scholarly journals Efficacy and Safety Profile of Bortezomib Based Regimens for Treatment of Newly Diagnosed Amyloidosis: A Systematic Review of Literature

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5583-5583
Author(s):  
Muhammad Abdullah Yousaf ◽  
Muhaddis Ejaz Ahmad ◽  
Maaz Ahmed Yusufi ◽  
Hamza Hassan ◽  
Adeela Mushtaq ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Cochrane Library ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Efficacy And Safety

Introduction: For more than a decade, bortezomib (V) has become an integral part of initial treatment of AL amyloidosis It is cytotoxic to plasma cells. We report published literature on efficacy and safety of bortezomib based regimens in patients (pts) with newly diagnosed amyloidosis (ND-AL). Methods: Following PRISMA guidelines, we performed a comprehensive literature search for articles published after 2007 using Pubmed, Embase, Clinical Trials.gov, Cochrane Library and Web of Science. Initially, 649 articles were identified and after a thorough screening, we finalized 9 studies involving 213 ND-AL patients. Prospective (n=91) and retrospective (n=122) studies were included. MeSH terms and keywords were bortezomib and newly diagnosed AL amyloidosis. Results: Chemotherapy followed by HDCT versus frontline HDCT / ASCT: In a retrospective study involving 31 pts by Scott et al., with induction chemotherapy with V-based regimens (n=12), with non-V-based regimens (n=6) and frontline (n=13) high dose melphalan (HDM) therapy followed by autologous stem cell transplant (ASCT). Overall hematological response (OHR) and organ response (OR) rates in the entire cohort after ASCT were 77% and 58% respectively. OHR and OR were 92% & 75% in V-pretreated group and 69% & 54% in pts who received no treatment. The trend was similar for other responses (Table 1). In a clinical trial by Huang, X., et al., induction therapy with Vd (V in combination with dexamethasone) prior to HDM/SCT was compared with frontline HDM/SCT in 58 patients. The OHR, and complete response (CR) between Vd+HDM/SCT (20 evaluable pts) and frontline HDM/SCT (23 evaluable pts) groups were 85.7% versus 53.5% and 67.9% versus 35.7% respectively. All organs showed better response in Vd+HDM/SCT group (Table 1). Vd/CyBorD (Cyclophosphamide, bortezomib, dexamethasone) prior to ASCT: In a prospective clinical trial by Sanchorawala et al., 35 pts were given induction with Vd before HDM and ASCT. Among 27 evaluable pts, OHR was 100% with CR in 76.9% and very good partial response (VGPR) in 23% pts. In a study by Hong et al., 20 patients received induction with Vd or CyBorD prior to ASCT. OHR was 89% with CR in 55%, partial response (PR) in 10% and VGPR in 33%. 5-year overall survival (OS) was 80% and 5-year progression free survival (PFS) was 69%. Vd/CyBorD without ASCT: In a retrospective study by Zhao et al., 23 pts received Vd. OHR was 100% with CR in 44% and PR in 38.9% pts. Median overall survival (mOS) was 38 months and 3-year OS was 41-72%. OR was 25% with kidney being the organ showing response in maximum pts (84%). Kikukawa et al., reported 8 pts who received CyBorD, OHR was 100% with CR in 50%, PR in 25% and VGPR in 25% pts. 63% pts showed OR in heart and/or kidney. In a study by Huang, B., et al., Vd was given to 12 renal ND-AL pts and among 10 evaluable pts, OHR was 80% with CR in 50% and PR in 10%. mOS was 8.2 months and OR was 50%. Other Regimens: In a study by Lee et al., involving 19 pts, VMP (bortezomib, melphalan, prednisone) was given as induction therapy. OHR was 84% with CR in 37%, PR in 26% and VGPR in 21% pts. OS was 39% at 2 years and PFS was 8 months. OR was 53% with heart (50%) and kidney (40%). In a retrospective review by Chari et al., 9 pts were treated with a triplet regimen (V, cyclophosphamide or lenalidomide/thalidomide and d). OHR was 88% with CR in 22% and PR in 66% pts. OR was 77% with heart and kidney both at 44%. Conclusion: In ND-AL pts, V-based combination regimens are very effective and well tolerated as induction therapy, or when used as therapy prior to HDM/ASCT and this approach resulted in better outcomes when compared to frontline HDM/ASCT. Three drug combination therapy with V is effective. Kidney and heart were the major organs to show improvement with therapy. Novel combinations need to be studied in randomized prospective clinical trials. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals A Systematic Review on Efficacy and Safety of Lenalidomide Based Regimens for Treatment of Newly Diagnosed Amyloidosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5584-5584
Author(s):  
Muhaddis Ejaz Ahmad ◽  
Muhammad Abdullah Yousaf ◽  
Mustafa Nadeem Malik ◽  
Abdul Rafae ◽  
Tariq Iqtidar Sadiq Syed ◽  
...  
Keyword(s):  
Partial Response ◽  
Plasma Cells ◽  
Nk Cell ◽  
Induction Agent ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Front Line

