[TerryH]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by TerryH on Tue Nov 08, 2011 10:03 pm

I looked a little bit closer at abstract #305 which I mentioned in my previous posting. It is about the potential new myeloma drug BT062.

I looked at this abstract in particular because there isn't a lot of information out there about BT062.

I'm definitely not an expert, but the data seem a bit underwhelming. I know the patients in the study already failed a number of other treatments, so they are not "easy to treat" patients. Also the drug was tested all by itself, without any dex or Revlimid or anything like that. Also the purpose of the study was to figure out the right dose to use for the drug. So a lot of different doses were tested including doses that people knew were going to be too low.

But if I understand the data correctly, only 3 out of 27 patients had a response to the drug, and two of the responses were minor responses and the other was a partial response.

The researchers felt the results were good enough to test the drug some more, and they are going to present updated results with more data at the meeting.

[STEVEN]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by STEVEN on Wed Nov 09, 2011 12:25 am

Hello,

Here are a few ASH abstracts that piqued my interest...if any of TMB staff have time to comment on these topics that would be great!
Thanks,

Steve


3940 Metascoring and Gene Expression Profiling in Clinical Routine in Multiple Myeloma

http://ash.confex.com/ash/2011/webprogram/Paper40944.html

629 Prediction of Cytogenetic Abnormalities in Multiple Myeloma Based on Gene Expression Profiles
http://ash.confex.com/ash/2011/webprogram/Paper44872.html

807 Are Gene Expression Signatures Treatment Specific?
http://ash.confex.com/ash/2011/webprogram/Paper41552.html

1850 Myeloma Exhibits Dependence on Atypical Glucose Transporters: Targeting MCL-1 Through GLUT4 Inhibition

http://ash.confex.com/ash/2011/webprogram/Paper43613.html

[suzierose]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by suzierose on Tue Nov 15, 2011 7:15 am

This abstract #2945 may be of interest for those with MGUS or Smoldering multiple myeloma:

http://ash.confex.com/ash/2011/webprogram/Paper43076.html

The study is a long-term follow up and discusses the use of anti-cytokine agents to delay progression to multiple myeloma. Reductions in C-reactive protein are important for PFS.

[suzierose]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by suzierose on Sat Nov 26, 2011 6:20 pm

Abstract 4156 on HSCT for Hi-Risk multiple myeloma patients
"Patients with HR myeloma had significantly worse outcome than patients with SR disease, even with novel agents and auto-HCT. In HR patients, maintenance therapy was associated with longer PFS and OS."
http://ash.confex.com/ash/2011/webprogram/Paper43731.html

Abstract 4142 on SCT for Newly DX multiple myeloma patients
"Our interim analysis of an ongoing clinical study suggests that treatment of newly diagnosed multiple myeloma patients with lenalidomide plus low-dose dexamethasone induction followed by upfront ASCT resulted in significantly improved ORR"
http://ash.confex.com/ash/2011/webprogram/Paper41262.html

Abstract 4135
Less than 10% multiple myeloma plasma cells has best outcome for HSCT
http://ash.confex.com/ash/2011/webprogram/Paper44396.html

Abstract 3964
Once a week bortezomib effective
"Once a week bortezomib with dexamethasone regimen is effective and well tolerated even in older patients with significant co-morbidities and should be considered as an important option in multiple myeloma"
http://ash.confex.com/ash/2011/webprogram/Paper39183.html

Abstract 2935
"ARRY-520 is a novel agent with a differentiated MOA relative to other myeloma drugs. ARRY‑520 shows promising evidence of single-agent clinical activity and an acceptable safety profile in heavily pretreated patients with multiple myeloma. Notably, ARRY‑520 has demonstrated activity in patients refractory to both LEN and BTZ, a population with limited treatment options"
http://ash.confex.com/ash/2011/webprogram/Paper40171.html

Abstract 2869 Characterizes Hypodiploid multiple myeloma
"These cases exhibit a high propensity for high-risk gene expression profiles and have a high prevalence of -13, -14, 1q gain and 1p loss as predicted. Given our findings it is likely that hypodiploid is not a separate category but rather the genetic “phenotype” of a more advanced clone."
http://ash.confex.com/ash/2011/webprogram/Paper37381.html

Abstract 1992..Hope for Hi Risk Patients using T cell depleted HDSCT
"these results demonstrate that long-lasting disease control can be achieved with TCD HSCT in pts with multiply relapsed and refractory myeloma including those with high-risk cytogenetics. Administration of calculated, low dose donor lymphocyte infusions can induce complete remission without inducing GvHD. Pts who failed to respond to standard chemotherapy pretransplant responded to reuse of this therapy post TCD HSCT. Based on these results, we are performing a phase II clinical trial at Memorial Sloan-Kettering Cancer Center for pts with relapsed multiple myeloma following auto SCT who had high-risk cytogenetics at diagnosis or at relapse as well as for patients with high-risk cytogenetics in the upfront setting following preceding auto SCT. "
http://ash.confex.com/ash/2011/webprogram/Paper42075.html

Abstract 2963 pomalidomide works very well in refractory multiple myeloma patients
"Pom/dex is remarkably active and well tolerated even in heavily pretreated patients. Responses are durable. Response rates and toxicity are similar between the 2 mg and 4 mg doses."
http://ash.confex.com/ash/2011/webprogram/Paper38348.html

Abstract 2933 BTZ not associated with increased secondary malignancies.
"Btz-based therapy for multiple myeloma does not appear to be associated with an increased risk of either hematologic or solid tumor SPMs, with IRs consistent with SEER data for IRs in the overall US population."http://ash.confex.com/ash/2011/webprogram/Paper39543.html

