scholarly journals Impact of Clinical Versus Biochemical Progression on Post-Progression Survival in Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1899-1899
Author(s):  
Rajshekhar Chakraborty ◽  
Hien D. Liu ◽  
Lisa Rybicki ◽  
Robert M. Dean ◽  
Beth M. Faiman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Time ◽  
Clinical Manifestations ◽  
Organ Damage ◽  
Fish Cytogenetics ◽  
End Organ Damage ◽  
Biochemical Progression

Abstract Background: Overall response rate and response duration in newly diagnosed multiple myeloma (ndMM) has increased in the last decade. However, majority of patients eventually progress and receive multiple lines of therapy. Progression in MM is defined by rise in monoclonal protein and/or clinical manifestations of end-organ damage. However, there is a lack of evidence on the prognostic implication of pattern of progression in the current era. We have hypothesized that patients with clinical manifestations of end-organ damage at first progression have an inferior post-progression overall survival (OS) compared to those with biochemical progression alone. Method: We evaluated all ndMM patients between 1/1/2008 and 12/31/2015 at the Cleveland Clinic. Key inclusion criterion was patients experiencing first progression requiring an additional line of therapy. Patients with primary refractory disease and those in continued 1st remission at latest follow-up were excluded. Progression was categorized into 2 groups: Biochemical Progression (BP) and Clinical Progression (CP; implying CRAB features). Patients with CP were further stratified based on the presence of extramedullary disease (EM): CP+EM and CP-EM. Progression-free survival (PFS) and OS from first progression were estimated with Kaplan-Meier curves and compared among groups with log-rank test. Cox analysis was used to identify prognostic factors for OS and PFS. Potential prognostic factors included progression pattern, age, gender, race, ISS stage at diagnosis, FISH cytogenetics at diagnosis, metaphase cytogenetics at diagnosis, time from diagnosis to first progression, best response at first remission, frontline autologous stem cell transplant (ASCT), and whether progression occurred while on therapy. Results: A total of 527 patients with ndMM were evaluated, among which, 257 experiencing 1st progression were included in our analysis. The median age at progression was 64 years. The median time from diagnosis to first progression was 23 months. An autologous stem cell transplantation (ASCT) after induction therapy in 1st remission was performed in 26% of patients. At 1st progression, BP alone was noted in 52% (n=134), CP -EM in 34% (n=87) and CP+EM in 14% (n=36) of patients. In the CP-EM group, the most common mode of progression was development of new bone lesions (76%) followed by anemia (33%), renal insufficiency (18%) and hypercalcemia (13%), with ≥1 mode in approximately one-third of patients. In the CP+EM group, the most common mode of EM progression was development of new plasmacytomas (89%), followed by emergence of circulating plasma cells (14%), with 1 patient having both. A total of 84% of patients progressed on anti-myeloma therapy, which reflects the contemporary practice of continuous therapy in MM. After first progression, 68% received proteasome inhibitors (PIs), 64% received immunomodulatory drugs (IMiDs) and 11% received monoclonal antibodies (MoAbs). Salvage ASCT in 2nd remission was performed in 12% of patients. A total of 105 patients (41%) were alive at latest follow-up, with the median follow-up of survivors being 26 months from 1st progression. Median time from diagnosis to 1st progression was shorter in the CP+EM (12 months) compared to CP-EM (25 months) and BP (24 months) groups (P<0.001). There was no significant difference in the progression pattern by depth of 1st remission. The 2-year post-progression OS in BP, CP-EM and CP+EM groups was 81%, 40% and 12% respectively (P<0.001; Figure I). The 2-year post-progression PFS in the respective groups were 35%, 8% and 7% respectively (P<0.001). On multivariable analysis for OS, independent prognostic factors included progression pattern, age at 1st progression and high-risk FISH cytogenetics at diagnosis (Table I). Conclusion: In the era of PIs, IMiDs and MoAbs, the pattern of 1st progression in MM has a strong and independent prognostic impact on post-progression OS. Patients progressing with clinical manifestations of end-organ damage or extramedullary disease have an inferior PFS and OS compared to those progressing with biochemical criteria alone. These results should be further validated in large prospective studies with data on FISH cytogenetics at relapse. It has clinical implication at the individual level and can also inform the design of clinical trials in relapsed MM. Disclosures Majhail: Anthem, Inc.: Consultancy; Incyte: Honoraria; Atara: Honoraria.

Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5232-5232
Author(s):  
Celso Mitsushi Massumoto ◽  
Edilson Pinheiro Junior ◽  
Otávio C.G. Baiocchi ◽  
Ronald Pinheiro ◽  
Adelson Alves
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Clinical Characteristics ◽  
Residual Disease ◽  
High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

Serum Free Light Chain Ratio in Distinguishing Smoldering Multiple Myeloma From Active Multiple Myeloma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3948-3948
Author(s):  
Jeremy T Larsen ◽  
Shaji Kumar ◽  
S. Vincent Rajkumar
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Predictive Value ◽  
Plasma Cells ◽  
Organ Damage ◽  
End Organ Damage ◽  
Cut Point ◽  
Smoldering Multiple Myeloma ◽  
Bone Marrow Plasma

Abstract Abstract 3948 Background: Smoldering multiple myeloma (SMM) is an asymptomatic precursor disease of multiple myeloma, and is defined by excess bone marrow plasma cells and monoclonal protein without evidence of end-organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions [CRAB]). The identification of SMM patients with more aggressive underlying disease remains a challenge. We hypothesize that SMM is a clinical entity comprised of both premalignant, high-risk MGUS and early multiple myeloma in transition to malignant disease, which may be differentiated with the use of the serum FLC (FLC) ratio. Methods: This was a retrospective analysis of 586 patients with newly diagnosed SMM from 1970–2010 with available stored serum samples around the time of diagnosis to be utilized for quantification of FLC ratios. SMM was defined by the International Myeloma Working Group 2003 definition; serum M-protein ≥ 3 g/dL and/or ≥ 10% bone marrow plasma cells with no evidence of CRAB features. The immunoglobulin FLC assay (Binding Site, U.K.) was used for testing. The FLC ratio was calculated as κ/λ (reference range 0.26–1.65). The involved/uninvolved FLC ratio was recorded to simplify the reporting of data. Receiver Operating Characteristics (ROC) curves were created to assess the ability of the FLC ratio to discriminate patients who progressed to symptomatic multiple myeloma (MM) in the first 2 years or at any point during follow-up versus patients without evidence of progression. Patients with less than 24 months follow-up without progression were censored. The optimal diagnostic cut-point for FLC involved/uninvolved ratio to identify patients with progressive disease from the ROC curve was >88.6 (equivalent to <0.011 or >88.6). For ease of clinical application, the optimal value for involved/uninvolved FLC ratio was rounded to >100. Time to progression (TTP) from date of the initial FLC to active MM was calculated using Kaplan-Meier analysis and compared to patients with a high (>100) and low (<100) involved/uninvolved FLC ratio at time of SMM diagnosis. TTP within 24 months of the initial FLC was also calculated. Results: During the study period, 54% of patients progressed to active MM. On ROC analysis, a cut-point of >100 corresponded to a sensitivity of 25% (95% CI, 20.5–30.4) and specificity of 99.3% (97.3–99.9), with positive likelihood (+LR) ratio of 33.9 (38.1–41.0), negative likelihood ratio (−LR) of 0.75 (0.2–3.0), positive predictive value (PPV) of 97.6 (91.5–99.7) and negative predictive value of 53.0 (48.5–57.4). Using the ROC to assess progression to MM within 24 months (Figure 1), sensitivity was 29.6% (23.5–36.4), specificity 94.5% (91.7–96.5), +LR 5.36 (4.3–6.6), -LR 0.75 (0.5–1.1), PPV 85.8 (77.7–91.8), and NPV 54.3 (49.8–58.9). Median TTP to active MM in the FLC >100 group was 15 months (9–17) versus 52 months (44–60) in the FLC <100 group (p <.0001) [Figure 2]. In the FLC ratio >100 group, progression at 1 year was 47%, 76% at 2 years, and 90% at 3 years. Only 25% of the FLC <100 patients had progressed at 2 years. The most common progression event was bone disease (42%), followed by anemia (26%), renal impairment (23%), and hypercalcemia (5%). Conclusion: Elevation of the FLC ratio >100 (or <0.01) is highly specific for the future development of active MM, with 76% of these patients developing end-organ damage requiring therapy within 2 years. Risk of transformation to MM in the FLC <100 group was similar to previously reported rates of 10% per year for the first 5 years. Development of an FLC ratio >100 is associated with increasing disease burden and in this study behaved in a malignant fashion rather than a precursor state. The FLC is a simple and useful predictor of progression to MM in SMM, and patients with FLC ratios of <0.01 or >100 within the first 2 years of SMM diagnosis should be monitored especially closely. Future studies are needed to determine optimum cutoffs for FLC ratio to where a change in definition of MM could be considered. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Single Autologous Stem Cell Transplant (ASCT) Followed By Two Years of Post-Transplant Therapy in Recently Diagnosed Elderly Multiple Myeloma (MM) Patients. Safety and Response Results from the Prospective Phase II Trial (NCT01849783)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2153-2153 ◽  
Author(s):  
Kalyan Nadiminti ◽  
Christopher Strouse ◽  
Praveen Vikas ◽  
Lindsay Dozeman ◽  
Allyson Schultz ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Maintenance Therapy ◽  
Median Time ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Conditioning Regimen ◽  
Safety And Efficacy

