous melphalan on Day 2 for a maximum of 8 cycles. In the Phase I component melphalan was given at 2.5, 5,7.5 and 10mg/m2 in a dose escalation scheme and the maximum tolerated dose (MTD) of 7.5mg/m2 was taken forward to an expanded Phase II component. Dexamethasone 20mg on the day of and the day after each dose of bortezomib was permitted for progressive or stable disease after 2 or 4 cycles respectively. Responses were defined by EBMT criteria. Results: 53 patients were enrolled (median age 61years [range 40–77]) with a median of 3 lines of prior therapy [range 1–5] of which 26 (67%) have had one previous autologous stem cell procedure and 4 (10%) have had two. 23 (59%) have had prior exposure to thalidomide and 4 (10%) to bortezomib. The overall response rate (≥PR) across all treatment levels (n=52) was 65% rising to 69% (CR 19%; nCR 4%; VGPR 6%; PR 40%; MR 15%) with the addition of dexamethasone in 27 cases for suboptimal response. Of the 32 patients treated at the MTD the overall response rate (≥PR) was 78% (CR 28%; nCR 6%; VGPR 6%; PR 38%; MR 9%). Rapid responses were seen with the median time to response being 1 month [range 1–6]. The median time to progression was 10 months and the median overall survival has not yet been reached at a median follow-up of 17 months. Of the patients that have had disease progression 7 (35%) had responses of longer duration than their previous therapy. The MTD was defined by unacceptable delays in administering treatment due to myelosuppresion. The toxicities have been acceptable with 13 SAEs reported of which 8 were hospitalisation due to infection. The most common grade 3–4 adverse events were: thrombocytopenia (53%), infections (25%), neutropenia (17%) and neuropathy (17%). Three grade 3 cardiac events were seen (myocardial infarction, atrial fibrillation and cardiac failure) and GCSF was administered to 13 patients as treatment and prophylaxis of grade 4 neutropenia. 19 patients were withdrawn from the study due to toxicity of which 7 were for neuropathy and 3 for delayed haematological recovery. Of note, 11 patients (28%) had pre-existing grade 1 neuropathy prior to starting therapy. Summary: The combination of bortezomib, low dose intravenous melphalan and dexamethasone appears to be highly effective in patients with relapsed multiple myeloma with a response rate (≥PR) at the MTD of 78% including 34% nCR/CR. The toxicity profile is predominantly haematological.

Bortezomib in Combination with Dexamethasone and Subsequent Thalidomide for Newly-Diagnosed Multiple Myeloma in Chinese Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4827-4827
Author(s):  
Zhen Cai ◽  
Weiyan Zheng ◽  
Guoqing Wei ◽  
Xiujin Ye ◽  
Jingsong He ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Response Rate ◽  
Response Rate ◽  
Staging System ◽  
Primary Treatment ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Overall Response ◽  
International Staging System ◽  
Grade 3

Abstract Background: Bortezomib-dexamethasone-thalidomide has been reported to be effective in newly-diagnosed multiple myeloma (MM) with an overall response rate of 92% and a CR rate of 18% (Alexanian et al, Hematology12(3):235–239, 2007), but this regimen has not been reported in Chinese patients. We now report our experience with this combination. Objectives: To investigate the efficacy and safety of bortezomib in combination of dexamethasone plus subsequent thalidomide as primary treatment for MM. Patients and Method: Between June 2006 and August 2007, 11 consecutive newly-diagnosed patients with symptomatic MM were treated with bortezomib at 1.3 mg/m2 IV on days 1, 4, 8 and 11, dexamethasone at 20 mg/m2 IV daily on the day of bortezomib and the day after. All patients received daily oral thalidomide that was escalated from 100 mg to 200 mg. Seven of 11 patients were male and 4 were female. Median age was 57 years (range 47–86). Seven of 11 patients were stage 2 according to the International Staging System, 4 out of 11 patients were stage 3. Eleven patients received a median of 2 cycles of therapy (range 1–6). The Blade criteria were used for response evaluation. Toxicities were evaluated according to the NCI Common Toxicity Criteria version 3. Results: Nine out of 11 patients (82%) achieved PR and 2 (18%) achieved CR; therefore the overall response rate was 100%. With a median follow-up duration of 5 months (1– 14 months), no patients died. Grade 3–4 toxicities included fatigue (3/11), thrombocytopenia (3/11), diarrhea (3/11) and orthostatic hypotension (2/11). Grade 2 neuropathy occurred in 3 out of 11 patients, herpes zoster occurred in 3 out of 11 patients. Routine anticoagulation or anti-thrombosis was not used. There was no DVT/PE in 11 patients. Conclusion: Our preliminary experience indicated that bortezomib-dexamethasone-thalidomide is highly effective in newly-diagnosed MM. Grade 3 and 4 toxicities were rare after median 2 cycles of therapy. The relative lower rates of neuropathy and DVT/PE in this report with Chinese MM patients are being cautiously observed.

