When the cancer comes back

BY GUEST BLOGGER | FEBRUARY 3, 2012

As my sister drove me to the hospital on a wintery night after my leukemia returned for the second time, I said over and over, "I'm never going to see my grandchildren. I'm never going to see my grandchildren."

I thought I was at the end of the line. I had already had three bone marrow transplants, each preceded by intensive chemotherapy, when my doctor told me that I had relapsed again.

On the night of Dec. 21, 2008, I had felt a little better after feeling sick for several days. My daughter and I were making cookies. Then I fell to the floor.

After she helped get me to bed, I took my temperature and discovered that I had a fever. I called Dr. Edwin Alyea, my physician at the Dana-Farber Cancer Institute, and he said he was sorry to tell me on the phone, but the pathology report on my latest bone marrow biopsy showed that I had relapsed.

He said he would understand if I didn't want to go through treatment again, but if I wanted to proceed, he had an idea for a new regimen.

I wanted to live. I wanted to see my three children, 16, 19 and 23, continue growing up into the wonderful adults I knew they would be.

I wanted to walk my Labrador retriever, play tennis, run a road race and return to my job as a newspaper reporter.

Dr. Alyea had said to go to the emergency room and get admitted, and then he would come see me and there would be a plan. It turns out I had pneumonia, so they had to treat that before they did anything else.

I was first diagnosed with acute myeloid leukemia in 2003 after feeling extremely tired while running a 10-kilometer road race near my home in South Hadley, Mass. Thinking I was probably anemic, not eating right or training poorly, I went to my internist. He said my blood counts were abnormal and sent me for a bone marrow biopsy. I soon learned that I had AML, a fast-moving cancer of the blood.

The "What, me?" response was pretty strong. I ate well and exercised, I didn't smoke and I was slender. But I had to accept it when, within about a week, I found myself in a bed at Boston's Brigham and Women's Hospital, about 90 miles from home. Under the care of doctors from Dana-Farber, I received three rounds of in-patient chemotherapy, with rest periods in between at home, and then my first bone marrow transplant.

It was an autologous transplant, meaning they used my own new, clean stem cells, removed after two rounds of chemotherapy and then returned to me in a rescue mission after a third and powerful round basically cleared out my bone marrow.

I was in remission, but my first Dana-Farber doctor, Daniel J. DeAngelo, told me that remission is not cure. He said that after two years you break out the Champagne, but only after five years can you use the word cure.

After two, then three-and-a-half years passed and normalcy wrapped its arms around me, I got another shock. The leukemia was back. I learned this just after I played in, and won, a doubles match at a tennis tournament.

"Leukemia is curable," DeAngelo said. "We'll get you back on your feet."

"I am on my feet," I thought to myself as I left his office. And then I burst into tears.

This time I would get an allogenic transplant, with stem cells coming from a donor. After the leukemia cells are killed by chemotherapy and healthy donor cells fill your bone marrow, the donor cells patrol your body to fight off any leukemia that might try to sneak back in.

But after six months, I learned a new term, graft failure: The donor cells had packed up and left, leaving my bone marrow almost empty. The cause was uncertain, and the donor was a good match who agreed to try again. After more chemotherapy, I had transplant No. 3.

Six months later, I had that second relapse.

There were so many things to worry about that a nurse who called me Nervous Nellie told me over and over, "Don't worry, they'll figure it out." And as you will see, the incredible doctors did just that.

I had a new donor and a new chemotherapy regimen consisting of three drugs. One of them, Atgam, is made from rabbit serum, and the nurses called it shake and bake, which is exactly what I did while I received it intravenously.

The transplant, on Jan. 31, 2009, went smoothly, but a few weeks later, I developed a severe blood infection, went into kidney failure and lapsed into a coma. One night, it was touch and go. My ex-husband brought my daughter and told my sons to come quickly and to bring their dark suits. Dr. Alyea met with them and said that there were many things wrong with me, but they would tackle them one by one.

And somehow I struggled to the surface, confused, scared and unable to speak. My legs were swollen like tree trunks, and I needed two nurses to turn me over. The nurses, who ranged from kind and gentle to kind and commanding, helped me pull through.

I regained my voice when a nurse nicknamed Big Red asked me, "What's my name?"

"Lisa," I answered in a grainy whisper.

"Say it loud!" she said.

It took all of my strength to say, "Lisa, Lisa, Lisa!"

But from then on I could speak.

After extended sessions of dialysis, my kidneys returned to normal. I was in bed for more than a month. When I got up, slowly and needing oxygen at first just to sit on the edge of the bed, I had to learn how to walk again. Total time in the hospital: three and a half months.

Recovery has been long and slow. Because you are like a baby with no immune system, during the first year you can't go into crowded places, and when you do go anywhere, you need to wear a mask and gloves. When I got back to walking, I was so wobbly I was like a Gumby doll. One day I fell over backwards, hitting my head on the pavement and earning a trip to the emergency room.

Two years after my transplant, I met my donor, Denise. Donors come from all over the world, but in an example of one degree of separation, Denise lives in New Jersey and is in a book group with one of my friends. Like all donors, she did an incredibly generous thing.

We hugged and grew teary as I thanked her multiple times and she thanked me for giving her a chance to save a life.

Now I am pretty much back to myself, despite graft-versus-host disease, a common complication after transplant in which the "graft" recognizes the "host" as foreign and attacks it. I don't have a bad case, but I do take big handfuls of pills and visit Dana-Farber for frequent check-ups.

I watched my daughter graduate from high school and go to college. I was at my middle son's college graduation and shared my older son's joy when he told me that he gave his wonderful girlfriend an engagement ring.

I rejoined my tennis team and, with my longtime doubles partner, won my first match back, an incredible thrill. I worked back up to running, which took a while, because when I first tried, my feet felt like they were made of lead. The Saturday after Thanksgiving this year, my son and I joined some 3,000 other runners in a scenic six-mile crossrace called the Talking Turkey.

I couldn't go back to work fulltime, but I have been doing freelance writing.

I am left with this question: How do you deal with it when you know that the same bus can hit you twice? You worry that all sorts of things – mainly fatigue - can signal a relapse. I talk to myself. "Maybe you're tired because you just played two hours of tennis." Oh, right.

