Thalidomide Response in African American Patients with Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5147-5147
Author(s):  
Ahmad Jajeh ◽  
Rose Catchatourian ◽  
Deimante Tamkus ◽  
David Osafo ◽  
Ghassan Zalzaleh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
Partial Response ◽  
Light Chain ◽  
Complete Response ◽  
Total Response Rate ◽  
Back Ground ◽  
One Year ◽  
Beta 2 Microglobulin ◽  
Good Partial Response

Abstract African american are not well presented in clinical trials. This is a retrospective analysis studying Thalidomide response in predominantly african american patients with multiple myeloma from January 2000 till August 2005. A total of fifty patients diagnosed with multiple myeloma started on Thalidomide which was given through the S.T.E.P. Program. Twenty one males and twenty nine females. Thirty six african americans (72%), eleven hispanics (22%), three whites and one other. Mean age at starting treatment is 63 years (range 41–76). All were stage II-III. Mean serum Albumin is 3.4mg/dL (range 2.2–4.7) and Beta 2 microglobulin is 3.8 (range 0.60–13.6), the normal range is 0–0.63 mg/dL. Twenty four patients with IgG kappa, twelve patients with IgG lambda, three with lambda light chain, three with kappa light chain, seven patients with IgA and one patient with non secretory MM. Mean Thalidomide dose is 100 mg Oraly, daily (range 50–200 mg). Medium duration of therapy is one year (range 3 months- three and a half years). Two patients stopped in the first few weeks because of intolerance due to side effects. Eighty percent of patients given treatment after failure to prior therapies. Fifty percent of patients recieved Thalidomide with Dexamethason. Response were evaluated as of Blade criterae. Seven patients (14%) achieved complete response CR or very good partial response. Partial response PR was achieved in nine patients (18%), minimal response was achieved in three patients (6%) and stable disease in six (12%). Total response rate of fifty percent(50%). Fifteen patients (30%) achieved a rise in back ground depressed serum level of IgA (range 1–3 folds of normal value). Two patients(4%) achieved arise in the back ground depressed level of IgG in IgA MM. Median time to progression in patients with CR and PR was not reached. However most of the progression occured at one and a half years from response. Conclusion: Thalidomide alone or in combination with Dexamethasone is a well tolerated regimen. Low dose as 50 to 100mg seem to be effective and tolerated in most of the african american patients. The rise in IgA level is an interesting phenomena. This is particularly seen in CR and very good partial response. Whether this is an immune response or an epiphenomena need to be investigated.

Cyclophosphamide, Bortezomib and Dexamethasone (CyBORD) Is a Feasible and Active Regimen for Non-Transplant Eligible Multiple Myeloma Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5751-5751 ◽  
Author(s):  
Victor H Jimenez Zepeda ◽  
Peter Duggan ◽  
Paola E. Neri ◽  
Nizar J Bahlis
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Median Time ◽  
Light Chain ◽  
Overall Response Rate ◽  
Response Rate ◽  
Complete Response ◽  
Overall Response ◽  
Novel Drugs ◽  
Good Partial Response

