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  • 1
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    Oral Acyclovir Is an Effective in Decreasing the Incidence of Bortezomib Associated Herpes Zoster in Patients with Multiple Myeloma.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4844-4844
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4844-4844
    Abstract: Introduction: Bortezomib, a proteasome inhibitor is an effective antimyeloma therapy. We recently reported that multiple myeloma patients treated with bortezomib or bortezomib based regimen resulted in a higher incidence of herpes zoster (HZ). The exact etiology of this side effect remains unknown though our investigation demonstrated prolonged lymphopenia among patients treated with bortezomib. The high incidence of HZ among bortezomib treated patients prompted to prospectively investigate the role of antiviral prophylaxis in this patient population. Here we report for the first time the efficacy of acyclovir as prophylaxis for bortezomib associated HZ. Patients and Methods: We prospectively evaluated the impact of oral acyclovir (400mg PO twice daily for the duration of bortezomib therapy) on the incidence of HZ. All patients with multiple myeloma who were treated with bortezomib or bortezomib based regimens, and received prophylactic acyclovir were evaluable for this analysis. To compare the overall proportion of HZ among patients who received acyclovir prophylaxis and the historical control, Fisher exact test was used. Results: A total of 51 consecutive patients (27 M and 24 F) received acyclovir as prophylaxis. The median age was 61 (range 40–81 years), with advance stage MM noted in 86% (n=44) patients. Among these 69% had previously untreated MM while 31% had relapsed or refractory disease. Single agent bortezomib was given to 11 patients and 40 patients received bortezomib in combination with other antimyeloma agents (such as thalidomide, pegylated liposomal doxorubicin, dexamethasone, cyclophosphamide and/or lenalidomide). The overall incidence of HZ was 0% among patients receiving the acyclovir prophylaxis vs. 13% in the historical control. There was a significant difference in the overall proportion of HZ among patients who received acyclovir prophylaxis and the historical control (p = 0.0026). Conclusion: This is the first report on the efficacy of acyclovir for the prevention of bortezomib associated HZ in MM patients. While bortezomib is an effective antimyeloma therapy, an important side effect with significant morbidity is reactivation of HZ. Here we demonstrate for the first time that this side effect can be effectively prevented by oral acyclovir. Our observation warrants further evaluation. Considering significant morbidity associated with HZ we recommend the routine use of prophylactic acyclovir (or other antiviral agents) for patients being treated with bortezomib or bortezomib-based therapies.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4844.4844
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 2
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    Renal Dysfunction Does Not Affect Clinical Response in Multiple Myeloma (MM) Patients Treated with Bortezomib-Based Regimens.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1477-1477
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1477-1477
    Abstract: Background: Renal dysfunction is a common consequence of MM. Patients can present with varying degrees of renal impairment during the course of their disease. Clinical management of these patients remains a challenge and the role of newer agents like bortezomib is still being defined in them. We have previously reported on the safety and efficacy of bortezomib in MM patients with advanced renal failure requiring dialysis. Here we further evaluate if varying degree of renal dysfunction as determined by the National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF K/DOQI), adversely affects the clinical outcome of bortezomib-based therapies. Methods: All MM patients treated with bortezomib or bortezomib-based therapies were evaluable for this analysis. Response to treatment was classified as per EBMT criteria. Renal function stratification was done for all the patients based on NKF K/DOQI guideline stages as per glomerular filteration rate (GFR; ml/min/1.73 m2). Stages 1, 2, 3, 4 and 5 were defined as GFR ≥ 90, 60–89, 30–59, 15–29, and & lt; 15/dialysis, respectively. To study the statistical relationship between pairs of nominal variables, Fisher’s exact test was used. To study the statistical relationship between nominal and ordinal variables, exact Wilcoxon test was used. A 0.05 nominal significance level was used in all testing. Results: Sixty six consecutive patients were evaluable. Amongst these, 32 (48.5%) were females and 34 (51.5%) males with a median age of 59.5 years (range 40–82 years). Fifty five (83%) patients had advanced MM; stage & gt; I as per Durie-Salmon (DS) criteria. Eligible patients had