Tomas Sandoval was about to become a father for the second time in June 2014, when he was devastated to learn he had non-Hodgkin lymphoma, a type of cancer that starts in the white blood cells. The College Station, Texas, resident underwent a stem cell transplant at MD Anderson that kept his disease in check – for a year.
In June 2015, doctors discovered a large chest mass that revealed Sandoval’s cancer had spread. With few options left, he joined a clinical trial testing CAR-T cell therapy for the treatment of lymphoma. Led by Sattva Neelapu, M.D., professor of Lymphoma and Myeloma, the study is the first multi-center trial of its kind for lymphoma.
How it works
In CAR-T therapy, a person’s own T cells – disease-fighting immune cells – are removed and sent to a lab where they are genetically re-engineered to produce chimeric antigen receptors (CARs) on their surface. CARs are proteins that allow T cells to recognize cancer.
The CAR T cells are then multiplied in the laboratory until there are millions. Next, they’re sent to the hospital and infused back into the patient’s bloodstream. These “attacker” cells not only recognize and kill cancer cells, but they may remain in the body long after the infusion has been completed and guard against cancer’s recurrence.
CAR-T cell therapy is part of a growing field of cancer treatment called immunotherapy, a broad term that covers a range of treatments that harness patients’ immune systems to fight cancer. Other forms of immunotherapy to treat cancer include monoclonal antibodies, which are designed to attach a very specific part of a cancer cell; vaccines, which stimulate an immune response against cancer; and immune checkpoint inhibitors, which take the “brakes” off the immune system so it can recognize and attack cancer cells.
Immunotherapy has proven successful in many cancers such as melanoma, lung and kidney cancer, and Hodgkin lymphoma with several drugs already FDA-approved. And with more than 65 trials underway to test immunotherapy’s effectiveness in battling blood cancers such as chronic lymphocytic leukemia, myelodysplastic syndrome, non-Hodgkin lymphoma and acute myeloid leukemia, MD Anderson is considered a leader in the field.
“Most major cancer centers have two or three leukemia trials using immunotherapy,” says Naval Daver, M.D., associate professor of Leukemia. “We have more than 15, and are very much out front. It’s an exciting area of study and we are seeing some encouraging results in patient responses.”
MD Anderson is conducting several dozen clinical trials involving investigators from multiple departments, programs and other institutions and companies that are studying various immunotherapy agents for blood cancer. Learn more about these trials in Conquest magazine.
Until recently, patients with smoldering myeloma had no option but to watch and wait for the inevitable progression to malignancy. But now, two clinical trials of immunotherapy drugs offer patients with the precancerous condition a chance to delay disease progression and perhaps add years to their lives.
Smoldering myeloma has no symptoms and is diagnosed chiefly by levels of myeloma-produced proteins (e.g., monoclonal protein, free light chain proteins) in the serum and clonal plasma cells in the bone marrow. These levels help clinicians classify patients’ disease as low, intermediate, or high risk.
Because smoldering myeloma is expected to progress to multiple myeloma, a patient’s risk level indicates how soon this progression is likely to occur. Intermediate-risk smoldering myeloma, for example, indicates a 50%–74% chance of progression to multiple myeloma within 5 years. Patients’ risk levels help determine the frequency of clinic visits to monitor their disease.
Although observation is the standard management strategy for smoldering myeloma, several clinical trials have evaluated the use of approved multiple myeloma chemotherapy regimens to delay the progression of smoldering myeloma. One recent study, a multicenter phase II trial, evaluated a regimen of carfilzomib, lenalidomide, and dexamethasone in patients with high-risk smoldering myeloma. The results were promising; however, the regimen was arduous for patients.
“Patients in that trial had two infusions a week for 8 months, plus stem cell collection for transplant-eligible patients,” said Elisabet Manasanch, M.D., an assistant professor in the Department of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center and a co-investigator of that trial. “Patients who have smoldering myeloma usually are not feeling sick, so it’s difficult for them to accept a disruptive treatment.”
In search of less invasive treatments to delay the progression of smoldering myeloma, Dr. Manasanch and her colleagues turned to immunotherapy. She is the principal investigator of two ongoing clinical trials of different immunotherapy approaches.
Pembrolizumab, which inhibits the immune checkpoint protein PD-1 (programmed cell death protein 1), is approved by the U.S. Food and Drug Administration (FDA) for the treatment of several advanced cancers and has been studied against multiple myeloma. Promising results from an early trial of pembrolizumab plus low-dose chemotherapy drugs in patients with relapsed/refractory multiple myeloma led to a similar phase III trial (No. 2015-1037), which is ongoing but no longer recruiting patients. To see if the drug can slow the progression of smoldering myeloma, Dr. Manasanch is leading a phase I trial (No. 2015-0371) of pembrolizumab.
