scholarly journals Lenalidomide Versus Thalidomide or Bortezomib As Maintenance Regimens for Non-Transplant Patients with Multiple Myeloma: Multi-Center Real World Experience in China

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4728-4728
Author(s):  
Zhe Zhuang ◽  
Lei Shi ◽  
Ying Tian ◽  
Dongmei Zou ◽  
Ru Feng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Real World ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Front Line ◽  
Negative Effects ◽  
Current Standard ◽  
Transplant Patients ◽  
Line Therapy

Abstract Background Maintenance (MT) after front-line therapy is the current standard for multiple myeloma (MM). However, no adequate data has shown the present situation of maintenance treatment in China yet, and autologous stem cell transplantation (ASCT) rate is still low in eligible newly diagnosed MM (NDMM) patients. Hence, we conducted this retrospective real-world study on efficacy and safety of the mainstream maintenance regimens in non-transplant NDMM patients-thalidomide (T-MT), lenalidomide (L-MT) and bortezomib (B-MT). Methods Clinical data were collected from 9 centers of North China MM Registry, during January 2010 to December 2020. The progression-free (PFS) and overall survival (OS) from maintenance, and drug toxicities were compared in T-MT, L-MT and B-MT groups. Thalidomide 75-150mg/day was administrated in T-MT group. L-MT group received lenalidomide as 25mg every other day or 10mg daily, on day 1-21 of a 28-day cycle. Bortezomib (1.3 mg/m 2 s.c.) was administered every other week or 4 vials every 3 months. Dexamethasone was given along with L or B in some patients. Results A total of 355 patients were enrolled including 159 in T-MT, 143 in L-MT and 53 in B-MT. At baseline, the gender ratio, paraprotein isotype, ISS and R-ISS stage, as well as response status before MT were comparable. Patients on L-MT were significantly older than the other groups. Meanwhile, greater proportions of patients in L-MT and B-MT groups had high-risk cytogenetic abnormalities (HRCA), defined as amplification 1q21 (1q21+), deletion 17p (17p-), t(4,14), t(14,16). The median follow-up duration since maintenance was 40.1, 19.6 and 22.2 months (m) in T-MT, L-MT and B-MT groups, respectively. There were 67.9%, 61.5% and 60.4% patients with T-MT, L-MT and B-MT achieving very good partial response (VGPR) or better before maintenance. Disease progression was recorded in 101 patients (63.5%) with T-MT, 54 (37.5%) with L-MT and 19 (35.8%) with B-MT. While mortality was 46 (28.9%), 22 (15.3%) and 4 (7.5%), respectively. The median PFS was 23m in T-MT, as compared with 26.9m in L-MT and 37.0m in B-MT (p=0.59). Median OS was 91.0M in T-MT, whereas not reached (NR) in the others (p=0.50). Patients reached complete response (CR) or stringent CR (sCR) before MT had prolonged PFS compared to those with VGPR or less in T-MT (28.0m vs 17.0m, p=0.06) and L-MT group (27.4m vs 18.2m, p=0.02), while comparable in B-MT (NR vs 30.8m, p=0.25). Meanwhile, patients in each group had similar OS despite of different responses before MT. Patients with 1q21+ on T-MT had shorter median PFS compared to those without (12.2m vs 21.0m, p=0.08), as well as impaired median OS (53.1m vs 81.0m, p= 0.004), despite various second line therapies. While the PFS of L-MT was 26.9m for patients with 1q21+ and 27.4months for those without (p=0.99). In B-MT group, the PFS was 43.5m and 30.2m (p=0.64), respectively. Median OS was not reached in both L-MT and B-MT. Only a few patients with 17p- in T-MT and B-MT, yet also presented remarkably inferior PFS (7.0m vs 21.0m, p=0.011) and OS (32.0m vs 81.0m, p=0.001) with thalidomide. As for L-MT, PFS (22.2m vs 27.4 m, p=0.19) and OS (NR vs NR, p=0.55) were not of discrepancy between 17p- or without. In B-MT, PFS (30.8m vs NR, p=0.99) was similar, though median OS was not reached, inferior tendency was observed (p= 0.04). As for patients with any adverse CA, T-MT resulted in impaired PFS (12.0m vs 23.0m, p=0.02) and OS (53.0m vs NR, p＜0.01). In contrast, PFS and OS were both comparable in patients with L-MT or B-MT no matter with HRCA or not. The main reason of maintenance withdrawal was disease progression. Among patients with detailed records of adverse effects, adverse event related discontinuation was seen in 5.3%(n=5), 6.1%(n=3) and 0 patients in T-MT, L-MT and B-MT, respectively. Conclusions In this multi-centered real-world maintenance study, thalidomide, lenalidomide or bortezomib after front-line therapy in non-transplant NDMM patients has similar PFS and OS. However, patients on L-MT and B-MT have greater proportion of HRCAs, which drags down survival in T-MT especially with 1q21+ and 17p-, while L-MT and B-MT mostly reverses the negative effects. Clinicians in the real practice prefer to select lenalidomide or bortezomib as maintenance in patients with HRCAs, while thalidomide is still an option for patients with standard risk. Figure 1. A) Baseline characteristics in three groups. * p＜ 0.05. B) PFS of the three groups. C) OS of the three groups. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Real-World Treatment Patterns in Relapsed or Refractory Multiple Myeloma: Evidence from a Cohort Review in the United Kingdom