Abstract Introduction : Melphalan 200mg/m2 has been the standard conditioning regimen for ASCT for multiple myeloma. Novel agents in combination with high dose melphan are being evaluated in clinical trials to improve outcomes. We previously reported results of early ASCT ( < 12 months from diagnosis) using VDT (Bortezomib, Thalidomide, Dexamethasone) plus Melphalan 200mg/m2 conditioning chemotherapy followed by combination maintenance therapy in younger MM patients (Age <65). This current prospective study evaluates the tolerance, safety and efficacy of early ASCT and maintenance therapy in MM patients who are ≥65 of age. Methods and patients: A total of 41 eligible patients with newly diagnosed multiple myeloma age ≥ 65 were prospectively enrolled in the IRB approved phase II trial beginning in June 2013. After an induction chemotherapy and stem cell collection, ASCT was performed with a preparative chemotherapy consisting of VDT-Melphalan 200mg/m2. The patients were considered to have high risk cytogenetics if they had 17p deletion, t(14;16), amp 1q, or t(4;14) by FISH on CD-138 sorted plasma cells. After engraftment and recovery, patients were started on maintenance therapy for 2 years. Planned regimen for the first year was a combination of VDT as 28 day cycles and year 2 therapy consisted of bortezomib, cyclophosphamide and dexamethasone( VCD) as 28 day cycles. Alternate regimens were used in case of toxicities. Primary end points include PFS, frequency of severe toxicities, ICU admissions, and percentage of patients able to complete the full course of maintenance. Responses were evaluated according to IMWG consensus criteria and adverse events were recorded according to CTCAE v 4.03. Results: 37 of the 41 patients enrolled received single ASCT between 2013 to 2016 of which 35 patients went to receive triple maintenance therapy and were included in this analysis. Median age was 68 (range: 65 to 75y). 12 (59%) and 15(40%) had standard risk and high risk cytogenetics by FISH, respectively. Median follow up was 27 months (3 months - 5 years). Major non-hematologic toxicities ≥ grade 3 were related to infections (25%), diarrhea (16%) and mucositis (11%). Median time to ANC and platelet engraftment was 11 and 17 days, respectively. There was one death within day 100 related to candida sepsis. Only 2 patients were re-hospitalized within 100 days but none required ICU admission. Median time to start post-transplant therapy was 73 days (range: 47 to 185 days). Best responses noted prior to initiation of maintenance were 17 sCR(47.2%), 3CR(8%), 10 VGPR(27%) and 6 PR(17%). 18 patients completed 2 years of maintenance therapy thus far and responses at the time of this analysis include sCR in 16 and CR in 2 patients. A total of 3 patients died during maintenance phase due to progressive disease. Median PFS and OS were not reached and 3 year PFS and OS were around 82 and 90%, respectively. Conclusions: This is the first trial to prospectively evaluate the safety and efficacy of early ASCT in elderly MM patients using a novel agent conditioning regimen followed by an intensive 2 year maintenance therapy. These results from the median follow up of 27 months indicate that the regimen is safe and tolerated without any increased mortality, and results in higher rates of deep and sustained responses. Major non hematologic toxicities included infections and GI related. No increased hospitalizations or ICU admissions were noted. Further follow up will determine the long term effects of the combination maintenance regimen, disease responses and survival in this group of elderly MM patients. Figure Figure. Disclosures No relevant conflicts of interest to declare.