The phase I trial began enrolling patients with intermediate- or high-risk smoldering myeloma in 2016 and has nearly completed enrollment. Patients receive one intravenous infusion of pembrolizumab per 3-week cycle for up to 24 cycles. The trial’s primary outcome measure is the response rate; response is defined as decreased levels of myeloma-produced proteins in the serum and urine and/or decreased levels of clonal plasma cells in the bone marrow.
Dr. Manasanch is encouraged by the early results seen in the 12 patients who have begun treatment, and she plans to present these findings at the American Society of Hematology annual meeting in December 2017. “These results are a breakthrough,” she said.
CD38 is a glycoprotein that is found on the surface of many lymphocytes and overexpressed on myeloma cells. One drug that inhibits CD38, daratumumab, is approved by the FDA for the treatment of relapsed/refractory multiple myeloma. A phase II clinical trial (No. 2015-0148) of another CD38 inhibitor, isatuximab, is currently enrolling patients who have high-risk smoldering myeloma.
Patients in the trial receive isatuximab intravenously every week for the first 28-day cycle, then every other week for five cycles, and finally every 4 weeks for up to 24 more cycles. The primary outcome measure is the response rate. The safety and feasibility of the treatment will also be evaluated.
“Our goal is to achieve a 70% response rate after 6 months of treatment,” Dr. Manasanch said. She added that she hopes to have preliminary results ready to present in 2018.
For patients with intermediate- or high-risk smoldering myeloma who wish to pursue treatment, immunotherapy drugs—with their lower toxicity profiles—are an attractive alternative to traditional chemotherapy regimens. Dr. Manasanch believes her research will help determine not only which immunotherapy drugs can best delay the progression of smoldering myeloma but also when patients need to be treated (see “Observational Study May Uncover Indicators of Smoldering Myeloma Progression,” below).
“These are important studies, and we’re finding out important things already,” Dr. Manasanch said. “We’re making major steps toward treating this disease.”
For more information, contact Dr. Elisabet Manasanch at 713-745-5067 or firstname.lastname@example.org.
Lee HC, Patel K, Kongtim P, et al. Multiple myeloma and other plasma cell dyscrasias. In: The MD Anderson Manual of Medical Oncology. 3rd ed. Kantarjian HM, Wolff RA, Eds. New York: McGraw-Hill Education; 2016:229–253.
OncoLog, August 2017, Volume 62, Issue 8
Immune-cell based therapies opening a new frontier for cancer treatment carry unique, potentially lethal side effects that provide a new challenge for oncologists, one addressed by a team led by clinicians at The University of Texas MD Anderson Cancer Center with proposed guidelines for systematically dealing with the toxicities of these drugs.
Their work, published recently in Nature Reviews Clinical Oncology, confronts the two main side effects of chimeric antigen receptor T cells, known as CAR T cells, white blood cells genetically engineered to strike cells with a specific target on their surface.
“CAR T cells provide an entirely new level of improved disease response among patients with certain blood cancers and hold promise for more wide-ranging use,” said Elizabeth Shpall, M.D., deputy chair and professor of Stem Cell Transplantation and Cellular Therapy at MD Anderson.
“The algorithms that we published are conservative, detailed, and will help us save lives as we move forward with these exciting but also more toxic therapies,” Shpall said.
The review covers wide-ranging research on CAR-T therapies by many institutions and includes insights based on more than 100 patients treated at MD Anderson, Moffitt Cancer Center in Tampa, Sylvester Cancer Center at the University of Miami, and Mayo Clinic Cancer Center in Rochester, Minn.
Patients were treated by the co-authors with CAR T cells under development at four different companies for leukemias and lymphomas that attack white blood cells called B cells. They target CD19, a protein found on the surface of both malignant and normal B cells.
Cytokine storms, brain stressors and safety
Two side effects have emerged during clinical trials that were previously uncommon to cancer treatments:
- Cytokine release syndrome (CRS), also known as cytokine storm, an escalated immune response that causes flu-like symptoms and can be fatal.
- Neurological toxicity that the researchers have named CAR-T-cell-related encephalopathy syndrome (CRES), which can sometimes lead to lethal swelling in the brain.
Both CRS and CRES are treatable, with early identification important to swift improvement. The review provides specific recommendations for pre-treatment preparation, monitoring of patients during and after CAR T infusion, identifying and staging emerging CRS and CRES, and tailored treatment of those side effects depending upon their severity.
Read more about the study in the MD Anderson Newsroom.
After my double mastectomy in 2002, I vividly remember running on the beach and hearing some teenagers making fun of my child-like figure. Their remarks hurt deeply.
Even though I went on to have my breast reconstruction surgery 29 long months later, I remained sensitive about my body image. Still, I thought I could handle all my emotions.