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5947-5947
Author(s):  
Huamao Mark Lin ◽  
Keith L Davis ◽  
James A. Kaye ◽  
Katarina Luptakova ◽  
Saurabh Nagar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Research Funding ◽  
Complete Response ◽  
Additional Benefit ◽  
Line Treatment ◽  
Second Line ◽  
Line Therapy ◽  
First Relapse ◽  
Third Line

Abstract INTRODUCTION: Despite advancements in induction and maintenance therapies leading to improved response rates and overall survival (OS), virtually all patients with multiple myeloma (MM) eventually relapse. Improvement in outcomes in relapsed and/or refractory multiple myeloma (RRMM) remains an area of unmet need, yet there is a shortage of data describing typical treatment patterns in these patients in real-world practice settings. Such data may help inform future health technology assessments and other regulatory evaluations of current and new therapies in RRMM. To help address this information gap, we analyzed retrospective data from a cohort of RRMM patients in the United Kingdom (UK). METHODS: A retrospective medical record review was conducted in a cohort (n = 216) of patients with RRMM in the UK. Patients were selected (based on randomly generated first letter of last name) from the caseloads of 41 hematology/oncology providers across the UK. Specific inclusion criteria were: ≥18 years of age at initial MM diagnosis; first determined to have RRMM between January 1, 2009 and December 31, 2011, where RRMM was defined by (1) receipt of a first-line (induction) treatment regimen of chemotherapy with or without stem cell transplant (SCT) and with or without post-induction/SCT maintenance therapy and (2) disease progression while on or at any time after completion of first-line therapy. Patients were retrospectively assessed on second- and third-line treatment regimens received, treatment duration, and reasons for treatment discontinuation from date of first relapse or progression (study index date). All analyses were descriptive and exploratory in nature. RESULTS: Demographic and clinical characteristics of the study sample are presented in Table 1. Mean (SD) age at study index (first relapse, or RRMM diagnosis) was 65.6 (8.7) years, with approximately half of patients (53%) having advanced age (≥65 years). The study sample was 62.5% male and more than two-thirds of patients (69%) were still alive at the time of the medical record review. Among the 216 patients studied, 208 (97%) received ≥1 additional line of systemic chemotherapy after first relapse (Table 2); 94 patients (43%) received ≥2 additional lines of therapy (i.e., at least second- and third-line therapy) during the observation period. The most common second-line regimen was bortezomib + dexamethasone with or without other agents (66% of second-line initiators), followed by lenalidomide + dexamethasone with or without other agents (20%). Median duration of second-line treatment was 6 cycles over a median of 5.4 months. Among the 98% of patients who discontinued second-line treatment, a majority (62%) stopped therapy due to reaching complete response with no additional benefit expected; 33 patients (16%) discontinued second-line treatment due to disease progression and 8% discontinued due to toxicities. Lenalidomide + dexamethasone with or without other agents was the predominant third-line regimen (67% of third-line initiators); bortezomib + dexamethasone with or without other agents was the next most common third-line regimen (14%). Among the 94 patients receiving third-line treatment, median duration was 6 cycles over a median of 5.7 months. The leading reason for third-line discontinuation was disease progression (48%); 30% of patients discontinued because they reached complete response with no anticipated additional benefit, and 20% discontinued because of loss or lack of response to therapy. CONCLUSIONS: In the RRMM cohort reviewed here, bortezomib-containing regimens were the predominant second-line therapy and lenalidomide + dexamethasone was the most common third-line regimen. The most common reasons for discontinuation of RRMM treatments were disease progression and physician-judged achievement of complete response with no additional benefit expected. While the most common reason for therapy discontinuation in second-line treatment was reaching complete response with no additional benefit expected, in third-line therapy it was disease progression. With growing evidence in the RRMM literature that treatment to progression may be superior to a fixed duration of therapy, as well as evidence of premature discontinuation being associated with inferior outcomes, the relatively short second-line duration reported here (<6 months) further highlights a potential unmet need in this disease area. Disclosures Lin: Takeda: Employment. Davis:Takeda: Research Funding. Kaye:Takeda: Research Funding. Luptakova:Takeda Oncology: Employment. Nagar:Takeda: Research Funding. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership.