Evaluation of Serum Free Light Chains and Outcome in Multiple Myeloma Patients with an Intact Monoclonal Immunoglobulin Treated with Autologous Stem Cell Transplantation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3323-3323
Author(s):  
Young Trieu ◽  
Wei Xu ◽  
Peter Anglin ◽  
Christine Chen ◽  
Vishal Kukreti ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Light Chain ◽  
Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Serum Free

Abstract Introduction: The serum free light chain (FLC) assay is a useful tool in diagnosing and monitoring multiple myeloma (MM) patients (pts) with non-secretory and light chain only disease. In addition, the detection of an abnormal serum FLC ratio is an adverse prognostic factor in pts with monoclonal gammopathy of undetermined significance. However, the relationship of the FLC assay to the outcome of patients with an intact monoclonal immunoglobulin following a single autologous stem cell transplantation (ASCT) has not been studied. Thus, the objective of this single centre, retrospective review study was to evaluate the usefulness of the FLC assay as a predictor for response rate and progression free survival (PFS) in this category of pts. Patients & Methods: We identified in our Princess Margaret Hospital MM database a total of 290 pts who underwent a single ASCT between June 2003 and May 2006. Of these, 65 had an intact monoclonal immunoglobulin (IgG in 47, IgA in 16 and IgD in 2) detected at diagnosis plus FLCs measured at referral. Normal range for FLC measurements is as follows: kappa 3.3–13.1 mg/L, lambda 5.7–26.3 mg/L, and kappa/lambda ratio of 0.26–1.65. Results: The median age at diagnosis was 59 years (range, 34–73); 33 (51%) were male. The median time from diagnosis to ASCT was 9.0 months (range, 5.0–29), with a median follow-up time of 27 months (range, 1.0–58.0). Assessment of best response following ASCT revealed that 20 (31%) pts achieved CR/nCR, 21 (32%) VGPR, 21 (32%) PR, 2 (3%) MR, and 1 (2%) was not evaluable for response. No prognostic factors for response were identified. To date, only 9 pts have died and the median overall survival is not yet reached. The median PFS is 25.4 months, with 36 patients progressing after ASCT. An elevated kappa and lambda light chain was detected in 30 (46%) and 22 (34%) of the 65 pts, respectively. Additionally, 52 (82%) of the 65 pts were found to have an abnormal kappa/lambda ratio. There was no significant difference in the PFS of patients with abnormal vs. normal free kappa light chains or FLC ratio. However, a decreased PFS was associated with elevated levels of serum free lambda light chains (p=0.01), β-2 microglobulin (p=0.007) and LDH (p=0.01). Conclusions: The majority of pts with an intact monoclonal immunoglobulin also have an abnormally high level of the corresponding serum FLC and an abnormal FLC ratio; an elevated serum free lambda level as well as increased β-2 microglobulin and LDH levels, as previously described, were identified as adverse prognostic factors for PFS in this population; we continue to routinely assess serum FLC for all pts at referral; however, longer follow-up is needed to further evaluate the prognostic significance of this parameter on the clinical outcome of pts.

Outcome of patients relapsing early after autologous stem cell transplantation for multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8022-8022
Author(s):  
S. T. Mahmood ◽  
S. Kumar ◽  
M. Q. Lacy ◽  
A. Dispenzieri ◽  
S. R. Hayman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Median Time ◽  
Late Relapse ◽  
Cell Transplant ◽  
Early Relapse ◽  
Clinical Records ◽  
Disease Free ◽  
Relapse Group

