Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide/Dexamethasone Who Achieve a Complete or near Complete Response Have Longer Overall Survival and Time to Progression Compared with Patients Achieving a Partial Response.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3598-3598 ◽  
Author(s):  
Jean-Luc Harousseau ◽  
Donna Weber ◽  
Meletios Dimopoulos ◽  
Marta Olesnyckyj ◽  
Zhinuan Yu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Adverse Events ◽  
Complete Response ◽  
Response To Therapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Refractory Multiple Myeloma ◽  
Duration Of Response

Abstract Background: There is ongoing debate about what would be considered an acceptable response to therapy in patients with relapsed/refractory multiple myeloma (MM). Lenalidomide (Len) is an immunomodulatory compound. Two recent phase III randomised trials (MM-009 and MM-010) showed Len in combination with Dexamethasone (Dex) provided significantly better overall response (OR), complete response (CR), overall survival (OS) and time to progression (TTP) compared with Dex alone in patients with relapsed/refractory MM. Approximately 60% of patients achieved an OR (61% in MM-009 and 60% in MM-010), including a CR in 15% (14% and 16%, respectively), Median OS was ≥29.5 months (29.5 and not yet reached) and median TTP was ≥11.1 months (11.1 months and 11.3 months, respectively). Here, we compare outcomes in patients with a CR or near CR (nCR) vs those with a partial response (PR). Methods: Data for patients who received Len/Dex in the MM-009 or MM-010 studies were pooled for this analysis. Patients received Len (25 mg/day on days 1–21 of every 28-day cycle) and Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After 4 cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, duration of response, and time to response, as well as adverse events were assessed. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]). Results: Of 353 patients treated with Len/Dex, 214 (61%) had PR or better (86 with CR/nCR; 128 with PR). Baseline characteristics were comparable between patient groups; most patients had stage III disease (63% vs 66%) and an Eastern Cooperative Oncology Group (ECOG) score of 0–1 (83% vs 90%). More patients with CR/nCR had received ≥2 prior antimyeloma regimens/stem cell transplant than patients with PR (88% vs 70%). Patients with CR/nCR had significantly longer median TTP and OS compared with those with PR (Table). The median duration of response was significantly higher among patients with CR/nCR (not yet reached vs 38 weeks; p<0.001). Fewer patients with CR/nCR relapsed compared with those with PR (38% vs 43%). The times to CR/nCR and PR were comparable. The most common grade 3–4 adverse events were neutropenia (43% vs 41%), thrombocytopenia (13% vs 16%), anaemia (12% vs 9%) and pneumonia (12% vs 6%). Rates of febrile neutropenia were low (1% vs 3%). Conclusion: Len/Dex treatment is associated with longer OS and TTP in patients with relapsed/refractory MM who achieve a CR than in patients who achieve a PR. Len/Dex CR/nCR (n=86) PR (n=128) P value Median OS (weeks) >132.7 >118.1 <0.01 Median TTP (weeks) >65.1 46.0 <0.001 (n=84) (n=126) Duration of response (weeks) NE 38 <0.001 Time to response (weeks) 10.2 10.9 NE = not yet evaluable

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

Lenalidomide Plus High-Dose Dexamethasone Provides Improved Overall Survival Compared to High-Dose Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma (MM): Results of 2 Phase III Studies (MM-009, MM-010) and Subgroup Analysis of Patients with Impaired Renal Function.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3547-3547 ◽  
Author(s):  
Donna Weber ◽  
Michael Wang ◽  
Christine Chen ◽  
Andrew Belch ◽  
Edward A. Stadtmauer ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Subgroup Analysis ◽  
Impaired Renal Function ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Duration Of Response

