This forum thread can be used to discuss the proceedings of the American Society of Clinical Oncology that take place on Day 3 (Sunday, June 5) 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 & 2, and Day 4.
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Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
This morning begins with a presentation session in which myeloma researchers will talk about a number of recent studies on the topics of Revlimid (lenalidomide) and secondary cancers, myeloma bone disease, and new drugs that are being developed for the treatment of multiple myeloma.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
The first speaker of the morning session was Dr. Antonio Palumbo from the University of Torino in Italy. He spoke about secondary cancers in his Revlimid maintenance study in newly diagnosed elderly myeloma patients. A third of the patients were treated with melphalan (Alkeran) and prednisone (MP), a third also received Revlimid at the same time (MPR), and the final third received the three-drug combination followed by long-term Revlimid maintenance therapy (MPR-R). As of February 28, there were 4 reported cases of secondary cancers in the MP group, 9 in the MPR group, and 12 in the MPR-R group. The differences were mainly due to the blood cancers myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). All patients who had complex cytogenetics (chromosomal abnormalities) were in the MPR and MPR-R groups. These patients were at significantly higher risk of developing a secondary cancer, which may explain, at least in part, the discrepancies in secondary cancers in the three treatment groups. The rate of secondary cancers in this study was similar to rates reported in other studies. Dr. Palumbo analyzed the relative risk of developing a secondary cancer versus disease progression/death and concluded that the benefit-risk ratio for Revlimid was favorable.
He then presented results from a retrospective study of 9 clinical trials. He compared the risk of secondary cancers in patients receiving Revlimid with an alkylating agent (CRD/CPR, MPR, ASCT followed by Revlimid maintenance) to patients who did not receive Revlimid (VMPT, MP, MPT, VMP). The results showed that Revlimid significantly reduces the risk of death from myeloma but also increases the risk of secondary cancer. In the general population, 2 percent of people 65 to 74 years old develop cancer each year. The rate of myeloma patients treated with Revlimid in this analysis was lower than expected based on the general population.
Dr. Palumbo concluded that Revlimid when used with melphalan increases the rate of secondary cancers, but Revlimid does not increase the rate when used with dexamethasone. Regardless, Dr. Palumbo said that the rate of secondary cancers is low and that the benefit-risk ratio is strongly in favor of continuous use of Revlimid for newly diagnosed myeloma patients.
He then presented results from a retrospective study of 9 clinical trials. He compared the risk of secondary cancers in patients receiving Revlimid with an alkylating agent (CRD/CPR, MPR, ASCT followed by Revlimid maintenance) to patients who did not receive Revlimid (VMPT, MP, MPT, VMP). The results showed that Revlimid significantly reduces the risk of death from myeloma but also increases the risk of secondary cancer. In the general population, 2 percent of people 65 to 74 years old develop cancer each year. The rate of myeloma patients treated with Revlimid in this analysis was lower than expected based on the general population.