8022 Background: Autologous stem cell transplant (ASCT) is the standard approach for eligible patients (pts) with multiple myeloma (MM). The median time to relapse after early ASCT is 2–3 yrs and overall survival (OS) is 4–5 yrs. Though various risk factors have been identified for early relapse, the outcome of this group of pts is not clearly described. With the advent of newer therapies, it is important to understand the natural history of MM in these pts to design treatment strategies. Methods: A total of 432 pts with MM, undergoing ASCT within 12 months (mos) of diagnosis, with a minimum follow up of 12 mos were studied. Clinical and laboratory data were obtained from a prospectively maintained database and clinical records. Pts were divided into 2 groups: early relapse (relapse <12 mos from ASCT) and late relapse (either relapsed >12 mos after ASCT or disease free at last follow up). Results: There were 94 pts (22%) in the early relapse group and among the late relapse group (N=338), 171 had relapsed beyond 12 mos and 167 were disease free at last follow up. The median time to ASCT was similar in all groups. The early relapse group had a significantly shorter median OS from diagnosis (23.9 vs. 82.2 months; P < 0.001) and from transplant (17.6 mos vs. not reached; P < 0.001). The median OS from relapse was 7.9 mos in this group compared to 39.6 months for the rest. In univariate analysis, elevated CRP, high BM plasma cell%, labeling index (PCLI) >1%, abnormal cytogenetics, presence of circulating PCs at harvest and lack of CR from ASCT predicted for early relapse. In multivariate analysis, an elevated PCLI (RR=2.9; P=0.002) and failure to achieve CR (RR 2.7; P=0.002) was associated with early relapse. Conclusions: Pts who relapse within 12 mos of an ASCT have a very short survival and should be offered trials evaluating novel therapies and combinations. Survival figures from this study represent the benchmark for the comparison of novel approaches in this population. Pts with poor prognostic factors have a short PFS after ASCT and should be considered for alternative approaches. Inability to achieve CR appears to predict shorter PFS and clinical trials evaluating maintenance therapy should be offered in these pts. No significant financial relationships to disclose.

Outcome of Patients with Multiple Myeloma Treated with Autologous Stem Cell Transplantation in the Era of Novel Therapies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1865-1865
Author(s):  
Hani Hassoun ◽  
Heather Landau ◽  
Chirag Surti ◽  
Nelly G. Adel ◽  
Xiaoyu Jia ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Initial Therapy ◽  
Novel Therapies ◽  
Single Institution ◽  
Baseline Characteristics

Abstract Abstract 1865 Poster Board I-890 Background: The incorporation of novel therapies, including thalidomide, bortezomib, and lenalidomide, in the treatment of multiple myeloma as induction, maintenance, or salvage therapy, along with autologous stem cell transplantation (ASCT) is expected to result in improved outcome. The impact of a single regimen or drug on Progression Free Survival (PFS) or overall survival (OS) is difficult to determine because, even within a single institution, these drugs and treatment modalities are used in varying sequences among patients. The goal of this retrospective analysis is to determine the PFS and OS of patients with multiple myeloma treated with ASCT at a single institution, in the era of novel therapeutic agents and to validate the significance of established prognostic factors. Methods: We performed a retrospective analysis of all patients with multiple myeloma who were eligible to undergo ASCT at MSKCC between 2000 and 2007 and received novel therapies including thalidomide, bortezomib, and lenalidomide during the course of their disease. During this period of time, 274 patients were transplanted and were analyzed for overall survival. Among them, a subset of 116 patients who received induction therapy, ASCT, and long term follow up at MSKCC, on whom baseline data and response analysis at all stages of disease was available, was used to analyze prognostic factors. Log-rank test was performed to assess the difference of OS and PFS among subgroups of patients stratified by baseline variables. A time-dependent Cox model was used to assess the effect of post treatment parameters on OS and PFS. Landmark analysis at 6 months after first ASCT was performed to assess the association between post-transplant response and survival endpoints. Results: For the entire study population of MM patients (n=274), with a median follow up of 4 years, the median OS measured from the time of transplant is 7 years [95% CI (6, not reached)]. For the subset of 116 patients treated exclusively at MSKCC, with a median follow up of 5 years, the median OS measured from initial treatment has not been reached and median PFS is 3 years =95% CI (2,4)] Using the subset of 116 patients treated exclusively at MSKCC, several baseline characteristics were analyzed as prognostic factors for OS and PFS including age =median age 57 (32 to 72)] gender =M 73, F 43] type of M-spike =IgGK 49, IgGL 21, FKLC 17, IgAK 13, FLLC 10, IgAL 5, IgMK 1] kappa to lambda ratio at diagnosis =Normal 15, Abnormal 75, Not available 26] ISS stage =I 50, II 49, III 16] and cytogenetic risk =standard 95, high 14, N/A 7] As reported by others, the type of monoclonal protein had a significant impact on OS (P = 0.02) with FKLC and IgAK having the worse prognosis. Other baseline characteristics including age, gender and K/L ratio did not influence OS and none affected the PFS. Several post treatment parameters were also analyzed including response to initial therapy =CR 15, nCR 18, VGPR 20, PR 42, SD 15, POD 5] response to ASCT =CR 73, VGPR 14, PR 29] response conversion =based on response before and after first ASCT: ≥VGPR - ≥ VGPR 51; < VGPR - ≥ VGPR 34, and < VGPR - < 0.0001, and P < 0.0001, respectively). Conclusion: This retrospective study confirms the marked improvement in OS for patients who undergo ASCT in the era of novel anti-myeloma therapies. It is difficult to ascribe this improvement to a specific regimen but rather probably to the abundance of successive options available to myeloma patients in the current era. Interestingly, we find no prognostic value to the response status to initial therapy or to ASCT for overall survival in contrast to PFS. Disclosures: Comenzo: Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Other Cancers in Patients with Chronic Lymphocytic Leukemia Requiring Therapy: Association with Prognostic Factors and Impact On Survival