Abstract 1933 Bendamustine less toxic than Melphan and good for stem cell harvesting.
"Bendamustine is a bifunctional alkylating agent with low toxicity that produces both single- and double-strand breaks in DNA, and shows only partial cross resistance with other alkylating drugs. Treatment of patients with newly diagnosed multiple myeloma using Bendamustine and Prednisone in comparison to Melphalan and Prednisone results in superior complete response rate and prolonged time to treatment failure (Poenisch et al, Res Clin Oncol 132: 205-212;2006). So far, however, reliable information on stem cell toxicity and mobilization of stem cells for autologous stem cell transplantation (SCT) after Bendamustine therapy is missing. "
Conclusion: the stem cell mobilization and autologous SCT is feasible in multiple myeloma patients who have received Bendamustine pretreatment.
http://ash.confex.com/ash/2011/webprogram/Paper42677.html

Abstract 2543...new test for cytogenetics more accurate than FISH
"Based on this preliminary study it is quite compelling that aCGH provides a more accurate biological or prognostic profile in 69% of cases (11/16) vs 19% (3/21) by conventional cytogenetics. Therefore we conclude that the first line standard testing in Multiple myeloma should be aCGH and FISH for the IgH rearrangements and not conventional cytogenetics and FISH."
http://ash.confex.com/ash/2011/webprogram/Paper44716.html

Abstract 3919..Need more than FISH after relapse to detect possible new multiple myeloma clones
"Conventional cytogenetics and cIG-FISH are both necessary in relapsed patient since clonal evolutions develop in many patients which may only be detected by one method. Full evaluation of cIg-FISH including non-poor prognostic factors may be considered since new clones evolve that can be a candidate of follow-up marker and since prognostic factors can change as treatment modality changes."
http://ash.confex.com/ash/2011/webprogram/Paper37102.html

Abstract 885 T cell immunotherapy effective for autologus transplants &works well for multiple myeloma with poor prognosis
"These results showed that T-cells harboring the anti-CD38-CAR definitively eliminated myeloma cells from the patients as well as myeloma cell lines. Anti-CD38 antibodies or antibody variants have been shown to provide therapeutics for the treatment of CD38-positive hematological malignancies. Introduction of the antibody against CD38 may, however, raise concerns of side effects such as an infusion reaction and pharmacological phenomena associated with the long half-life of the antibody. Although antibodies against CD38 have been administered to patients with myeloma or B-cell lymphoma, there has been no report of adverse effects. Indeed, daratumumab, a novel therapeutic human CD38 antibody and humanized monoclonal CD38 antibody, is currently in clinical trials. In this study, we demonstrated that human T-cells with the anti-CD38-CAR were highly cytotoxic against myeloma cells strongly expressing CD38. Improvements to immunotherapy using autologous T-cells transduced with the anti-CD38-CAR might shed further light on the treatment of myeloma patients with a poor prognosis."
http://ash.confex.com/ash/2011/webprogram/Paper37290.html

[suzierose]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by suzierose on Thu Dec 01, 2011 5:41 pm

This sounds like it could be positive news for multiple myeloma as well as both are B-cell driven cancers.

"Importantly, our studies indicate that CFZ causes cytotoxicity in primary CLL cells irrespective of p53 status. This tumor suppressor, which is functional in most CLL patients at the time of diagnosis, is mutated or deleted in at least one allele in approximately 40% of patients with advanced CLL, and p53 pathway dysfunction is associated with resistance to standard therapies and poor overall survival. Therefore, the ability of CFZ to induce apoptosis irrespective of p53 function is of important clinical significance."

http://ash.confex.com/ash/2011/webprogram/Paper44499.html

[suzierose]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by suzierose on Sun Dec 04, 2011 8:51 am

Disease Biology and poor cytogenetics trump treatment intensification. Sequential dual agents recommended over triple agent therapy

IOW's less is more with advanced disease and high-risk genes.

Abstract 1878

http://ash.confex.com/ash/2011/webprogram/Paper42010.html

"This retrospective analysis suggests that a sequence of doublets is associated with improved survival among patients with myeloma as compared to regimens with 3 or more agents in patients with high risk cytogenetics. While the limitations of this retrospective study limit drawing definitive conclusions, it appears that poor cytogenetics and disease biology trumps treatment intensification."

[Dr. Peter Voorhees]

Re: ASH 2011 Annual Meeting - Multiple Myeloma

by Dr. Peter Voorhees on Mon Dec 05, 2011 3:24 am

Dear Suzierose,

These are very interesting data, but I would interpret the results cautiously.

The patients were not randomly assigned to less intensive vs more intensive therapy. As such, there may have been other features of the myeloma beyond cytogenetics that led to the physician choosing a 3-drug over a 2-drug regimen (International Stage, LDH, etc). For example, if a patient was treated with Revlimid (lenalidomide) and dexamethasone at initial diagnosis and had their disease progress substantially on treatment, they very well may have received a 3 or more drug, Velcade (bortezomib)-containing regimen rather than Velcade as a single agent.

In other words, the worse outcome of those treated more aggressively may have absolutely nothing to do with the way the disease was treated, but have more to do with the underlying biology of the disease.

Additionally, there was likely some degree of variability in what intensive treatment was utilized from one patient to the next. Lastly, the number of patients in the study was small.

I think this study emphasizes the need to address this issue more carefully. On-going, prospective randomized trials should help in this regard.

Take care!

Pete V.