Global Approaches in Myeloma: Critical Trials That May Change Practice

2018 ◽  
pp. 656-661 ◽  
Author(s):  
Philippe Moreau ◽  
Cyrille Touzeau
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Therapeutic Strategies ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
The Past ◽  
Induced Changes ◽  
The Impact ◽  
Specific Section

The treatment of multiple myeloma (MM) has changed dramatically in the past decade with the introduction of new drugs into therapeutic strategies both in the frontline and relapse settings. With the availability of at least six different classes of agents that can be combined in doublet, triplet, or even quadruplet regimens and used together with high-dose therapy and autologous stem cell transplantation, the choice of the optimal strategy at diagnosis and at relapse represents a challenge for physicians. Also problematic is the lack of trials addressing questions, such as sequencing or the duration of maintenance. This review will focus on the results of recent clinical trials both in the frontline and relapse settings that have induced changes in clinical practice and will discuss the impact of important ongoing trials. A specific section will discuss therapeutic strategies when new drugs are not available.

Retrospective Comparison of Transplant Outcomes in Patients with Multiple Myeloma According to Induction Therapy with Thalidomide/Dexamethasone (TD) with or without Bortezomib (VTD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 948-948 ◽  
Author(s):  
Sergio Giralt ◽  
Rupi Thandi ◽  
Muzaffar Qazilbash ◽  
Floralyn Mendoza ◽  
Eric Han ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Therapy ◽  
Response Rates ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Treatment Characteristics ◽  
The Impact

Abstract Background: Thalidomide/Dexamethasone (TD) has become one of the most commonly used induction therapies for patients with symptomatic multiple myeloma (MM) eligible for high dose therapy (HDT) intensification with autologous stem cell transplant (ASCT). Bortezomib (Velcade) has been added to the combination of TD (VTD) in an effort to reduce MM tumor burden further prior to HDT.The impact of this addition on HDT outcomes has not been fully explored. Purpose: To determine the impact of the addition of bortezomib to TD induction therapy in patients with MM undergoing HDT and ASCT consolidation. Patients and Methods: Patients were eligible for this analysis if they had undergone HDT with ASCT for first remission consolidation or primary refractory disease within 12 months of diagnosis between 9/03 and 12/05 and had received either TD or VTD as induction therapy. Patients receiving VTD after TD were excluded. Patients receiving more than 1 chemo regimen other than TD or VTD were excluded. Chemomobilization was NOT considered an exclusion criteria. Results A total of 78 patients qualified for the analysis (27 VTD; 51 TD). Patient and treatment characteristics are summarized in table 1. In brief, the patients receiving VTD had a higher rate of cytogenetic abnormalities and received less cycles of chemotherapy prior to SCT. Although pre-SCT response rates were similar between patients receiving VTD or TD (95% vs 92%) there was a trend for a higher CR rate in the VTD group (15% vs 6%). Post transplants response rates assessed between 3–6 months demonstrated that 28% and 38% of VTD patients achieved near CR and CR respectively while 19% and 23% had these responses post TD induction. There was no difference in 2 year OS and PFS among patients receiving VTD or TD (91% vs 81% and 35% and 56% respectively). Conclusion: Both VTD and TD as induction treatment are associated with high response rates prior to SCT as well as 6 months post SCT. In this retrospective analysis no survival benefit was seen for induction therapy with VTD over TD, despite higher near CR and CR rates. However randomized trials need to be performed addressing type of induction as well as duration of induction therapy prior to high dose therapy consolidation. Patient and Treatment Characteristics Variables VTD TD N 27 51 Median Age 54 (34–71) 56 (34–71) %ISS> 1 76% 65% % CG Abnormal 37% 19% p=.009 B2M @ Dx 2.99 3.19 Cycles Prior to SCT 2 4 p=.00009 % Mel 200 74% 69% Post SCT Maintenance 15/27 23/51