Dr. Palumbo concluded that Revlimid when used with melphalan increases the rate of secondary cancers, but Revlimid does not increase the rate when used with dexamethasone. Regardless, Dr. Palumbo said that the rate of secondary cancers is low and that the benefit-risk ratio is strongly in favor of continuous use of Revlimid for newly diagnosed myeloma patients.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
Dr. Adrianna Rossi from the Weill Cornell Medical College and New York Presbyterian Hospital spoke next about secondary malignancies after 6 years follow-up in 72 newly diagnosed myeloma patients treated with clarithromycin (Biaxin), Revlimid, and dexamethasone (BiRD). The regimen was very effective with an overall response of 90 percent (53 percent complete response, 21 percent very good partial response, 17 percent partial response). At four years, the overall survival was 82 percent. 16 percent of the participants developed a second cancer after an average of 31 cycles of Revlimid. The secondary cancers included skin (6), colon (2), prostate (1), pancreas (1), and metastatic melanoma (1). No patients developed MDS or AML. The secondary cancers were not associated with specific chromosomal abnormalities, stem cell transplant, patients still on Revlimid, or gender. The frequency of secondary cancers in this study (2.85 percent per year) was similar to cancer rates in non-myeloma individuals of similar age (2.1 percent per year). Dr. Rossi pointed out that there are some limitations to her analysis: the study included a small number of patients, it was a retrospective analysis, there was no bone marrow surveillance looking for MDS.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
Dr. Ruben Niesvizky from Weill Cornell Medical College then spoke about secondary cancers in two trials in which relapsed / refractory myeloma patients were treated with Revlimid and dexamethasone or dexamethasone alone until disease progression. With a median follow-up time of 48 months, 8 secondary cancers (including 2 cases of MDS) were reported for the Revlimid-dexamethasone arm, compared to 2 secondary cancers for the dexamethasone alone arm. No cases of AML were reported. Time to progression or development of a second cancer was 12.4 months for Revlimid-dexamethasone versus 4.6 months for dexamethasone alone. Taking into account that Revlimid plus dexamethasone significantly extended survival (overall survival of 31 months compared to 24 months) and that older ages are associated with a higher risk of cancer, observed secondary cancer rates in both treatment arms were comparable to expected rates based on the general population. Dr. Niesvizky pointed out that there are some limitations in regard to secondary cancer data: reporting is not required after patients progress or discontinue therapy so there may be imbalances in reporting if time to progression is significantly different between the arms, and early stage secondary cancers may not be detected in patients who are dying from myeloma. He concluded based on his analyses that the benefit-risk ratio for Revlimid remains strongly positive.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
These three talks were then followed-up by a discussion led by Dr. Ola Landgren from the National Cancer Institute. Dr. Landgren reviewed several studies from over the years that showed a number of myeloma patients have developed AML after being treated with melphalan. He then talked about the three current Revlimid maintenance studies that have all shown a higher rate of secondary cancers in the Revlimid arms. Despite patients in the Revlimid arms having a higher risk of developing a second cancer, overall survival in one of these studies was significantly longer for the Revlimid group than the placebo group (90 percent versus 83 percent survival at 28 months). Dr. Landgren stressed the need to understand the mechanisms causing these second cancers and to be able to identify which myeloma patients are most likely to develop a second cancer.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
The next section of talks was about bisphosphonates for myeloma bone disease. All of the talks centered around a study comparing Zometa (zoledronic acid) with Bonefos (clodronate), which is not approved for use in the United States.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
Dr. Gareth Morgan from the Royal Marsden Hospital in London gave the first talk. His talk discussed whether all myeloma patients should be treated with bisphosphonates, or only those who have already developed bone disease. About 30 percent of myeloma patients do not have any bone disease at the time of their myeloma diagnosis. The results showed that Zometa reduces the risk of a skeletal-related event (vertebral fracture, other fracture, spinal cord compress, radiation or surgery for bone disease, etc.), regardless of whether the patient had bone disease. This supports initiating Zometa treatment in all newly diagnosed myeloma patients, regardless of bone disease status.
Additional analysis showed a survival benefit for Zometa compared to Bonefos in patients with bone disease, but not those without bone disease. The results also showed that Zometa was significantly more effective at reducing skeletal-related events in low-risk myeloma patients, but there was not much difference between the two therapies in high-risk patients.
