[SimonChai]

Thanks for the info, Jack. The haplo transplant sounds too much like a transplant to me but I’m grateful to know about it.

No, I’m sticking with Vidaza/Dacogen. I consulted with the folks at Hutch a few months ago and they agreed with the path I’m on. The MDS/leukemia expert there said that he doesn’t think induction chemo would work in my case (my feeling also) and my only other option would be a Phase One trial. Since I know the limitations of animal research, I’m staying away from a Phase One and there don’t seem to be any promising Phase Twos or Threes that I qualify for.

[SimonChai]

Hi, Jack. Thanks for your email.

No, I’m not having another transplant. No one suggested it and I frankly couldn’t handle another one.

I’ve had a rough four months since my relapse–in and out of the hospital, lots of fevers, more and more transfusion-dependent, etc.

I just finished round 5 of Vidaza and still hoping it’ll kick into high gear. My doc wants to switch me to Dacogen in January if it doesn’t.

No, I don’t know what’s happening at Hopkins and don’t even know what a haplo is. What do you know about it?

How are you? It’s great you’ve stayed on this list as you are so knowledgeable.

All the best,
Simon

[SimonChai]

Hi,Kirby and Judith:

Thanks for your thoughts on Vidaza injections and infusions. I don’t have a port and only one good arm (which recently was swollen after an IV with Vidaza slipped from the vein into the tissue) so that’s why my doc switched me to injections. But I also don’t have much fat so maybe that’s why they hurt so much. Anyway, none of this is as important as whether or not the Vidaza is working. Still have my fingers crossed on that one.

[SimonChai]

I have had two rounds so far. I thought it was the Aranesp but you’re right, it could be the Vidaza ;(

[SimonChai]

I agree with Julie. I believe induction is always inpatient–at least when I had induction two years ago, it was inpatient (at Fred Hutch). And when my doctor just recently offered it to me, it was inpatient (at George Washington University.)

[SimonChai]

Hi, Jack. I don’t know if I responded to your last comment to me. Thanks so much for cheering me on!

I have two sets of questions:

* I wanted to ask about your wife’s MDS. As you may remember, I also got MDS from breast cancer chemo. I’m working on an article on this topic for my blog. Do you mind my asking a few questions? I would love to know if the doctors know which chemo caused the MDS. I also would like to know if you or she know whether her doctor reported it to the drug company. I have a suspicion that more women are developing MDS than is currently known.
* Can you tell me more about the “Natural Killer Cello haplo” that you mentioned?

Thank you!

[SimonChai]

Hi, Sandy. Thanks for your email and your kind words. I chose the double cord blood transplant because I couldn’t find a bone marrow donor and the doctors said I would have a year or less to live otherwise. My original diagnosis was MDS-RAEB with loss of chromosome damage including loss of chromosome 7 and inversion of #3 (I also got the MDS from previous chemo.) No, I’m not sorry I did the transplant even though it was so difficult. Despite the cGVHD I’ve dealt with for the past two years, I’ve appreciated the time and have been able to work, contribute to causes I care about, and enjoy myself. Yes, I do have a blog; it’s http://schaitowitz.blogspot.com/

Thanks again for your good wishes. I’m sorry that your husand isn’t eligible for the transplant. What sort of treatment is he undergoing?

[SimonChai]

Here’s the news release distributed by Vidaza’s manufacturer.

VIDAZA(R) Receives Expanded FDA Approval to Include Overall Survival in Higher-Risk MDS

First and only drug to significantly extend survival for patients with higher-risk MDS i First drug approved by FDA for treatment of all MDS risk categories i First drug to achieve a transfusion independence rate of greater than 40 percent across all MDS risk categories i First MDS drug approved with multiple routes of administration (SC and IV)

Last update: 7:30 a.m. EDT Aug. 21, 2008

SUMMIT, N.J., Aug 21, 2008 (BUSINESS WIRE) — Celgene Corporation (CELG:71.75, -0.59, -0.8%) today announced VIDAZA (azacitidine) received expanded U.S. Food and Drug Administration (FDA) approval to reflect new overall survival achieved in the AZA-001 survival study of patients with higher-risk myelodysplastic syndromes (MDS). This expanded indication supplements the 2004 FDA authorization of VIDAZA as the first therapy approved in the U.S. for the treatment of patients with all five French American British (FAB) subtypes of MDS. VIDAZA is also the first and only drug to show a statistically significant and clinically meaningful extension of survival in higher-risk MDS patients.