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3896-3896
Author(s):  
Lorenzo Falchi ◽  
Michael J. Keating ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
Sara S. Strom ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Median Time ◽  
Causes Of Death ◽  
Stem Cell Transplant ◽  
Lymphocytic Leukemia ◽  
Cell Transplant ◽  
Post Therapy

Abstract Abstract 3896 Chronic lymphocytic leukemia (CLL) is associated with an increased incidence of other cancers (OC). Potential risk factors for OC in CLL include immune disturbances, shared risk factors, genetic predisposition and chemotherapy. While reports on OC in patients with CLL have been typically descriptive in nature, detailed information regarding the clinical features of OC, relationship with the time of diagnosis of CLL, patient characteristics, prognostic factors and survival have been missing. We report an analysis of OC in pts with CLL requiring therapy, with a post therapy observation time of 5 years or longer. We reviewed our database and selected pts with CLL seen at our center who underwent treatment and who have a follow-up of at least 5 years after therapy. We studied pts with an OC either before or after the diagnosis and/or treatment of CLL and compared them with patients without OC. Richter's transformation of CLL was not considered an OC in this analysis. A total of 1,364 pts with CLL referred between 1963 and 2007 with a median follow up time of 8.2 years (range 5–28) were studied. Among these, we identified 324 pts (24%) with OC. Sixty-eight pts were diagnosed with >1 OC [2 OC (62 pts), 3 OC (4 pts) or 4 OC (2 pts)], for a total of 400 individual OC. Of the 324 pts with OC, OC preceded the diagnosis of CLL in 117 pts (36%), with a median time from OC to CLL of 80 (0–455) months, OC occurred after the diagnosis of CLL but before treatment in 49 pts (15%), with median time from CLL to OC of 22 (0–131) months. OC occurred after treatment of CLL in 158 pts (49%), with a median time from treatment to OC of 94 (0–304) months. The type, frequency and timing of OC are summarized in table 1. Clinical characteristics and traditional prognostic factors were not significantly different between pts with and without OC, with the exception of age, as pts with OC are older than pts without OC at the time of referral (median age: 60 vs 55 years, p<.0001). We next analyzed the distribution of the newer prognostic parameters in these two groups. Fifty-three % of pts with OC had unmutated IGHV genes, 65% were ZAP70+, 22% CD38+, 8% had del17p, 27% del11q, 22% +12, 20% negative FISH, and 23% del13q. Sixty-one % of pts without OC had unmutated IGHV genes, 58% were ZAP70+, 26% CD38+, 6% had del17p, 17% del11q, 22% +12, 26% negative FISH, and 29% del13q. A trend toward significance (p.07) for a higher incidence of del11q was observed in pts with OC. At the time of this analysis 536 (39%) pts have died and 828 (61%) are alive. One hundred seventy six/324 (54%) pts with OC are alive, vs 652/1040 (63%) pts without OC (p<.007). Median overall survival (OS) has not been reached in either pt group at a median follow up of 95 (61–284) months for pts with OC and 98 (61–340) months for pts without OC. Causes of death were: progression of CLL (99), CLL-related complications (121), OC (43), complications of stem cell transplant (16), events unrelated to CLL (39) and unknown causes (218). In pts with OC, the OC itself was the cause of death in 37%. Other causes of death were CLL/CLL-related complications in 44%, complications of stem cell transplant in 8%, and events unrelated to CLL in 11%. In contrast, in pts without OC CLL/CLL-related complications accounted for 83% of deaths, complications of stem cell transplant for 4%, and events unrelated to CLL for 13%. In conclusion, in pts with CLL requiring therapy and with post therapy follow up of >5 years, the incidence of OC is 24%. Among pts with OC, there is a trend for higher number of pts with del11q. In pts with OC, OC itself is a major cause of death, while the vast majority of deaths among pts without OC are caused by CLL or CLL-related complications. Table 1. Distribution of OC (1364 pts). Site of OC 1st case Total cases OC prior/at CLL OC after CLL After diagnosis After treatment NMSC1 124 144 41 26 77 PROSTATE 43 54 18 7 29 MELANOMA 26 34 16 2 16 BREAST 23 26 14 2 10 MDS/AML2 16 18 0 0 18 LUNG 14 21 0 1 20 NEUROENDOCRINE 3 6 1 0 5 HEAD AND NECK 12 16 3 2 11 UROTHELIAL CELL CANCERS 11 12 7 2 3 GI3 (including pancreas and liver) 10 18 4 3 11 KIDNEY 10 11 4 3 4 NHL4 and MM5 8 12 0 0 12 TESTIS/OVARY 6 6 4 0 2 THYROID 6 7 5 1 1 SARCOMAS 4 5 4 0 1 UTERUS 2 3 3 0 0 OTHERS6 6 7 3 0 4 TOTALS 324 400 127 49 224 1 non-melanoma skin cancers; 2 myelodysplastic syndrome/acute myeloid leukemia; 3 gastrointestinal; 4 non-Hodgkin's lymphoma; 5 multiple myeloma; 6 includes: brain, nasopharyngeal, penis carcinoma, mesothelioma, unknown primary. Disclosures: No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation for Multiple Myeloma: Identification of Prognostic Factors