Isatuximab plus carfilzomib and dexamethasone in east Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20015-e20015
Author(s):  
Kihyun Kim ◽  
Chang Ki Min ◽  
Youngil Koh ◽  
Kenichi Ishizawa ◽  
Sung-Hyun Kim ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Disease Progression ◽  
Residual Disease ◽  
East Asian ◽  
Progression Free Survival ◽  
Complete Response ◽  
Efficacy And Safety ◽  
Asian Patients ◽  
Number Of Patients ◽  
East Asian Patients

e20015 Background: The Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) plus carfilzomib and dexamethasone (Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (hazard ratio [HR] 0.53; 99% confidence interval [CI] 0.32–0.89; P= 0.0007). We evaluated the efficacy and safety of Isa-Kd in the East Asian patients (19 Japanese, 27 Korean). Methods: RMM pts who received 1-3 prior lines of therapy were stratified to receive Isa-Kd or Kd. Isa-Kd arm received Isa (10 mg/kg intravenously) weekly for 4 weeks, then every 2 weeks. Both arms received K (20 mg/m2 days 1-2, 56 mg/m2 thereafter) twice-weekly for 3 of 4 weeks, and d (20 mg) twice-weekly. Treatment continued until disease progression or unacceptable adverse events (AE). The primary endpoint was prolongation of PFS. Key secondary endpoints included; very good partial response or better (≥VGPR), complete response (CR) rate and minimal residual disease negativity (MRD–) rate. Results: East Asian pts (25 Isa-Kd, 21 Kd) were randomized. Pt characteristics were similar in the East Asian subgroup compared with the intent to treat (ITT) population (N = 302). Median age (Isa-Kd 64.0 [range 45–83] years vs Kd 60.0 [range 33–73] years); median prior lines Isa-Kd 2.0 (range 1–3) vs Kd 1.0 (range 1–3); refractory to lenalidomide 16.0% Isa-Kd vs 47.6% Kd; refractory to PI 20.0% Isa-Kd vs 33.3% Kd; high-risk cytogenetics 48.0% Isa-Kd vs 42.9% Kd. After a median follow-up of 20.7 months, the addition of Isa to Kd improved ≥VGPR, CR and MRD– rates (Table). The HR 0.64 (95%CI: 0.231-1.764) for disease progression or death favored Isa-Kd. Grade ≥3 AEs were observed in 79.2% Isa-Kd vs 55.0% Kd pts, serious TEAEs in 45.8% Isa-Kd vs 50.0% Kd; TEAEs leading to treatment discontinuation were lower in the Isa-Kd group (4.2% Isa-Kd vs 10.0% Kd). Overall, 64.0% Isa-Kd vs 42.9% Kd pts were still receiving treatment. Conclusions: Efficacy and safety results of Isa-Kd in East Asian pts are consistent with the results of the overall IKEMA population, in which significantly better efficacy (PFS, CR, ≥VGPR and MRD– rate) was reported in favor of Isa-Kd without an increase in the number of patients with serious TEAEs or discontinuations. Isa-Kd is a potential treatment option for East Asian pts with RMM. Clinical trial information: NCT03275285. [Table: see text]