Then, when I completed my treatments and my oncologist told me he’d see me again in three months, I felt totally lost and frightened. Three months? What was I supposed to do with myself? I had been safely isolated in MD Anderson’s cocoon of care for over a year -- walking the halls, having scans, meeting with my oncologist, surgeon, radiation oncologist and my plastic surgeon.
Finally, my oncologist said, “Estelle, what you need right now is not something I can help you with. What you need is to talk with a therapist who can help you to move forward.”
Seeking support after cancer treatment
Despite my initial hesitation, I agreed to visit MD Anderson’s Psychiatric Oncology Center. It proved to be exactly what I needed. Therapy helped me overcome my what-if fears and taught me to greet each day that comes. I learned to appreciate all the little things– the sunrise, the sunset and the changing of the seasons.
My therapist encouraged me to love my body exactly the way it is. That helped me transform my negative experience on the beach into an opportunity to be thankful that I’m still alive and able to run with my two legs, and it gave me the strength to withstand future incidents. I was once in a store trying on a backless dress when a sales rep told me, “You can’t wear that – you have those scars down your back.” I said, “Oh, yes, I can. Those scars are part of me and my life.” I bought the dress and wore it -- and my breast reconstruction surgery scars -- proudly.
Therapy played such an important role in my cancer journey, but it wasn’t the only support MD Anderson has offered me through the years. The Integrative Medicine Center also helped me nurse my wellbeing. During my breast cancer treatment, an MD Anderson dietitian guided me back to a healthy weight, and acupuncture relieved my anxiety when I developed osteoporosis 11 years into remission.
Joining the effort to improve support for cancer patients
The help I received at MD Anderson has been life-changing, which is why I recently agreed to join the hospital’s Psychosocial Council, an initiative that seeks to enhance patient care beyond medical treatment. This effort includes physicians, nurses, patients, social work counselors, psychologists, health educators, as well as representatives from Chaplaincy, communications, ethics, Patient Advocacy, Volunteer Services and Rehabilitation Services, and we’re all working together to make sure patients receive the best support possible.
Since I joined the council, I’ve learned about all the services that MD Anderson offers to accommodate patients’ needs: the Fatigue Clinic for patients experiencing ongoing exhaustion, Neuropsychology for those dealing with chemobrain, Oncofertility Clinic for patients who may want to have children in the future, Supportive Care, Pain Management and Rehabilitation Services to address life-altering side effects, Social Work for patients and family members who need help coping with the impact of cancer or who want to create advance care directives, the Tobacco Treatment Program for those who wish to quit smoking – and the list goes on.
Cancer doesn’t have be a lonely journey. These services are available because many of us need them. So don’t be afraid to talk to your doctor about what you’re really experiencing or feeling. The support that’s waiting for you could make a big difference in your life. It definitely made an impact in mine.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
As a bald, sick, 26-year-old cancer patient, I wasn't expecting to fall in love. I only weighed about 100 pounds, was taking multiple medications (each with a different set of side effects) and was generally looking unattractive. But that's exactly what happened after I met the woman who would eventually become my wife.
Laura and I connected through an online Catholic dating service in February 2008. We'd only known each other a few weeks when I was re-diagnosed with T-cell lymphoma — a type of non-Hodgkin’s lymphoma. I tried to break it off with her, thinking no woman in her right mind would ever want to date a cancer patient. I was wrong.
Most people would've run the other way, but not her. That’s one reason I knew Laura was “the one” very early on. In fact, the first time we saw each other in person, I thought, “I’ve found my future wife.”
Connecting during my non-Hodgkin’s lymphoma treatment
Initially, our conversations just made me happy. They gave me something to look forward to and think about during treatment. But as we became closer, our conversations seemed to revolve more around us as a normal couple, not around me and the cancer. Laura treated me as if I wasn't sick. With her, it sometimes felt like I didn't even have cancer.
Laura visited me in Houston quite a bit while I was preparing for an allogeneic stem cell transplant. And even though I was experiencing memory lapses, joint pain, digestive problems and other side effects, I was happier than I’d been in years. Just having someone there to constantly reinforce the good things in life made the experience easier to bear and put me in a much better mood.
Even when we talked about my cancer, everything Laura said was positive. She told me funny stories and prayed for me a lot. Those things may not sound like much, but to me, they made a world of difference.
Love and parenthood after my allogeneic stem cell transplant
Any woman who can endure the hard times when her boyfriend is fighting cancer is definitely a keeper. So naturally, when Laura stood by my side through it all, it only reinforced my belief that she was “the one.” I proposed in February 2009, and we married in July of that same year.
When Laura still hadn’t gotten pregnant after we’d been married a few years, we decided to expand our family through adoption. I’d been told that the stem cell transplant would probably leave me sterile, but I chose not to bank my sperm beforehand. We decided to let God grow our family the way He wanted to.
That’s how Audrey came into our lives in 2013, and Aaron in 2015. And it’s how we’re hoping to bring another child into our family.