High-Dose Therapy Followed by Autologous HSCT in Patients with Multiple Myeloma. Results of a Retrospective Multicenter Analysis Conducted by The Polish Myeloma Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5108-5108
Author(s):  
Wanda M. Knopinska-Posluszny ◽  
Andrzej Hellmann ◽  
Michal Taszner ◽  
Anna Dmoszynska ◽  
Wiktor Jedrzejczak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progenitor Cells ◽  
Bone Structure ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Albumin Level ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Abstract In recent years high-dose therapy with autoHSCT has become the treatment of choice for eligible patients with multiple myeloma. This disease is now one of the most common indications for autotransplantation. The aim of this study was the clinical assessment of patients who underwent autotransplantation of progenitor cells and an analysis of the results of conducted treatment. The Polish Myeloma Group collected results of auto HSCT from 12 transplantology centres in Poland conducted between 1995 and 2006. We analyzed retrospectively the prognostic influence of pre-transplant characteristics on response and survival in 498 patients. Virtually all the patients received peripheral blood stem cell support after conditioning with melphalan (95%). We evaluated the influence of age, type of myeloma, Durie-Salmon stage, presence of renal impairment, plasma cell infiltration, albumin and b2 microglobulin level at diagnosis, status prior to and post HSCT, time from diagnosis to HSCT on overall survival (OS) and progression-free survival (PFS) to define patients with better prognosis. 232 females and 266 males underwent auto HSCT, and these included 297 (59,6%) with IgG, 97 (19,5%) with IgA, 31 (6%) with B-J, 22 (4,4%) with non-secretory myeloma. Bone structure changes were ascertained in 355 patients (71%). Bone marrow involvement higher than 20% was found in 282 patients (56,6%) at diagnosis. A decreased level of albumin (<35g/l) was determined in 168 patients (33,7%), and b2microglobuline level above 3,5 mg/l in 124 patients (24,9%). Transplantation of progenitor cells was conducted as consolidation of first line treatment following chemotherapy according to VAD in the majority of patients (74,7%). This number increased to 246 (49,4%) following transplantation. Double transplantation was conducted in 132 patients (26,5%). Median OS and PFS obtained were 3272 (1391–4232) and 1158 (102–3767) days respectively. CR achieved before transplantation, normal renal function, albumin level above 35g/l, b2 mikroglobulin below 3,5mg/l and DS stage I, were associated with a longer OS and PFS (p<0,05). This retrospective, multicenter study confirms the efficacy and safety of autoHSCT in multiple myeloma patients. Additional confirmation is given of the increased rate of CR, and the significantly prolonged survival observed in complete responders. Taking the above into account the employment of new drugs, such as thalidomide or bortezomib, which allow the achievement of a higher percentage of remissions should in the future bring about an improvement of the efficacy of transplantation in multiple myeloma.

Consolidation with Bortezomib, Thalidomide and Dexamethasone After High Dose Therapy Is Feasible, Safe and Effective In De Novo Multiple Myeloma Patients Who Already Received New Drugs Containing-Induction Regimen

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3041-3041 ◽  
Author(s):  
Murielle Roussel ◽  
Gaëlle Dörr ◽  
Willy Vaillant ◽  
Anne Huynh ◽  
Michel Attal
Keyword(s):  
Multiple Myeloma ◽  
Research Funding ◽  
Residual Disease ◽  
Complete Response ◽  
New Drugs ◽  
High Dose ◽  
Consolidation Therapy ◽  
High Dose Therapy ◽  
Induction Regimen ◽  
Immunophenotypic Analysis