Additional analysis showed a survival benefit for Zometa compared to Bonefos in patients with bone disease, but not those without bone disease. The results also showed that Zometa was significantly more effective at reducing skeletal-related events in low-risk myeloma patients, but there was not much difference between the two therapies in high-risk patients.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
Dr. Faith Davies from the Institute of Cancer Research in the United Kingdom spoke about the timing of the benefits of Zometa. Patients who received Zometa had a significant survival benefit (5.5 months) over those who received Bonefos. The survival benefit was first apparent during month two of treatment and was especially profound during the first four months, supporting early use of Zometa for potential anticancer effects in patients with newly diagnosed myeloma. Zometa also significantly reduced the risk of skeletal-related events throughout the five years of therapy, supporting ongoing use to prevent complications of bone disease.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
Re: ASCO 2011 Multiple Myeloma Discussion - Day 3
These two talks were then followed-up by a discussion led by Dr. David Roodman from the University of Pittsburgh Medical Center. Dr. Roodman pointed out that Zometa is a much more potent bisphosphonate than Bonefos. Although the current study indicates Zometa has anticancer effects, a previous study showed that Zometa did not affect time to progression in smoldering myeloma patients. In a discussion of whether newly diagnosed myeloma patients without bone disease should receive Zometa treatment, Dr. Roodman repeated the results that Zometa does not have a survival benefit in this patient population, but it does reduce the risk of skeletal-related events. At the same time, it also increases the risk of osteonecrosis of the jaw (ONJ, loss of blood supply to the jaw that causes jawbone death). He concluded that the clinical-economic benefit of treating all myeloma patients with Zometa still needs to be determined. He then discussed whether Zometa should be continued beyond two years. He said that a long-term benefit of Zometa has been shown. However, longer treatment increases the risk of ONJ, especially around three years of treatment. He pointed out that good dental surveillance has significantly decreased the rate of ONJ.
Dr. Roodman said that several questions remain at this time:
Would using other regimens that target bone disease (such as Velcade-based regimens) have benefits similar to Zometa?
Do patients without bone disease need less frequent administration of Zometa or other bisphosphonates with lower risk of ONJ?
Will the lower risk of ONJ with dental prophylaxis (preventative treatment) remain low for patients receiving longer Zometa treatment?
Several comments and questions were also brought up during the question and answer session that followed:
Dr. Rafael Fonseca from the Mayo Clinic said that he is increasingly convinced that Zometa does not have a significant survival benefit, especially now that Dr. Morgan showed no survival benefit for high-risk myeloma patients.
Another physician asked whether the data really show that there is a benefit to continuing Zometa versus stopping therapy. The current analyses compare skeletal-related events and survival for patients who continue on Zometa or Bonefos, but they do not compare this to those who discontinue bisphosphonate therapy after a given period. Dr. Davies pointed out that the number of patients discontinuing therapy at a given time point is low and will require modeling that is currently underway.
Another physician asked how long bisphosphonate therapy should be continued in patients who achieve a complete response after their anti-myeloma therapy, given that their bone disease should also be under better control at that point. Dr. Morgan said that this is an important question that needs to be addressed. Dr. Roodman said that Dr. Davies’ charts support long-term therapy, but ONJ needs to be better controlled.
Dr. Roodman said that several questions remain at this time:
Would using other regimens that target bone disease (such as Velcade-based regimens) have benefits similar to Zometa?
Do patients without bone disease need less frequent administration of Zometa or other bisphosphonates with lower risk of ONJ?
Will the lower risk of ONJ with dental prophylaxis (preventative treatment) remain low for patients receiving longer Zometa treatment?
Several comments and questions were also brought up during the question and answer session that followed:
Dr. Rafael Fonseca from the Mayo Clinic said that he is increasingly convinced that Zometa does not have a significant survival benefit, especially now that Dr. Morgan showed no survival benefit for high-risk myeloma patients.
Another physician asked whether the data really show that there is a benefit to continuing Zometa versus stopping therapy. The current analyses compare skeletal-related events and survival for patients who continue on Zometa or Bonefos, but they do not compare this to those who discontinue bisphosphonate therapy after a given period. Dr. Davies pointed out that the number of patients discontinuing therapy at a given time point is low and will require modeling that is currently underway.
Another physician asked how long bisphosphonate therapy should be continued in patients who achieve a complete response after their anti-myeloma therapy, given that their bone disease should also be under better control at that point. Dr. Morgan said that this is an important question that needs to be addressed. Dr. Roodman said that Dr. Davies’ charts support long-term therapy, but ONJ needs to be better controlled.
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Julie Shilane - Name: Julie Shilane, Beacon Staff
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