Introduction: Lenalidomide (L), a commonly used drug for the treatment of Multiple Myeloma, but currently it is not being not used as front line agent for the treatment of AL amyloidosis. It works through various mechanism, can cause direct toxicity to plasma cells, inhibits angiogenesis, and promotes tumor apoptosis. Cyclophosphamide (Cy), causes cross links between DNA which leads to cell apoptosis. For last decade, Cy is being used in combination with agents like Velcade for more than and decade, there is paucity of literature about its use in combination with L. L based regimen may be necessary in patients who have contraindications to bortezomib use, additionally targeted immunotherapy based combinations with daratumumab, through NK cell mediated cytotoxicity, may be more effective in the presence of immunomodulatory drugs. Our main objective is to analyze the published literature for the efficacy and toxicity of L based regimens for the treatment of newly diagnosed Amyloidosis (ND-AL). Methods: A systematic search of databases using (per PRISMA guidelines) PubMed, Embase, Web of science, Cochrane database and Clinicaltrials.gov was performed from January 2012 onward, with no restrictions of publication language. A total of 649 articles were identified initially and after a detailed screening, we finalized 9 studies involving 223 ND-AL patients. Results: Lenalidomide, dexamethasone, Cyclophosphamide (LCyD): In a phase II trial by Ciberia et al, (n=28) ND-AL patients (pts) were treated with LCyD. Overall hematological response (OHR) was 46% with complete response (CR) in 25%, very good partial response (VGPR) in 18% and partial response (PR) in 3% pts. Organ response (OR) was 46% with maximum pts. showing response in kidney (43%) and heart (26%). In a study by Kastritis et al., involving 24 pts, LCyD induced, OHR was observed in 55% pts with CR in 8 % (Table 1). For comparison with regimens like Cy, Bortezomib and Dexamethasone (CyBorD), in a retrospective study by Hong et al., 24 pts were given CyBorD. OHR was 89% with CR, VGPR and PR demonstrated in 55%, 33% and 10% pts respectively. 5-yr OS was 80% and 5-yr PFS was 69% (Table 1). Mikhael et al., reported 17 pts given CyBorD. OHR was 94% with CR in 71% and PR in 24% pts. Venner et al., et al. (n=43) reported 20 patients of ND-AL treated with CyBorD showed OHR of 81.4%, with CR in 41.9% and PR in 39.5%. 46% pts showed OR. Chari et al. reported 9 pts. who were given extensive combinations of Cyc and L. OHR was 88%, with CR in 22% and PR in 66% pts. 77% pts showed an OR (Table 1). Induction with L prior to High dose Melphalan (HDM) and stem cell transplant (SCT) vs front line HDM/SCT: In a study by Cowan et al., (n=45) pts in group A (n=21) received induction therapy using novel agent induction using agents like Bortezomib and Lenalidomide prior to HDM/SCT. CR was observed in 50%, VGPR in 7% and PR in 7% pts. Group B (n=24) pts were given HDM/SCT upfront. CR was observed in 28%, VGPR in 14% and PR in 14% pts. Similarly study by Scott et. al., 31 pts who received HDM consolidation were categorized in 3 groups i.e no induction, induction with V-based regimen and induction with other regimens including L. In pts with len/dex (n=2) OHR was 100%, with CR observed in 100% pts (Table 1). Melphalan (M), Lenalidomide (L) and Dexamethasone (d): In a clinical trial (NCT00890552), 25 pts who were given L, M and d, showed a CR of 8%, VGPR of 16% and PR of 33% pts. mOS was 12 mo (Table 1). Conclusion: There is paucity of literature about the use of Lenalidomide for the treatment of newly diagnosed AL patients. In ND-AL pts, CyBorD and as well as Lenalidomide/dexamethasone-based regimens has shown excellent overall hematological responses (up to 100%). Major adverse effects were anemia, thrombocytopenia, neutropenia and rash. We recommend, with adequate sample size, prospective studies need to be conducted for better understanding of efficacy and safety of L based therapies in newer combinations for the treatment of AL Amyloidosis. With good efficacy and tolerance data to support its use, Lenalidomide may have a potential role for its use as an induction agent, salvage therapy as well as post induction long term term maintenance therapy for select AL amyloidosis cases who cant achieve complete remission with induction and / or consolidation regimens. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Efficacy and Safety Profile of Proteasome Inhibitor Based Drug Regimens for Treatment of Newly Diagnosed AL Amyloidosis: A Systematic Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-32
Author(s):  
Saad Javed ◽  
Tariq Iqtidar Sadiq Syed ◽  
Hejab Fatima ◽  
Syed Hashim Ali Inam ◽  
Tayyab Rehan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Retrospective Study ◽  
Partial Response ◽  
Proteasome Inhibitor ◽  
Phase Iii ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Phase Iii Trial ◽  
Drug Regimens