Longitudinal Evaluation of Minimal Residual Disease in Patients with Multiple Myeloma who Achieve Complete Response After First Line Therapy

2019 ◽  
Vol 19 (10) ◽  
pp. e185-e186
Author(s):  
Ioannis V. Kostopoulos ◽  
Efstathios Kastritis ◽  
Aristea-Maria Papanota ◽  
Paraskevi Micheli ◽  
Panagiotis Malandrakis ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Complete Response ◽  
First Line ◽  
Longitudinal Evaluation ◽  
First Line Therapy ◽  
Line Therapy ◽  
Minimal Residual

Serum Free Light Chain Analysis Improves Monitoring of Multiple Myeloma Patients Receiving First-Line Therapy with the Combination of Velcade, Doxil, and Dexamethasone (VDD).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2736-2736
Author(s):  
Daniel Lebovic ◽  
Tara Kendall ◽  
Christine Brozo ◽  
Amanda McAllister ◽  
Malathi Hari ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Disease Progression ◽  
Light Chain ◽  
Residual Disease ◽  
Clinical Information ◽  
Complete Response ◽  
Response To Therapy ◽  
Controlled Clinical Trial ◽  
Serum Free

Abstract Introduction: Serum free light chains (sFLC) have a short 2–6hr serum half-life compared with up to 3 weeks for intact immunoglobulins (Ig). sFLC analysis (Freelite™, The Binding Site Inc) therefore provides earlier therapeutic information for Intact Ig Multiple Myeloma (IIMM) patients producing monoclonal FLC. Also, it may be a more sensitive method than urinary Bence Jones protein (BJP) analysis for monitoring light chain MM (LCMM) patients. We assessed the benefits of monitoring sFLC in addition to serum and urine M-protein in previously untreated MM patients receiving combination therapy with Velcade, Doxil, and Dexamethasone (VDD). Methods: 38/40 patients enrolled in a Phase II clinical trial received up to six 3-week VDD cycles (Velcade: 1.3 mg/m2IV; Days 1, 4, 8, 11, Doxil: 30 mg/m2 IV; Day 4, and Dexamethasone: 20 mg PO; Days 1, 2, 4, 5, 8, 9, 11, 12. During the first cycle, Dexamethasone was given at 40 mg per dose, with the first 10 patients receiving Dexamethasone at 40 mg PO on Days 1 – 4). Responses were determined based on uniform response criteria (URC, Durie et al. (2006) Leukemia20, 1467). 31/38 patients had IIMM (16 IgGκ, 8 IgGλ, 5 IgAκ, 2 IgAλ). 7/38 patients had LCMM (3 κFLC, 4 λFLC). 8/31 IIMM and 2/7 LCMM patients had sFLC levels <10mg/dL at baseline, too low to define measurable disease according to the URC. Results: sFLC and intact Ig response was similar in 16/31 IIMM patients (at least partial response (PR), 4/16 had baseline sFLC levels <10mg/dL). In 7/31, the difference between involved and uninvolved sFLC levels fell to <50% of baseline one cycle or more earlier than intact Ig levels indicated at least PR (for 3/7, intact Ig levels indicated stable disease). In 1 patient, intact Ig levels fell to <50% of baseline before sFLC. 2/31 patients displayed probable light chain escape during treatment, with a third patient’s disease progression indicated earlier by sFLC than intact Ig. In 4/31 patients, sFLC analysis provided no useful information. sFLC ratios normalised in 6/31 IIMM patients, supportive of a stringent complete response. 16/31 IIMM patients had no significant BJP; in 15/31 with BJP, changes in sFLC and BJP levels were similar. Changes in sFLC and BJP levels agreed in 5/7 LCMM patients. 2/7 became negative for BJP while continuing abnormal sFLC levels suggested residual disease (in both these patients, baseline sFLC levels were <10mg/dL). Conclusion: Analysing sFLC in addition to intact Ig generated clinically relevant detail in 10/31 (32%) IIMM patients, with earlier response identified in 7 patients and probable disease progression in 3 patients. sFLC analysis provided a more sensitive means of monitoring response to therapy and identifying residual disease in 2/7 (29%) LCMM patients. No clinical information would have been lost by replacing BJP with sFLC analysis when monitoring either IIMM or LCMM. Our data suggests that the URC 10mg/dL baseline sFLC cut-off may not always be appropriate, as sFLC analysis of some patients with <10mg/dL was informative. Furthermore, sFLC analysis can be used in assessing stringent complete response. This analysis of data from a controlled clinical trial shows that sFLC can be used not only as a useful tool to monitor initial therapy of multiple myeloma, but also as a possible replacement for 24-hr BJP analysis.