Abstract Lenalidomide is a novel, orally administered immunomodulatory drug (IMiD) that has single-agent activity against multiple myeloma (MM) and additive effects when combined with dexamethasone. We have previously reported improved response (OR), time to progression (TTP) and overall survival (OS) with lenalidomide-dexamethasone (Len-Dex) compared to dexamethasone-placebo (Dex) based on the results of 2 phase III trials (MM-009, North American, 353 pts; MM-010, Europe, Australia, and Israel, 351 pts). In both trials patients with relapsed or refractory MM not resistant to dexamethasone, were treated with dexamethasone 40 mg daily on days 1–4, 9–12, and 17–20 every 28 days and were randomized to receive either lenalidomide 25 mg daily orally on days 1–21 every 28 days or placebo. Beginning at cycle 5, Dex was reduced to 40 mg daily on days 1–4 only, every 28 days. Patients were also 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). At a median follow-up from randomization of 17.1 mos (MM-009) and 16.5 mos (MM-010), both studies continue to show significant improvement with Len-Dex compared to Dex in OR (MM-009: 61% vs 20.5%, p<.001; MM-010: 59.1% vs. 24%, p<.001, respectively), TTP (MM-009: 11.1mos vs. 4.7mos, p<.001; MM-010: 11.3mos vs. 4.7mos, p<.001, respectively), and OS (MM-009: 29.6mos vs. 20.5mos, p<.001; MM-010: not estimable vs 20.6mos, p<.001, respectively). Pooled data from both trials demonstrates a significant improvement in duration of response for pts achieving ≥ PR with 122/216 pts (56.5%) who received Len-Dex continuing in remission (med. duration of response not reached but > 68.1 wks) compared to only 22/76 pts (28.9%) treated with dexamethasone alone (med. duration of response 22.1 wks, p<.001). An additional subgroup analysis was performed on pts with impaired creatinine clearance (cr cl). No significant difference in response rate, TTP, or OS was noted for patients with cr cl above or below 50 ml/min who were treated with Len-Dex, but for 16 pts with cr cl <30ml/min, med. TTP and OS was shorter than for those with cr cl >30ml/min, but still significantly higher than for pts treated with Dex. Grade 3–4 thrombocytopenia was significantly higher in pts with impaired renal function (<50ml/min, 13.8%; >50ml/min 4.6%, p<.01; <30ml/min, 18.8%, >30 ml/min, 5.5%, p<.05), but there was no difference for G3–4 neutropenia at either cutoff. Phase I–II evaluation to establish appropriate dosing in pts with cr cl < 30ml/min, particularly with respect to thrombocytopenia is warranted, but should not underscore improved OR, TTP, and OS for pts treated with Len-Dex regardless of creatinine clearance.

Circularly Permuted TRAIL (CPT) combined with Thalidomide for the Treatment of Relapsed or Refractory Multiple Myeloma: An Open-Label, Multicenter Phase II Clinical Trial.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2958-2958 ◽  
Author(s):  
Wenming Chen ◽  
Jian Hou ◽  
Yaozhong Zhao ◽  
Lugui Qiu ◽  
Xiaoyan Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Open Label ◽  
Refractory Multiple Myeloma ◽  
Phase Ii Studies ◽  
Better Than

Abstract Abstract 2958 Background: Circularly permuted TRAIL (CPT) is a recombinant mutant of human Apo2L/TRAIL developed by Beijing Sunbio Biotech Co. Ltd. as a targeted therapy for multiple myeloma and other hematologic malignancies. CPT is a dual pro-apoptotic receptor agonist that directly activates both pro-apoptotic receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5). CPT selectively induces apoptosis in a variety of cancer cells, while sparing most normal cells in preclinical models. Objective: CPT as a mono-therapy has shown definitive activities for patients with relapsed or refractory multiple myeloma (Rel/Ref MM) in phase I and phase II studies. The aim of this study is to observe the effect and safety of CPT in combination with thalidomide for Rel/Ref MM patients. Methods: In this multiple-center, open-label, single arm phase II study, 43 Rel/Ref MM patients who had received prior therapies and were resistant to thalidomide were recruited. These patients were divided into three groups, and received CPT 5.0mg/kg, 8.0mg/kg, and 10.0mg/kg on days1–5 of each 21-day cycle, respectively, until having finished six cycle‘s treatment or progression disease or intolerant adverse events. All the patients received thalidomide 100mg daily until to the disease progression or intolerant adverse events. Clinical responses of CPT were assessed by an independent review committee according to the criteria of the European Group for Blood and Marrow Transplantation (EBMT). Results: Among the 43 patients, 41 patients can be evaluated. There were 11, 15 and 15 patients in the three groups respectively. Among the 41 patients, two patients achieved complete response (CR), three showed near complete responses (nCR), four exhibited partial responses (PR), and five obtained minor responses (MR). The total response rates were 34% (including MR or better than MR), or 22% (including PR or better than PR). Among the three groups, the dose of 10mg/kg seemed to be optimal with 26.7% response rate (including PR or better than PR), superior to the other two groups. Duration of response of CPT was not evaluated accurately, because most patients who achieved PR, nCR, or CR were progression free at the end of the trial. The common treatment related adverse events (≥10%) were neutropenia, leucopoenia, fever, AST/ALT/LDH elevation, and thrombocytopenia. The grade 3 non-haematological toxicities were AST elevation (4.65%) and LDH elevation (2.33%). The elevation of AST and LDH seems to be related to tumor lysis, but not to liver injury. The grade 4 haematological toxicities were neutropenia and thrombocytopenia (2.33%, respectively) which might be related to thalidomide. Conclusions: The CPT combined with thalidomide was well-tolerated and an effective regimen for the treatment of Rel/Ref MM. The combination of CPT and thalidomide seems to be superior to CPT alone in CR/nCR response rate. Disclosures: Zheng: Beijing Sunbio Biotech Co., Ltd.: Employment. Zhu:Beijing Sunbio Biotech Co., Ltd.: Employment. Yang:Beijing Sunbio Biotech Co., Ltd.: Employment.

