This forum thread can be used to discuss the proceedings of the American Society of Hematology (ASH) meeting that take place on Day 4 (Tuesday, December 7) of the conference. Feel free to use this space to highlight interesting abstracts, summarize the presentations as they happen, ask questions, and discuss any relevant topics. Everyone is encouraged to participate.
Feel free to also check out the discussions for Day 1, Day 2, and Day 3.
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Re: ASH 2010 Multiple Myeloma Discussion - Day 4
Dr. David Siegel just presented results from a study of single-agent carfilzomib in heavily pretreated relapsed/refractory myeloma patients. 266 patients were treated with 20 mg/m2 carfilzomib for the first cycle, and based on those results were then treated with 27 mg/m2 for all other cycles of treatment.
Responses included 24% overall response, 10% minimal response, and 35% stable disease. Duration of response was 8.3 months. In patients with unfavorable chromosomal abnormalities, overall response was 28%, so they responded as well as standard-risk patients.
Progression-free survival was 3.7 months: 11.6 months for patients achieving a VGPR, 8.8 months for PR, 8.1 months for MR, 3.6 months for SD, and 0.5 months for progressive disease.
Overall survival was 15.5 months: median survival has not yet been reached for patients achieving a VGPR, PR, or MR, 12.7 months for SD, and 5.3 months for progressive disease.
In regard to hematological side effects, Dr. Siegel said that there were “surprisingly few,” especially in regard to severe side effects. Only two patients (0.8%) developed severe peripheral neuropathy; 12% developed some amount of neuropathy.
16% of patients completed all 12 cycles. The majority of patients who discontinued therapy did so because of disease progression. 9% of patients died on study, mostly due to disease progression.
Dr. Siegel concluded by saying he thought carfilzomib is “an amazing new drug.”
Responses included 24% overall response, 10% minimal response, and 35% stable disease. Duration of response was 8.3 months. In patients with unfavorable chromosomal abnormalities, overall response was 28%, so they responded as well as standard-risk patients.
Progression-free survival was 3.7 months: 11.6 months for patients achieving a VGPR, 8.8 months for PR, 8.1 months for MR, 3.6 months for SD, and 0.5 months for progressive disease.
Overall survival was 15.5 months: median survival has not yet been reached for patients achieving a VGPR, PR, or MR, 12.7 months for SD, and 5.3 months for progressive disease.
In regard to hematological side effects, Dr. Siegel said that there were “surprisingly few,” especially in regard to severe side effects. Only two patients (0.8%) developed severe peripheral neuropathy; 12% developed some amount of neuropathy.
16% of patients completed all 12 cycles. The majority of patients who discontinued therapy did so because of disease progression. 9% of patients died on study, mostly due to disease progression.
Dr. Siegel concluded by saying he thought carfilzomib is “an amazing new drug.”
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
Next, Dr. Paul Richardson presented a Phase 2 study of elotuzumab in combination with Revlimid and low dose dexamethasone (Rd) in relapsed/refractory patients. Elotuzumab is a humanized monoclonal antibody that was given on a weekly basis with Rd until progression or unacceptable tolerability.
Patients previously treated with Revlimid were excluded.
Half of the patients received 10 mg/kg elotuzumab, and the other half received 20 mg/kg.
90% of participants achieved at least a PR for the 10 mg/kg dose of elotuzumab and 72% for 20 mg/kg, indicating more favorable results with the lower dose. Median time to response was 2 months, and the median PFS was not yet reached during the 4.9 months of follow-up. PFS was more than 1 year in the Phase 1 trial.
Side effects were manageable in the majority of patients and were predominantly side effects seen with Rd. The most common Elotuzumab-related side effect was fever. Prophylactic treatment cut injection site reactions in half. No treatment-related deaths occurred.
The researchers will be going forward with the 10 mg/kg dose of elotuzumab in a Phase 3 trial that will start in early 2011.
Patients previously treated with Revlimid were excluded.
Half of the patients received 10 mg/kg elotuzumab, and the other half received 20 mg/kg.
90% of participants achieved at least a PR for the 10 mg/kg dose of elotuzumab and 72% for 20 mg/kg, indicating more favorable results with the lower dose. Median time to response was 2 months, and the median PFS was not yet reached during the 4.9 months of follow-up. PFS was more than 1 year in the Phase 1 trial.
Side effects were manageable in the majority of patients and were predominantly side effects seen with Rd. The most common Elotuzumab-related side effect was fever. Prophylactic treatment cut injection site reactions in half. No treatment-related deaths occurred.
The researchers will be going forward with the 10 mg/kg dose of elotuzumab in a Phase 3 trial that will start in early 2011.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
Dr. Suzanne Lentzsh presented results of a Phase 1 study of Treanda (bendamustine) in combination with Revlimid and dexamethasone in relapsed and refractory myeloma patients. Treanda is an alkylating agent approved to treat two types of leukemias. The goal of this study was to determine the maximum tolerated doses of Treanda and Revlimid in this combination.
Treanda was tested at 75 and 100 mg/m2 on days 1 and 2 of a 28 day cycle. Revlimid was tested at 5 and 10 mg days 1-21, doses much lower than what is commonly used in myeloma. The maximum tolerated dose was 75 mg/m2 Treanda and 10 mg Revlimid.