First Asia-Pacific Co-Operative Multicenter Multiple Myeloma Clinical Trial: Preliminary Results of the “dtZ”/“DAZZLE” Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4940-4940
Author(s):  
Gerrard Teoh ◽  
Kihyun Kim ◽  
Alok Srivastava ◽  
Vasant Pai ◽  
Sung-Soo Yoon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Osteonecrosis Of The Jaw ◽  
High Rate ◽  
Asia Pacific ◽  
Hematopoietic Stem ◽  
Asian Patients ◽  
Tract Infections

Abstract Abstract 4940 Introduction Many physicians have anecdotally reported that Asian patients with multiple myeloma (MM) are frequently unable to tolerate full doses of dexamethasone (Dex) and/or thalidomide (Thal). Unfortunately, co-operative clinical studies from the Asia-Pacific countries are presently lacking and the effective dose of the Dex/Thal combination in Asians is unknown. Since higher doses of zoledronic acid (Zol) have been shown to exert an anti-MM effect in pre-clinical models of MM, we investigated whether higher frequency dosing of Zol combined with lower doses of Dex/Thal could be an effective and better tolerated regimen in Asian patients. Moreover, since attainment of very good partial response (VGPR), near complete response (nCR) or complete response (CR) prior to autologous hematopoietic stem cell transplantation (AHSCT) correlates with good outcome in MM, we wanted to determine if this lower-dose Dex/Thal with higher-frequency dosing Zol regimen could be a good preparative regimen in transplant-eligible patients. Patients and Methods In this international co-operative multicenter phase II non-randomized single arm study in previously untreated patients with MM (n=44), all patients received up to 6 cycles of three-weekly Dex/Thal/Zol (or “dtZ”). Doses of Dex ranged from 20 mg weekly to 20 mg four times a week; and doses of Thal ranged from 50 mg weekly to 100 mg every night. Zol 4 mg was given three-weekly. Response was graded using Blade's criteria. Results The study population included 67.3% Oriental (Korean and Chinese), 30.8% Indian and 1.9% Malay patients. 15.4% of patients were ISS stage I, 61.5% stage II and 23.1% stage III prior to treatment. 39 (88.6%) patients demonstrated at least a partial response (PR); and 23 (52.3%) of patients achieved VGPR (18.2%), near nCR (15.9%) or CR (18.2%). The fastest time to VGPR/nCR/CR was 1 cycle. Most patients tolerated treatment very well and were managed in the outpatient clinic. Sepsis was the most frequently reported grade 3 or 4 toxicity – 8 (18.2%) patients developed bronchopneumonia, and 3 (6.8%) gastrointestinal or urinary tract infections. 1 (2.3%) patient was suspected of having pulmonary embolism. There were 4 (9.1%) deaths – 3 from severe sepsis and 1 from an unknown cause. Importantly, there were no reports of peripheral neuropathy, osteonecrosis of the jaw (ONJ) or end stage renal failure. In fact, there was an overall 2.4% improvement in the median creatinine clearance time (CCT). Finally, the percentage of CD34 stem cells was not adversely affected by treatment with dtZ. Conclusions The dtZ regimen appears to be an effective and well-tolerated treatment regimen for Asian patients with newly-diagnosed MM. The high rate of VGPR/nCR/CR will greatly facilitate AHSCT in transplant-eligible patients. Judicious use of low-dose Thal has abrogated the numerous side-effects associated with Thal and greatly improved patient tolerance. Even though Zol is administered at a higher frequency, it is not associated with worsening of renal function or ONJ. Infections are the most frequent and worrisome complications of treatment. These are likely to be related to the dose of Dex. Accordingly, it is probably wise to further lower the dose of Dex in future studies. (This study is registered with NIH PRS # 00263484.) Disclosures No relevant conflicts of interest to declare.