Introduction: Light chain amyloidosis (AL) is a plasma cell disorder associated with detrimental manifestations in multiple organ systems of the body. It is estimated that approximately 1275-3200 new cases occur in the United States annually. Proteasome inhibitors (PI), such as bortezomib, carfilzomib, and ixazomib used for multiple myeloma treatment are also used for the treatment of AL amyloidosis. Our aim in this review is to evaluate the efficacy and safety profile of PI-based regimens for the treatment of newly diagnosed AL Amyloidosis (ND-AL). Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive literature search on PubMed, Cochrane, ClinicalTrials.gov, and Embase on June 23rd, 2020. We were able to identify 901 articles, 325 articles from PubMed, 50 from Cochrane, 23 from Clinical Trials.org, and 253 from Embase. After the screening, we selected 11 published studies (n=436) including 5 phase lll trials, 2 phase I/II trials. Results: Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) with or without Daratumumab (Dara): In a Phase lll trial (ANDEROMADA study), Palldini et al. (2020) studied the efficacy of Dara+ CyBorD vs CyBorD in ND-AL pts (n=28). The addition of Dara to CyBorD showed an improved overall hematological response (ORR) in 96% with complete response (CR) in 54% pts at a median follow up of 17.6 months (Table 1). In a retrospective study by Lim et al. (2017), CyBorD was given to ND-AL pts (n=39) which showed an ORR in 63% with very good partial response (VGPR) in 50% pts. In a retrospective study by Diaz-Pallares et al. (2020), CyBord was given to ND-AL pts (n=34) which showed an ORR in 91% with CR, VGPR, and partial response (PR) in 26%, 26%, and 38% pts, respectively. Progression-free survival (PFS) and overall survival (OS) were reported at 26.7 months and 22 months (P=0.06) respectively (Table 1). Bortezomib, Melphalan, Dexamethasone (BMD): In a phase III trial (EMN-03 study), Kastritis et al. (2020) studied the efficacy of BMD vs MD in ND-AL pts (n=109). Addition of B to MD showed an improved ORR: 81% vs 56% (p=0.001) with CR/VGPR in 53% vs 28% pts. No significant difference in survival outcome was observed. In a phase III trial, Kastritis et al. (2015) studied the efficacy of BMD vs MD in ND-AL pts (n=69). Addition of B to MD showed an improved ORR: 75% vs 53% (p=0.075) with CR/VGPR in 56% vs 42% pts (p=0.277). OS and PFS were also improved in BMD group as compared to control group: 83% vs 72% (p= 0.295) and 61% vs 49% (p=0.079) at 2 years, respectively (Table 1). Bortezomib, Melphalan, Prednisolone (BMP): In a retrospective study by Lee et al. (2014), BMP was given to ND-AL pts (n=19) which showed an ORR in 84% pts with CR, VGPR and PR in 37%, 21% and 26% pts, respectively (Table 1). Induction with B based regimens for ASCT: In a Phase lll trial (HOVON 104), Minnema et al. (2019), studied the efficacy of BD induction prior to HDM/ASCT in pts (n=35) with ND-AL. At 6 months, BD induction prior to HDM/ASCT vs No BD Induction prior to HDM/ASCT showed an ORR: 80% vs 80% with an improved CR: 43% vs 5% and VGPR: 54% vs 51%. In a Phase I/II trial by Sanchorawala et al. (2015), BD induction followed by B-HDM conditioning for ASCT was done in pts (n=27) with ND-AL. ORR at 6 months post ASCT was observed in 100% pts with CR and VGPR in 63% and 37% pts, respectively (Table 1). Induction with B based regimen prior to ASCT vs Upfront ASCT: In a retrospective analysis by Scharman et al. (2017), 53 pts who received ASCT were categorized into 3 groups i.e. Upfront ASCT, induction with B based regimen and induction with other regimens. ND-AL Patients (n=34/53) receiving B based induction vs no induction showed an improved ORR: 94% vs 69% (p=0.04). OS also improved in B based induction as compared to no induction group: 87% vs 77% (p=0.22) at 3 years. PFS at 3 years was 61% vs 69%, respectively (Table 1). Conclusions: PI-based regimens have shown favorable outcomes in the treatment of ND-AL and are effective therapeutic options. The most promising results are observed with CyBorD+Dara. The adverse events associated with PI-based therapy are peripheral neuropathy, anemia, thrombocytopenia, and infections. Further prospective clinical trials are warranted for a broader understanding of the safety and efficacy profile of PI-based regimens and correlation with individual pts characteristics. Table Caption: Table 1: Comparative efficacy and safety of proteasome-inhibitor based drug regimens in ND-AL Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Dartumumab in Pretreated AL Amyloidosis: A Systematic Review