Abstract Introduction With the advent of novel drugs for the treatment of Multiple Myeloma (MM), the clinical outcomes have significantly improved over the last decade both in the setting of stem cell transplant eligible and non-eligible patients. Combinations of novel drugs have improved and deepened response and this is true for CyBORD, a regimen able to induce rapid and deep responses. Based on the above mentioned, we aimed to assess the role and feasibility of CyBORD as upfront therapy for non-transplant eligible patients with MM. Methods. All consecutive patients with documented symptomatic MM not eligible for transplant treated with CyBORD at our Institution were evaluated. Treatment consisted of a 28-day cycle of bortezomib 1.3 mg/m2 or 1.5 mg/m2 intravenously or subcutaneously on days 1, 8, and 15, cyclophosphamide 300 mg/m2 orally administered on days 1, 8, and 15 and dexamethasone 20-40 mg orally on weekly basis. Definitions of response and progression were used according to the EBMT modified criteria and a category of very good partial response (VGPR) was added. The primary endpoint of the study was to assess the efficacy and feasibility of CyBORD in this group of patients. All analyses were performed using the SPSS 20.0 software and all p-values were 2-sided and statistically significant if <0.05. Results Between 07/11 and 07/14, 20 patients were identified for the study. Clinical and laboratory characteristics are listed in Table 1. The median age for this cohort of patients was 76 years (range 66-90). Sixty-five percent of patients had IgG isotype, 5% had IgA, and 30% had light chain only disease. After a median of 5 cycles, the overall response rate was 95% (19/20) with 70% of patients achieving VGPR or better response. (Table 2 ) The median time to first response was 6 weeks with majority of cases achieving at least PR after 2 cycles of therapy. At a median follow-up of 9.5 months, all patients are alive and 5 had already progressed at a median time of 12 months. With regards to toxicity, 6 patients experienced non-hematological grade 3/4 adverse events (20%), including muscle weakness, sepsis and pneumonia. Neutropenia and thrombocytopenia were seen in 2 patients (10%), both patients required dose reduction of cyclophosphamide with one patient being discontinued of cyclophosphamide after 2 cycles but still receiving bortezomib and dexamethasone. In conclusion, CyBORD is a highly active and viable option for the treatment of non-transplant eligible patients with MM. As suggested by other studies, elderly patients required dose adjustments and special considerations while receiving active therapy, balancing the efficacy and toxicity given by the different drug combinations. Table 1. Clinical and Laboratory characteristics of non-transplant eligible MM patients treated with CyBORD Characteristic N Median Range % Age (years) 20 76 66-90 Gender -Male -Female 11 9 55% 45% ISS Stage I II III 5 7 8 25% 35% 40% Heavy chain IgG IgA Free light chain only Light chainKappa Lambda 13 1 6 11 9 65% 5% 30% 55% 45% Hemoglobin (g/L) 20 106 73-158 Creatinine (µmol/L) 20 117 49-671 Calcium (µmol/L) 20 2.4 2.0-2.99 LDH (IU/L) 20 229 118-814 B2-microglobulin (mg/L) 20 4.1 1.41-19 Albumin (g/L) 20 32 22-37 FISH Cytogenetics Standard risk High risk 18 2 90% 10% Table 2. Response rates for non-transplant eligible MM patients treated with CyBORD Characteristic Median (Range) N % Number of cycles 5 (1-12) Overall Response rate 19/20 95% Near Complete Response Complete Response 1 2 5% 10% Very Good Partial Response 11 55% Partial Response 5 25% Less than PR 1 5% Progression 5/20 25% Time to progression (months) 12 (3-15) Alive 20 100% CyBORD: Cyclophosphamide, bortezomib and dexamethasone Disclosures Jimenez Zepeda: Janssen Ortho: Honoraria. Bahlis:Celgene: Honoraria, Research Funding.

scholarly journals Autologous haematopoietic stem cell transplantation in patients with multiple myeloma complicated by dialysis-dependent renal failure

2020 ◽  
Vol 92 (7) ◽  
pp. 70-76
Author(s):  
M. V. Firsova ◽  
L. P. Mendeleeva ◽  
M. V. Solovev ◽  
I. G. Rekhtina ◽  
O. S. Pokrovskaya ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Stem Cell ◽  
Partial Response ◽  
Stem Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Complete Response ◽  
Haematopoietic Stem Cell ◽  
Renal Response ◽  
Good Partial Response