5-Azacytidine Before or After Stem Cell Transplantation in Acute Myeloid Leukaemia (AML) and Myelodysplastic Syndromes (MDS)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4267-4267
Author(s):  
Ana Garrido ◽  
Miguel Ortín ◽  
Rodrigo Martino ◽  
Josep Nomdedeu ◽  
Ana Aventin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Complete Response ◽  
Cell Transplant ◽  
Safe Procedure

Abstract Abstract 4267 The acceptable toxic profile of 5-aza-citidine (5-aza) allows its use in fragile or elderly patients in whom intensive chemotherapy should be avoided. Whether it is possible to take advantage of this low toxicity in patients awaiting for donor search and/or stem cell transplant (SCT) and in those experiencing leukemia recurrences after the procedure remains unknown. We analysed the clinical results of using 5-aza in these two settings to define the feasibility, safety and results of this approach. Patients and methods: From 2007 to 2011, 15 patients (11 males, 4 females) received 5-aza as last treatment prior to an allogeneic SCT (n=13) or as rescue after an early post-transplant relapse (n=2) at our centre. Diagnosis was MDS in 3 cases (median age 62; range 58–63) and AML in 12 cases (median age 58; range 37–67). Patients with MDS received a median of 6 courses of 5-aza (range 3–8) as the only treatment from diagnosis, except for one patient who had received panobinostat prior to 5-aza. Amongst patients with AML, 12 patients received 5-aza either as treatment for AML (2/12) or after remission (8/12) because of the high relapse risk while awaiting for a suitable donor to be found. Two patients with AML received 5-aza as treatment for early post-SCT relapse. AML patients treated with 5-aza before SCT received a median of 5 courses (range 1–19), whilst patients receiving treatment for relapse received 1 and 3 courses, respectively. Ten patients received a nonmyeloablative conditioning regimen, 1 received a conventional conditioning regimen, 2 patients are still in the process of donor search and the other 2 patients received 5-aza after an autologous stem cell transplantation relapse. RESULTS: All MDS patients engrafted and are in complete remission (CR) after a median of 696 days of follow-up (range 377–1227). One of those patients died because of aGvHD. Nine of 12 AML patients receiving 5-aza prior to SCT are alive after a median 373 days follow-up (133–995). One patient showing refractoriness to 3 different lines of treatment died from disease progression after 211 days. All patients receiving 5-aza as treatment for early relapse are dead, 41 and 401 days after starting treatment. Most interestingly, AML patients receiving 5-aza as maintenance of an already-achieved CR while awaiting transplantation did not experience disease progression despite the median time they remained on this treatment was prolonged (9 months). Graft-versus-host disease ≥ grade II was seen in 3 patients. No graft failures were seen and all patients who received an allogeneic stem cell transplantation remain in complete response. CONCLUSION: The use of 5-aza for maintaining or achieving a response in patients with AML who are awaiting SCT is a safe procedure and adds flexibility to schedule the treatment without the need to administer potentially toxic therapy. The use of 5-aza before transplant did not appear to interfere either with engraftment, incidence of GvHD or short-term relapse after transplant. Disclosures: No relevant conflicts of interest to declare.

