Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 943-943
    Abstract: Abstract 943 Introduction: Bendamustine has emerged as attractive treatment option for low grade lymphomas and seems to exert synergistic activity with bortezomib. Here we evaluate the efficacy and tolerance of bendamustine in combination with bortezomib-dexamethasone in patients with relapsed/refractory multiple myeloma and focus on individual factors associated with outcome. Patients and Methods: 74 patients with relapsed/refractory MM have been enrolled. Median age: 65 years (range 40–86), male/female: 34/40, ISS stage I/II/III: 24, 30, and 20, respectively. ECOG status 0/I/II: 39, 32, and 3 patients, respectively. Previous treatment lines: 1–2: 48, 3–4: 21, 〉 4: 5 patients, respectively. Full data documentation for response evaluation (≥ 2 cycles) is available for 66 patients. Treatment regimen: bendamustine 70 mg/m2 day 1+4, bortezomib 1.3 mg/m2days 1, 4, 8 and 11, dexamethasone 20 mg on days 1, 4, 8 and 11, repeated every 4 weeks. Planned number of treatment cycles was 8, with discontinuation after 4 cycles in case of no response. Kaplan Mayer curves were compared using the log-rank test and Cox regression was used for univariate and multivariate analysis of possible prognostic factors (FISH, age, LDH, Hb, Ca, pretreatment with lenalidomide, bortezomib and both lenalidomide+bortezomib). Results: After a median follow up of 8.9 months, myeloma response (ORR: CR+VGPR+PR) was noted in 43 (65.2%) of the 66 evaluable patients. 14 (21.2%) patients achieved CR/nCR, 11 (16.7%) VGPR, 18 (27.3%) PR, 10 (15.2%) MR, and 13 (19.7%) remained stable; PD was not observed within the first 4 cycles. Median time to response was 108 days (3.65 months). Responses (CR-PR) were seen in 14 of 24 (58.3%) of patients with FISH determined high risk [ampl.1q21, del17p, t (4; 14)] and in 23 of 33 (69.7%) with standard risk (del13 or no aberration) cytogenetics (p=0.84). ORR (CR-PR) was 69.7% (30 of 43) and 56.5% (13 of 23) in patients with 1–2 or 3–6 prior treatment lines, respectively (p=0.77). Median PFS was 9.7 months in the entire cohort and 12.9 and 7.8 months in patients with 1–2 or 3–6 prior treatment lines. Median overall survival in the entire cohort was 21 months. Univariate analysis showed a significant impact of pre-treatment with lenalidomide + bortezomib on response rate (p 〈 0.03), TTP (p 〈 0.0001) and OS (p 〈 0.022), while in multivariate analysis, pre-exposure with Revlimid was correlated with a lower response rate (p=0.04) and shorter TTP (p 〈 0.007). Other parameters correlating in multivariate analysis independently with TTP were age above 70 years (p 〈 0.006) and increased LDH (p 〈 0.04). Tolerance. The regimen was well tolerated with low incidence of infections and gastrointestinal toxicities. Hematological toxicity remained stable from baseline to cycle 4, with G4 anemia, leucopenia and thrombopenia being recorded in 〈 5%. Patient self reported neuropathic symptoms at baseline were recorded as G1-2 in 54.7% and as G3-4 in 18.7%, respectively. This pattern changed from cycle 1 to 8 with twice as many (42.9%) patients reporting G3-4 PNP at cycle 8. A similar pattern was noted for physician assessed neurotoxicity using the CTC grading system. Frequency of G1-2 PNP increased from 18.9% at baseline to 63.2% at termination of therapy (cycle 8). Grade 3–4 PNP was reported only occasionally. Conclusions: The BBD regimen yielded an ORR rate of 65.2% and median PFS of 9.7 months in the generally heavily pretreated patients. Poor risk cytogenetics were not associated with inferior outcome, but pre-treatment with lenalidomide was established as independent prognostic marker for lower response rate and shorter TTP. Although patients reported a doubling of the incidence of self-assessed G3-4 neurotoxicity from baseline to cycle 8, no unexpected or increased other toxicities were observed. These results highlight the BBD regimen as an active, relatively well tolerated protocol for patients with relapsed refractory multiple myeloma. Disclosures: Ludwig: Celgene: Honoraria; Janssen Cilag: Honoraria; Mundipharma: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 2871-2871
    Abstract: Abstract 2871 Poster Board II-847 Introduction: AL amyloidosis is characterized by misfolding of structurally unstable light chains that form deposits in various organs thereby causing impaired organ function. Treatment of AL amyloidosis remains challenging and is primarily directed towards the underlying abnormal plasma cell clone. Novel agents with proven efficacy in multiple myeloma like the proteasome inhibitor bortezomib have also shown initial promising results in patients with AL amyloidosis, but its value needs to be further established. In this retrospective analysis, we have collected data regarding efficacy and tolerability of treatment with bortezomib plus dexamethasone in patients with AL amyloidosis. Patients and Methods: 25 patients with histologically proven systemic AL amyloidosis were included in this analysis. All patients received bortezomib at a standard dose of 1.3mg/m2 (days 1, 4, 8, 11 of a 3-week cycle) in combination with dexamethasone (8mg to 20mg administered on the day of bortezomib and the day after). Routine clinical and laboratory parameters including evaluation were obtained on a monthly basis. Results: Patients (male n=13, female n=12) were at a median age of 57 years (range 42-83), and 17 patients (68%) received bortezomib/dexamethasone