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 46-47
Author(s):  
Iqraa Ansar ◽  
Karun Neupane ◽  
Hamid Ehsan ◽  
Muhammad Yasir Anwar ◽  
Hassaan Imtiaz ◽  
...  
Keyword(s):  
Heart Failure ◽  
Partial Response ◽  
Light Chain ◽  
Response Rate ◽  
Renal Involvement ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Efficacy And Safety ◽  
Mesh Terms ◽  
Combination Regimens

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the efficacy and safety of daratumumab alone or in combination with other therapies in pretreated AL amyloidosis. After excluding duplicates, non-relevant, and review articles, we selected four prospective and twelve retrospective studies. RESULTS: In our review, data on 482 patients were included. The ages ranged from 35-88 years. The median number of prior therapies was 3 (ranges:2-6), and the most common therapy was bortezomib in 90% of patients followed by immunomodulators in 55% and stem cell transplant in 35%. A total of 260 (54%) patients received Dara monotherapy, 126 (26%) received Dara plus Dexamethasone (d), and 96 (20%) patients received other Dara containing two or three-drug regimens. The time from the diagnosis to the start of Dara therapy varied from 1 to 137 months. 71 % of patients had cardiac, and 62 % had renal involvement. There was a greater than 30 % reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) in cardiac patients responsive to therapy. 1. Daratumumab monotherapy: Dara monotherapy achieved an overall response rate (ORR) of 76% (191/249), complete response (CR) of 30% (69/224), very good partial response (VGPR) of 41% (79/192) and partial response (PR) of 14% (19/140). The overall survival (OS) ranges from 59-100% at 10-12 months were noted. Table 1. 2. Daratumumab+ Dexamethasone: Dara plus d achieved ORR of 81% (86/106), CR of 51% (53/102), VGPR of 29% (18/62), PR of 15% (15/102), and OS of 87% at 24 months. Table 1. 3. Daratumumab with combination regimens: The use of Dara based combination regimens of Dara+pomalidomide (P)+d (36% of patients), Dara+lenalidomide (R)+d (32%) and Dara+bortezomib (V)+d (18%), reported by Abeykoon et al., showed an ORR of 88% (14/16), CR of 19 % (3/16), VGPR of 63% (10/16), PR of 6 %(1/16), OS of 89 % at 10 months and progression-free survival (PFS) of 83% at 10 months. Godara et al. reported an ORR of 100% (9/9) using a combination of Dara and birtamimab. The combination of D+cyclophosphamide (c)+V+d reported by Palladini et al. achieved an ORR of 96 % (27/28), CR of 36 % (11/28), VGPR of 29 % (8/28) and PR of 14 % (4/28).Table 1. The most reported adverse event was infusion-related reactions; grade 3-4 adverse were less than 10 % and mostly related to the heart (heart failure & atrial fibrillation). The most-reported hematological adverse effects were anemia, thrombocytopenia, neutropenia, infections, and sepsis. The most common non-hematological adverse events were heart failure, bronchitis, pneumonia, fatigue, nausea, and diarrhea. Table 2. Conclusion: Dara therapy is associated with promising efficacy with a response rate of more than 70% when used alone and more than 80% when used in combination. These regimens are well tolerated in advanced cardiac disease patients with a tolerable risk of volume overload and infusion-related complications. Additional multicenter randomized, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Role of autologous stem cell transplant after induction therapy with bortezomib-lenolidomide or bortezomib-thalidomide in newly diagnosed multiple myeloma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
N. Shah ◽  
D. Weber ◽  
R. Orlowski ◽  
M. Wang ◽  
S. K. Thomas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Highly Active