Bortezomib with Dexamethasone in Newly Diagnosed Patients with Primary Systemic Light Chain Amyloidosis or Multiple Myeloma-Associated AL Amyloidosis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5036-5036 ◽  
Author(s):  
Beihui Huang ◽  
Juan Li ◽  
Junru Liu ◽  
Dong Zheng ◽  
Mei Chen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Side Effects ◽  
Light Chain ◽  
Conflicts Of Interest ◽  
Complete Response ◽  
Al Amyloidosis ◽  
Newly Diagnosed ◽  
Hematologic Response ◽  
Best Response ◽  
Organ Response

Abstract Abstract 5036 Objective: To assess the efficacy and tolerability of bortezomib with dexamethasone for patients with primary systemic light chain (AL) amyloidosis or multiple myeloma-associated AL amyloidosis. Methods: Twelve newly diagnosed patients with primary systemic AL amyloidosis and six patient with multiple myeloma-associated AL amyloidosis were treated with a combination of bortezomib (1. 3 mg/m2 d1, 4, 8, 11) and dexamethasone (20 mg d1–4). Results: Sixteen patients was evaluable. 12/16 had a hematologic response and 6/16 (37. 5%) a hematologic complete response. Median cycles to response was 1 cycle and median cycles to best response was 2 cycles. In patients with primary AL amyloidosis, 8/10 (80. 0%) had a hematologic response and 5/10 (50. 0%) a hematologic complete response. In patients with myeloma-associated AL amyloidosis, 7/10 (70. 0%) had a hematologic response and 1/6 (16. 7%) a hematologic complete response. Twelve patients (75. 0%) had a response in at least one affected organ, in which 7 in patients with primary AL amyloidosis and 5 in myeloma-associated AL amyloidosis. Person correlation between hematologic response and organ response was 0. 667 (p=0. 005). Fatigue, diarrhea and infection were the most frequent side effects. Three patients developed herpes zoster and had to stop chemotherapy. Conclusions: VD produces rapid and high hematological responses in the majority of patients with newly diagnosed AL regardless of primary or associated with myeloma. It is well tolerated with few side effects. This treatment may be a valid option as first-line treatment for newly diagnosed patients with primary systemic AL amyloidosis and multiple myeloma-associated AL amyloidosis. Disclosures: No relevant conflicts of interest to declare.

The Ki67/CD138 Ratio Independently Predicts Overall Survival in the Upfront Treatment of Newly Diagnosed Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2016-2016
Author(s):  
Tomer M Mark ◽  
Peter Forsberg ◽  
Ihsane Ouansafi ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Complete Response ◽  
Newly Diagnosed ◽  
First Line ◽  
Advisory Committees ◽  
Line Therapy