Low blood counts were common, including 48% of patients experiencing severe low white blood cell counts. Fatigue was the most common non-hematological side effect (12%).
Responses included: 9% VGPR, 57% PR, 9% MR, 17% SD, 9% PD. The time to best response was 1.8 months.
Median time to progression was 4.3 months, and overall survival was 10.9 months.
Dr. Lentzsh said that this combination may be particularly well suited for older patients or those with peripheral neuropathy.
There were several questions from the audience about the dosing choices used in the study.
Treanda was tested at 75 and 100 mg/m2 on days 1 and 2 of a 28 day cycle. Revlimid was tested at 5 and 10 mg days 1-21, doses much lower than what is commonly used in myeloma. The maximum tolerated dose was 75 mg/m2 Treanda and 10 mg Revlimid.
Low blood counts were common, including 48% of patients experiencing severe low white blood cell counts. Fatigue was the most common non-hematological side effect (12%).
Responses included: 9% VGPR, 57% PR, 9% MR, 17% SD, 9% PD. The time to best response was 1.8 months.
Median time to progression was 4.3 months, and overall survival was 10.9 months.
Dr. Lentzsh said that this combination may be particularly well suited for older patients or those with peripheral neuropathy.
There were several questions from the audience about the dosing choices used in the study.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
The final presentation of the session, and the final myeloma-related presentation of the conference, was given by Dr. Irene Ghobrial. Dr. Ghobrial presented results from a Phase 1/2 study of Torisel (temsirolimus) in combination with weekly Velcade.
Torisel is approved for the treatment of advanced kidney cancer. A previous study showed that the overall response rate with Torisel alone is 43% in myeloma patients.
In this study, 20 patients were treated in Phase 1 and 43 patients in Phase 2. Participants were heavily pre-treated with a median of 4-5 lines of previous therapy. 81% had received Velcade previously, and 63% were refractory to their last Velcade treatment.
Velcade was tested at 1.3 and 1.6 mg/m2, and Torisel was tested at 15 and 25 mg. The maximum tolerated dose was 1.6 mg/m2 Velcade and 25 mg Torisel.
Almost all patients experienced side effects, especially thrombocytopenia, which is associated with both Velcade and Torisel. Other cytopenias were common as well. 1 patient died due to septic shock.
Responses were the following: 5% CR, 9% VGPR, 19% PR, 14% MR, and 44% SD (47% achieved at least an MR). For patients previously treated with Velcade, responses were predominantly SD (20% achieved at least an MR).
PFS was 5.6 months, time to progression was 5.7 months, overall survival was 18.8 months, and the 12 month overall survival was 57%.
Dr. Ghobrial said these results were promising in heavily pretreated patients and that the combination warrants further evaluation.
Torisel is approved for the treatment of advanced kidney cancer. A previous study showed that the overall response rate with Torisel alone is 43% in myeloma patients.
In this study, 20 patients were treated in Phase 1 and 43 patients in Phase 2. Participants were heavily pre-treated with a median of 4-5 lines of previous therapy. 81% had received Velcade previously, and 63% were refractory to their last Velcade treatment.
Velcade was tested at 1.3 and 1.6 mg/m2, and Torisel was tested at 15 and 25 mg. The maximum tolerated dose was 1.6 mg/m2 Velcade and 25 mg Torisel.
Almost all patients experienced side effects, especially thrombocytopenia, which is associated with both Velcade and Torisel. Other cytopenias were common as well. 1 patient died due to septic shock.
Responses were the following: 5% CR, 9% VGPR, 19% PR, 14% MR, and 44% SD (47% achieved at least an MR). For patients previously treated with Velcade, responses were predominantly SD (20% achieved at least an MR).
PFS was 5.6 months, time to progression was 5.7 months, overall survival was 18.8 months, and the 12 month overall survival was 57%.
Dr. Ghobrial said these results were promising in heavily pretreated patients and that the combination warrants further evaluation.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
Do you have any idea why they excluded patients previously treated with Velcade in the elotuzumab trial?
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Perseverance - When were you/they diagnosed?: 2010
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
Hi Perseverance,
Good question. I thought that seemed strange as well. I looked into it further and it was actually patients previously treated with Revlimid who were excluded, which makes more sense since elotuzumab was given in combination with Revlimid and dexamethasone in this study. Thanks for checking on that!
Good question. I thought that seemed strange as well. I looked into it further and it was actually patients previously treated with Revlimid who were excluded, which makes more sense since elotuzumab was given in combination with Revlimid and dexamethasone in this study. Thanks for checking on that!
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASH 2010 Multiple Myeloma Discussion - Day 4
julie.shilane wrote:Hi Perseverance,
Good question. I thought that seemed strange as well. I looked into it further and it was actually patients previously treated with Revlimid who were excluded, which makes more sense since elotuzumab was given in combination with Revlimid and dexamethasone in this study. Thanks for checking on that!
Thanks very much. This makes sense.
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Perseverance - When were you/they diagnosed?: 2010
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