The passage of time helps. So does hitting the ball on the sweet spot, or doing yoga, or feeling my feet hit the ground when I run, or sitting on the couch watching TV with whichever child is home, or watching the dog lie in the sun at my feet while I write or read. I laugh a lot. Sometimes when I roll over in bed, I flash back to when I couldn't do it myself, and I am so grateful to do that simple thing that I never would have thought about before.

I try to take it one step at a time, appreciating all that I have and looking forward to the good things.

Born and raised in New York, Ronni Gordon lives in South Hadley, Mass., where she raised her three children, Ben, 26; Joe, 22; and Katie, 19. She is a graduate of Vassar College with a master's degree in journalism from Boston University. She spent most of her career in daily journalism as a features writer at the Republican, in Springfield, Mass., and has been published in The New York Times, The Philadelphia Inquirer and elsewhere. She now spends her time freelancing, writing her blog (runnerwrites.blogspot.com) and working on her tennis game.

• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions
• Drug approved specifically for treating myelofibrosis

Emerging treatment option for myeloma presented at hematology meeting

BY GUEST BLOGGER | JANUARY 6, 2012

CURE invited Diane Gambill, PhD, a CURE advisory board member, to share her thoughts on advancements in myeloma highlighted at the 2011 annual meeting of the American Society of Hematology.

I have blogged about the 'next generation' proteasome inhibitor carfilzomib and will likely have a chance to do so again as this interesting class of drugs expands. The proteasome inhibitors are a favorite of mine because they target a very interesting complex of proteins inside cells that was discovered in the 1990s. The proteasome helps the cell get rid of proteins that are made incorrectly or that get damaged once they are already made. Since myeloma cells grow rapidly and are actively making lots of proteins, they accumulate damaged proteins more quickly than normal cells. If cells cannot get rid of damaged proteins, they will die.

This explains, at least in part, why the proteasome inhibitor currently available in the clinic, Velcade (bortezomib), is effective in treating myeloma. Velcade and the immunomodulator Revlimid (lenalidomide) have become standard therapies for myeloma; unfortunately, not all myeloma cells are killed by standard treatments. Some myeloma cells are naturally resistant to treatment (referred to as treatment refractory) while others become resistant during treatment. Several studies are under way or completed that suggest carfilzomib might be active in myeloma that is refractory to treatment or becomes resistant during the course of treatment.

Two phase 2 trials have been conducted to study the efficacy of single-agent carfilzomib in treatment refractory or resistant myeloma. The PS0-171-003-A1 trial was reported at ASCO in 2011 [Proteasome inhibitors in myeloma: The next generation] and showed that 24% of patients who had previously received Velcade or Revlimid responded to carfilzomib. These responses were long lasting and there was a relatively low incidence of adverse events, including peripheral neuropathy (1% grade 3/4). Grade 3/4 peripheral neuropathy, which is considered moderate to severe neuropathy, occurs in about 8% of patients treated with Velcade for relapsed/refractory myeloma.

The second phase 2 trial with final results reported at ASH 2011, PX-171-004, showed similar results. This trial examined response to carfilzomib in patients who had relapsed or refractory disease but had not previously received Velcade. The response rates in this trial ranged from 42% to 52% depending on the dose of carfilzomib (20 mg/m2 or 27 mg/m2) with the higher response rate achieved with the higher dose. Responses were durable with a median time to disease progression of 8.3 months and 13.1 months at the low and high dose, respectively. This is an important result because the majority of patients had previously received an average of two prior therapies including Revlimid and/or stem cell transplant. The safety profile was similar to that seen in the PX-171-003-A1 trial.

One question frequently asked about carfilzomib is whether the decreased rate of adverse events is 'real.' In other words, do these statistics have any meaning for individual patients? The answer appears to be yes. A pooled analysis of overall safety from these phase 2 studies was also reported at ASH 2011. The pooled analysis showed that only 10% of the 526 patients on these studies required a dose reduction because of side effects. Eighteen percent of patients were able to stay on the treatment for at least 12 cycles. With regard to peripheral neuropathy, only five patients (1%) required dose reduction or discontinued therapy.

The ability of patients to tolerate their therapy for multiple cycles is important in achieving a response. Preliminary results of a continuation study suggest there are no cumulative long-term effects of single-agent carfilzomib.

Based on the results of PX-171-003-A1, the FDA has granted a standard review for consideration of approval of carfilzomib. This means a decision on approval will likely occur in the fall of 2012. A word about phase 2 trials, though: We have seen many instances where phase 2 results are not substantiated in randomized phase 3 trials. Even if approved on the basis of the phase 2 trial, the FDA will likely require a phase 3 study to confirm the phase 2 results. Phase 3 trials are under way in Europe and the U.S. The European trial, FOCUS, is evaluating carfilzomib versus best supportive care in patients who have had three or more prior therapies. The U.S. trial, ASPIRE, is assessing combination therapy with Revlimid/dexamethasone with and without carfilzomib in patients who have received one to three prior therapies.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions
• Drug approved specifically for treating myelofibrosis

Studies highlight progress in lymphoma, pose more questions

BY GUEST BLOGGER | DECEMBER 30, 2011

CURE asked Anas Younes, MD, professor in the department of lymphoma/myeloma, division of cancer medicine at M.D. Anderson Cancer Center in Houston, and a CURE advisory board member, for his thoughts on the lymphoma advancements announced at this year's American Society of Hematology.

I finally got to blog on what is news at this year's ASH meeting in San Diego. Almost 20,000 people attended the meeting, and more than 1,000 studies were presented on hematologic malignancies and benign hematologic disorders. But for lymphoma, I think the most important studies are the following three. That is not to say that other studies are not significant, but I think the following ones have a more relevant impact on the treatment of lymphoma. I will explain why.