Abstract Background: Assessment of malignant plasma cell cycling via plasma cell labeling index (PCLI) has been a validated prognostic tool in multiple myeloma (MM) but the test requires specialized technical expertise and is not widely available. Ki67 is a well-known protein marker of cellular proliferation on immunohistochemical (IHC) staining with prognostic utility in other malignancies. In an effort to develop a simpler system to provide analogous information to PCLI, we used a novel IHC co-staining technique for CD138 and Ki67 to quantify plasma cells in active cycling. We then performed a retrospective analysis of the ratio of Ki67/CD138 (Ki67%) in newly diagnosed patients with multiple myeloma receiving 1st-line therapy to correlate with clinical outcomes. Methods: A retrospective cohort study of patients (pts) with treated symptomatic MM was performed by interrogation of the clinical database at the Weill Cornell Medical College / New York Presbyterian Hospital. For inclusion in the analysis, subjects must have started first-line treatment in the period of 2005-2010, and had available bone marrow biopsies. Double-staining with Ki67 and CD138 was performed by IHC. The Ki67% was calculated as the percent of plasma cells expressing CD138 that were also found to express Ki67. Treatment outcomes were stratified and compared based on %Ki67. Response was determined by monthly serum protein electrophoresis / immunofixation (IFX) with free light chain analysis according to International Multiple Myeloma Working Group (IMWG) guidelines. Pts who were IFX negative but had no subsequent bone marrow biopsy were classified as being in unconfirmed complete remission. Results: We identified 151 patients with newly diagnosed MM and available %Ki67 expression who received first-line therapy over the period of 2005-2010. Patient were subdivided into two groups based on %Ki67: Low: %ki67 <= 5%, n = 87; and High: %Ki67 >5, n=64, to allow for comparison of treatment response and survival analysis. Specific therapeutic agent exposure history did not differ significantly between patients. Both groups had similar depth of response rates (ORR) to front-line therapy, Table 1. Median progression-free survival for the high versus low %Ki67 groups approached statistical significance at 54 months (95% CI 30.8,67.4) versus 26.9 months (95% CI 21.6,40.2), respectively (P = 0.083). At data cut-off, there were 30 deaths in the low %Ki67 group (1-yr OS 93%, 5-yr OS 71%) and 36 deaths in the high %Ki67 group (1-yr OS 94%, 5-yr OS 62%). Median overall survival (OS) was not reached for Ki67% <= 5% (95% CI 97.3,NR) vs. 78.9 months (95% CI 55.9,93.1) for Ki67% > 5%, (P = 0.0434), Figure 1. Multivariate cox regression for factors with influence on OS showed that only high-risk cytogenetics (HR 2.05, 95% CI 1.17, 2.92, P = 0.027), ISS (HR 1.835, 95% CI 1.33, 3.60, P = 0.000), and %Ki67 group status had an independent effect on survival outcome. Low (<=5%) versus high (>5%) %Ki67 influenced overall survival with a hazard ratio of 1.76 (CI 1.07,2.92, P = 0.027). Survival after ASCT was significantly longer in the low %Ki67 group with median OS not reached (95%CI, 97.3, NR) versus 86.9 months (95% CI 43.9, NR) for high %Ki67 group (P = 0.04). Discussion: The ratio of IHC double positive Ki67 and CD138 of > 5% is an independent prognostic marker for overall survival in newly diagnosed MM undergoing 1st line therapy. The %Ki67 serves as a simpler and widely available analog to PCLI that can be presently performed in most hematopathology laboratories. Table 1: First Line Treatment and Best Response (modified IMWG Criteria) Ki67% <= 5(N = 87)n (%) Ki67% > 5(N = 64)n (%) P Treatment Exposure* Lenalidomide 59 (67.8) 48 (75) 0.34 Thalidomide 30 (34.5) 14 (21.9) 0.09 Bortezomib 25 (28.7) 14 (21.9) 0.34 Alkylating agent 11 (12.6) 4 (6.3) 0.19 ASCT 27 (31) 22 (34.4) 0.66 Best Response Overall Response (>= Partial response) 77 (88.4) 57 (89.1) 0.41 Complete response 15 (17.2) 22 (34.4) Unconfirmed complete response** 14 (16.1) 8 (12.5) Very good partial response 23 (26.4) 15 (23.4) Partial response 25 (28.7) 12 (18.8) Stable disease 9 (10.3) 5 (7.8) Progressive disease 1 (1.2) 2 (3.1) * Percentages do not add to 100% due to instances of concurrent therapy use ** Unconfirmed complete response: immunofixation negative, but no confirmatory bone marrow biopsy available Figure 1 Overall Survival by %Ki67 Figure 1. Overall Survival by %Ki67 Disclosures Mark: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Research Funding, Speakers Bureau. Rossi:Celgene: Speakers Bureau. Pekle:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Perry:Celgene: Speakers Bureau. Coleman:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Honoraria. Niesvizky:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4210-4210
Author(s):  
Luiza soares Vieira ◽  
Edvan de queiroz Crusoe ◽  
Manuella de S. Sampaio Almeida ◽  
Lais Sousa ◽  
ana Lucia Perez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Conflicts Of Interest ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Oligoclonal Bands ◽  
High Dose ◽  
Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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