Aim.To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) patients with dialysis-dependent renal failure. Materials and methods.During a period from May 2010 to December 2016 fourteen MM patients with dialysis-dependent renal failure aged 48 to 65 years underwent auto-HSCT. After the induction therapy complete response, very good partial response, partial response were documented in 64, 29, 7% of patients, respectively. In no case was a renal response achieved. Haematopoietic stem cell mobilization in most patients (13/14) was performed according to the scheme: G-CSF 10 g/kg. Melphalan in 3 dosages was used as pre-transplant conditioning: 100, 140 and 200 mg/m2; 13 patients underwent a single and in one case underwent a tandem auto-HSCT against the background of hemodialysis. Evaluation of the antitumor and renal response was assessed on the 100th day after auto-HSCT. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100200 mg/m2), 13 patients underwent a single and one patient underwent a tandem auto-HSCT. At +100 days after auto-HSCT, an antitumor response and renal response were assessed. Results.The period of agranulocytosis after auto-HSCT was from 5 to 12 days (median 8,5) and was accompanied by infectious complications, cardiac and neurological dysfunctions. At +100 days after auto-HSCT, the complete response was confirmed in 71% patients and very good partial response was confirmed in 29% patients. The minimal renal response was registered in 2 patients (14%), hemodialysis was stopped. The transplant-related mortality was absent. After a median follow-up of 53 months 5-year progression-free survival was 59%, and overall survival was 93%. Conclusion.Carrying out auto-HSCT in patients with dialysis-dependent renal failure contributed to the achievement of a minimal renal response in 14% of cases, which allowed these patients to stop hemodialysis. Patients whose conditioning regimen was performed using melphalan at a dose of 200 mg/m2showed more frequent complications in the early post-transplant period compared to patients who received a lower dose of melphalan (100140 mg/m2). Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, which in some cases contributes to independence from hemodialysis.

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.

scholarly journals Realistic Lenalidomide Dose Adjustment Strategy for Transplant-Ineligible Elderly Patients with Relapsed/Refractory Multiple Myeloma: Japanese Real-World Experience

2017 ◽  
Vol 138 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Aya Nakaya ◽  
Shinya Fujita ◽  
Atsushi Satake ◽  
Takahisa Nakanishi ◽  
Yoshiko Azuma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Elderly Patients ◽  
Complete Response ◽  
Hematologic Disorder ◽  
Adjustment Strategy ◽  
Immunomodulatory Drug ◽  
Grade 3 ◽  
Tolerable Dose ◽  
Good Partial Response

Lenalidomide is an immunomodulatory drug administered orally in the treatment of multiple myeloma. Some elderly patients require a reduced lenalidomide dose because of comorbidities and/or adverse events. This study investigated the actual dose of lenalidomide in elderly patients, finding that most received reduced (5-10 mg) doses. The most common reasons for dose reduction were renal dysfunction (54% of patients), fatigue (grade ≥3; 20%), hematologic disorder (grade ≥3; 14%), and rash (grade ≥3; 9%). Their median time to progression was 11.8 months and their median overall survival was 39.2 months. The overall response rate was 73%, including 17% with a complete response, 19% with a very good partial response, and 37% with a partial response. These results showed that, contrary to western countries, most patients were treated with a reduced dose of lenalidomide in Japan. However, it is suggested that continued treatment with a tolerable dose may yield favorable outcomes.

scholarly journals Clinical Outcome of Bortezomib Retreatment in Patients with Relapsed or Refractory Multiple Myeloma

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Jae-Sook Ahn ◽  
Sung-Hoon Jung ◽  
Seung-Shin Lee ◽  
Seo-Yeon Ahn ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Sensory Neuropathy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3 ◽  
Peripheral Sensory ◽  
Good Partial Response

This retrospective study investigated the clinical efficacy and safety of bortezomib retreatment in patients with relapsed or refractory multiple myeloma (MM). A total of 30 patients who relapsed or progressed after≥6 months since the last dose of their previous bortezomib therapy were included in this study. During the median 6 cycles (range: 2–12) of bortezomib retreatment, 10 (33.3%), 2 (6.7%), and 6 (20.0%) patients achieved complete response, very good partial response, and partial response, respectively. Grade 3 or 4 neutropenia (47.0%), thrombocytopenia (43.0%), anemia (10.0%), and peripheral sensory neuropathy (3.0%) were observed. The median time to progression, progression-free survival, and overall survival were 5.8 months (95% CI: 2.6–9.0), 5.5 months (95% CI: 4.2–6.8), and 13.4 months (95% CI: 6.1–20.7), respectively. Patients who received bortezomib retreatment≥12 months from initial last therapy had a 1-year OS rate of 65.8% (95% CI: 43.5–88.1) while patients receiving retreatment after 6–12 months interval had a 1-year OS rate of 41.7% (95% CI: 13.9–69.5) (P=0.038). In conclusion, this study demonstrates that retreatment with bortezomib is an effective strategy for patients with MM who relapsed at a long interval after initial bortezomib therapy.