A Phase III Randomized Intergroup Trial (SWOG S0016) of CHOP Chemotherapy Plus Rituximab Vs. CHOP Chemotherapy Plus Iodine-131-Tositumomab for the Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphoma We all know that radioimmunotherapy (RIT) is active therapy for lymphoma. Two drugs (Iodine-131-Tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are already approved by the FDA for the treatment of relapsed follicular and indolent lymphoma. But in clinical practice, the use of RIT has been relatively modest compared to other newly approved drugs. Despite the documented safety of these agents, there is still a perception among oncologists and patients that these agents are not as safe as other drugs. Many of us wanted to see whether the use of RIT may improve patients' survival, which has not been shown in a randomized study. If so, such data would certainly re-energize the RIT field. This phase 3 randomized study was positioned to answer such a question.

Unfortunately, there was no difference between RCHOP and CHOP followed by Bexxar. I am sure many experts will try to dissect the data in many different ways, including whether this data is applicable to all RITs or just Bexxar. Should we do another randomized study with Zevalin? May be with rituximab maintenance? Should we include rituximab in both treatment arms as part of the induction? But at the end of the day, this trial as good as it is, will not help move RIT forward. With the current competitive environment that includes many new promising agents that have minimal side effects, I think the use of RIT, as we currently know it, will continue to decline.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma Brentuximab vedotin (or SGN-35) has produces 75 percent response rate in heavily pre-treated patients with relapsed Hodgkin lymphoma (HL). So, it makes sense to move it up front and test in newly diagnosed patients whose tumors are less resistant to therapy. Because HL is highly curable with chemotherapy, such as ABVD, it is unethical to test brentuximab alone in these patients. Instead, it makes more sense to add it to ABVD hoping the combined brentuximab + ABVD will be more effective. However, to prove the point, multiple steps needed to be taken. The first step was the core of this clinical trial: Is it safe to combine brentuximab with ABVD, and what is the optimal dose that we can use in such combination? Because ABVD is the standard regimen, it is kept intact while the doses of brentuximab are escalated to maximum dose.

During the conduct of this study, an increase in the incidence of lung complications were observed, which were similar to bleomicin toxicity: shortness of breath, dry cough and lung infiltrate. This toxicity was reversible in 9 of 10 patients with simple measures that included discontinuation of bleomycin and administration of steroids. But because bleomycin is the weakest drug in the ABVD regimen, and usually associated with unpredictable lung toxicity, it was eliminated to generate a brentuximab + AVD combination. At the time of the study presentation, brentuximab + AVD was not associated with any lung toxicity.

What was presented at ASH and was not in the printed abstract is the results of interim PET scan results after two cycles of therapy. With ABVD alone, we typically see 20 percent to 30 percent of the patients continue to have PET positive scans after 2 cycles, which usually correlate with bad prognosis. In contrast, after 2 cycles of brentuximab-based therapy (with ABVD or AVD), only 3 percent of the patients had positive PET. So these results look very encouraging, but of course we need more time and longer follow up to find out what this all means. Obviously, the ultimate test will be to compare the standard ABVD with the new regimen brentuximab + AVD in a randomized trial. This study is planned for the end of 2012. The outcome of such trial may indeed change the standard of care for patients with HL.

The Bruton's Tyrosine Kinase (BTK) Inhibitor PCI-32765 Induces Durable Responses in Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Follow-up of a Phase Ib/II Study and The Bruton's Tyrosine Kinase Inhibitor PCI-32765 Is Highly Active As Single-Agent Therapy in Previously-Treated Mantle Cell Lymphoma (MCL): Preliminary Results of a Phase II Trial There is a lot of buzz about the promising clinical results with the oral small molecule inhibitor PCI-32765, which inhibits an enzyme called Bruton kinase. Last year, there was emerging data from a phase 1 study that also got a lot of attention. This year, the early results are now confirmed in a larger number of patients with CLL and MCL, both are practically incurable lymphoid malignancies.

In CLL, a 70 percent response rate was seen in 27 patients treated with 420 mg daily. This single-agent activity data is so impressive, so a randomized phase 3 study is being planned.

In MCL, results from an ongoing phase 2 study reported a response rate of 67 percent, which is also very impressive for a single agent in this disease. If this data continues to hold as more patients are enrolled, a phase 3 randomized study in relapsed MCL will be the obvious next step. There is a clear need for new agents for patients with MCL, and PCI-32765 may as well what we all have been waiting for!

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Drug approved specifically for treating myelofibrosis

With every heartbeat

BY GUEST BLOGGER | OCTOBER 7, 2011

There are some Wednesdays when I sit through chemo wishing that I were somewhere else. Today is different. I know that I'm blessed to be here. I'm thankful for the ability to receive this treatment and to buy more time with family. My dreams take me far into the future.

It has been a sobering week which makes me even more appreciative of this moment. I've lost two friends and my husband's cousin to cancer. I just heard that Steve Jobs died and another friend is in surgery as I type. He is fighting an infection that has spread to his brain.

He had surgery to remove a brain lesion a few weeks ago and has been in rehab since. We talked on the phone yesterday and his stamina and determination warmed my heart. He is regaining the ability to use his hand again and was so happy to be able to actually squeeze it tight! It's a small improvement that in reality is a monumental milestone. We celebrated his accomplishment together, not knowing what the next few hours would hold. After hanging up, I shed tears of joy. Our conversation held emotion that I will never forget, and a friendship with his family that is dear. Hours later, I learned about the infection and his quick need for surgery. I'm thankful now that we had moment to share his triumph, and I am hopeful that soon we will be celebrating another. I also realize had the severity of the infection been known, our joy would have never occurred.

So as my treatment drips, I appreciate the mystery that tomorrow holds. It gives me reason to appreciate the gift of now and to be present and grateful. Ronnie and I walked to the lake tonight and watched the clouds as they drifted in soft peaks; amazed at the sight of the setting sun as daylight turned to dusk. I realize every day what being a "breath away from death" has given to me...and am thankful for the hope that is held with every heartbeat. How fortunate I am to share this with a happy, healthy family and a life that is never less than full.