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]

Depth of response prior to autologous stem cell transplantation to predict survival in light chain amyloidosis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8516-8516
Author(s):  
Iuliana Vaxman ◽  
M Hasib Sidiqi ◽  
Abdullah S. Al Saleh ◽  
Shaji Kumar ◽  
Eli Muchtar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Light Chain ◽  
Multivariable Analysis ◽  
Al Amyloidosis ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Depth Of Response ◽  
The Impact

8516 Background: The role of induction therapy prior to autologous stem cell transplant (ASCT) in immunoglobulin light chain (AL) amyloidosis remains controversial. Data on the prognostic impact of response to induction in a transplanted cohort are lacking. The aim of this study was to assess the impact of response to induction therapy on survival in patients undergoing ASCT for AL amyloidosis. Methods: We conducted a retrospective study of all newly diagnosed AL amyloidosis patients who received induction prior to ASCT between January 2007 and August 2017 at Mayo Clinic, Rochester, Minnesota. Patients receiving only corticosteroids prior to transplant were excluded as were those with an involved light chain of less than 5 mg/dL (not measurable for response). Results: 134 patients met inclusion criteria. The median age at diagnosis was 60 (range 36-74) and 85 (63%) were men. The most commonly used induction regimen was proteasome inhibitor-based (73.1%, n=98). The overall response rate to induction was 83% (complete response 17%, very good partial response 30% and partial response 36%). With a median follow up of 56.5 months, the median PFS and OS was 48.5 months and not reached, respectively. Response depth to induction therapy was associated with improved PFS and OS and was independent of the bone marrow plasma cell percentage. The median PFS was not reached for patients achieving ≥VGPR prior to ASCT and 33.8 months for patient achieving PR or less (P=0.001). The median OS was longer in patients with deeper responses (not reached for patients achieving ≥VGPR vs. 128 months for patients achieving PR or less (P=0.02). On multivariable analysis, independent predictors of OS were melphalan conditioning dose (RR= 0.38; P=0.018) and depth of response prior to transplant (RR 2.52; P=0.039). Conclusions: Hematologic response prior to transplant predicts post-transplant outcomes in patients with AL amyloidosis. [Table: see text]

Analysis of Outcome after Autologous Stem Transplantation in Patients with Newly Diagnosed Myeloma: Comparison of Different Induction Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3079-3079 ◽  
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Single Agent ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Free Survival