Efficacy Of Bortezomib-Based Regimens With Or Without An Immunomodulatory Agent In Older Adults With Multiple Myeloma: A Systematic Review and Meta-Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5580-5580
Author(s):  
Jordan Atkins ◽  
Susan A Fowler ◽  
Methodius Tuuli ◽  
Aimee S James ◽  
Tanya M Wildes
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Partial Response ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Complete Response ◽  
Inclusion Criteria ◽  
Free Survival ◽  
Good Partial Response

Abstract Introduction Multiple myeloma (MM) is an incurable disease within older adults, caused by the malignant proliferation of plasma cells and destruction of skeletal structure, with subsequent end-organ dysfunction. In the elderly and transplant ineligible population, chemotherapeutic regimens that include novel and conventional drugs are currently being employed to attain optimal response and survival outcomes. We performed a systematic review and meta-analysis to investigate the efficacy of the proteasome inhibitor bortezomib, in combination with an immunomodulatory drug (IMiD) versus bortezomib-containing regimens alone in improving overall survival, progression-free survival, and response in patients aged 65 and older ineligible for stem cell transplant. Methods We searched Pubmed/Medline, Embase, Scopus, CENTRAL, DARE, and clinicaltrials.gov databases for randomized controlled trials (RCTs) published from January 1946 until March 2013 using search terms such as: “bortezomib” “thalidomide/analogs and derivatives” and “lenalidomide.” Primary outcomes such as overall survival “OS” and progression-free survival “PFS” were harvested from standard indexes and on-topic articles. We abstracted data from relevant studies for analysis. Heterogeneity was assessed using Cochrane's Q and Higgin's I2 with p<0.1 considered significant. Pooled risk ratios (RR) and hazard ratios (HR) were estimated using DerSimonain and Laird random effect models. Results We identified 762 studies, 201 of which were duplicates that were excluded. Of these studies, 561 met initial inclusion criteria. After screening and systematic review, we found a majority of the articles originated from sub-analyses or reviews of 2 major studies which fully met inclusion criteria: 1) bortezomib-melphalan-prednisone-thalidomide (VMPT) versus bortezomib-melphalan-prednisone (VMP) [Palumbo JCO 2010] and 2) bortezomib-thalidomide-prednisone (VTP) versus VMP [Mateos Lancet Onc 2010). Of the two studies included, 384 patients received thalidomide and bortezomib-containing regimens (VMPT or VTP), and 387 patients received VMP. Thalidomide-containing combinations were associated with improvement in complete response (pooled RR 1.55 [95% Confidence intervals 1.23-1.95]) and very good partial response (pooled RR 1.19 [95% Confidence intervals 1.04-1.38]). There was no evidence of significant heterogeneity associated with either of these outcomes across the studies (I2=0; p=0.559 and I2=0; p=0.600). There were no significant differences in partial response (pooled RR 1.08; 95% CI 0.98-1.19), overall survival (pooled HR 1.04; 95% CI 0.65-1.44), or progression-free survival (pooled HR 0.91; 95% CI 0.29-1.42). There were also no significant differences in toxic side effects (Table). Conclusion Based on the limited data included in this meta-analysis, we found that the addition of thalidomide to a bortezomib-based regimen was associated with improved complete response and very good partial response, but no improvement in overall or progression-free survival. Larger studies of thalidomide and other immunomodulatory agents are required to further clarify the role of adding IMiDs to bortezomib-based regimens in the treatment of MM. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High serum-free light chain levels and their rapid reduction in response to therapy define an aggressive multiple myeloma subtype with poor prognosis

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 827-832 ◽  
Author(s):  
Frits van Rhee ◽  
Vanessa Bolejack ◽  
Klaus Hollmig ◽  
Mauricio Pineda-Roman ◽  
Elias Anaissie ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Light Chain ◽  
Prognostic Significance ◽  
Complete Response ◽  
High Serum ◽  
Free Light Chain ◽  
Response To Therapy ◽  
Rapid Reduction ◽  
Serum Free ◽  
Serum Free Light Chain