May you feel the hope with every heartbeat,
Suzanne

Suzanne Lindley has been living with metastatic colorectal cancer since 1998. She is the founder of YES, an organization for individuals living with metastatic liver tumors, and an advocate for C3: Colorectal Cancer Coalition.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions

Dr. Younes highlights important lymphoma studies from ASCO

BY GUEST BLOGGER | JUNE 7, 2011

CURE asked Anas Younes, MD, professor in the department of lymphoma/myeloma, division of cancer medicine at MD Anderson Cancer Center in Houston, and a CURE advisory board member, for his thoughts on the lymphoma advancements announced at this year's American Society of Clinical Oncology.

For the 80,000 or so patients with Hodgkin and non-Hodgkin lymphoma who are diagnosed annually in the U.S., the largest oncology congress in the world, ASCO (American Society of Clinical Oncology), brought some good news and hope for the future. But as expected, several well-designed clinical studies also failed to demonstrate substantial benefits. Going through the large number of presentations, I will highlight the most important ones here.

More is not better for newly diagnosed patients with advances stage diffuse large B cell lymphoma (DLBCL)

DLBCL is a curable lymphoma. However, with current standard R-CHOP chemotherapy, the average cure rate of patients with advanced stage is approximately 50%. When patients relapse, they are treated with a second-line regimen, such as RICE or DHAP, and responding patients get autologous stem cell transplant (ASCT). This strategy can cure up to 50% of responding patients in the relapsed setting. So wouldn't it make sense to offer ASCT (or other forms of more intensive therapy) upfront rather than wait for relapsed disease? But four independent groups, using different strategies, reported that the answer is "No." Thus, RCHOP-21 remains the standard of care.

In the first study from the United Kingdom, Cunningham et al compared dose-dense RCHOP given every 14 days (RCHOP14) with standard RCHOP-21 in 1080 patients. With a median follow up of 39 months, there was no difference in the overall response rate (88% for RCHOP-21 vs 90% for RCHOP-14), complete remission rate, progression free survival (PFS) or overall survival (OS) in the two treatment groups.

Stiff et al compared CHOP-21 (or RCHOP-21) x 8 with CHOP/RCHOP x 6 followed by autologous stem cell transplant (ASCT) in 397 patients with high-intermediate or high-risk (HI/H) age-adjusted international prognostic index (IPI). Although there was a trend for improved PFS for the ASCT arm, there was no difference in OS (74% for chemo + ASCT vs 71% for chemo alone). This means that it did not matter whether a patient had ASCT upfront or at the time of relapsed disease. However, from a practical point of view, keeping ASCT for the time of relapse seems more appropriate.

Schmitz et al also compared intensive front-line therapy with stem cell rescue using 3 sequential courses of R-Mega-CHOEP with R-CHOEP-14 in 306 young high-risk patients with aggressive B cell lymphoma and found no significant difference between the two treatment arms.

Finally, Milpied and colleagues compared 8 cycles of RCHOP14 to a different regimen that incorporated ASCT and reported no difference between the two treatment approaches, and RCHOP14 was as good as the ASCT-containing regimen. Because RCHOP14 is as good as RCHOP21, as discussed above, the standard of care remains RCHOP21.

Increasing impact of targeted therapy and small molecules

So if more is not better, how do we improve on RCHOP21? Incorporating novel targeted therapy with RCHOP is the way to go. But for these trials to be successful, we need to incorporate biomarker analysis to preselect patients who are likely to benefit from these novel approaches. Some of these clinical trials have already started. Examples, RCHOP + lenalidomide, RCHOP + bortezomib, and RCHOP + everolimus. Patients are encouraged to participate in these clinical trials so we can hopefully improve the standard of care and move beyond RCHOP.

The best example of successful targeted therapy in preselected patients based on biomarkers is the antibody drug conjugates (ADCs). In this strategy, a naked antibody is conjugated to a drug, or a toxic chemical, that binds to a specific receptor, internalize, and kill the tumor cell by releasing the toxic drug. At least one ADC, brentuximab vedotin (or SGN-35) is expected to gain FDA approval before the end of the year for the treatment of patients with relapsed Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL).

In a study of 102 patients with relapsed HL after failing stem cell transplant, the overall response rate was 75% and the CR rate was 34%. With a median follow up of 9 months, more than half of the patients who achieved CRs remain in remission. Brentuximab vedotin is currently being combined with ABVD in newly diagnosed patients with HL, and other combination studies will be conducted soon. The second study of brentuximab vedotin was in systemic ALCL. The response rate was 86% in 58 treated patients, with 53% achieving CRs. Tomorrow information on the duration of response will be presented demonstrating durable remissions for responding patients, especially those with CRs. A combination study of brentuximab vedotin with CHOP chemotherapy in newly diagnosed ALCL is currently enrolling patients.

But sometimes less specific drugs may give better outcome, as long as toxicity is not increased. An example is lenalidomide, which works by several mechanisms, including antiangiogenesis, immune-stimulatory property, and direct anti-tumor effect. Lenalidomide alone has a good single-agent activity in patients with relapsed diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (28% and 27% response rates, respectively). Because lenalidomide can enhance the immune response, it has been shown to be particularly active when combined with monoclonal antibodies, such as rituximab.

With this background, two groups combined lenalidomide with rituximab (RR) alone or with RCHOP for the treatment of newly diagnosed indolent/follicular lymphoma and DLBCL. In the first trial, Samaniego et al from MD Anderson Cancer Center reported the RR regimen produced an overall response rate of 90% in 70 evaluable patients, with 60% achieving complete remissions (CRs). The overall response rate in 41 FL patients was 87% with the vast majority achieving CRs. These results compare favorably with chemotherapy-based frontline regimens, including RCHOP and R-bendamustine. A randomized study comparing RR with R-Chemo is under development. A second trail combined lenalidomide with standard RCHOP in a phase 1/2 study in patients with newly diagnosed DLBCL. Nowakowski et al from Mayo Clinic treated 30 patients with DLBCL or follicular lymphoma grade 3. Lenalidomide was given on days 1-10 of each cycle, and all patients required prophylaxis with pegfilgrastim. The investigators reported a response rate of 100% with CR rate of 83%. For comparison, the expected response rate with RCHOP alone is 84%-88% with CR rate of 63%-75%. So once again, there seems to be a benefit of combining lenalidomide with standard RCHOP, perhaps due to the enhancement of rituximab activity. Of course, more patients need to be enrolled on the phase 2 part, and if the data continue to hold, a randomized study will be required. As I discussed in my earlier post, as intensified front-line therapy failed to improve treatment outcome compared with standard RCHOP, progress will be made by incorporating targeted and biologic agents in smarter trials. The lenalidomide + RCHOP study is a good example.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions

Starting a Yoga Practice: Practical advice from a survivor turned yoga teacher

BY GUEST BLOGGER | MAY 3, 2011

Libby Lowe, of Yoga Bear, a non-profit organization that provides yoga to cancer patients and survivors, shares how those new to yoga can begin practicing after a cancer diagnosis. Lowe shares Jean Di Carlo-Wagner's story of beginning yoga and later became an instructor for other cancer patients and survivors.