either relapsed/refractory disease (n=33) or were previously untreated (n=33). NKF K/DOQI renal function stages were 1, 2, 3, 4 and 5 in 9 (13.6%), 29 (44%), 22 (33.4%), 3 (4.5%) and 3 (4.5%) patients, respectively. Clinical response observed was complete remission (CR) in 8 (12%), partial remission (PR) in 25 (38%), stable disease (SD) in 27 (41%) and progressive disease (PD) in 6 (9%) patients. There was no significant association between renal function and patient age (p = 0.0808; 95% CI -0.0246, 0.4367), DS stage (p = 0.1722; 95% CI -0.0806, 0.4744), Ig type (p = 0.5288), untreated vs. relapsed/refractory disease (p = 0.1352), or response to treatment (p = 0.5292; 95% CI -0.1601, 0.3114). Conclusions: In this paper we investigated the correlation of NKF K/DOQI renal function stage in myeloma patients with clinical response to bortezomib. We noted that patients treated with bortezomib-based therapies experienced similar clinical benefit irrespective of the NKF K/DOQI renal function stage. These findings further support our previous observation that bortezomib is an effective therapeutic option for MM patients with renal dysfunction. Best Response to Treatment in Each NKF K/DOQI Stage Stage Best Response To Treatment NKF K/DOQI; National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative, PD; Progressive Disease, SD; Stable Disease, PR; Partial Remission, CR; Complete Remission PD SD PR CR Total 1 1 3 4 1 9 2 3 14 10 2 29 3 2 6 9 5 22 4 0 1 2 0 3 5 0 3 0 0 3 Total 6 27 25 8 66
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1477.1477
    RVK:
    XA 33000
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    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 3
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    bcl-2 Translocation [t(14;18) (q32;q21)] Does Not Correlate with Poor Clinical Outcome in Multiple Myeloma Patients Treated with Bortezomib.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1498-1498
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1498-1498
    Abstract: Background: Overexpression of bcl-2 gene mediated by t(14;18) (q32;q21) results in increased transcription of the anti-apoptotic bcl-2 protein. This is associated with aggressive clinical behavior, resistance to conventional chemotherapy regimens and poor survival in multiple myeloma (MM) patients. Impact of novel therapeutic agents such as bortezomib has not been studied in context with this adverse molecular marker. Thus we investigated the clinical efficacy of bortezomib in MM patients who were positive for bcl-2 translocation. Methods: All MM patients treated with bortezomib or bortezomib-based therapies were evaluable for this analysis. bcl-2 translocation was studied by a nested PCR-based assay of patient bone marrow samples. The test is reproducibly sensitive to a detection level of 1:100,000 and reported as positive or negative, indicating either the presence or absence of t(14;18). Response to treatment was classified as per EBMT criteria. To study the statistical relationship between pairs of nominal variables, Fisher’s exact test was used. To study the statistical relationship between nominal and ordinal variables, exact Wilcoxon test was used. A 0.05 nominal significance level was used in all testing. Results: Sixty six patients met the inclusion criteria of MM diagnosis and treatment with bortezomib-based regimens. Of these, bcl-2 analysis was available for 41 patients. Six patients (14.6%) were bcl-2 positive and 35 (85.4%) were bcl-2 negative. Median age was 61 years (range 40–80 years), with 18 (43.9%) females and 23 (56.1%) males. Twenty three patients (56.1%) had Durie-Salmon (DS) stage IIIA disease. Lytic bony lesions were present in 31 (75.6%) patients and most common Ig type was IgG kappa (43.9%). Seven patients (17%) achieved CR, 14 (34%) had PR, 16 (39%) had stable disease (SD) and 4 (10%) had progressive disease (PD). There was no significant association found between t(14;18) result and patient age (p = 0.4985), gender (p = 0.6786), DS stage (p = 0.6117), ISS stage (p = 0.5541), presence of bony lytic lesions (p = 0.1435), patients being paraprotein secretors or non-secretors (p = 1), Ig type (p = 0.0584), or response to treatment (p = 0.1066). Conclusions: Presence of bcl-2 translocation is associated with aggressive clinical course and suboptimal response to conventional chemotherapy in myeloma patients. Although, the number of patients analyzed in this analysis is small, we did not find the presence of bcl-2 translocation to be an adverse prognostic marker in myeloma patients treated with bortezomib-based regimens.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1498.1498
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
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  • 4
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    Improved Sensitivity of Bone Marrow Magnetic Resonance Imaging (BM-MRI) in Quantifying the Extent of Bone Marrow Involvement in Patients with Multiple Myeloma (MM).