scholarly journals Phase II Study of Thalidomide Plus Dexamethasone Induction Followed by Tandem Melphalan-Based Autotransplantation and Thalidomide-Plus-Prednisone Maintenance for Untreated Multiple Myeloma: A Southwest Oncology Group Trial (S0204)

2009 ◽  
Vol 27 (21) ◽  
pp. 3510-3517 ◽  
Author(s):  
Mohamad A. Hussein ◽  
Vanessa Bolejack ◽  
Jeffrey A. Zonder ◽  
Brian G.M. Durie ◽  
Andrzej J. Jakubowiak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Phase Ii ◽  
Staging System ◽  
Complete Response ◽  
Phase Iii ◽  
Second Transplantation ◽  
Timely Fashion ◽  
International Staging System ◽  
Stage 1

Purpose Thalidomide-dexamethasone (THAL-DEX) is standard induction therapy for multiple myeloma (MM). Tandem melphalan-based transplantations have yielded superior results to single transplantations. Phase II trial S0204 was designed to improve survival results reported for the predecessor, phase III trial S9321 by 50%. Patients and Methods Newly diagnosed patients with MM were eligible for S0204 with THAL-DEX induction, tandem melphalan-based tandem transplantation, and THAL-prednisone maintenance. Results Of 143 eligible patients, 142 started induction, 73% completed first transplantation, 58% completed second transplantation, and 56% started maintenance. The quantity of stem cells required for two transplantations was reached in 88% of 111 patients undergoing collection, 74% of whom completed both transplantations. Partial response, very good partial remission, and complete response were documented after 12 months of maintenance therapy in 87%, 72%, and 22% of patients, respectively. During a median follow-up time of 37 months, 4-year estimates of event-free and overall survival were 50% and 64%, respectively. Survival outcomes were superior for International Staging System (ISS) stage 1 disease, when lactate dehydrogenase (LDH) levels were normal and a second transplantation was applied in a timely fashion. Conclusion Both overall survival (P = .0002) and event-free survival (P < .0001) were significantly improved with S0204 compared with S9321 when 121 and 363 patients, respectively, were matched on ISS stage and LDH.

scholarly journals Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
Yali Tao ◽  
Hui Zhou ◽  
Ting Niu
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Response Rate ◽  
Complete Response Rate ◽  
Meta Analysis ◽  
Complete Response ◽  
Cochrane Central Register ◽  
Safety And Efficacy ◽  
Grade 3

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p &lt; 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p &lt; 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p &lt; 0.00001), nausea (72 vs 52%, p &lt; 0.00001), vomiting (41 vs 23%, p &lt; 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p &lt; 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.

scholarly journals Original Versus Generic Lenalidomide in Patients with Relapsed Multipl Myeloma: Comprasion of Effectivity and Adverse Events

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5594-5594
Author(s):  
Zahit Bolaman ◽  
Sehmus Ertop ◽  
Atakan Turgutkaya ◽  
Selim Cem ◽  
Ayse Hilal Eroglu Kucukerdiler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Adverse Events ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Muscle Cramp ◽  
P Value ◽  
Medicine Department ◽  
School Of Medicine ◽  
Number Of Patients

Original versus generic lenalidomide in patients with relapsed multipl myeloma: Comprasion of effectivity and adverse events Ali Zahit Bolaman1, Sehmus Ertop2 Atakan Turgutkaya1, Cem Selim, 1 Ayse Hilal Eroglu Kucukerdiler1, Birsen Sahip2, Irfan Yavasoglu1. 1 Adnan Menderes University, School of Medicine, Department of Hematology AYDIN/TURKEY 2 Bulent Ecevit University School of Medicine, Department of Hematology ZONGULDAK/TURKEY Backround: Lenalidomide is an effective IMID derivative drug in the treatment of patients with multiple myeloma. Lenalidomide is available as original and generic forms in our country. So far, there is no any clinical study comparing generic and original lenalidomine for effectivity and adverse events. We compared generic and original lenalidomide effects and adverse events (AEs) in patients with relapsed multiple myeloma (RMM). Methods: The patients with RMM using original or generic lenalidomide were evaluated as retrospectively. Overall response (OR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease and progressive disease rates and also for adverse events, development rates of neutropenia, anemia, thrombocytopenia, febrile neutropenia, anorexia, constipation diarrhea, nausea, vomiting, creatinine increase, transaminase increase, asthenia, fatigue, pyrexia, peripheral edema, upper respiratory system infection, pneumonia, another infection, muscle cramp, back pain, bone pain, muscle weakness, arthralgia, headache, tremor, paresthesia, deep vein thrombosis, pulmonary embolism, hyperglycemia, hypokalemia, hypocalcemia, hypomagnesaemia, skin dry and skin erythema were investigated in myeloma patients. All data were analyzed using the PASW for Windows version 19.0 (SPSS Inc., Chicago, IL, USA). The results were described as a number, frequency, and percentage. The chi-squared test and Fisher's exact test were used for the analysis of categorical data and independence between variables. The results were assessed at 95% confidence interval and p-value of less than 0.05 was accepted as significant. Results: The number of patients using original lenalidomide was 55 and the number of patients using generic lenalidomide was 43. OR rate was 60 % versus 39.5% in patients using original and generic lenalidomide, respectively. CR rate was 14.5%, VGPR was rate 45.4% in original group while CR rate was 20.9 and VGPR 18.6 in patients using generic lenalidomide. AEs were low in original lenalidomide group than generic group. AEs were usually grade 1 or 2. Response and AEs rates are shown in Table 1. Conclusion: Our study showed original and generic forms of lenalidomide are effective for the treatment of RMM. OR rate was higher in original lenalidomide than generic lenalidomide. The AEs of original lenalidomide were lower than generic lenalidomide without statistically significance. Further studies involving a larger number of patients with RMM would be useful for comparing the efficacy and AEs of original or generic lenalidomide. Disclosures No relevant conflicts of interest to declare.

Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression

2007 ◽  
Vol 25 (25) ◽  
pp. 3892-3901 ◽  
Author(s):  
Robert Z. Orlowski ◽  
Arnon Nagler ◽  
Pieter Sonneveld ◽  
Joan Bladé ◽  
Roman Hajek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Combination Therapy ◽  
Liposomal Doxorubicin ◽  
Pegylated Liposomal Doxorubicin ◽  
International Study ◽  
Phase Iii ◽  
Combination Group ◽  
Time To Progression ◽  
Refractory Multiple Myeloma ◽  
Grade 3

PurposeThis phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin (PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.Patients and MethodsSix hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m2on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m2on day 4.ResultsMedian time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination (P = .000004; hazard ratio, 1.82 [monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15-month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone (P = .03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months (P = .0008) with PLD + bortezomib. Grade 3/4 adverse events were more frequent in the combination group (80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand-foot syndrome.ConclusionPLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.

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]

Treatment sequencing patterns for relapsed refractory multiple myeloma (RRMM) in the era of new therapies in a single center institution.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19513-e19513
Author(s):  
Alexandre Tungesvik ◽  
Praneeth Reddy Sudalagunta ◽  
Jessica Huang ◽  
Elizabeth Dimaggio ◽  
Gabe De Avila ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Response To Therapy ◽  
Cancer Center ◽  
Free Survival ◽  
New Therapies ◽  
First Response ◽  
Line Of Therapy

e19513 Background: Although there is much to be optimistic about in the multiple myeloma community as the approval of new therapies and regimen-combinations for relapsed refractory disease continues to grow, determining the best option for a patient can be complicated. Both carfilzomib- (C) and daratumumab- (D) based regimens have demonstrated superior efficacy in this setting, but there is a paucity of data supporting which should be selected first, and if regimen sequence influences outcomes. The aim of this study is to describe sequencing patterns in the era of these newer agents and to determine if there is a difference in outcomes for patients with RRMM who received one of the following treatment sequences: C-regimen with a D-regimen given immediately prior (DC); C-regimen without any prior D (C only); D-regimen with a C-regimen given immediately prior (CD); or D-regimen without any prior C (D only). Methods: This is a retrospective analysis of patients with RRMM consecutively treated at Moffitt Cancer Center between 1/1/2015 and 6/25/18. Response to therapy was assessed using the International Myeloma Working Group (IMWG) criteria. Progression-free survival (PFS) was measured in days from the start of therapy to progression. Time to response (TTR) was measured in days from the start of therapy to first response. Results: 132 patients with RRMM who received 1-3 prior lines of therapy with at least one line of therapy containing either C or D were identified. Overall, the majority of patients were treated with C only (n = 101), 10 received DC, 31 received D only, and 35 received CD. In patients that received C only, partial response (PR) was achieved in 38%, very good partial response (VGPR) was 20%, and stringent complete response (sCR) was 2%. In patients that received DC, PR was 20% and VGPR was 10%; no patient achieved a sCR. Of the patients that received D only, PR was 29%, VGPR was 10%, and sCR was 3%. In patients that received CD, PR was 31% and VGPR was 26%; no patient achieved sCR. Median PFS in patients who received C only, DC, D only, and CD was 117 days, 126 days, 104 days, and 190 days, respectively. TTR in patients who received C only, DC, D only, and CD was 82 days, 39 days, 98 days, and 88 days, respectively. Conclusions: The data suggests that RRMM patients who receive either CD or DC appear to have a PFS advantage over those patients who did not. Notably, an early TTR was found in patients that received DC. Further analysis is ongoing.

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