Jean Di Carlo-Wagner's battles with cancer have been as both a survivor and a caregiver. She began her yoga practice before her own fight with stage 3 colon cancer, and as it evolved to accommodate her recovery, her practice remained a source of healing and inspiration. Today, Jean lives and teaches in San Diego, Calif.

"For me, cancer meant starting over and not knowing how long I had or what to do -- it was like being 19 in a 50-year-old body. I knew more about myself, but needed a lot of prayer and meditation. I tried to go to yoga classes, but it was too humiliating. I had no muscle tone and pulled a hamstring folding forward. I didn't know my new body; and my mind and body were not together. I started practicing at home with a tape but I could only do the first 10 minutes, sometimes only five. So, that's what I did ... over and over again. I needed to work on a scale that I had never had to work on," she says.

She realized she couldn't be the only one struggling. Wanting to help others, Jean got certified as a yoga instructor and began by teaching a group of friends before going on to complete a 200-hour certification as well as special training to work with seniors. Today, she teaches many survivors one on one.

"One of the reasons I became a yoga teacher for cancer survivors was to offer a class where students could learn to assess their bodies and move within the integrity of their bodies. In theory, all yoga classes have this self-reflective component, but their baseline for normal is assumed. In a class designed for cancer survivors, or special populations, the practice of relearning our bodies is encouraged and we find our new normal."

Here, Jean offers advice for people interested in returning to or beginning a yoga practice.

First, talk to your doctor to get a sense of what is OK for you. "Bending over may not feel very good to you if you are on chemotherapy, and twists aren't good for everyone either. If you have a mass in your abdomen, for example, it may not feel very good to twist and compress your internal organs. One of my cancer buddies was a long time hula dancer and yogi, but after her first dose of chemotherapy for breast cancer, bending over made her dizzy and weak. She asked me what she should do and I told her that anything that doesn't feel good means it isn't good for her right now," Jean says.

Finding the Right Class

Once you've got the green light and feel ready to try a class, the first step is finding the right one. One great way to get started is to check out Jean's video for beginning students and search Yoga Bear's map of free or discounted classes across the country. Many are specifically geared toward cancer survivors!

You might also start by asking the social worker at your cancer center if there is a yoga program for survivors affiliated with the hospital. If not, call the American Cancer Society and ask if there is one in the community. If you can't find any special programs for cancer survivors, ask if there are programs for seniors. "Most people don't realize that community college classes for seniors accept younger students after they meet their quota of seniors. Most senior class work on increasing range of motion, balance and strength," says Jean.

Here's Jean's self-assessment list to help you determine where you might want to begin:
• Can you walk half of a mile without getting winded?
• Can you fold forward to touch your knees, shins, or the floor without getting dizzy?
• Can you lie comfortably on your back, your hip and your stomach?
• Can you get down on all fours?
• Can you twist, raise your hands above your head; balance on one foot?

If you answered "no" to three or more questions, don't worry! You can still do yoga. Jean suggests starting with a restorative class or chair yoga.

If you answered no to two or more questions, you might like a gentle beginning class that is no more than an hour.

"The more times you answered yes, the more choices you have. However, during cancer treatment, staying active is encouraged, but metering out your energy is also advisable. There's no point in blowing a whole day's energy on one activity," says Jean.

Once you have a sense of your level, search local studios online; don't be afraid to call and ask specific questions to find the right instructor and class for your level. Many studios offer introductory classes or series. These courses are a great way to get started and connect with a community of other beginners. Because there isn't a national, standardized certification for teaching survivors, ask questions and do your homework before taking any class.

Here are some questions that might be helpful:
• What is the level of students who usually come to your class?
• Are you familiar with cancer treatments?
• Do you have experience working with people with illness or injury?
• Do you give alternatives movements for people with special needs?
• How long have you been practicing, teaching?

Classes with names like Gentle Yoga or Restorative Yoga are usually great for beginners and those with illnesses or injuries.

"Gentle yoga can mean different things to different people, but it's an indication that the class will be slower. Studios that specialize in working with students that are health challenged are out there and growing," says Jean. "My original training at A Gentle Way in La Mesa, Calif. is run by Lanita Varshell, a plus-size woman with fibromyalgia. When you walk into the studio, you can tell from the abundance of blankets, pillows, straps and blocks that the studio has many yoga props and adaptations."

Restorative classes incorporate many props and focus is on breath awareness, deep and total relaxation and allowing gravity and proper propping to ease muscles into position. One the other hand, classes with words like "power," "hot" and "core" in the title will be too intense for beginners--especially those in treatment or recovery.

Setting Your Intention

Above all, yoga should feel good. Ideally, when you walk out of class you will be grateful for the time you dedicated to yourself, feel empowered in your own skin and proud of what your body can do.

When Jean started her post-treatment practice, she realized she had to honor where her body was and not get hung up on what she once was able to do.

"Ask yourself what the main goal for your yoga practice is and be willing to do less and feel more. During cancer, a good day for me was taking a shower, making dinner and possibly feeding the cat. I was very frustrated that my regular routine of exercise was interrupted and I had no idea who to ask or where to go. After abdominal surgery for colon cancer, I was given three weeks to recover and chemotherapy was started. I crawled into bed and stayed there, unless I was throwing up."