“The overall survival detailed in the expanded FDA approval of VIDAZA is extremely important for patients with higher-risk MDS, a group with limited options and median survival of about 15 months with classical treatments,” said Pierre Fenaux, M.D., Ph.D. of the Universite of Paris and lead investigator of the AZA-011 survival trial. “VIDAZA, however, is also effective across a broad range of MDS subgroups, including WHO-classified AML patients, the largest subgroup in our study.”

The approval is based upon the significant improvement in overall survival achieved in the VIDAZA survival trial (AZA-001), the largest, international randomized Phase III controlled study ever conducted in higher-risk MDS. The median overall survival for patients treated with VIDAZA in the study was 24.5 months compared to 15 months for conventional care regimens (CCR), demonstrating a survival benefit of over 9 additional months with a stratified log-rank p-value of 0.0001. The hazard ratio describing this treatment effect was 0.58 (95 percent confidence interval of 0.43 to 0.77). The extension of survival was seen across the relevant patient subgroups including those greater than 65 years, as well as poorer prognostic groups such as those with World Health Organization (WHO) classified acute myelogenous leukemia (AML), which formed 31 percent of the enrolled patients, and patients with poor risk cytogenics. In the trial, the two-year survival rate for patients with higher-risk MDS treated with VIDAZA was almost doubled with 50.8 percent compared to 26.2 percent for CCR. Patients treated with VIDAZA received treatment for a median of nine cycles.

“The clinical data from this randomized Phase III controlled study demonstrated that patients with higher-risk MDS treated with VIDAZA benefit from a significant survival advantage, a critical measure of a drug’s effectiveness,” said Lewis Silverman, M.D., of the Mount Sinai Medical Center in New York City. Dr. Silverman was the lead author and Principal Investigator for the original VIDAZA approval study (CALGB 9221) and an author and investigator of the international AZA-001 survival trial. “Additionally, the efficacy and safety profile of VIDAZA allows for long-term therapy in patients with higher-risk MDS, underscoring the ability to treat until disease progression for optimal survival benefit.”

In the AZA-001 study, the most commonly occurring adverse reactions for patients with higher-risk MDS receiving VIDAZA were thrombocytopenia (69.7%), neutropenia (65.7%) and anemia (51.4%).

“This decision by the FDA reflects the unprecedented survival advantage demonstrated by VIDAZA in patients with higher risk MDS,” said Mohamad A. Hussein, M.D., Global Head, Medical Affairs, Hematology of Celgene, formerly of the H. Lee Moffitt Cancer Center and Research Institute. “VIDAZA is another example of Celgene developing novel therapies for critical blood diseases that are enabling patients to live for years, rather than weeks and months. Today’s decision strengthens our Company’s ability to deliver VIDAZA and our other therapies to patients in need around the world.”

IMPORTANT SAFETY INFORMATION
— VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors.
— In Study 1 (a randomized, open-label, controlled trial carried out in 53 U.S. sites compared the safety and efficacy of subcutaneous VIDAZA plus supportive care with supportive care alone (“observation”) in patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS)) and Study 2 (a multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML), the most commonly occurring adverse reactions by SC route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%), and ecchymosis (30.5%) Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), and malaise (10.9%). In Study 3, the most common adverse reactions by IV route also included petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia (31.3%).
— In Study 4 (the AZA-001 survival trial), the most commonly occurring adverse reactions were thrombocytopenia (69.7%), neutropenia (65.7%), anemia (51.4%), constipation (50.3%), nausea (48.0%), injection site erythema (42.9%), and pyrexia (30.3%). The most commonly occurring Grade 3/4 adverse reactions were neutropenia (61.1%), thrombocytopenia (58.3%), leukopenia (14.9%), anemia (13.7%) and febrile neutropenia (12.6%).
— Because treatment with VIDAZA is associated with anemia, neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle.
— Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
— VIDAZA may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be apprised of the potential hazard to the fetus. Men should be advised not to father a child while receiving VIDAZA.
— Nursing mothers discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.
About VIDAZA
In May 2004, VIDAZA became the first drug approved by the FDA for the treatment of patients with Myelodysplastic Syndromes (MDS). The FDA approved VIDAZA, the first in a new class of drugs called demethylation agents, for treatment of all five MDS subtypes, which include both low-risk and high-risk patients. These MDS FAB subtypes include according to the French American British (FAB classification: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).
About Epigenetics
VIDAZA is an epigenetic compound believed to exert antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of VIDAZA required for maximum
inhibition of DNA methylation in-vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of VIDAZA cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non- proliferating cells are relatively insensitive to VIDAZA. VIDAZA was approved for IV administration in January 2007.
About Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a group of hematologic malignancies that affect approximately 300,000 people worldwide. Myelodysplastic syndromes occur when blood cells remain in an immature or “blast” stage within the bone marrow and never develop into mature cells capable of performing their necessary functions. Eventually, the bone marrow may be filled with blast cells suppressing normal cell development. According to the American Cancer Society, 10,000 to 20,000 new cases of MDS are diagnosed each year in the United States. Patients with higher risk MDS have a median survival of only approximately 6-12 months. MDS patients must often rely on blood transfusions to manage symptoms of anemia and fatigue and may develop life-threatening iron overload and/or toxicity from frequent transfusions, thus underscoring the critical need for new therapies targeting the cause of the condition rather than simply managing its symptoms.
About Celgene
Celgene Corporation, based in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company’s website at http://www.celgene.com.
This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company’s control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company’s filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.
SOURCE: Celgene Corporation
Celgene Corporation
David Gryska, 908-673-9059
Sr. Vice President and Chief Financial Officer
OR
Brian P. Gill, 908-673-9530
Vice President,
Corporate Communications