I can't imagine my life without Laura and our beautiful children. Our road to marriage and parenthood wasn’t the traditional one, but it’s still a miracle.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
Whether you’ve just been diagnosed with cancer or told your disease is terminal, there’s always a place for hope. I truly believe I wouldn’t have made it this far if that wasn’t true.
In 2001, I was diagnosed with a very rare extraskeletal osteosarcoma that had spread to my left kidney. Serious odds were stacked against me, but I pulled through. Unfortunately, sarcoma turned out to be just the beginning of my care at MD Anderson; I’ve since been treated for major side effects, melanoma, and now, stage IV colorectal cancer.
At the end of 2015, I learned that my body wasn’t responding to the treatment, and it was time to focus on improving the quality of my life instead of trying to prolong it.
Making that shift seemed like an impossible task, especially after all that I’d already overcome. Thankfully, I didn’t have to figure it out alone. Dr. Ali Haider, Dr. Suresh Reddy, Diana Guzman Gutierrez and the rest of palliative care team at MD Anderson’s Supportive Care Center have been by my side, helping me cope with the emotional and physical pain that accompanies this life-altering disease.
Accepting my terminal cancer diagnosis
At first, I didn’t think I could ever achieve peace or happiness. I was so afraid of dying that it had consumed my psyche and blinded me from seeing anything else in my life. I also didn’t want to break the news to my family, whom, up until that point, I’d protected from the details of my diagnosis.
During counseling, we had many conversations about living with a terminal diagnosis and finding joy in the days I have left. I learned how to appreciate all the richness that still exists in my life and use the time I have to enjoy my family instead of pushing them away.
Embracing my loved ones and communicating openly with them helped us all eventually accept the situation, and that has turned out to be another source of emotional healing for me. None of us have forsaken hope on our ability to be happy and at peace. That is a blessing on its own.
Making my last chapter count
At some point, I also realized that this is another chapter in my life and a whole bunch of new experiences and memories could be made in it. That’s certainly been the case.
I took Dr. Reddy’s advice and reached out to my friends, so now people from all over the country are coming to visit. We talk about everything under the sun, and we have a great time. In fact, many who thought they were coming to say goodbye were quite surprised that wasn’t my mindset.
This also has been an opportunity to rekindle my spirituality. I had some gut-wrenching intellectual discussions with one of MD Anderson’s chaplains, and that helped me reprioritize what I want to accomplish in my remaining life. I now refuse to waste any time harboring anger toward anyone or anything -- for any reason. Instead, I use that energy to pray for people I love and for things I want.
On the toughest days, I resort to reading because it removes me from the stress of thinking about everything. Yet no matter how lousy I feel, I always take the time to say, “Hi,” and smile at everyone I encounter. Doing so lifts my spirits and has led me to new friendships and experiences, such as serving in an advisory role to a support group organization that I once belonged to.
View life through a different lens
Over the last year and half, I have been able to see life from a new perspective. I've learned that "quality of life" are more than words; they’re a tangible strategy that I can hold onto and guide me in those moments when peace seems to elude me.
The truth is, we all have a choice: wallow in self-pity – and it would be justified – and remain miserable, or get out of the mindset of dying and focus on living. I can tell you right now: choosing the latter is so much better. So travel if you can, appreciate your loved ones, make memories, enjoy your hobbies and smile. Don’t give up hope or any of the things that made you happy before you got sick. You’re still living. Choose to celebrate that.
Request an appointment at MD Anderson online or by calling 1-877-632-6789.
DoCMessages contains feature stories about patient care successes, fellowship research & education, faculty & staff accolades, division events, and administrative updates.
- Harvey Heroes (Vol.14 No.6)
- 2017 Employee Award Winners (special edition)
- The DoCM Idea Survey (Vol.14 No.5)
- ASCO Awards & Trainee Research Day Prizes (Vol.14 No.4)
- Changing the way we schedule patients: Making appointments matter (Vol.14 No.3)
- Women faculty in the spotlight (Vol.14 No.2)
- Saluting our military reservists (Vol.14 No.1)
- Two-time survivor continues to sail through life (Vol.13 No.3)
- Stories of hope: Patients in remission (Vol.13 No.2)
- OneConnect: Countdown to the launch (Vol.13 No.1)
- Lymphoma survivor diagnosed while pregnant delivers healthy baby (Vol.12 No.4)
- Tech guru named Heart of MD Anderson (Vol.12 No.3)
- Immunotherapy trailblazer Patrick Hwu, M.D., new division head (Vol.12 No.2)
- Culture of compassion gives liver cancer patient courage to fight (Vol.12 No.1)
- Spotlight on physician assistants (Vol.11 No.3)
- Teen AML survivor forms gaming community (Vol.11 No.2)
- Preparing for a game-changing code change (Vol.11 No.1)