Jean advises beginners or those returning to exercise not to get caught up in trying to master specific poses, but to get in touch with the original intention of yoga: deep meditation. When she started her own practice, she admits that the relaxation at the end of class--called savasana--seemed like a waste of time to her. As her practice deepened, that chance to relax and full let go became the central focus.

"Be curious about the journey you are embarking on and allow a sense of humor into your practice. Yoga is for our joy, our gratitude and our love of life. It is a life-affirming activity that brings us back to very basics of being alive: it focuses us on our breath and our heartbeat. As long as you are breathing consciously, you are doing yoga. When you outstretch your hand to help another, you are practicing Karma yoga. When you kiss a beloved and hold their gaze, you are practicing Bhakti yoga. We are never not practicing yoga, we are just not attending to our practice."

The basics:
Many people are nervous walking into their first class. Here are some tips to make it easier.
• Go barefoot and wear clothing that is comfortable but not too loose. Loose clothes can get in the way.
• Bring water and a towel.
• It's okay to take breaks during class or leave to go to the restroom.
• Most studios have mats your can borrow, but check before you go. If you have joint issues, you may want to consider purchasing an extra-thick mat or using two mats.
• Respect your limits. It's okay not to do a pose if it's uncomfortable. An instructor who crosses over from encouraging to pushy isn't the right person for you.
• Yoga is about finding joy in the present. Don't worry about "doing it right." Have fun and celebrate what you can do.

Libby Lowe is social media manager for Yoga Bear.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions

Exciting data released at ASH encourages the MMRF

BY GUEST BLOGGER | DECEMBER 22, 2010

CURE invited Anne Quinn Young, vice president of communications of the Multiple Myeloma Research Foundation, to offer her thoughts on the 2010 annual meeting of the American Society of Hematology and its impact on myeloma.

This year's American Society of Hematology annual meeting featured exciting new data related to optimizing currently available therapies, as well as incorporating next-generation treatments into the treatment paradigm for multiple myeloma. Below is a summary of highlights from key oral and poster sessions focused on multiple myeloma.

• The inclusion of Velcade (bortezomib) in an induction regimen prior to high-dose melphalan and stem cell transplant, as well as consolidation and maintenance therapy post-transplant, continues to lead to high response rates, particularly complete responses (CRs) and near CRs. Moreover, Velcade continues to work as or nearly as effectively in patients with high-risk features like the deletion of chromosome 13q or translocation of chromosomes 4 and 14, ie, t(4;14).

• Maintenance therapy with Revlimid (lenalidomide) continues to delay disease progression (recurrence) when administered in low doses (5-15 mg continuously or for 21/28 days/month) following high-dose chemotherapy and autologous stem cell transplant. It is important to understand that we do not yet know if there is a survival benefit, and longer follow-up is needed. We also do not yet know if there are specific patients who are more likely to benefit from maintenance and/or if there are patients who may not need maintenance therapy given the low risk nature of their disease. The MMRF is committed to better understanding the right therapy for each patient and is investing in research to help answer these types of questions.

• In standard-risk multiple myeloma patients, after three years of follow-up there was no benefit in terms of delay of disease progression or survival for patients who received an autologous stem cell transplant plus a mini-allogeneic transplant versus two autologous stem cell transplants. Given these results and the high rate of toxicities, any type of allogeneic transplant should be carefully discussed with your doctor and only considered within the context of a clinical trial. Follow-up of patients in the trial will continue should the long-term results yield new insights.

• Encouraging results of a phase 2b study of carfilzomib, a next-generation proteasome inhibitor that was facilitated by the Multiple Myeloma Research Consortium, were presented. Of 257 patients evaluated in the study, patients had an overall response rate of 24% to carfilzomib and a median duration of response of more than 7 months. Notably, no patients discontinued treatment due to either new or worsening peripheral neuropathy. A separate analysis of patient responses revealed that patients who had high-risk features such as chromosome 13 deletions, deletion of chromosome 17p and/or t(4;14) or t(14;16) had similar response rates. Based on these positive results, Onyx, the manufacturer, expects to file for FDA approval sometime in 2011. Meanwhile, a phase 3 trial comparing carfilzomib/Revlimid/dexamethasone to Revlimid/dexamethasone is open and accruing patients.

• New data from several trials involving the exciting new immunomodulating drug pomalidomide were also presented. The trials, conducted in the US (one of which was conducted through the MMRC) and in France, included patients who were refractory to both Velcade and Revlimid--patients who are in urgent need of new treatment options. Regardless of the dose schedule under study, at least 30% of patients receiving 4 mg in each trial responded to therapy. There was no evidence of the incidence or worsening of peripheral neuropathy. A phase 3 trial is expected to open in early 2011.

• The novel therapy Zolinza (vorinostat), a histone deacetylase inhibitor, continues to appear to be a promising new option for myeloma patients in combination with standard therapies like Velcade and Revlimid. Poster presentations at ASH revealed compelling but early data on Zolinza in combination with Velcade and/or Revlimid, both for newly diagnosed and for relapsed/refractory patients. Excitingly, one trial, conducted in part through the MMRC, found it could re-sensitize Velcade-resistant patients to the combination of Velcade and Zolinza. This combination drug is being studied in a phase 3 trial and, if the results are promising, it could be FDA-approved for myeloma as early as 2012.

• The results of a phase 2 study of elotuzumab in combination with Revlimid and dexamethasone, a trial that advanced from an earlier MMRC study, were presented. Although treated patients had not previously received Revlimid, the overall response rate was 85%, with a 31% very good partial response or complete response. This is a very early look at the data, but the results are encouraging. Additional data on early studies of elotuzumab plus Revlimid/dexamethasone, as well as elotuzumab plus Velcade/dexamethasone, both of which were advanced through the MMRC, show similarly encouraging data. A phase 3 clinical trial comparing elotuzumab/Revlimid/dexamethasone to Revlimid/dexamethasone is expected to open early next year.

To learn more about these topics and to stay current on the latest multiple myeloma information, visit the MMRF's website at www.multiplemyeloma.org.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions

The research decision paradigm shift

BY GUEST BLOGGER | DECEMBER 11, 2010

CURE invited Kathleen (Kat) Werner, a breast cancer survivor, to serve as a guest blogger during the 33rd annual San Antonio Breast Cancer Symposium, December 8-12. You can read her full story here.

