ASH 2010 Multiple Myeloma Update – Day Four

Tuesday was the last day of the American Society of Hematology annual meeting in Orlando. The myeloma portion of the conference concluded with one session of talks in the morning about treatments under development.
The first talk was given by Dr. David Siegel of Hackensack University Medical Center in New Jersey. Dr. Siegel presented results from a study of single-agent carfilzomib in myeloma patients who had relapsed multiple times and did not respond to their last treatment (abstract).
Among the 257 evaluable participants, 24 percent achieved at least a partial response, 10 percent a minimal response, and 35 percent stable disease. Importantly, carfilzomib was as effective in patients with unfavorable chromosomal abnormalities (28 percent achieved at least a partial response).
Patients responded to carfilzomib for a median of 8.3 months, and median overall survival was 15.5 months. Disease progression and survival were both dependent on the patient’s response to treatment. Better responses corresponded with longer progression-free survival and survival.
Dr. Siegel said that there were “surprisingly few” blood-related side effects, particularly in terms of severe side effects Twelve percent of patients developed peripheral neuropathy (nerve damage to the extremities that can cause pain and tingling sensations), but less than 1 percent developed severe neuropathy.
Sixteen percent of patients completed all 12 cycles of treatment. The majority of patients who discontinued therapy did so because of disease progression. Nine percent of patients died on study, also mostly due to disease progression.
Dr. Siegel concluded by saying he thought carfilzomib is “an amazing new drug.”
Next, Dr. Paul Richardson from the Dana-Farber Cancer Center in Boston presented a Phase 2 study of elotuzumab, a humanized monoclonal antibody (abstract). Elotuzumab was given in combination with Revlimid (lenalidomide) and low-dose dexamethasone (Decadron) to relapsed/refractory multiple myeloma patients who had not received prior Revlimid therapy.
A total of 63 patients received treatment. Half of the patients received 10 mg/kg elotuzumab, and the other half received 20 mg/kg.
In the low-dose elotuzumab group, 90 percent of participants achieved at least a partial response. In the high-dose group, 72 percent achieved the same response, indicating more favorable results with the lower dose. Median time to response was 2 months.
The median progression-free survival was not yet reached during the 4.9 months of follow-up. However, progression-free survival 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 Revlimid and dexamethasone. The most common elotuzumab-related side effect was fever. Preventative treatment helped to reduce, but not eliminate, the occurrence of injection site reactions. No treatment-related deaths occurred.
The researchers will be going forward with the lower dose of elotuzumab in a Phase 3 trial that will start in early 2011.
Next, Dr. Suzanne Lentzsh presented results of a Phase 1 study of Treanda (bendamustine) in combination with Revlimid and dexamethasone in patients with relapsed or refractory multiple myeloma (abstract). 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, and Revlimid was tested at 5 and 10 mg on days 1 to 21. The doses tested for Revlimid are much lower than what is commonly used for induction treatment in myeloma, causing several questions from the audience about the dosing choices used in the study.
The maximum tolerated dose was 75 mg/m2 Treanda and 10 mg Revlimid plus dexamethasone.
Low blood cell counts were common with this regimen. Almost half of the participants experienced severe low white blood cell counts. Fatigue was the most common side effect that was not blood-related.
Among the 26 study participants, 9 percent achieved a very good partial response, 57 percent a partial response, and 9 percent a minimal response. Half of the patients achieved their best response within 1.8 months.
Median time to progression was 4.3 months, and median 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.
The final myeloma-related presentation of the conference was given by Dr. Irene Ghobrial, who presented results from a Phase 1/2 study of Torisel (temsirolimus) in combination with weekly Velcade (bortezomib) (abstract).
Torisel is approved for the treatment of advanced kidney cancer. A previous study showed that the overall response rate with Torisel alone is 43 percent in myeloma patients.
This study included heavily pre-treated patients, most of whom had relapsed or were resistant to Velcade treatment. Phase 1 of the study included 20 patients, and Phase 2 included 43 patients.
The purpose of Phase 1 was to test the safety of the combination to determine the maximum tolerated doses of both drugs. Velcade was tested at 1.3 and 1.6 mg/m2, and Torisel was tested at 15 and 25 mg. The maximum tolerated doses were 1.6 mg/m2 Velcade 4 out of 5 weeks and 25 mg Torisel weekly.
Almost all patients experienced side effects, especially low platelet counts, which are associated with both Velcade and Torisel. Other types of low blood cell counts were common as well. One patient died due to septic shock.
In the Phase 2 study, 47 percent of patients responded to treatment with 5 percent complete responses, 9 percent very good partial responses, 19 percent partial responses, and 14 percent minimal responses. For patients previously treated with Velcade, responses were predominantly stable disease, with 20 percent achieving a minimal response or better.
Progression-free survival was 5.6 months, and overall survival was 18.8 months.
Dr. Ghobrial said the trial results were promising in heavily pretreated myeloma patients and that the combination of Torisel and Velcade warrants further evaluation.
Earlier this week, The Myeloma Beacon published “as it happens” updates from the fourth day of ASH in this thread in the Beacon’s myeloma forums.
Related Articles:
- Nelfinavir-Velcade Combination Very Active In Advanced, Velcade-Resistant Multiple Myeloma
- ASCO 2018 Update – Expert Perspectives On The Key Multiple Myeloma-Related Oral Presentations
- bb2121 Continues To Impress As Potential New Multiple Myeloma Therapy (ASCO 2018)
- Nelfinavir Shows Only Limited Success In Overcoming Revlimid Resistance In Multiple Myeloma Patients
- Eyelid-Related Complications Of Velcade Therapy: New Insights And Recommendations
Julie
Thank you, and all at the MB, for four days of excellent reporting from the ASH conference in Orlando. I join all MM patients in following the exciting news as it further unfolds in the Beacon.
Sean M.
Excellent coverage of the ASH conference Julie. The use of layman language combined with disclosure of the major statistics provided an understandable format for the MM patients. Thanks for the clear communications geared to the technical level of your audience.
Thanks, Sean and John! All of us here at The Myeloma Beacon are glad to hear that you found our coverage helpful and easy to understand.
Julie, thank you from our group also.
Great job!!!! Peter
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