Copyright Business Wire 2008

[SimonChai]

Hi, Jack. Yes, I remember you as well. Please call me Simon. Thanks for your email.

Unfortunately, I’ve relapsed. My doctor says I’m on the borderline between MDS/leukemia. The transplant worked well (other than cGVHD) for just over two years and then suddenly the chromosome damage returned to my old immune system–just about two months ago. I had been 100 percent engrafted until then.
Sounds like your wife has been through a lot as well. Horrible diseases we are dealing with!

Simon C.http://schaitowitz.blogspot.com/

[SimonChai]

Hello everyone. I see there are some folks who are contemplating cord blood transplants and I wanted to offer any bit of help I could in making decisions. I had a double-cord transplant in April 06 at Fred Hutch for chemo-induced MDS. It wasn’t the expanded cell trial, just a double-cord, following Univ of Minnesota’s protocol. I was in remission (dealing with lots of GVHD issues but in pretty decent shape) until just recently. I’m on medical leave doing Vidaza (my second time–it got me to transplant in 06) so I’m on email a lot. If I can help in any way, let me know. All the best to everyone. I used to participate in this list before my transplant.

[SimonChai]

Dear Celebrations: I am not an expert on your question, but in my case, the doctors recommended a transplant because they said that my MDS would evolve into leukemia and that I had probably had only a year to live. In my case, they said the transplant was the only curative approach–if it worked.

[SimonChai]

Hi, Jack. Please call me Simon!

My blast count before I went to transplant was about 2 percent. Unfortunately, I had to do induction chemo and a round of Vidaza to get my blast count that low. (They wouldn’t do the transplant unless my blast count was 5 percent or under as I was part of a study that had those requirements.) When I first was diagnosed, it was around 5 percent (I think) but it creeped up to 13 percent just before I was supposed to have the transplant. So, then I did induction chemo but it didn’t work well enough. My blast count was still too high–around 7 percent. So, then I did a round of Vidaza and Enbrel (also a study) and my count went down to around 2 percent.

[SimonChai]

Hi, Jack. Nice to hear from you. Sounds like you and your wife are in good hands at Sloan-Kettering.

To answer your questions:

* I was 53 at the time of the transplant.
* I was in the hospital about two and a half weeks for the transplant (although I spent another three weeks in the hospital before and after the transplant for induction chemo and other reasons).
* I ended up with GVHD of the gut and mouth. The mouth GVHD is very mild and I don’t treat it but my gut GVHD has been a problem. I haven’t been able to get off Prednisone and Cyclosporin because of it. Whenever I’ve tried to taper off of these drugs, the GVHD comes back. But I’m on another taper now and so far, so good. I am keeping my fingers crossed.
* The first few months after the transplant, I had my blood taken frequently. I can’t remember exactly how much–maybe a few times a week. Now, 10 months post-transplant — I only go in for blood checks every two weeks.

Please let me know if you have any other questions. Is your wife having a reduced-intensity transplant? I wish you the best! I will be thinking of you both.

[SimonChai]

Zoe: Could you afford to see Dr. Raza even though you’re in Ohio? I know she takes out-of-state patients as I considered seeing her once and I live in DC.

Simon C.

[SimonChai]

Thank you so much, Sarah, for your kind words. Yes, it’s true. I have been blessed and believe me, I try to remember to appreciate my good fortune every day.

I am so sorry for what you and your husband endured. What an awful disease MDS is.

But I’m glad you are still on our list as I also think about you and your husband. It’s so good to hear from you.

[Author]

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