There were two unique presentations today that were less about heady science and more about changing the paradigm of research and how doctors practice. It was a refreshing perspective on the big picture and how we can change direction to make bigger strides in research rather than the small baby steps that make some feel like we are standing still while the cancer world spins around us.

The morning talk was by Dan Ariely, an Israel-born professor of psychology and behavioral economics who teaches at Duke University. I'll admit I had never heard of him when he stepped up to the podium. His talk was a fascinating glimpse into a non-cancer specific examination of the decision-making practice that can be applied to health care providers and how they consult with their patients.

I wish he had had more time to speak, because he only just touched on the issues he has published in his bestsellers, Predictably Irrational and Upside of Irrationality. He explores that we are often trained into what becomes our "gut reaction," and that this instinct can often be guided by so many other societal pressures, and often it is flat-out wrong.

He challenged the audience of researchers, advocates and health care providers to consider a paradigm shift from status quo or standard practice and really think of what is best for each patient rather than what is easy, takes less work or may be counterintuitive. He gave an example of something called, "The Jam Study" in which people where given 24 choices as opposed to six choices of jam and the sheer quantity of choices made the person less likely to buy jam at all. The argument could be made that this is a study of people's choice in fruit preserves and not something nearly as important as major health care decisions, but his data actually proves otherwise.

Health care providers need to be mindful that a balance needs to be struck with patients in providing good viable options, but overwhelming the patient, without coming alongside them to make sure they are properly educated, can cause the patient to shut down and refrain from really considering the details and real cost of all options.

In the afternoon, Dr. George Sledge from Indiana University Simon Cancer Center (and current president of ASCO, the American Society of Clinical Oncology) gave the William L. McGuire Memorial Lecture (a honor given once a year in memory of Dr. McGuire, one of the founders of SABCS.)

By the title, "What would Bill do? Channeling your inner McGuire" it would seem, at first glance, like a witty discussion on the state of where research is going. Dr. Sledge did not mince words in really laying out some priority changes that need to happen within breast cancer research if we want to get serious about finding cures.

His seven point "rules" touched on some important issues that are being ignored by many researchers. His primary issue was the respect we need to have for the tissue sample itself; keeping it long term, obtaining demographics around it and collecting normal breast tissue for comparison. (For the record, Susan G. Komen for the Cure has established the Komen Tissue Bank at Indiana University for exactly this purpose.) Dr. Sledge also spoke to the importance of the research environment both in practice and the people who practice it. He chided the room to be serious in pushing for clinical trials rather than becoming dependent on diagnostic studies. He also sang the praises of how he had surrounded himself with "excellence" but working alongside great researchers who were always willing to challenge the status quo. Most importantly, Dr. Sledge reminded us that, "The clinic is the final laboratory."

This tremendously important issue calls to mind that just because something works in cell lines, mouse models or data sets, does not mean it will work in the human patient. The media is quick to jump on data showing huge promise in these models (see the excitement over breast cancer vaccine studies) but the reality is, we just have not seen most of these exciting advancements in the human being. Last time I checked I was not a rodent, and thankfully my research validity did not die after 14 days when I was dissected for research. These are, of course, important stepping stones in the research process, but they need to be considered for what they are--simply a start.

Kathleen "Kat" Werner is a cancer research advocate after being diagnosed with breast cancer at age 31. She travels the country and sits at the table with private and government agencies, fighting for the best treatments for newly diagnosed women and ultimately a cure for breast cancer. She lives is Blacksburg, Virginia with her husband of 11 years, Jeff, and her three young children. Read her blog, "Next Generation Research Advocate."

• Breast cancer research in 2010 and the Breast Cancer Deadline 2020
• Where are we in breast cancer research?
• Another SABCS comes to a close
• Why is the San Antonio Breast Cancer Symposium so unique and special?
• A disquieting moment: Two steps backwards?

Power with the patient

BY GUEST BLOGGER | DECEMBER 9, 2010

CURE invited Kathleen (Kat) Werner, a breast cancer survivor, to serve as a guest blogger during the 33rd annual San Antonio Breast Cancer Symposium, December 8-12. You can read her full story here.

There were three main sessions today at the San Antonio Breast Cancer Symposium (SABCS) that had some of my fellow advocates discouraged that we weren't getting very far on the fight against breast cancer. I saw the sessions a little differently, giving some of the power to the patient to decide how they are going to attack breast cancer without having to worry about overcomplicated issues clouding their decisions.

A session in the morning shared various endocrine treatments for hormone-positive cancers and their comparisons of effectiveness. Then I attended a mid-day heated discussion on the evidence for and against changing mammography guidelines for women ages 40 to 49. In the afternoon, we had a frank look at BMI (Body Mass Index) and survival outcomes for women with breast cancer.

At first glance, all three seemed to be a recycle of the same issues and no new really revolutionary findings, but what I saw in these sessions was the ability for the patient to have some control in screening, treatment and even long-term outcomes.

The first session presented data from eight trials looking at various endocrine therapies (primarily aromatase Inhibitors or "AIs") with trade names like: Arimidex, Aromasin and Femara. Each study wanted to examine the effectiveness of different AIs verses tamoxifin or each other or perhaps in different doses over different time periods. The simplified bottom line, to most of these studies, is that that new medicines are not working much more effectively than some of the old standards, and that most AIs can be interchangeable without sacrificing efficacy.

This may seem discouraging to those of us looking for the next great cure, but the silver lining in all this is that the old (and often much cheaper) drugs can work for patients. Also, it means that if patients are having issues with AIs, such as joint pain, they can try other AIs and not feel like they are sacrificing their long-term outcomes. This may seem like a step backward, but it is a short-term victory for patients who don't have access or funding for the latest and greatest drugs being offered on the market.

At the session on mammography guidelines, the audience knew it was in for some varied opinions just from the title, "Controversies in Screening for Breast Cancer." I don't think anyone walked into that room naïve enough to think the mammography debates would be solved within an hour's time, but some great diverging opinions (all fairly well supported with various studies) definitely emerged. The one area all seemed to agree on was that WAY more information was needed to assess the whether benefits outweigh the harms for patients, especially those in the 40-to-49 age group, before everyone can feel confident a concrete guideline can be set. The standard for success also needs to show the full range of outcomes including: surgery type, treatment, chemotherapy, node involvement and most often missed, quality of life.