Abstract Serum-free light chain (SFLC) levels are useful for diagnosing nonsecretory myeloma and monitoring response in light-chain–only disease, especially in the presence of renal failure. As part of a tandem autotransplantation trial for newly diagnosed multiple myeloma, SFLC levels were measured at baseline, within 7 days of starting the first cycle, and before both the second induction cycle and the first transplantation. SFLC baseline levels higher than 75 mg/dL (top tertile) identified 33% of 301 patients with higher near-complete response rate (n-CR) to induction therapy (37% vs 20%, P = .002) yet inferior 24-month overall survival (OS: 76% vs 91%, P < .001) and event-free survival (EFS: 73% vs 90%, P < .001), retaining independent prognostic significance for both EFS (HR = 2.40, P = .008) and OS (HR = 2.43, P = .016). Baseline SFLC higher than 75 mg/dL was associated with light-chain–only secretion (P < .001), creatinine level 176.8 μM (2 mg/dL) or higher (P < .001), beta-2-microglobulin 297.5 nM/L (3.5 mg/L) or higher (P < .001), lactate dehydrogenase 190 U/L or higher (P < .001), and bone marrow plasmacytosis higher than 30% (P = .003). Additional independent adverse implications were conferred by top-tertile SFLC reductions before cycle 2 (OS: HR = 2.97, P = .003; EFS: HR = 2.56, P = .003) and before transplantation (OS: HR = 3.31, P = .001; EFS: HR = 2.65, P = .003). Unlike baseline and follow-up analyses of serum and urine M-proteins, high SFLC levels at baseline—reflecting more aggressive disease—and steeper reductions after therapy identified patients with inferior survival.

scholarly journals CyBorD-DARA is potent initial induction for MM and enhances ADCP: initial results of the 16-BCNI-001/CTRIAL-IE 16-02 study

2019 ◽  
Vol 3 (12) ◽  
pp. 1815-1825 ◽  
Author(s):  
M. O’Dwyer ◽  
R. Henderson ◽  
S. D. Naicker ◽  
M. R. Cahill ◽  
P. Murphy ◽  
...  
Keyword(s):  
Partial Response ◽  
Group Performance ◽  
Residual Disease ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Staging System ◽  
Complete Response ◽  
Weekly Schedule ◽  
Intention To Treat ◽  
Good Partial Response

Abstract Daratumumab (DARA) has shown impressive activity in combination with other agents for the treatment of multiple myeloma (MM). We conducted a phase 1b study to assess the safety and preliminary efficacy, as well as potential mechanisms of action, of DARA (16 mg/kg) in combination with a weekly schedule of subcutaneous bortezomib (1.3-1.5 mg/m2), cyclophosphamide (150-300 mg/m2), and dexamethasone (40 mg) (CyBorD DARA) as initial induction before autologous stem cell transplantation (ASCT). Eligible patients were ≤70 years of age with untreated MM requiring treatment and who lacked significant comorbidities. A total of 18 patients were enrolled. Their median age was 56 years (range, 32-66 years), and all patients had Eastern Cooperative Oncology Group performance status ≤1. The International Staging System stages were I, II, and III in 78%, 17%, and 6% of patients, respectively; 28% of patients had high-risk genetic features. There was no dose-limiting toxicity, and the incidence of grade 3 or 4 infection or neutropenia was &lt;10%. On an intention-to-treat basis, 94% achieved ≥very good partial response with ≥complete response in 44% of patients. Among 14 of 15 patients who underwent ASCT and were evaluable for response, all 14 achieved at least very good partial response, with 8 (57%) of 14 achieving complete response. After ASCT, 10 (83%) of 12 patients in whom minimal residual disease analysis was possible were negative at a sensitivity of 10−5 (56% on intention-to-treat/whole study population) according to next-generation sequencing. Flow cytometry analysis of patient samples indicated CyBorD DARA induced activation of macrophage-mediated antibody-dependent cellular phagocytosis. This trial was registered at www.clinicaltrials.gov as #NCT02955810.