Abstract Background: Autologous stem cell transplantation (SCT) improves survival in patients (pts) with multiple myeloma (MM). We have previously demonstrated that the degree of response at transplant does not impact on the outcome of transplant. However, newer induction regimens such as thalidomide and dexamethasone (Thal-Dex) result in higher response rates compared to previously used regimens such as single agent dexamethasone or vincristine, doxorubicin, and dexamethasone (VAD). We examined the outcome of SCT following three different induction therapies for newly diagnosed MM, namely VAD, single agent Dex, and Thal-Dex. Patients and Methods: 340 patients with MM who received their SCT within 12 mos of diagnosis (median 5.8, range 3–12) were studied. Patients receiving more than one induction therapy as well as those in whom thalidomide was added to dexamethasone for lack of response were excluded from the analysis. There were 105 pts in the VAD group, 140 in the Dex group and 95 in the Thal-Dex group. Responses were defined using standard criteria. Results: The study cohort consisted of 209 males (59%), with a median age of 57 years (range 30–76) at transplant. Baseline characteristics were similar in the 3 groups, except for lower age in the VAD group (median 55.8) compared to Dex (59.6) and Thal Dex (57.4) and shorter time to transplant in the Dex group (5.4 m) compared to VAD (6.4) and Thal Dex (5.9). Markers of disease activity pre-transplant, including B2M and marrow plasma cell percentage were higher in the Dex group compared to either VAD or Thal Dex. The proportion of patients with any response to induction therapy was lower in the Dex group compared to the other two. All pts in the Dex and the Thal-Dex groups received melphalan only conditioning compared to 70% in the VAD group, the rest receiving Melphalan/TBI. An objective response was achieved after SCT in 96%, 97%, and 98% of pts in the VAD, Dex and Thal-Dex groups respectively (P=0.8). A complete response to SCT was seen in 49% of patients in VAD group, 45% among those in the Dex group and 38% among those in the Thal Dex group (P=0.38). There was no difference in the median progression free survival after transplant (P=0.21) or overall survival from diagnosis (P=.34) between the three groups. The proportion free from progression at 2 years post transplant was 54%, 55% and 46% for Dex, VAD and Thal-Dex respectively. The proportion surviving at 4 years from diagnosis was 64%, 65.4% and 72% respectively for the three groups. Conclusion: We did not observe any difference in the response rates including complete responses to SCT in the three groups with nearly all pts in each group achieving a response. The progression free survival and overall survival appear to be comparable between the three groups. The results from initial therapy cannot be compared between the three regimens since the study population is restricted to patients reaching stem cell transplant. Within the limits of the study, there does not appear to be any long term impact of the initial therapy for the patients going onto an early stem cell transplant. Figure Figure

scholarly journals Early response predicts myeloma outcome

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2332-2333 ◽  
Author(s):  
Antonio Palumbo
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
Early Response ◽  
Free Survival

In this issue of Blood, Gertz and colleagues present a retrospective study that analyzes progression-free survival and overall survival in 286 patients comparing those who did not reach a partial response or progressed during induction therapy with a regimen including thalidomide or lenalidomide to those who did achieve at least a partial response.

scholarly journals Melphalan Based Regimens for Treatment of Newly Diagnosed Amyloidosis, Lessons from Clinical Literature: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5561-5561
Author(s):  
Muhaddis Ejaz Ahmad ◽  
Muhammad Abdullah Yousaf ◽  
Abdul Rafae ◽  
Mustafa Nadeem Malik ◽  
Tariq Iqtidar Sadiq Syed ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cochrane Library ◽  
High Dose ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Group A ◽  
Group B ◽  
High Dose Melphalan ◽  
Combination Regimens