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 4776-4776
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 4776-4776
    Abstract: Background: Traditionally, bone marrow aspirate/biopsy (BM-Bx) has been used for diagnosis and quantification of the extent of disease as well as response to therapy in MM patients. This information is used to make decision for treatment initiation. Since MM is not a contiguous disease, marrow involvement can be patchy and BM-Bx may be misleading in assessing the true extent of the disease. BM-MRI is a non-invasive technique that can evaluate a large amount of marrow for tumor infiltration. We prospectively investigated the sensitivity of BM-MRI and compared its results with those obtained by BM-Bx as well as with the clinical stage of disease. Methods: All patients with the diagnosis of MM who had BM-MRI at our center were evaluable. Patients must have received a BM-Bx within 4 weeks of the BM-MRI. In these patients sagittal T1 and fast spin echo inversion recovery sequences of the cervical, thoracic and lumbosacral spine and coronal T1 and fast spin echo inversion recovery sequences of the sacrum and pelvic bones were reviewed on the MRI. Durie-Salmon (DS) staging criteria were used for correlation. To study the statistical relationship between pairs of ordinal variables the test corresponding to the Spearman correlation was used. To study the statistical relationship between nominal and ordinal variables, the Wilcoxon or Kruskal-Wallis test was used. A 0.05 nominal significance level was used in all testing. Following staging system was defined for evaluation of the involvement of the marrow by BM-MRI: A (0%), B ( 〈 10%), C (10%–25%), D (26%–50%), E ( 〉 50%). Results of this were then compared with the extent of involvement reported on histological evaluation of the BM-Bx. Results: A total of 50 patients (23 females and 27 males) were identified. Median age was 61.5 years (range 35–82 years) with 23 (46%) having stage IIIA disease. As per the staging system defined above, 6%, 10%, 10%, 22% and 52% of the patients had categories A, B, C, D and E involvement as per BM-MRI, respectively. Similarly, involvement observed on the BM-Bx was 8%, 24%, 22%, 16% and 30%, respectively. Categories of marrow involvement on BM-Bx and BM-MRI were concordant in 23 (46%) and discordant in 27 (54%) patients. Of the patients that showed discordance, 89% had a more extensive BM involvement detected by the BM-MRI and 11% had a higher reading on BM-Bx. The estimated Spearman correlation coefficient between MRI involvement and MM stage was 0.4849 (95% CI; 0.2494, 0.7205), showing a significant association between BM-MRI involvement and MM stage (p =0.0002). The estimated Spearman correlation coefficient between BM-Bx involvement and MM stage was 0.1775 (95% CI; −0.1406, 0.4956), showing no significant association between BM-Bx involvement and MM stage (p = 0.2764). Conclusions: We demonstrate for the first time that BM-MRI is a more sensitive technique to assess the true disease burden in MM and is significantly better than BM-Bx. We also observe that the extent of marrow infiltration noted on the BM-MRI correlates significantly with other prognostic characteristics like DS stage. Based on this observation we recommend that BM-MRI should be considered as part of the pre-treatment evaluation of patients with multiple myeloma.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.4776.4776
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 5
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    Lenalidomide Associated Tumor Flare Reaction Correlates with Clinical Response in Patients with Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 4163-4163
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 4163-4163
    Abstract: INTRODUCTION: We have previously reported that in patients with B-CLL, lenalidomide induces a tumor flare reaction (TFR) that is clinically characterized by painful, tender enlargement of disease involved lymph nodes, spleen and/or liver along with low grade fever. The underlying mechanism as well as the impact of TFR on treatment outcomes remains unknown. We analyzed data from our phase II clinical trial in which the clinical efficacy of lenalidomide alone was investigated in patients with relapsed or refractory B-CLL and correlated the severity of TFR with clinical efficacy. METHODS: Forty five patients with relapsed refractory CLL, enrolled in a phase II study were divided into two groups; group A consisted of first 29 patients who were treated with 25 mg of lenalidomide for 21 days of a 28 day cycle without any prophylaxis for tumor flare reaction, group B consisted of subsequent 16 patients who received 10 mg per day of lenalidomide initially with subsequent escalations of 5 mg every 1–2 weeks to a maximum dose of 25 mg along-prednisone prophylaxis (20 mg/day for 5 days followed by 10 mg/day for 5 days) was given to this group during cycle 1 only. RESULTS: Thirty of the 45 patients (67%) developed clinically significant TFR. Of these 20 (67%) were grade I, 7 (23%) grade II and 3 (10%) grade III. The median time to TFR was 6 days (range 0–56 days). The median time to resolution was 14 days (95% CI: 10–26 days). In over 90% of cases flare occurred only during first treatment cycle. Median age for those who either developed or did not develop flare reaction was 61 and 71 years respectively (p=0.004, 2-sided, Wilcoxon test). Nineteen patients (66%) in group A and 11 (69%) in group B developed TFR. Grade II/III flare was observed in 9 (47%) and 1 (9%) patients in group A and B, respectively (p=0.05). The median time to onset of TFR was 4 days in group A and 9 days in group B (p=0.01). The median duration of TFR was 13 and 28 days in groups A and B respectively (p=0.16). A total of 8 patients achieved molecular complete remission (mCR). All but 1 patient who achieved mCR had a flare reaction (p=0.24). The median progression free survival of patients with or without TFR was 19.9 and 19.4 months, respectively. There was a trend to improvement of progression free survival in group A patients compared to group B patients, 23 vs. 17.8 months, respectively (p=0.74, log rank test), however, this difference did not reach statistical significance. TFR reaction was managed by non-steroidal anti-inflammatory agent with or without oral morphine. Eleven of the 30 patients with TFR required treatment and only 3 patients received supplemental morphine. None of patient required discontinuation of lenalidomide for TFR. CONCLUSION: Although the mechanism of TFR remains to be determined clinically it appears to be an immunologically mediated phenomenon that is uniquely seen in CLL patients. We observe that the occurrence and severity of TFR appears to correlate with clinical response to lenalidomide. Steroid prophylaxis decreases the severity but not the incidence of TFR. The effect on overall efficacy of steroid pre-treatment for prevention of TFR remains to be determined in larger cohort of patients.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.4163.4163
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
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  • 6
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    Bortezomib in Combination with Pegylated Liposomal Doxorubicin and Thalidomide (VDT), An Effective Steroid Independent Regimen for Previously Untreated Multiple Myeloma Patients: Final Result of a Phase II Study.
    American Society of Hematology ; 2009
    In:  Blood Vol. 114, No. 22 ( 2009-11-20), p. 618-618
    Details
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 618-618
    Abstract: Abstract 618 Introduction: Steroids have been an important component of multiple myeloma (MM) therapeutics. High doses steroids as used in MM are associated with significant toxicity and morbidity. Development of steroid independent or steroid-lite regimens remains an important area of investigation in MM. Orlowski et al combined Doxil (D) with bortezomib (V) and showed enhanced anti-myeloma activity. In a phase II study in relapsed refractory MM patients, we observed further improvement in clinical efficacy with addition of thalidomide (T) to VD combination (VDT regimen). Encouraged by high response rates of this steroid sparing novel combination we investigated VDT regimen in treatment naïve MM patients. Final results of this phase II trial are reported here. Methods: Patients with previously untreated MM were eligible for this phase II trial. VDT regimen (V 1.3mg/m2 on days 1, 4,15,18; D 20mg/m2 on days 1,15 and T 200 mg daily continuously) given on a 4-week cycle for a maximum of 8 cycles. Acyclovir (400 mg BID) and weight adjusted low-dose warfarin (1 or 2mg for absolute body weight 〈 70kg or ≥70kg, respectively) was given for prophylaxis of herpes zoster and deep vein thrombosis (DVT), respectively. Response was assessed using the modified Blade criteria. Results: Forty patients (26 males, 14 females; median age 60.5, range 40-80 yrs) were enrolled on this study. Among these 58%(n=23) had stage III (Durie-Salmon) disease with a median b2 microglobulin of 3.7 (range 1.6-16.5 mg/L) and median LDH of 443 (range 152-129 IU/L). Thirty-nine patients are eligible for response evaluation (1 too early for assessment). Overall response rate (CR/nCR+PR) was 79.4% (n=31) with 38% (n=15) patients achieving CR/nCR. The median progression free (PFS) and overall survival (OS) has not been reached. At 1 year the PFS and OS is 81% and 97%, respectively (1 patient died from disease progression to leukemic phase). Toxicity: Neutropenia was the most significant hematological toxicity with grade 3 and 4 neutropenia observed in 22.5% and 2.5% of the patients, respectively. Only 1 (2.2%) patient had febrile neutropenia. Clinically significant neuropathy (grade ≥2) was seen in 20% while grade ≥2 palmer planter erythrodysesthesia was seen in 15% (n=6) of the patients. Other grade 3 non-hematological toxicities included pneumonia (20%), pleural effusion (10%), pulmonary embolism (2%), DVT (2%), congestive heart failure (5%) and interstitial pneumonitis (2%). Conclusion Although effective, steroid based treatment regimen can be associated with significant toxicity especially among patients with concurrent co morbid conditions such as hypertension and diabetes mellitus. Furthermore, recent investigations demonstrate that decreasing steroid doses may actually improve PFS and OS despite a comparatively low initial ORR. In this clinical trial we hypothesized that rational combination of novel myeloma agents may actually preclude the need to rely on high-dose steroids without significantly compromising ORR. Consistent with our expectations, the VDT regimen has ORR comparable to some of the steroid-inclusive triple drug combinations. The toxicity profile of this combination was acceptable and the regimen was well tolerated. Thus we note that VDT is an effective and well tolerated steroid-independent induction regimen for MM patients. Disclosures: Off Label Use: A Phase II study of a novel combination in newly diagnosed myeloma patients. Miller: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. Czuczman:Centocor Ortho Biotech: Research Funding. Sood:Celgene: Stock. Chanan-Khan:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immunogen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V114.22.618.618