Abstract Abstract 3041 High dose therapy (HDT) with autologous stem cell transplantation (ASCT) is a standard treatment option for frontline myeloma patients (pts). However, after a single or a double transplantation, almost all pts ultimately relapse. Thus, new strategies are required to control the residual disease after HDT. Consolidation therapy, given early after HDT, could enhance the depth of response and further improve progression free survival (PFS) and overall survival (OS). The IFM (Intergroupe Francophone du Myélome) previously reported that either Thalidomide or Lenalidomide, administered after HDT, was able to reduce this residual disease (IFM 99-02 and 2005-02 trials, Attal M et al. Blood 2006 and ASCO 2010). Ladetto M et al. (JCO 2010) also reported a major shrinking of residual tumor cell burden in myeloma pts undergoing early consolidation with Bortezomib, Thalidomide and Dexamethasone (VTD) after ASCT. None of these pts had previously received treatment with Thalidomide and/or Bortezomib during induction. The aim of this study was to evaluate the feasibility, safety and efficacy of early consolidation therapy in pts who had received new drugs containing-induction therapies before ASCT. Patients and Methods: In this prospective monocenter study,patients were eligible if they had the following: 1) at least partial response (PR) after HD melphalan (HDM), 2) no grade ≥ 2 peripheral neuropathy (PNY). The consolidation therapy with vTD had to be started within 3 months from ASCT for a total of 2 cycles. Each 4-week cycle consisted of: a) Bortezomib: 1mg/m2 as an IV injection twice weekly (on days 1, 4, 8, 11); b) oral Thalidomide: 100 mg/day; c) oral Dexamethasone 40 mg/day once a week (on days 1, 8, 15 and 22). Pts did not receive maintenance therapy after vTD consolidation. A systematic prophylactic anticoagulation therapy was given either by aspirin or low molecular weight heparin. Pts also received systematic anti herpes zoster prophylaxis with valacyclovir. Toxicities were graded according to the CTAECv4 at each cycle. Response was assessed according to modified European group for Blood and Marrow Transplantion criteria including very good partial response (VGPR), 1 month after the last cycle of vTD. As no immunophenotypic analysis was available routinely in our institute, we did not evaluate stingent complete response. Results: From August 2008 to May 2010, 90 newly diagnosed multiple myeloma pts under 65 received HDM followed by ASCT in the Toulouse's hospital bone marrow transplant unit, FRANCE. Forty-six pts were eligible for this study and started on consolidation. Two pts are ongoing their treatment and 41 received the whole planned treatment. Two pts withdrawn thalidomide and 1 pt did not receive the second cycle of consolidation because of toxicities. Forty-four pts were excluded mainly because of PN (27%). Initial characteristics were: age=58 years (range,44-65); ISS: 1= 50%, 2= 23%, 3=18%, NA= 9%; DS stage: I=4,5%, II=4,5%, III=91%; median beta-2microglobulin=2,9 mg/l (1,3-11,3); FISH analysis: t(4-14) and/or del 17p= 4/29 evaluable pts. The induction regimen was: Bortezomib/Dexamethasone (82%), vTD (11%), or another regimen (7%). Before consolidation therapy, response rates were: PR=16%, VGPR=48%, near complete response (nCR)=14% and CR=23%. In an Intend to treat basis, 17 pts (39%) improved their responses after consolidation with vTD: 3 pts (7%) from PR to VGPR, 8 pts (18%) from VGPR to nCR, and 6 pts (14%) from VGPR to CR. Response improvement was also reported in the 5 pts who already received induction therapy with vTD; three pts (60%) improved their response: 1 pt from PR to VGPR and 2 pts from VGPR to nCR. As immunophenotypic analysis was not avalaible, response improvement might be underestimate for CR pts. Overall, consolidation therapy with 2 cycles of vTD was efficient; 16 pts (36%) acheived CR, 30 pts (68%) CR+nCR and 40 pts (91%) VGPR or better. Considering the safety profile, there was no toxic death or grade 3/4 hematological toxicity. Non-hematological toxicities reported were: fatigue=18%, PNY (all grades)= 9%, pneumonia=7%, vertigo= 7%, constipation= 6%, and deep-vein thrombosis= 4,5%. Conclusions: Early consolidation with vTD in pts who already received Thalidomide and/or Bortezomib as induction therapy is feasible, safe and effective. Response rates improved in almost 40% of pts. Disclosures: Roussel: Janssen: Consultancy, Research Funding, orator; celgene: Consultancy, Orator, Research Funding. Off Label Use: bortezomib and thalidomide as consolidation therapy after High Dose Melphalan. Attal:celgene: Consultancy, Research Funding; janssen: Consultancy, Research Funding.

scholarly journals Adverse Cytogenetics, with or without Trisomies, in Patients Undergoing High Dose Therapy for Multiple Myeloma and Impact of Post-Transplant Maintenance Therapy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3456-3456
Author(s):  
Gregory P Kaufman ◽  
Morie A Gertz ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Single Agent ◽  
Prognostic Significance ◽  
Common Mechanism ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
The Impact