Clarithromycin (Biaxin®), Low Dose Thalidomide and Dexamethasone (BLT-D) in Newly Diagnosed and Previously Treated African American Patients with Multiple Myeloma: A Retrospective, Single Institution Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3501-3501
Author(s):  
Jack Jacoub ◽  
Joao L. Ascensao ◽  
Boyer James ◽  
Thomas O’Connor ◽  
Reema Batra ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
African American ◽  
Partial Response ◽  
Plasma Cells ◽  
Progression Free Survival ◽  
Staging System ◽  
Stage I ◽  
M Protein ◽  
Duration Of Treatment ◽  
Previously Treated

Abstract Introduction : African-Americans (AA) are twice as likely to develop multiple myeloma (MM) than Caucasians but are largely underrepresented in clinical trials. Thalidmode plus dexamethasone is an established therapy in MM. Biaxin® may augment the efficacy of this combination possibly via potentiating steroid activity (M. Coleman, et al. Leuk Lymphoma 2002, R. Niesvizky, et al. Blood 2003, Abs #832). Methods : We conducted a retrospective review of all AA patients (pts) with symptomatic MM treated with BLT-D from 2002-present. Treatment consisted of Thalidomide 50–200mg daily, Biaxin 500mg twice daily and dexamethasone 40mg weekly. All pts received monthly bisphosphonate therapy and aspirin 81–325mg daily. Response criteria was defined as follows: complete response (CR) = no detectable M-protein, marrow plasma cells &lt;5%; very good partial response (VGPR) = decrease in M-protein by &gt;90%; partial response (PR) = decrease in M-protein by &gt;50%; stable disease (SD) = M-protein decrease by &lt;50% without clinical progression; no response (NR)= progression with no change or increase in M-protein or response &lt;4wks. Progression free survival (PFS) was defined from the start of BLT-D until discontinuation or change in therapy due to progressive disease as clinically indicated. Toxicity was graded according to WHO criteria. Results :15 pts received BLT-D and their characteristics were as follows: all were males; median age 66 (range 30–78); IgG=53%, IgA=20%, light chain only=27%; Durie-Salmon stage I=20%, II=33%, III=47%; International Staging System stage I=20%, II=47%, III=13%, undefined = 20%; 7 were previously treated (5 pts had 1 prior regimen, 2 pts had ≥2 prior regimens). In previously treated pts (n=7) responses were as follows: no CR, 2 VGPR (28%), 3 PR (43%), 1 SD (14%) and 1 NR (14%) for an overall response rate (ORR) of 87%. Their duration of treatment ranged from 4–32 mos and median PFS in responders (VGPR+PR+SD) was 29.5 mos (range 23–35). 3 pts had BLT-D discontinued after 12–15 months of therapy and remained in stable plateau phase off therapy for &gt; 1 year; one was referred for ASCT after 14 mo; one continues stable at 15 mo and the third relapsed at 12 months but failed to respond again to BLT-D. Responses in treatment naive pts (n=8) were as follows: no CR, 3 VGPR (38%), 1 PR (13%) and 2 SD (25%), 2 NR (25%) for an ORR of 75%. Their duration of therapy ranged from 3–20 mos and median PFS in responding patients was 11 mos (range 7–20). The longest survivor in this group (37 mos) received an ASCT after 12 mos of therapy. 13 pts (87%) remain alive at a median follow-up of 24 mos (range 8–37). Grade 3–4 toxicity consisted of 3 DVTs + 1 PE (27%), 5 hypergycemias (33%), 2 infections (13%) and 1 peripheral neuropathy (7%). Additionally, 1 pt developed superficial thrombophlebitis; 1 QT prolongation resolving with Biaxin discontinuation; 5 others with neuropathy; and 2 others with hyperglycemia. Conclusion : BLT-D is feasible and effective therapy in African-American patients with MM and is capable of inducing durable responses. However, we encountered significant thrombotic and endocrine toxicity that appears out of proportion to what has been previously reported with thalidomide plus dexamethasone alone. Furthermore, aspirin thromboprophylaxis at daily doses of 81–325 mg appears suboptimal in preventing thromboembolic events in this group of patients when prescribed this regimen.

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.

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