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 7
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    Novel Agents Overcome the Adverse Prognosis Imparted by Compromised Renal Function in Patients with Multiple Myeloma
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 2726-2726
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 2726-2726
    Abstract: INTRODUCTION: Impaired renal function in patients with multiple myeloma (MM) is associated with adverse clinical outcome. Historically, the renal status is reported as serum creatinine (SCr) only. Introduction of novel agents (thalidomide, lenalidomide, bortezomib and pegylated liposomal doxorubicin) in MM therapeutics has improved clinical responses and overall survival. An important question that remains largely unanswered is if these agents deliver equal benefit to patients with impaired renal function. Thus we investigate the overall benefit of novel agents in MM patients with renal impairment. METHODS: All MM patients treated between January 2000 and December 2007 at Roswell Park Cancer Institute (RPCI) where included in this analysis. Extent of disease was assessed based on the Durie-Salmon staging system. We determined glomerular filtration rate (GFR) to asses renal function more accurately. GFR was calculated utilizing the Modification of Diet in Renal Disease (MDRD) equation. Patient cohorts were defined based on severity of renal impairment per the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKD-KDOQI) guidelines based on the GFR value into normal & gt;90, mild 60–89, moderate 30–59, severe 15–29 and kidney failure & lt;15 ml/min/1.73m^2. Because there were only few patients in the last two groups (GFR of 15–29 =11 and GFR & lt;15 =13), they were combined into a single cohort of severe renal impairment (GFR & lt;30=24). We also defined patient cohorts based on a previously reported classification in MM wherein patients were divided based on severity of renal impairment into normal & gt;80, mild 50–80, moderate 30–49 and severe & lt;30 ml/min/1.73m^2. Survival curves and median survival were calculated by Kaplan-Meier method. Survival differences were calculated using a log-rank test. A 0.05 nominal significance level was used in all statistical testing. RESULTS: A total of 175 patients (M=88, F=87) with a median age 60 years (range 34–88) were evaluated. Majority of patients had stage III disease (64%), 57.1% had IgG myeloma and lytic bone disease present in 67.4% of the patients. Median values for SCr, serum calcium, blood urea nitrogen, serum albumin and hemoglobin were 1.1mg/dl (range-0.5–10.3), 9.5 mg/dl (range-7.5- 7.2), 18 mg/dl (range-5–107), 4.0 g/dl (range-2.2–5.5) and 11.5 g/dl (range-6.8–17.1) respectively. SCr & gt;2 mg/dl was seen in only 16% patients and 41.1% patients had GFR in the range of 60–89 ml/min/1.73m^2. Patients received an average of 2 treatments. Use of at least one of the novel agent was seen in 86.3% patients (Immunomodulatory drugs =130, Bortezomib = 97, Pegylated liposomal doxorubicin =65). Median survival for patients with SCr & lt;2.0 and SCr & gt;2.0 was 67.4 months (45.4 – 92.7 months) and 38.4 months (15.3 months – not reached) respectively. Median survival for patients with normal GFR and mild, moderate and severe renal impairment based on the NKD-KDOQI guidelines was 76.1 months (37.5 months – not reached), 55.32 months (34.8 months – not reached), 67.4 months (45.4 months – not reached) and 24.9 months (15.3 months – not reached) respectively. Median survival for patient cohorts defined based on a previously reported classification in MM was similar to that seen with the NKD-KDOQI classification. We noted no significant survival advantage of normal renal function over renally impaired patients (Figure 1 & 2) despite evaluations based either by using the traditional approach of SCr (p=0.15; log rank test) or by more sensitive renal function assessment by GFR (p=0.21; log rank test). CONCLUSIONS: We conclude that in MM patients the previously reported and commonly perceived adverse prognosis imparted by impaired renal function can no longer be validated and that routine incorporation of novel agents has overcome this adverse prognosis. These findings are consistent with the impact of novel agents reported in context with MM with aggressive molecular profiles. Figure 1: Kaplan-Meier curve for survival by serum creatinine (SCr) Figure 1:. Kaplan-Meier curve for survival by serum creatinine (SCr)
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.2726.2726
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
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  • 8
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    Determining the Extent of Disease with Magnetic Resonance Imaging of the Bone Marrow (BM-MRI) in Patients with Multiple Myeloma (MM).