Abstract Background FISH abnormalities including t(14;16), t(14;20), t(4;14) and the loss of P53 remain a common mechanism for classifying patients (pts) with newly diagnosed multiple myeloma (MM) as adverse risk. In contrast, trisomies in MM are associated with superior outcomes and may ameliorate the negative prognostic significance conferred by adverse FISH abnormalities. High dose therapy (HDT) consisting of high dose melphalan and autologous stem cell transplantation with consideration of maintenance therapy is a common treatment strategy for transplant eligible MM pts. However, there is limited information regarding the impact of various cytogenetic abnormalities, alone or in combination with trisomies, in the context of HDT, and the efficacy of maintenance approaches in the novel agent era. Aim To determine the clinical significance of FISH abnormalities in MM pts undergoing HDT and subsequent consideration of maintenance therapy in recent years. Methods We retrospectively examined a cohort of all pts with MM who underwent first HDT at Mayo Clinic Rochester between 2008 and 2012. Medical records were reviewed under IRB approval in accordance with the principals of the Helsinki declaration. FISH results were obtained from within 6 months of diagnosis (Dx), and if unavailable pts were excluded. Pts were considered for maintenance therapy following response assessment by their treating hematologist, typically around day 100 following HDT, and were categorized based on the intent of that discussion; length of maintenance and dose reductions were not evaluated. PFS and OS were calculated from date of transplant and OS was also estimated from Dx. Timing of HDT was restricted to within one year of MM Dx (early HDT). Results 300 pts had available FISH and underwent early HDT. Median age at dx was 60 (23-75), and median follow up from Dx was 40 months (7.5-90) with 229 (76%) alive at time of analysis. The median time to HDT from Dx was 5.8 months (95% CI 5.4-8.0). At the time of HDT 249 pts (83%) were in a partial response or better. Overall, 73 pts (24%) had adverse risk FISH from dx as described, 154 pts (51%) had at least one trisomy, and 32 pts (10.7%) had a concomitant adverse FISH abnormality and a trisomy. Of all pts, 112 (37%) received maintenance therapy of some sort, most commonly single agent lenalidomide (n=67 pts) or bortezomib (n=36). Of the 73 pts with adverse FISH, 54 (74%) received maintenance therapy following initial HDT compared with 58 of 227 pts (26%) with non-adverse FISH. Among pts with adverse FISH, median PFS and OS was 21 months (95% CI 16-24) and 57 months (95% CI 41-NR) respectively, compared with 24 months (95% CI 21-26) and not met respectively for pts with no adverse FISH (p =0.08 and p=0.04). The OS from Dx was 63 months (95% CI 46-NR) and not met, respectively for pts with adverse FISH and no adverse FISH (p=0.04). Among adverse FISH pts, PFS following initial HDT was improved with any maintenance therapy (23 months (95% CI 18-33) versus 13 months (95% CI 6-22), p=0.0016). OS was not statistically different among pts with adverse FISH whether or not they received maintenance therapy, both from date of HDT as well as from Dx. For pts with non-adverse FISH at Dx similar findings were observed, with an increase in PFS following HDT with any maintenance therapy (30 months (95% CI 23-48) versus 22 months (18-24)), without a difference in OS. Further analysis of the group of pts with adverse FISH status revealed the PFS benefit seen with maintenance therapy was greatest for a subgroup of pts with concomitant trisomies (29 months (95%CI 18-38) versus 14 months (95%CI 8-16) p=0.0003) as compared to pts with adverse FISH without concomitant trisomies (19 months (95%CI 13-35) versus 12 months (95% CI 3-24) p=0.204) (figure 1). However, OS either from HDT or Dx did not differ for pts with adverse FISH with or without concomitant trisomies regardless of maintenance status. Conclusions Our data support an improvement in PFS with maintenance therapy following initial HDT amongst adverse risk FISH MM pts, however no OS benefit was observed with maintenance therapy irrespective of FISH status. Among pts with adverse FISH, maintenance strategies improve PFS for pts with a concomitant trisomy. No PFS benefit was seen with maintenance therapy in pts without concomitant trisomies. Future trials of maintenance therapy post HDT should consider evaluating and reporting on the subgroup of adverse FISH pts with concomitant trisomies. Figure 1 Figure 1. Disclosures Kumar: Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi-Aventis: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Millennium: The Takeda Oncology Co.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 240-246
Author(s):  
Julia Driessen ◽  
Sanne H. Tonino ◽  
Alison J. Moskowitz ◽  
Marie José Kersten
Keyword(s):  
Clinical Trials ◽  
Hodgkin Lymphoma ◽  
Checkpoint Inhibitors ◽  
Phase 1 ◽  
New Drugs ◽  
High Dose ◽  
Cell Transplant ◽  
Novel Therapies ◽  
The Past

Abstract Approximately 10% to 30% of patients with classical Hodgkin lymphoma (cHL) develop relapsed or refractory (R/R) disease. Of those patients, 50% to 60% show long-term progression-free survival after standard salvage chemotherapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). In the past decade, novel therapies have been developed, such as the CD30-directed antibody–drug conjugate brentuximab vedotin and immune checkpoint inhibitors, which have greatly extended the treatment possibilities for patients with R/R cHL. Several phase 1/2 clinical trials have shown promising results of these new drugs as monotherapy or in combination with chemotherapy, but unfortunately, very few randomized phase 3 trials have been performed in this setting, making it difficult to give evidence-based recommendations for optimal treatment sequencing. Two important goals for the improvement in the treatment of R/R cHL can be identified: (1) increasing long-term progression-free and overall survival by optimizing risk-adapted treatment and (2) decreasing toxicity in patients with a low risk of relapse of disease by evaluating the need for HDCT/ASCT in these patients. In this review, we discuss treatment options for patients with R/R cHL in different settings: patients with a first relapse, primary refractory disease, and in patients who are ineligible or unfit for ASCT. Results of clinical trials investigating novel therapies or strategies published over the past 5 years are summarized.

Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2345-2350 ◽  
Author(s):  
Ranjit K. Dasgupta ◽  
Peter J. Adamson ◽  
Faith E. Davies ◽  
Sara Rollinson ◽  
Philippa L. Roddam ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Standard Dose ◽  
Progression Free Survival ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Glutathione S Transferase ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
The Impact

Abstract Glutathione S-transferase P1 (GSTP1) is a phase 2 drug metabolism enzyme involved in the metabolism and detoxification of a range of chemotherapeutic agents. A single nucleotide polymorphism (Ile105Val) results in a variant enzyme with lower thermal stability and altered catalytic activity. We hypothesized that patients with the less stable variant have a decreased ability to detoxify chemotherapeutic substrates, including melphalan, and have an altered outcome following treatment for multiple myeloma. We have assessed the impact of GSTP1 codon 105 polymorphisms in 222 patients entered into the Medical Research Council (MRC) myeloma VII trial (comparing standard-dose chemotherapy with high-dose therapy). In the standard-dose arm, patients with the variant allele (105Val) had an improved progression-free survival (PFS) (adjusted hazard ratios for PFS were 0.55 for heterozygotes and 0.52 for 105Val homozygotes, compared with 105Ile homozygotes; P for trend = .04); this was supported by a trend to improved overall survival, greater likelihood of entering plateau and shorter time to reach plateau in patients with the 105Val allele. No difference in outcome by genotype was found for patients treated with high-dose therapy. However, the progression-free survival advantage of the high-dose arm was seen only in patients homozygous for 105Ile (P = .008). (Blood. 2003;102:2345-2350)

scholarly journals Frontline therapy of multiple myeloma

Blood ◽  
2015 ◽  
Vol 125 (20) ◽  
pp. 3076-3084 ◽  
Author(s):  
Philippe Moreau ◽  
Michel Attal ◽  
Thierry Facon
Keyword(s):  
Multiple Myeloma ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Therapeutic Approaches ◽  
Time To Progression ◽  
High Dose Therapy ◽  
Free Survival ◽  
The Past ◽  
Frontline Treatment

Abstract In the past decade, one of the major advances in the management of patients with symptomatic newly diagnosed multiple myeloma has been the introduction of novel agents, thalidomide, bortezomib, and lenalidomide, as part of frontline treatment in both transplant and nontransplant candidates. These drugs have markedly improved the rate of complete remission, and time to progression, progression-free survival, and overall survival have significantly increased. This article focuses on more recent frontline therapeutic approaches both in older patients, not eligible for high-dose therapy and autologous stem cell transplantation (ASCT), and in younger patients eligible for early ASCT.

scholarly journals A complex of methods of radiation diagnostics in a patient with multiple myeloma (clinical case)

2020 ◽  
Vol 24 (4) ◽  
pp. 133-145
Author(s):  
E. V. Kryukov ◽  
V. N. Troyan ◽  
O. A. Rukavitsyn ◽  
S. A. Alekseev ◽  
S. I. Kurbanov ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Multiple Myeloma ◽  
Autologous Transplantation ◽  
Emission Tomography ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Stem ◽  
X Ray ◽  
Positron Emission ◽  
Pet Ct

The article presents the possibilities of the complex application of methods of radiation diagnostics: bone x-ray, dual-energy X-ray absorptiometry, computed tomography, positron emission tomography combined with computed tomography using fluorodeoxyglucose labeled with 18-fluorine (PET/CT with 18F-FDG) in a patient with multiple myeloma, which was treated in the amount of high-dose therapy with autologous transplantation of hematopoietic stem cells. The diagnosis was established immunohistochemically. The use of these methods allowed us to dynamically assess the pathological changes characteristic of multiple myeloma.