2013 ◽  
Vol 13 (1) ◽  
pp. 32-41 ◽  
Author(s):  
Lalit Kumar ◽  
Sunu L. Cyriac ◽  
Tilak V.S.V.G.K. Tejomurtula ◽  
Ankur Bahl ◽  
Bivas Biswas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Prognostic Factors ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation

Multiple Myeloma: Most Common End-Organ Damage and Management

2007 ◽  
Vol 5 (2) ◽  
pp. 170-178 ◽  
Author(s):  
Mohamad A. Hussein
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Percutaneous Vertebroplasty ◽  
Surgical Techniques ◽  
Organ Damage ◽  
Early Mortality ◽  
Adjunctive Treatment ◽  
Plasma Cell Dyscrasia ◽  
End Organ Damage ◽  
Minimally Invasive Surgical

End-organ damage is the factor that differentiates plasma cell dyscrasia requiring therapy (active multiple myeloma [MM]) from disease that does not require therapy (monoclonal gammopathy of undetermined significance and smoldering [asymptomatic] MM). Progressive skeletal destruction is the hallmark of MM and responsible for principle morbidity in the disease. The spine is the most afflicted skeletal organ, and vertebral fractures have significantly contributed to its poor prognosis. Early mortality in MM is usually attributed to the combined effects of active disease and comorbid factors. Infection and renal failure are the main direct causes of early mortality. Using bisphosphonates to manage skeletal events mainly by preventing or slowing the destructive process has become an important adjunctive treatment in MM. Advances in minimally invasive surgical techniques, such as percutaneous vertebroplasty and kyphoplasty, offer these patients less-invasive options for treating vertebral collapse and restoring function. The aggressive management of other complications of the disease through more effective and less toxic therapy that targets the primary disease, in addition to supportive care, is resulting in patients experiencing less morbidity and probably lower mortality. This article reviews recent advances in the understanding of bone disease in MM, the role of bisphosphonates in preventing skeletal events, and available data on percutaneous vertebroplasty and kyphoplasty, and discusses the management of infection and renal failure, which seem to be responsible for high initial mortality and thereby compromise the current advances in therapy.

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