Introduction: Melphalan causes cross linkage between DNA, causes cytotoxicity in both dividing and non-dividing tumor cells. Our objective is to analyze and summarize the published literature for the efficacy of melphalan based regimen used for the treatment of newly diagnosed Amyloidosis (ND-AL). Methods: We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after June 2006, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library and Web of Science. Total 649 articles were identified initially and after detailed screening, we finalized 10 studies involving 616 ND-AL patients. Results: Melphalan (M), Bortezomib (V) and dexamethasone (d)/prednisone (p): A retrospective study by Zhao et al., included 123 ND-AL patients (pts) were given M, V, and d. Overall hematological response (OHR) was 100% with complete response (CR) in 44% and partial response (PR) in 38.9% pts. Median overall survival (mOS) was 38 months (mo) and 3-yr survival ranged from 41-72%. Organ response (OR) was 25%. In a study by Lee et al., with 19 pts who received M, V, and p demonstrated OHR of 84% (Table 1). Melphalan (M) and dexamethasone (d): Sanchorawala et al. (n=70) reported patients treated with M and d showed OHR of 69%, with CR in 13% and PR in 25%. Similarly, a study by Lebovic et al. reported 40 pts who were given M, d. OHR was 58% and 13% pts showed CR (Table 1). High dose Melphalan/Stem Cell Transplant (HDM/SCT) with and without induction: In study by Cowan et al., (n=45) pts in group A (n=21) were given novel induction using agents like protease inhibitor (PI), cyclophosphamide, bortezomib and dexamethasone (CyBorD), Lenalidomide (L), dexamethasone (d) prior to high-dose melphalan (HDM). CR was observed in 50%, VGPR in 7% and PR in 7% pts. Group B (n=24) pts were given frontline HDM/SCT upfront. CR was observed in 28%, VGPR in 14% and PR in 14% pts. In a study by Scott et. al., 31 pts were categorized in 3 groups who received HDCT either with no induction, induction with V-based regimen and induction with other regimens including lenalidomide/dexamethasone (len/dex), melphalan/dexamethasone (mel/dex) and thalidomide/dexamethasone (Thal/dex). OHR in mel/dex cohort (n=3) was 67% (Table 1). In a study by Huang, X. et al., 56 pts were divided in two groups of 28 pts each. Pts in group A received Vd+HDM/SCT demonstrated CR in 67.9%, VGPR in 7.1%, PR in 10 .7 % and no response (NR) in 7.1 % pts. In group B, pts received with HDM/SCT upfront demonstrated CR in 35.7%, VGPR in 10.7%, PR in 2.1 % and no response NR in 21.4 % pts (Table 1). Randomized Standard dose Melphalan (SDM) versus HDM: In a study by Jaccard et al., there were two groups. The OHR was 68% in group A pts who were given SDM and high-dose dexamethasone (HD-dex) with CR in 31% and PR in 36% pts. The OHR was 67% in group B pts who were given HDM+ASCT with CR in 40% and PR in 25% pts (Table 1). Melphalan with Total body irradiaton (TBI): Vesole et al., reported 107 pts who were given M and TBI. OHR was 32% with CR in 16% and PR in 16% pts. mOS was 47.2 mo (Table 1). Melphalan (M), dexamethasone (d), Lenalidomide (L): In a clinical trial (NCT00890552) involving 25 pts M, d, and lenalidomide were give. CR, VGPR and PR were observed in 8%, 16% and 33%. 37.5% pts showed no-response (Table 1). Conclusion: Despite heterogeneity in the AL patient population and various regimens used in published literature, melphalan based regimens are very effective for treatment. Induction regimens and supportive care have evolved over the years. Novel combination regimens used for induction followed by HD-Melphalan consolidation along with careful selection of patients for high dose chemotherapy consolidation and stem cell transplantation in routine clinical practice is the best approach for personalized therapy selection for AL amyloidosis. Cytopenias of three cell lines are the major side effects reported with Mel therapy. Just like melphalan use for treatment of multiple myeloma in novel combination regimens, future randomized prospective trials are needed to better understand the efficacy and safety profile of melphalan based newer combination regimens for AL amyloidosis treatment. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

The Dream of a Cure in Multiple Myeloma: A 15-Year Single Center Retrospective Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5503-5503
Author(s):  
Stefano Pulini ◽  
Annalisa Natale ◽  
Anna Maria Morelli ◽  
Antonio Spadano ◽  
Stefano Angelini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Progressive Disease ◽  
Diagnostic Tools ◽  
Cell Transplant ◽  
The Past ◽  
Line Therapy