as their first line treatment. The majority of patients had an ECOG performance status of 〈 2. Twelve patients (48%) had only one organ involved, whereas 〉 2 organs were involved in 6 patients (24%). Organs most frequently involved were kidneys (100%), heart (28%), liver (12%) and the gastrointestinal tract (12%). At the time of analysis, a median of 3 cycles of bortezomib/dexamethasone (range, 1 to 8) have been administered. A hematologic response was observed in 14 patients (56%) including 5 patients (20%) qualifying for a complete response (CR). All CR patients received bortezomib/dexamethasone as their first line treatment, and parameters of organ function also improved in these patients. Median overall survival has not yet been reached after a median follow-up of 12 months. Grade 3 and 4 toxicities were rare and consisted predominantly of transient thrombocytopenia. Grade 2 neurotoxicity was observed in 24% of patients. Other grade 1/2 toxicities observed at higher frequencies included hypotension (16%), edema (16%), and fatigue (12%). Conclusion: Our results confirm the activity of bortezomib/dexamethasone in patients with AL amyloidosis (hematologic response rate 56% including a 20% CR rate). Disclosures: Ludwig: Celgene: Honoraria; Mundipharma: Honoraria; AMGEN: Honoraria; Ortho-Biotech : Honoraria; Janssen-Cilag: Research Funding; Roche: Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 5114-5114
    Abstract: Abstract 5114 Introduction: Light chain-induced renal failure (LC-ARF) is a severe complication of MM associated with increased risk of infections, dependency on chronic hemodialysis and shortened survival. Reversibility of renal impairment depends on the degree of renal damage, the duration of renal failure and the quality of response to anti-myeloma therapy. In this phase II trial we assess the efficacy of lenalidomide-dexamethasone in reducing pathogenic light chains and restoring renal function. In addition, we analyze the kinetics of treatment response in patients with LC-ARF. Patients and Methods: 24 patients with LC-ARF as formerly defined (JCO 2010) have been enrolled so far. Age (median): 65.5 years (range: 46–78 years), Gender: male/female: 12/12. All patients presented with ISS stage III. 20 (83.3%) had de novo MM and 4 (16.7%) previously treated, but relapsing disease. Median GFR was 19.9 ml/min (range 6.1 – 37.2 ml/min). ECOG performance was 0 in 6, I-II in 14 and III-IV in 4 patients, respectively. One patient died before first study medication, 3 patients died within the first cycle and 2 patients dropped out early ( 〈 2 cycles). Lenalidomide was given from d 1–21 with dose adaptation according to GFR. Dexamethasone 40 mg was administered on d 1–4, 9–12, 17–20 during cycle 1; thereafter 1x/week. Cycles were repeated q 4 weeks. Results: Presently, 17 patients are evaluable for response (completed ≥2 cycles and fully documented). The median number of cycles is 9 (range 2–9). CR was achieved in 5 (31.3%), nCR in 4 (25%), VGPR in 2 (12.5%) and PR in 5 (25%) patients, respectively, yielding an ORR (CR+nCR+VGPR+PR) of 94% for the evaluable and 69.6% for the ITT population. Median time to best tumor response was 132 days. The greatest proportional reduction in 24 hour urinary excretion (86%) in responding patients occurred within the first 4 weeks of therapy, with only little further improvement beyond that time (figure 1). Renal response was assessed as formerly defined (JCO 2010). 3 patients achieved CRrenal, 3 PRrenal and 5 MRrenal, yielding an ORRrenal in 11 patients (64.7% of the evaluable and 47.8% of the ITT population). Median time to best renal response was 83 days. 3 of 10 dialysis dependent patients became dialysis independent. Median GFR of evaluable patients increased from 15.2 (range 6.1 – 35.1 ml/min) at baseline to a median best GFR of 28.3 ml/min (range 11.3 – 101.1 ml/min) (p 〈 0.0075). The greatest increase in median GFR was noted in the 5 patients with CR (26.7 to 60.9 ml/min, p 〈 0.024) while in those with nCR/VGPR/PR a less pronounced improvement in GFR (10.6 to 22.4 ml/min, p 〈 0.025) was observed Tolerance: Full documentation of adverse events is presently available in 23 patients. Four patients died, 1 (4.3%) each due to infection and cardiac arrest and 2 (8.7%) with unknown causes of death (sudden death). Grade 3/4 anemia, thrombopenia and leucopenia, were seen in 11 (47.8%), 7 (30.4%), and 3 (13%) patients, respectively. Other common grade 3/4 toxicities were infection/sepsis in 9 (39.1%), and cardiac dysfunction in 5 (21.7%) patients, respectively. Exanthema and fatigue were seen in 2 patients (8.7%), and pulmonary embolism and macula edema in 1 patient each (4.3%). Conclusions: LD showed significant anti-myeloma activity with an overall response rate of 94% in the evaluable and of 69.9% in the ITT population. The greatest proportional decrease in 24 hour proteinuria (86%) was obtained already within the first 4 weeks of therapy while renal recovery occurred with delay only. Improvement in renal function was obtained in 65% of the evaluable and in 48% of the ITT population. Toxicity of the LD regimen with the lenalidomide dose adjusted to GFR was as expected in this high risk population. Updated results will be presented. Disclosures: Ludwig: Celgene: Research Funding, Speakers Bureau.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2011
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. Further information can be found on the KOBV privacy pages