scholarly journals Efficacy of Modified Vrd-Lite for Transplant Ineligible Multiple Myeloma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-4
Author(s):  
Mizuki Ogura ◽  
Tadao Ishida ◽  
Moe Nomura ◽  
Hirofumi Irita ◽  
Junichiro Nashimoto ◽  
...  
Keyword(s):  
Adverse Effect ◽  
Multiple Myeloma ◽  
Cardiac Amyloidosis ◽  
Staging System ◽  
Treatment Interruption ◽  
Cardiac Complications ◽  
High Dose ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
The Impact

BACKGROUND: High dose chemotherapy followed by autologous peripheral blood stem cell transplantation is an effective treatment for multiple myeloma. However, many patients with newly diagnosed multiple myeloma are transplant-ineligible because of their age and complications, result in a poorer prognosis than transplant-eligible patients. Furthermore, many of them cannot complete normal chemotherapy because of low tolerability. Here, we investigated the efficacy and safety of modified bortezomib with lenalidomide and dexamethasone (mVRD-lite) for transplant-ineligible patients with newly diagnosed multiple myeloma. STUDY DESIGN: A retrospective observational analysis was performed on patients who received mVRd-lite for the first line chemotherapy between Jan. 2016 and Mar. 2020 in our hospital. Patients who received high dose dexamethasone to reduce tumor burden, and patients who received bortezomib with dexamethasone or lenalidomide with dexamethasone as a reduction regimen of mVRd-lite were also included. We evaluated ORR, OS, PFS and adverse effect. mVRD-lite at first was administered over a 28-day cycle. Bortezomib 1.3 mg/m2 weekly was administered subcutaneously on days 1, 8, 15 and 22. Lenalidomide 15 mg was given orally 18 days, omitted on days 1, 8, 15, which are the days of bortezomib administration. Dexamethasone 20 mg was given orally on days 1, 2, 8, 9, 15, 16, 22, which are the day of and day after bortezomib. We also reviewed patients background, especially complication of light-chain amyloidosis and considered the impact of cardiac amyloidosis on patient prognosis. This study was conducted with the permission of the Ethics Review Board in our hospital. RESULTS: The subjects analyzed totaled 40 transplant-ineligible patients. 11(27.5%) patients were AL amyloidosis associated with multiple myeloma and 8(20%) patients had cardiac amyloidosis. Median age at diagnosis was 73 (range 48-86) and Male:Female=1:1. Most of them were judged inadequate to transplantation due to their age, general condition, or complication. One patient was ruled unfit to transplantation, because of his refusion. The Revised International Staging System (R-ISS) were I in 5 (12.5%), II in 25 (62.5%) and III in 8 (20%). 5(25%) patients switched to maintenance therapy. 17(42.5%) patients discontinued treatment, because of adverse effect (cardiac failure 4 ; two of them combined with cardiac amyloidosis, rash 4, peripheral neuropathy 3, infection 3, etc). 2(5%) patients died during treatment by mVRd-lite, because of Grade 4 adverse effect, such as pneumonia. 11(27.5%) patients died during observation period and causes of death were primary disease and TRM. 1(2.5%) patient was died of heart failure associated with cardiac amyloidosis. The overall response rate(ORR) during treatment period of mVRd-lite was obtained in 34(85%), including sCR in 5 (12.5%), VGPR in 13 (32.5%) and PR in 14(30%). 2(5%) patients achieved MRD negative. SD were observed in 3(7.5%) patients. 3(7.5%) patients were not evaluated efficacy because of treatment interruption by adverse effect. Overall survival rate at two year is 64.3%, median OS was not reached, at a median follow-up of 20 months. CONCLUSIONS: Transplant-ineligible multiple myeloma patients are associated with poor prognosis. Modified RVD-lite is one of the appropriate therapeutic options, in the transplant-ineligible multiple myeloma patients. Twenty-five percent of patients with cardiac amyloidosis had treatment discontinued due to cardiac complications. Further study is needed for treatment of patients with multiple myeloma complicated with cardiac amyloidosis. Disclosures Ishida: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Ono pharmaceutical co: Speakers Bureau; Takeda pharmaceutical co: Speakers Bureau. Nashimoto:Janssen: Speakers Bureau; Celgene: Speakers Bureau. Tsukada:Takeda pharmaceutical co: Speakers Bureau. Suzuki:Takeda, Amgen, Janssen and Celgene: Consultancy; Takeda, Celgene, ONO, Amgen, Novartis, Sanofi, Bristol-Myers Squibb, AbbVie and Janssen: Honoraria; Bristol-Myers Squibb, Celgene and Amgen: Research Funding.

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