Phase I-II Trial of Oral Cyclophosphamide, Prednisone and Lenalidomide (Revlimid®) (CPR) for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1874-1874 ◽  
Author(s):  
Donna E. Reece ◽  
Esther Masih-Khan ◽  
Arooj Khan ◽  
Saima Dean ◽  
Peter Anglin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Dose Level ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Oral Cyclophosphamide ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 1874 Poster Board I-899 Lenalidomide (Revlimid®) and dexamethasone is an effective regimen in relapsed/refractory multiple myeloma (MM) patients (pts), with an overall response rate of 60.6% and median time to progression (TTP) of 13.4 months (Dimopoulos MA, et al, Leukemia 2009 Jul 23 [Epub ahead of print]). Oral cyclophosphamide and prednisone is an older regimen with excellent patient tolerance, and we sought to enhance the efficacy of lenalidomide by adding oral cyclophosphamide and prednisone in this phase I-II trial. The CPR regimen consisted of cyclophosphamide on days 1, 8 and 15; lenalidomide on days 1–21; and prednisone 100 mg every other day in a 28 day cycle. ASA 81 mg/day was given to all pts as DVT prophylaxis. Three dose levels were evaluated using a 3 by 3 dose escalation design. Between 11/2007–07/2009, 31 pts with relapsed/refractory MM who had not previously received lenalidomide were entered onto study. Median age was 61 (40–78) years and 61% were male. Immunoglobulin subtype was IgG in 19 pts (61%), IgA in 8 pts (26%) and light chain only in 4 pts (13%). Median number of prior regimens was 2 (1–5) and 28 pts had undergone previous ASCT, including double transplants in 6 pts. Prior therapy included thalidomide in 9 (29%) and bortezomib in 15 (48%). FISH cytogenetics were available in 13 pts; one had 13q deletion but none had t(4;14) or p53 deletion. At the time of protocol entry, median β 2-microglobulin level was 246 (92–767) nm/L, albumin 39 (34–48) g/L, creatinine 83 (50–126) μmol/L, platelet count 230 (75–337) × 109/L and ANC 2.5 (1.1–6.1) x 109/L. Protocol treatment is summarized in Table 1. Dose limiting toxicity was not observed during cycle 1 at any dose level. Grade 3–4 toxicities included thrombocytopenia in 5 pts (16%) and neutropenia in 9 pts (29%). These were managed with dose reduction and/or growth factor support. Four episodes of febrile neutropenia occurred. Other grade 3–4 non-hematologic toxicities included abdominal pain/bacteremia in 1 pt in cohort 1; hypokalemia in 1 pt in cohort 2; and DVT in 2 pts, dizziness in 2 pts and fatigue in 1 pt in cohort 3. Using the International uniform response criteria (Durie BG, et al, Leukemia 2006; 20:1467–1473), the best response was documented at a median of 6 (1–5) cycles and included the following: dose level 1 (1 CR, 2 PR); dose level 2 (1 VGPR, 2 PR); dose level 3 (5 CR, 9 VGPR, 9 PR, 1 MR and 1 stable disease). At a median follow-up (F/U) of 12 (8–21) months, 20 pts remain on study, 2 have withdrawn and 9 pts have progressed at a median of 9 (4–13) months; only 1 one has died (due to MM). We conclude: 1) the combination of full doses of the agents in CPR can be given in a 28 day cycle with minimal toxicity; 2) the overall response rate (CR + VGPR + PR) in 31 pts to date is 93%; 3) at a median F/U of 1 year, only 9 pts (29%) have progressed; 4) longer follow-up is required to assess the TTP and survival of the CPR regimen. Disclosures: Reece: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Lenalidomide in combination with drugs other than dexamethasone. Anglin:Celgene: Honoraria. Chen:Celgene: Honoraria, Research Funding. Kukreti:Celgene: Honoraria. Mikhael:Celgene: Honoraria. Trudel:Celgene: Honoraria.

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