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1483-1483
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1483-1483
    Abstract: Background: MM remains an incurable cancer. Treatment is often initiated with progressive increase in tumor burden and clinical symptoms. Tumor burden assessment is commonly done by disease stage, presence of lytic bone disease and beta-2 microglobulin (B2M). We investigated bone marrow imaging as a novel approach to quantify disease burden. In a separate report, we observed that MRI is more sensitive than BM aspirate/biopsy (BM-Bx) for assessing extent of marrow involvement in MM patients. In this study we validate that extent of marrow disease detected by BM-MRI correlates with the clinical stage, presence of lytic bone lesions, B2M and secretor vs. non-secretor status of MM patients. Methods: Extent of marrow involvement as evaluated by BM-MRI included sagittal T1 and fast spin echo inversion recovery sequences of the cervical, thoracic and lumbosacral spine and coronal T1 and fast spin echo inversion recovery sequences of the sacrum and pelvic bones. Clinical staging was done as per Durie-Salmon (DS) and the International Staging System (ISS) while lytic bone lesions were assessed by skeletal radiographs. Secretory MM was identified by presence of M-protein in serum or urine by electrophoresis. To study the statistical relationship between pairs of ordinal variables the test corresponding to the Spearman correlation was used and statistical relationship between nominal and ordinal variables was determined by the Wilcoxon or Kruskal-Wallis test. A 0.05 nominal significance level was used in all testing. Following staging system was defined for evaluation of the marrow involvement by BM-MRI: A (0%), B ( & lt; 10%), C (10%–25%), D (26%–50%), E ( & gt; 50%). Results: We evaluated 170 consecutive patients (77 females and 93 males). Median age was 61 years (range 35–83). Advance stage disease ( & gt; stage 1) based on DS or the ISS criteria was observed in 47.6% (n=81) and 53.3% (n=77) patients, respectively. Lytic lesions were noted in 70.6% (n=120) patients and secretory disease in 85.9% (n=146) patients. Estimated Spearman correlation coefficient between BM-MRI involvement and DS stage was 0.2795 (p = 0.0006; 95% CI 0.1222, 0.4368) demonstrating a significant association between BM-MRI involvement and DS stage. This correlation with clinical stage remained significant using the ISS system (p = 0.0001). The correlation of marrow infiltration on BM-MRI was also significantly associated with the presence of lytic bone disease (p & lt;0.0001) as well as the B2M levels (p & lt;0.0001). There was no significant association between MRI involvement and patient age (p = 0.7921) or the Ig type (p=0.8123). Interestingly, marrow involvement on BM-MRI had a significant association with secretor-status of the patients (p=0.0081). Conclusions: BM-MRI is novel approach to quantify disease burden in patients with MM. Our investigation in a large cohort of patients demonstrates that the extent of marrow involvement determined by this method correlates accurately with other conventional methods used to assess myeloma disease burden such as clinical stage, lytic bone disease or B2M. We therefore conclude that BM-MRI can be routinely used to determine disease burden in patients with multiple and can be effectively employed in monitoring response to therapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1483.1483
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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