Abstract Multiple Myeloma (MM) is still considered an incurable disease despite a substantial global outcome improvement observed during the past decade. Despite better understanding of biological pathways, availability of sophisticated diagnostic tools and increasing number of therapeutic options almost all patients experience disease relapse. The aim of our retrospective study was to analyze global outcome in newly diagnosed MM patients eligible for high dose chemotherapy and autologous stem cell transplant (ASCT) treated in our Institution in the last 15 years. We evaluated 177 MM patients transplanted in our Institution from November 1999 to February 2015. Median age at start therapy was 58 years (range 36-71) and median follow up time (from start therapy to last follow up) was 52 months (range 7-185). Patients received different induction therapies before transplant reflecting the availability of new drugs and consequently more therapeutic choices. 65 patients received conventional chemotherapy-based induction (VAD 27, 15%, Total Therapy 2-like 37, 22%, EDAP 1 patient); 15 patients thalidomide-based (TD, 8%); 88 patients bortezomib-based (VTD 74, 43%; VCD 8, 5%; PAD 3, 1%; VD 3, 1%) and 9 patients lenalidomide-based (RD, 5%). After induction regimen 23 patients (13%) received additional therapy before transplant: 14 for Progressive Disease (PD), 9 were considered in suboptimal/unsatisfactory response (5 in Partial Response, PR and 4 in Stable Disease, SD). 71 patients received a single ASCT, 106 patients double ASCT; 11 tandem autologous and allogeneic SCT. All patients had a PR/VGPR/CR after ASCT. Treatment related mortality was 1% (3 patients: 2 of them after Allogenic ASCT, 1 for acute Graft versus Host Disease, 1 for Veno Occlusive Disease). After first line therapy 7 patients died: 3 for progressive disease, 4 for other causes (2 myocardial infarction, 1 intestinal ischemia and 1 breast cancer). 90 patients (51%) experienced MM relapse (median time from ASCT 24 months) and were treated according to different chemotherapy schedules. At last follow-up 115 patients were alive (65%), 61 of them in Complete Response, 31 in Very Good Partial Response, 8 in Partial Response, 4 in SD, 11 in PD. Median global overall survival (OS) was 109 months, median global Progression Free Survival1 (PFS1) 51 months and median global PFS2 (time from start therapy to second disease progression or death from any cause) 80 months. According to different induction therapy (chemotherapy vs bortezomib vs thalidomide vs lenalidomide-based) median OS was 117 months vs not reached (more than 96) vs 68 vs not reached (more than 60); median PFS1 was 47 months vs 60 vs 35 vs not reached (more than 60); median PFS2 was 76 months vs 92 vs 57 vs not reached (more than 60), respectively. As reported in literature the improvement of biological, diagnostic and clinical knowledge and the availability of new therapeutic tools translates in improved outcome in MM patients treated in our Center. The introduction of the proteasome inhibitor bortezomib in the induction therapy gave the best results in terms of OS, control of the disease (PFS) and response to second line therapy after relapse (PFS2). Considering the remarkable progress done in the past decade the dream of a cure is a challenge for the future. Disclosures No relevant conflicts of interest to declare.

Early versus delayed autologous stem cell transplant (ASCT) in patients receiving induction therapy with lenalidomide, bortezomib, and dexamethasone (RVD) for newly diagnosed multiple myeloma (MM).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8540-8540
Author(s):  
Ajay K. Nooka ◽  
Amelia A. Langston ◽  
Edmund K. Waller ◽  
Leonard T. Heffner ◽  
Charise Gleason ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Median Time ◽  
Induction Therapy ◽  
Survival Rates ◽  
Initial Therapy ◽  
Autologous Stem Cell Transplant ◽  
Optimal Timing ◽  
Cell Transplant ◽  
Newly Diagnosed

8540 Background: Lenalidomide, bortezomib and dexamethasone (RVD) is an active, tolerable induction regimen with superior response rates (≥VGPR rates of 80%) in newly diagnosed MM pts. However, the optimal timing of ASCT with this triplet combination is uncertain. We have evaluated our institutional experience to provide an insight for the best timing of ASCT, where specific patients were offered delayed ASCT based on risk, response and toxicity of therapy. Methods: 222 consecutive transplant-eligible pts with newly diagnosed MM that received at least 3 cycles of RVD and harvested stem cells were included in the analysis from May 2007 until October 2011. Patients underwent early ASCT (received planned ASCT immediately after stem cell harvest, n=136) or delayed transplant (received planned maintenance therapy after collection with intent to proceed with ASCT at first relapse, n=86). Results: Median age of the patients at the time of diagnosis is 60.5 yrs (32-77) vs. 60 yrs (22-73) for early vs. delayed groups. ISS stage 3 disease was seen in 31% patients and 10% patients; high risk cytogenetics were seen in 11% and 7% patients in early vs. delayed groups, respectively. Median time from initiation of induction therapy to ASCT in early group is 5.45 months (range, 3.19-12.68 months). In the delayed SCT group, 28 patients underwent ASCT at a median time of 26.21 months (range, 13.67-41.72 months) from initiation of therapy. At a median follow up of 32 months, 5-year overall survival from diagnosis was 68% and 88% in patients undergoing early and delayed ASCT, respectively (p = 0.106). Conclusions: Transplantation-eligible patients who receive RVD as initial therapy followed by early vs. delayed ASCT result in comparable overall survival. In carefully selected newly diagnosed myeloma patients with lower ISS stage receiving RVD as induction therapy, planned delayed ASCT results in 5-year survival rates close to 90%.

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