Five-year survival rates are not the only outcome that is important. A question from the audience was very telling, "Can we trust already overburdened primary care doctors to be knowledgeable enough about what constitutes a high-risk patient when guidelines suggest they are suppose to help guide patients through this decision process?"

Applause erupted. At the end of the day, the burden falls to the patient. We are the ones that need to equip ourselves to know our family history, possible genetic counseling and our breast cancer risks. In this day and age, there is little excuse to access of information. A greater concern can definitely be put on the quality of this information, but this problem is one we can solve. The patient has the power to seek opinions to more knowledgeable providers if needed. The patient has the power to ask questions when they are unclear. The patient has the power to contact government programs, local advocacy groups and their insurers to get services if needed. These resources, while often strained, are available and can be a great catalyst to worthy change of the system.

Lastly, a sobering reality on the direction of general health concerns in our country. A session covering three studies looking at the role of obesity, as measured by BMI, and how it affects outcomes in effectiveness of treatment, recurrence rates, disease-free survival and overall survival. All three studies showed that for women who have hormone-positive breast cancer have worse outcomes in several areas. Even when they account for dosage and account for levels of medicine relative to body size, the women who had a BMI of 30 or greater had significantly worse outcomes than those who had a lower BMI.

Of those women who did have a recurrence, their average time of recurrence to death was also shorter. It can be hard not to feel like if you are an obese woman and you are diagnosed with breast cancer that you do not have a death sentence. However, this research has spurred researchers to look very seriously at lifestyle change, nutritional counseling and reducing BMI as a real viable option in helping women reduce their recurrence rates.

This should be looked at as a positive message that women have an issue that they can work at to make a real change in their outcomes. The power is in the patient to make healthy lifestyle choices and reduce their BMI to make a measureable change in reducing their future breast cancer risks. More research is needed in how quickly and to what level these changes can be made to make the most impact on these numbers.

Kathleen "Kat" Werner is a cancer research advocate after being diagnosed with breast cancer at age 31. She travels the country and sits at the table with private and government agencies, fighting for the best treatments for newly diagnosed women and ultimately a cure for breast cancer. She lives is Blacksburg, Virginia with her husband of 11 years, Jeff, and her three young children. Read her blog, "Next Generation Research Advocate."

• Breast cancer research in 2010 and the Breast Cancer Deadline 2020
• Where are we in breast cancer research?
• Another SABCS comes to a close
• Why is the San Antonio Breast Cancer Symposium so unique and special?
• A disquieting moment: Two steps backwards?

Dial it in: Cancer patients find relief from pain, depression through phone calls

BY GUEST BLOGGER | JULY 21, 2010

Audrey Rabalais, a senior journalism major at Ohio University, is a summer editorial intern with CURE.

No matter the cancer type, the two most common symptoms, pain and depression, are sometimes unavoidable and too often overlooked.

"Because oncologists are busy with testing, chemotherapy, and other treatments, they often have too little time left for quality-of-life issues, like pain and depression," says Kurt Kroenke, MD, of the Regenstrief Institute in Indianapolis, the main investigator in a new study by the Indiana University School of Medicine. The study showed automated phone calls and follow-up calls by nurse managers help mitigate the symptoms of pain and depression in cancer patients.

Over 400 patients from 16 community-based oncology practices participated in the 12-month Indiana Cancer Pain and Depression (INCPAD) trial. Participants, with an average age of 59, lived in both rural and urban areas and had expressed symptoms of pain, depression, or both.

Patients were randomly assigned to one of two groups and then stratified by symptom type. The control group received standard care, which included informing patients of their pain and depression symptoms and then providing screening results to their oncologists. No further medical attention was given for these symptoms unless emergency situations arose. The intervention group used home-based symptom monitoring. They received phone calls from a nurse care manager four times during the first three months of the study. The nurse care manager then worked with a specialist to discuss symptom management and treatment. Any treatment recommendations were then sent to the patients' oncologists.

The automated monitoring was administered through either phone calls or online surveys that decreased in frequency as the study progressed. Patients were asked to assess their pain and depression through a 21-item survey. If the patient indicated symptoms had worsened, medication was not being taken, or there were adverse effects, the nurse care manager was automatically alerted.

Patients in the intervention group reported greater improvements in pain and depression severity than the control group. Improvements in the intervention group were also seen in other areas, such as vitality and anxiety.

According to the study, which was published in The Journal of the American Medical Association, the INCPAD trial confirmed that telephone-based centralized symptom management can be effectively used across geographically dispersed urban and rural community-based practices when coupled with human and technology care systems. This is good news for oncologists, who can rely on "collaborative care" with other team members to help their patients in areas that they may be stretched to provide assistance. This way, the oncologist can focus on prescribing medicines and a course of action while patients receive all-around care. So, while the oncologist may benefit, the patient surely comes out a winner in this deal, receiving optimum, focused care for their physical and psychological symptoms.

Also, in the information age, the use of telephone and online communication is quick and convenient so patients don't have to leave their homes and care managers don't have to leave the office. The electronic system also may be a more comfortable way for patients to assess their own levels of pain and depression. When one is sitting in a doctor's office and put on the spot to speak critically about symptoms, the pressure to answer on the spot and without a source of relevance is enough to make one clam up or just plain forget. However, if I have something in front of me with a 1 to 10 scale, and no one is staring me down for an answer, I have time and ease to truly assess what is being asked of me. This is especially important for pain management, as any pain could be an indication of conditions that need attention. Electronic surveys are efficient and accurate, so the turnaround time for treatment is much faster than with standard care.

If you're doing the mental math with me, we'll come to the conclusion that technology means faster response time, a reduction in costs, and a more accurate symptom assessment. This means more time and money to treat more cancer patients. I think that sounds like a good step toward more birthdays.

• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology
• Studies highlight progress in lymphoma, pose more questions